EarlyOriginsOfHealth ElsevierNov2011

Volume 115 Supplement 1 November 2011 ISSN 0020-7292
GYNECOLOGY
International Journal of
& OBSTETRICS
Early Origins of Health:

The Role of Maternal Health on Current and Future Burden
of Chronic Noncommunicable Diseases
Official publication of FIGO Guest Editors:

The International Federation
of Gynecology and Obstetrics Luis Cabero Roura, Moshe Hod, Anil Kapur, Nicolai Lohse
GYNECOLOGY
& OBSTETRICS
Volume 115, Supplement 1 (2011)
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Supplement to
International Journal of Gynecology & Obstetrics
Volume 115, Supplement 1
Early origins of health:

The role of maternal health on current and future burden
of chronic noncommunicable diseases
Guest editors:
Luis Cabero Roura, Moshe Hod, Anil Kapur, Nicolai Lohse
This Supplement was funded through an unrestricted educational grant from Novo Nordisk A/S, Denmark
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GYNECOLOGY CONTENTS
& OBSTETRICS Volume 115, Supplement 1, November 2011
Early origins of health: The role of maternal health on current and future burden of chronic
noncommunicable diseases
EDITORIAL
L. Cabero Roura, M. Hod, A. Kapur, From biology to policy: The link between maternal health and current S1
N. Lohse and future burden of chronic noncommunicable diseases
Spain, Israel, Denmark
ARTICLES
M.A. Hanson, P.D. Gluckman Developmental origins of health and disease: Moving from biological S3
UK, New Zealand concepts to interventions and policy
New insights into developmental origins of noncommunicable diseases reveal biomarkers of
susceptibility and suggest intervention avenues to reduce risk beyond just focusing on adult
lifestyle.
A. Aviram, M. Hod, Y. Yogev Maternal obesity: Implications for pregnancy outcome and S6
Israel long-term risks—a link to maternal nutrition
The impact of obesity and maternal nutrition on short-term pregnancy outcome and
long-term child health.
R. Gangopadhyay, M. Karoshi, Anemia and pregnancy: A link to maternal chronic diseases S11
L. Keith The anemic condition is often worsened by the presence of chronic diseases such as malaria,
tuberculosis, HIV, and diabetes, which in turn worsen the anemic condition.
UK, USA
D.L. Christensen, A. Kapur, Physiological adaption to maternal malaria and other adverse exposure: S16
I.C. Bygbjerg Low birth weight, functional capacity, and possible metabolic disease in
Denmark adult life
Maternal malaria in some parts of the world is the most common cause of low birth weight
that could potentially impart a future higher risk of diabetes and metabolic syndrome in the
offspring. This relationship has not been studied and needs to be investigated.
N. Lohse, E. Marseille, J.G. Kahn Development of a model to assess the cost-effectiveness of gestational S20
Denmark, USA diabetes mellitus screening and lifestyle change for the prevention of
type 2 diabetes mellitus
The GDModel estimates the effect of gestational diabetes screening and management on
life-long prevention of diabetes. Model development and preliminary results from India and
Israel are described.
H.D. McIntyre, J.J.N. Oats, W. Zeck, Matching diagnosis and management of diabetes in pregnancy to local S26
V. Seshiah, M. Hod priorities and resources: An international approach
Australia, Nepal, Austria, USA, India, The International Association of the Diabetes and Pregnancy Study Groups’ recommendations
regarding diagnosis of hyperglycemia in pregnancy are considered in the context of differing
Israel
healthcare contexts in high-, middle-, and low-income countries, in an attempt to match the
health impact of this condition with available healthcare resources.
M.M. Agarwal, B. Weigl, M. Hod Gestational diabetes screening: The low-cost algorithm S30
United Arab Emirates, USA, Israel The demanding IADPSG algorithm for screening of gestational diabetes could be simplified
with the use of fasting plasma glucose and alternate new technologies, resulting in a cost-
effective and patient-friendly alternative especially for low-resource settings.
W.K. Maina Integrating noncommunicable disease prevention into maternal and S34
Kenya child health programs: Can it be done and what will it take?
Integration of noncommunicable disease (NCD) prevention and control into maternal and
child health programs to improve access to NCD services is described.
S.A. Norris Designing feasible interventions for healthy pregnancies in S37
South Africa low-resource settings
Fostering data demand and evidence utilization, identifying the critical health concern, and
engaging stakeholders early on, are important in designing and implementing interventions
that promote healthy pregnancies.
A. Madhab, V.M. Prasad, A. Kapur Gestational diabetes mellitus: Advocating for policy change in India S41
India, Denmark Media can play a vital role in policy advocacy and formulation for positive policy changes
surrounding noncommunicable diseases in low-resource countries.
N. Lieberman, O. Kalter-Leibovici, Global adaptation of IADPSG recommendations: A national approach S45

M. Hod A one-step approach, recommended by the IADPSG, for the screening of gestational diabetes
is not only cost-effective but cost-saving, even using conservative estimates.
Israel
COMMENTARIES
G.I. Serour, L. Cabero Roura FIGO—A professional nonprofit organization: Reproductive, maternal, S48
Egypt, Spain and child health policy and programs to address noncommunicable
childhood disease
A. Kapur Pregnancy: A window of opportunity for improving current and future S50
Denmark health
ARTICLE
N. Lohse, C. Ersbøll, L. Kingo Taking on the challenge of noncommunicable diseases: We all hold a S52
Denmark piece of the puzzle
Sustainable solutions to the growing global burden of noncommunicable diseases require
broad collaboration between governments, intergovernmental organizations, nongovernmental
organizations, businesses, and the people we serve.
International Journal of Gynecology and Obstetrics 115 Suppl. 1 (2011) S1–S2
Contents lists available at ScienceDirect
International Journal of Gynecology and Obstetrics

j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j g o
EDITORIAL
From biology to policy: The link between maternal health and current and future
burden of chronic noncommunicable diseases
On the back of the United Nations High-level Meeting on Non- circle and describes how anemia in pregnant women with chronic
Communicable Diseases (NCDs) held in New York (September disease leads to small babies, which in return is associated with
19–20, 2011), this Supplement to the International Journal of chronic disease occurrence when the child grows up. The latter
Gynecology and Obstetrics takes a comprehensive view on an spotlights an as yet remarkably overlooked potential link between
important aspect of the burgeoning NCD epidemic that is currently one of the major infectious diseases in the southern hemisphere,
sweeping across the world. This global health challenge has left no malaria, and the NCD epidemic. This link has yet to be proven, but
country untouched and bridges the divide between rich and poor according to the authors more data will shortly be forthcoming. We
countries. We are all affected by the rising prevalence of chronic are waiting with excitement!
NCDs, wherever one takes a closer look. One of the few interventions with an effect on short-term
The concept that the foundation for lifelong risk and susceptibility complications, built on solid evidence from randomized trials, is
to numerous diseases begins in the womb and in early life— detection and management of diabetes in pregnancy—so-called
now referred to by the term Developmental Origins of Health gestational diabetes mellitus (GDM). Proper GDM management
and Disease (DOHaD)—is not entirely new, but has only recently leads to fewer birth complications [5,6], and intensive lifestyle
gained acceptance from the broader scientific community because interventions after birth seem to reduce the risk of chronic
of a swathe of good research producing hard evidence of the disease for many years [7]. But for these interventions to be
link. The biological evidence is there, but its knowledge has taken up by a health system, the balance between cost and effect
remained confined to the academic environment and needs wider needs to be right. Lohse et al. [8] have developed and tested
dissemination. To move from evidence to policy change requires a a mathematical model on data from India and Israel, and have
broad evidence base of proven solutions, including assessments of produced encouraging estimates of the cost-effectiveness of GDM
how much it costs, over how long a period of time, and what health screening on lifetime risk of chronic diseases. If one trusts their
benefits are expected. But policy is never dictated by hard evidence results, introducing GDM screening at population level seems to
alone. It requires advocacy, persistence, and resourceful arguments. be a no-brainer. However encouraging, results from models should
This is particularly important in the current global economic setting be interpreted with caution, and preferably undergo repeated
where there is fierce competition for limited resources and the testing under different conditions. One way to increase real-life
focus on maximizing health impact for the money spent is even cost-effectiveness even further could be to tailor the screening
stronger. and treatment strategies to local GDM prevalence and economic
Economic arguments make focusing on the link between capacity of the healthcare system. While McIntyre et al. [9] suggest
maternal health and future health burden even more relevant and a tiered approach to GDM testing, treatment, and postpregnancy
attractive. We know that provision of good services for maternal follow-up in different income level settings, Agarwal et al. [10]
and child health (MCH) is needed to stimulate development and reanalyze the solid data from the HAPO study in a middle-eastern
reduce high rates of maternal and child morbidity and mortality; cohort of pregnant women and come up with a “lighter” screening
addressing the DOHaD link presents another compelling reason to algorithm in this high GDM prevalence group. They also give
do so with more vigor. The marginal cost of linking MCH services us a glimpse of new candidate technologies for GDM screening,
with health promotion efforts directed at prevention of NCDs is reminding us how an easy-to-use, portable, noninvasive technology
low, but the future savings may be manifold. Who would not want that does not require the woman to be fasting could revolutionize
to prioritize such a low-risk strategy that has high potential gain? access to GDM screening among the millions of women who live
The link has for many years only been discussed and debated in in areas where the distance from home to health centers that have
small circles, so to make this a high priority we need to create more up-to-date equipment available is a major barrier to accessing good
awareness. People working in maternal health are not the only ones quality health care.
who should be aware—we also urge anyone working in NCD control While part of the answer to increased access may lie in new
to address the link in their prevention strategies. technologies, another solution may be to leverage existing systems
This Supplement is an attempt to bring more awareness to the and services. This is the focus of the article by Maina [11] who
issue. It contains articles from global experts, covering the broad rightly and wisely recommends that GDM screening be integrated
range of topics mentioned above. Hanson and Gluckman [1] take into MCH programs. The effect of such integrated programs will
us through the biological basis, including how undernutrition in the need to be tested, and Norris [12] shares with us his experiences as
pregnant mother makes her child vulnerable to a range of chronic he carefully guides us through the steps that should be considered
NCDs over its lifespan. Aviram et al. [2] list the extensive evidence when designing such intervention studies.
for maternal obesity as a risk factor for complications in the mother But no dramatic changes happen in any health system without
and her offspring. Gangopadhyay et al. [3] and Christensen et al. [4] the acceptance from policy makers. Not only do we need solid
cover two aspects of anemia in pregnancy. The former closes the evidence and economic evaluations, we need to package the
0020-7292/$ – see front matter © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
S2 EDITORIAL / International Journal of Gynecology and Obstetrics 115S1 (2011) S1–S2
information in the right way and deliver it to policy makers at the 3. Gangopadhyay R, Karoshi M, Keith L. Anemia and pregnancy: A link to maternal
right time in an understandable manner. This is exactly what both chronic diseases. Int J Gynecol Obstet 2011;115(Suppl 1):S11–5.
4. Christensen DL, Kapur A, Bygbjerg IC. Physiological adaption to maternal malaria
Madhab et al. [13] and Lieberman et al. [14] are doing, but in two
and other adverse exposure: Low birth weight, functional capacity, and possible
very different countries and with the use of quite different methods. metabolic disease in adult life. Int J Gynecol Obstet 2011;115(Suppl 1):S16–9.
The former has stimulated policy change through a media campaign 5. Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, et al. A
targeted at both the general public and at policy makers, while the multicenter, randomized trial of treatment for mild gestational diabetes. N Engl
J Med 2009;361(14):1339–48.
latter has used local data on cost and health impact to create health
6. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of
economic arguments presented to a national committee of scientific treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med
specialists and policy makers. 2005;352(24):2477–86.
Getting attention to the subject of DOHaD on the global scene 7. Ratner RE, Christophi CA, Metzger BE, Dabelea D, Bennett PH, Pi-Sunyer X, et al.
requires buy-in from a global voice. The International Federation of Prevention of diabetes in women with a history of gestational diabetes: effects
of metformin and lifestyle interventions. J Clin Endocrinol Metab 2008;93(12):
Gynecology and Obstetrics (FIGO) is such a voice. Without losing 4774–9.
the focus on major causes of maternal morbidity and mortality, 8. Lohse N, Marseille E, Kahn JG. Development of a model to assess the
FIGO President, Gamal Serour [15], stresses the life-course link cost-effectiveness of gestational diabetes mellitus screening and lifestyle
between NCDs and maternal health, and the unique opportunity we change for the prevention of type 2 diabetes mellitus. Int J Gynecol Obstet
2011;115(Suppl 1):S20–5.
have now for change—an opportunity we should not miss. World 9. McIntyre HD, Oats JJN, Zeck W, Seshiah V, Hod M. Matching diagnosis
Diabetes Foundation President, Anil Kapur [16], makes a call to the and management of diabetes in pregnancy to local priorities and resources:
whole international community for more attention and funding. An international approach. Int J Gynecol Obstet 2011;115(Suppl 1):S26–9.
Finally, Lohse et al. [17] explain the emerging willingness expressed 10. Agarwal MM, Weigl B, Hod M. Gestational diabetes screening: The low-cost
algorithm. Int J Gynecol Obstet 2011;115(Suppl 1):S30–3.
by the for-profit sector to play an active role in global health
11. Maina WK. Integrating noncommunicable disease prevention into maternal and
governance; and specifically the role of businesses to undertake child health programs: Can it be done and what will it take? Int J Gynecol Obstet
part of the daunting task of stemming the tide of NCDs. 2011;115(Suppl 1):S34–6.
Thus, the message of the intergenerational effects of NCDs 12. Norris SA. Designing feasible interventions for healthy pregnancies in
low-resource settings. Int J Gynecol Obstet 2011;115(Suppl 1):S37–40.
and the unique prevention opportunity represented by a healthy
13. Madhab A, Prasad VM, Kapur A. Gestational diabetes mellitus: Advocating for
pregnancy has yet to reach broadly to individuals, organizations, policy change in India. Int J Gynecol Obstet 2011;115(Suppl 1):S41–4.
and governments. Transforming the biological evidence into real- 14. Lieberman N, Kalter-Leibovici O, Hod M. Global adaptation of IADPSG
life change—so-called knowledge translation—is far from complete. recommendations: A national approach. Int J Gynecol Obstet 2011;115(Suppl 1):
But the seed has been planted and it is growing. We are hopeful and S45–7.
15. Serour GI, Cabero Roura L. FIGO—A professional nonprofit organization:
confident that this Supplement, with its views on the topic spanning Reproductive, maternal, and child health policy and programs to address
from biology and epidemiology to policy and service delivery, will noncommunicable childhood disease. Int J Gynecol Obstet 2011;115(Suppl 1):
serve as a source of inspiration and provide valuable information. S48–9.
This Supplement is for anyone who is interested in understanding 16. Kapur A. Pregnancy: A window of opportunity for improving current and future
health. Int J Gynecol Obstet 2011;115(Suppl 1):S50–1.
the developmental roots of the NCD epidemic, and who would like 17. Lohse N, Ersbøll C, Kingo L. Taking on the challenge of noncommunicable
to bring about new knowledge and induce changes at any level. diseases: We all hold a piece of the puzzle. Int J Gynecol Obstet 2011;
115(Suppl 1):S52–4.
Conflict of interest statement

Luis Cabero Roura
Nicolai Lohse is a full-time employee of Novo Nordisk A/S, a Autonomous University of Barcelona, Spain
research-based pharmaceutical company with a strong focus on
diabetes. The other authors have no conflict of interest to report. Moshe Hod
Rabin Medical Center, Tel Aviv University, Israel
References
Anil Kapur
1. Hanson MA, Gluckman PD. Developmental origins of health and disease: Moving World Diabetes Foundation, Denmark
from biological concepts to interventions and policy. Int J Gynecol Obstet 2011;
115(Suppl 1):S3–5.
2. Aviram A, Hod M, Yogev Y. Maternal obesity: Implications for pregnancy Nicolai Lohse *
outcome and long-term risks—a link to maternal nutrition. Int J Gynecol Obstet Novo Nordisk A/S, Denmark
2011;115(Suppl 1):S6–10. *E-mail address: [email protected].

ARTICLE
Developmental origins of health and disease: Moving from biological concepts to

interventions and policy
Mark A. Hanson a, *, Peter D. Gluckman b,c

a Instituteof Developmental Sciences, University of Southampton, Southampton, UK
b LigginsInstitute, The University of Auckland, Auckland, New Zealand
c Singapore Institute for Clinical Sciences, A*STAR, Singapore
article info abstract
Keywords: The rising incidence of noncommunicable diseases (NCDs), especially in young adults, presents great humanitarian
Development and economic challenges to high-resource and, increasingly, to low-resource countries. No longer considered to
Diabetes be diseases of affluence, NCDs are exacerbated by urbanization and changes in social and lifestyle factors such
Interventions as diet and family size. New research emphasizes the importance of early life factors in establishing the risk
Life-course of NCDs through inadequate responses to later challenges, such as an obesogenic environment. A new focus on
Mismatch interventions to promote a good start to life in at-risk populations necessitates revision of public health policy,
Noncommunicable disease with implications for the health, education, and empowerment of women and children in particular.
Obesity © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction: A changing world first-born children rises and they have a greater risk of developing
obesity than subsequent siblings [4]. Such observations raise
Noncommunicable diseases (NCDs), in particular cardiovascular
many concerns, e.g. in relation to China’s one-child policy. Nearly
disease, diabetes, chronic lung disease, and some forms of cancer,
80 million women worldwide suffer from gestational diabetes,
are the world’s biggest killers. Far from resulting from the “diseases
increasing the risk of obesity in their children [5]. Many women
of affluence,” 80% of these deaths occur in low- and middle-income
consume unbalanced diets before and during pregnancy, and weight
countries, especially as these countries undergo socioeconomic
gain in pregnancy is often excessive or, in Japan, inadequate [6].
improvement following reductions in the burden of infectious In some societies, pregnant women undertake substantial physical
disease [1]. WHO predicts an increase of 17% in NCDs over the workloads, in industry or agriculture. Pregnancy in adolescent
next decade globally—higher in some regions, e.g. parts of Sub- girls compromises fetal development and leads to young mothers
Saharan Africa. The risks of NCDs are exacerbated by sedentary dropping out of school. Addressing these problems—for example,
lifestyles and poor diet high in sugar, salt, and fats. This is the in delaying first pregnancy until several years after menarche—
concept of “mismatch” between the developmental environment necessitates empowerment of young women, but raises culturally
and that experienced in young adulthood [2]—a phenomenon of sensitive issues such as access to contraception and loss of
increasing importance in the lifestyle transitions that have occurred earnings.
between generations recently. But individual risk in the mismatched The increasing use of technology associated with reproduction
environment depends on genetic and developmental factors that makes matters worse still. There are steady increases in the use of
affect individual sensitivity to an obesogenic world [3]. Unless this assisted conception services in some societies and alarmingly high
is appreciated there is a risk that the focus of preventative strategies rates of birth by cesarean delivery, reaching 80% of deliveries in
could be misplaced. Alarmingly, NCDs are increasingly present in parts of Brazil, for example [7].
young adults, many in their thirties in low-income regions of the
world, and in individuals who are not necessarily obese by Western 2. The impact of NCDs
standards.
Other demographic and social changes raise additional concerns The substantial financial and humanitarian costs of NCDs may
destabilize the economies of low-income countries, where risk
in light of recent evidence of their effects on risk factors for NCDs
markers become evident early in the process of socioeconomic
in the next generation. As family size falls, the relative number of
improvement and well below the level of affluence associated with
* Corresponding author. Mark Hanson. Institute of Developmental them in high-income nations [8]. This is the “double burden of
Sciences, University of Southampton, Mailpoint 887, Southampton poverty,” but the scale of widening global inequalities in health
General Hospital, Tremona Road, Southampton SO16 6YD, UK. associated with NCDs has only recently been recognized.
Tel: +44 2380 798421; Fax + 44 2380 795255. The increases in NCDs in low- and middle-income countries
E-mail address: [email protected] (M. Hanson). in young adults will have substantial effects on productivity and
S4 M.A. Hanson, P.D. Gluckman / International Journal of Gynecology and Obstetrics 115S1 (2011) S3–S5
lifelong healthcare costs. WHO expenditure on communicable factors operate in all pregnancies, to a greater or lesser extent, and
diseases is disproportionate to that on NCDs—when considered in we are now beginning to understand how aspects of the external
relation to mortality and the disability-adjusted life-years burden— environment are transduced by the mother, during both fetal life
especially in the Western Pacific region compared with Africa [9]. and nursing, and then act via developmental plasticity to affect
The costs of these diseases are of great concern in countries where the characteristics of the offspring [3]. Paternal factors are also
healthcare resources are low. The true costs are not known because indicated by some recent observations [21].
previous attempts to measure such costs focused on the sequelae of
low birth weight and a limited range of outcomes. Newer economic
4. Theoretical considerations
modeling approaches aim to include the impact on cognitive and
noncognitive abilities and on health capital across generations and Such “parental effects” appear to have evolved because they confer
the entire range of human early development [10]. Darwinian fitness by inducing characteristics appropriate to the
NCDs are generally preventable, although promoting such environment in which the mother lives and in which the fetus
prevention was missing from the Millennium Development Goals predicts it will grow up: we termed them predictive adaptive
(MDGs). Thus, new initiatives are now urgently needed. In high- responses [22]. The characteristics affect particular aspects of life-
income countries, current programs aimed at lifestyle alteration course biology such as metabolic homeostasis; numbers of fat,
in adults have been met with limited and variable success, with skeletal, and cardiac muscle cells; nephron numbers; and the
the exception of reducing smoking. Progress in understanding the setting of control systems such as appetite, stress responses, timing
underlying causes of susceptibility to NCD has been slow owing to of puberty, and so forth. Together they affect the ways in which
excessive emphasis on adult lifestyle as the trigger and on fixed the adolescent and adult respond to their environment and so the
genomic variations as determinants of inherited susceptibility [11]. person’s risk of NCD [23]. Because the predictions will be slightly
The concepts of path dependency are clearly relevant. Some different in each individual, they contribute to the differences in
individual variation in susceptibility to environmental stressors is risk of disease between individuals, even if they apparently have
genetic; for example, polymorphisms have been associated with very similar lifestyles.
smoking addiction and the risk of obesity. But fixed genetic Developmental changes made on the basis of such predictions can
variations (for example small mutations and single nucleotide turn out to be inappropriate either because the signals sent by the
polymorphisms, repeat sequences, etc.) can account for only a small mother to her offspring are inaccurate (for example, as a result of
fraction of such risk [11]. Equally, there is some overstatement placental dysfunction or because she consumes an unbalanced diet)
of the effectiveness of lifestyle interventions in adults [12]. The or because the environment has changed from one generation to the
prevalence of obesity in high-income countries continues to rise next. The resulting mismatch between the offspring’s characteristics
and there remains great reliance on medical interventions. Further, and the environment in which it lives confers a major risk of
these diseases are characterized by subtle prolonged prodromes NCDs [2]. We now know that mismatch processes also operate
with subclinical pathophysiology, suggesting an origin much earlier across the spectrum of environmental signals; for example, an
in life. Insulin resistance and abnormal vascular function can be unbalanced maternal diet that is inadequate in a low-income setting
detected in children [13] and considerable data point to prenatal can be as potentially harmful as the high glycemic diet consumed
and early life factors affecting later life disease risk [14]. in many high-income countries.
Whereas the original focus of attention in developmental origins
of disease centered on children born small, even though they might
3. How best to intervene
constitute only a small proportion of the population, it is now clear
Greater attention now needs to be paid to how risks are established that the developmental environment impacts on the life-course risk
in early life. Understanding how the developmental environment trajectory for NCDs of every individual. The story does not end at
influences an individual’s responses to their later lifestyle, and thus birth: epigenetic development can be influenced by how the child
their risk of NCDs, is now largely focused on processes that involve is nursed, by infection or allergen exposure, and perhaps by how
nongenomic inheritance, especially epigenetic processes [15]. the gut is colonized with commensal bacteria [24].
These affect gene expression and development without altering the
genes we inherit from our parents.
5. Policy implications
New evidence demonstrates great opportunities for novel
biomarkers of risk to be devised for use in early life. Such Reductions in child mortality from infectious disease and increased
studies may point to pathways to target for intervention and may life expectancy are changing the age structure of many populations,
pave the way to much more effective approaches to improving and the patterns of disease. The demography of disease is changing
health across the life-course, which can perhaps be customized to quickly around the world, from a pattern dominated by infectious
individual risk. For example, we recently showed that measurement disease to one dominated by NCDs. Ten times as many people now
of an epigenetic change in perinatal tissues at birth can predict a suffer from NCDs as from HIV/AIDS, and according to the World
substantial fraction of the variation in body fat in children aged Economic Forum the likely economic impact of NCDs eclipses that
6–9 years [16]. Further, this epigenetic change is related to the of infectious diseases [25]. This is not to imply that investment
mother’s diet in pregnancy. In experimental studies such epigenetic in infectious disease prevention and treatment should be scaled
changes are mechanistically linked to altered metabolic function back, but rather that strategies for both infectious disease and
and, in proof of principle studies, can be reversed by developmental NCDs should be integrated more closely. HIV infection or malaria
nutritional, pharmacological, or hormonal interventions [17,18]. infestation have detrimental effects on the health of pregnant
The specific aspects of the developmental environment, such as women and alter placental function and the health of the fetus.
the mother’s diet or her body composition, stress levels, her level Similar considerations apply to linking NCD prevention to other
of physical activity, her age, and whether this is her first pregnancy, initiatives in maternal and child health. Programs aimed at reducing
have been shown to influence risk factors for later disease in her maternal and infant mortality and preterm birth and the promotion
children. This occurs in part through maternal constraint of fetal of breastfeeding are good examples. Such programs have received
development [19], which generates potentially greater mismatch substantial funding from government, NGOs, and philanthropic
postnatally and may affect the offspring’s behavior and put it at sources, and as part of the MDGs there is much infrastructure
greater risk, for example by altering appetite control [20]. These in place that could be harnessed for NCD prevention. Exclusive
M.A. Hanson, P.D. Gluckman / International Journal of Gynecology and Obstetrics 115S1 (2011) S3–S5 S5
breastfeeding, ideally for 6 months after delivery, reduces the risk 8. Ezzati M, Vander Hoorn S, Lawes CM, Leach R, James WP, Lopez AD, et al.
of developing obesity, and promotes neurocognitive development Rethinking the “diseases of affluence” paradigm: global patterns of nutritional
risks in relation to economic development. PLoS Med 2005;2(5):e133.
and immune function in the child [26,27]. Breastfeeding practices
9. Stuckler D, King L, Robinson H, McKee M. WHO’s budgetary allocations and
vary widely across societies, as does the support for mothers burden of disease: a comparative analysis. Lancet 2008;372(9649):1563–9.
undertaking it in public and even private settings. Cultural 10. Franko KL, O’Connor KC, Morton SMB. The economics of developmental origins
sensitivities have to be recognized here, but should not deter of health and disease: modelling the benefit of a healthy start to life. In:
programs to promote breastfeeding. Newnham JP, Ross MG, eds. Early life origins of human health and disease. Basel,
The phenotypic outcomes that have long-term consequences for Switzerland: Karger; 2009:21–8.
11. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al.
NCD risk involve constant interplay between genetic, developmen-
Finding the missing heritability of complex diseases. Nature 2009;461(7265):
tal, and environmental influences. It is impossible to pull them 747–53.
apart. But this apparent complexity, a fundamental property of 12. Beaglehole R, Bonita R, Horton R, Adams C, Alleyne G, Asaria P, et al. Priority
integrated biological systems, should not deter us from addressing actions for the non-communicable disease crisis. Lancet 2011;377(9775):
the moral imperative to provide a healthy start to life for the 1438–47.
13. Gale CR, Jiang B, Robinson SM, Godfrey KM, Law CM, Martyn CN. Maternal diet
next generation. Indeed, the evidence would suggest that while
during pregnancy and carotid intima-media thickness in children. Arterioscler
the genetic component is fixed and the environmental component Thromb Vasc Biol 2006;26(8):1877–82.
rather difficult to change, the developmental component represents 14. Gluckman PD, Hanson MA, eds. Developmental origins of health and disease.
a stage in the life-course when prevention and intervention are Cambridge, UK: Cambridge University Press; 2006.
both realistic and can achieve a broad range of public health 15. Hanson M, Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD. Developmental
plasticity and developmental origins of non-communicable disease: theoretical
and developmental goals. The successive cycles of disease risk
considerations and epigenetic mechanisms. Prog Biophys Mol Biol 2011;106(1):
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demographic changes, can no longer be ignored. We need to pay 16. Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, et al.
urgent attention to this global problem—for economic and political Epigenetic gene promoter methylation at birth is associated with child’s later
as well as humanitarian reasons. adiposity. Diabetes 2011;60(5):1528–34.
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Neonatal leptin treatment reverses developmental programming. Endocrinology
Acknowledgements 2005;146(10):4211–6.
18. Gluckman PD, Lillycrop KA, Vickers MH, Pleasants AB, Phillips ES, Beedle AS, et al.
MAH is supported by the British Heart Foundation. PDG is Metabolic plasticity during mammalian development is directionally dependent
supported by the National Research Centre for Growth and on early nutritional status. Proc Natl Acad Sci USA 2007;104(31):12796–800.
Development (NZ) and the Singapore Institute for Clinical Sciences. 19. Gluckman PD, Hanson MA. Maternal constraint of fetal growth and its
consequences. Semin Fetal Neonatal Med 2004;9(5):419–25.
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Conflict of interest statement of hyperphagia, obesity, and hypertension and postnatal amplification by
hypercaloric nutrition. Am J Physiol Endocrinol Metab 2000;279(1):E83–7.
The authors declare that they have no conflicts of interest. 21. Carone BR, Fauquier L, Habib N, Shea JM, Hart CE, Li R, et al. Paternally induced
transgenerational environmental reprogramming of metabolic gene expression
in mammals. Cell 2010;143(7):1084–96.
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ARTICLE
Maternal obesity: Implications for pregnancy outcome and long-term risks—a link to
maternal nutrition
Amir Aviram, Moshe Hod, Yariv Yogev *

Department of Obstetrics and Gynecology, Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tiqva, Israel
Keywords: As obesity becomes a worldwide epidemic, its prevalence during reproductive age is also increased. Alarming
Maternal nutrition reports state that two-thirds of adults in the USA are overweight or obese, with half of them in the latter
Obesity category, and the rate of obese pregnant women is estimated at 18–38%. These women are of major concern
Pregnancy to women’s health providers because they encounter numerous pregnancy-related complications. Obesity-related
Pregnancy outcomes reproductive health complications range from infertility to a wide spectrum of diseases such as hypertensive
Weight gain disorders, coagulopathies, gestational diabetes mellitus, respiratory complications, and fetal complications such as
large-for-gestational-age infants, congenital malformations, stillbirth, and shoulder dystocia. Recent reports suggest
that obesity during pregnancy can be a risk factor for developing obesity, diabetes, and cardiovascular diseases in
the newborn later in life. This review will address the implication of obesity on pregnancy and child health, and
explore recent literature on obesity during pregnancy.
© 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction disorders, gestational diabetes, respiratory complications, and

thromboembolic events [2–4]. As delivery approaches, overweight
Obesity has long been recognized as a global health concern, be it
women have a slower labor progression rate, higher rates
among adults, adolescents, or children, of both sexes. The World
of cesarean deliveries, and more surgery-related complications
Health Organization’s (WHO) reports convey alarming figures
such as difficult spinal, epidural, or general anesthesia, wound
regarding this phenomenon, with up to 1.6 billion overweight
infection, and endometritis [2–4]. From the fetal and newborn
adults and 400 million obese adults in 2005 [1]. WHO and the
perspective, complications include congenital malformations, large-
National Institutes of Health (NIH) define overweight as a body
for-gestational-age (LGA) infants, stillbirth, shoulder dystocia, and
mass index (BMI) of 25–29.9 and obesity as a BMI of 30 or greater.
adolescent complications such as obesity and diabetes [2–4].
Obesity is also subcategorized into 3 subgroups: Class I (BMI 30–
34.9), Class II (BMI 35–39.9), and Class III (BMI 40 or greater) [1].
2. Hypertensive disorders
Current predictions assess that by the year 2015, 2.3 billion adults
will be overweight and 700 million obese. Results from the United Hypertensive disorders are associated with obesity in the pregnant
States National Health and Nutrition Examination Survey (NHANES) as well as the nonpregnant state. The risk of pregnancy-induced
indicate that 66.3% of adults in the USA are either overweight or hypertension or pre-eclampsia is significantly greater if the mother
obese, with half of them in the latter category. is overweight as assessed by BMI in early pregnancy, with an
As obesity becomes an ever-growing concern, the number of up to 2–3-fold increased risk for pre-eclampsia with a BMI
women of reproductive age who are overweight or obese increases, greater than 30 [5–7]. Epidemiological studies have shown a
and the incidence of obesity among pregnant women is now relationship between pregnancies complicated by pre-eclampsia
estimated at between 18.5% and 38.3% [2]. Maternal overweight and an increased risk of maternal coronary heart disease in later
is now a known risk factor that affects the vast continuum life. The reported increase in the relative risk of death from ischemic
of pregnancy. Fertility and fecundity rates are lower among heart disease in association with a history of pre-eclampsia or
overweight and obese women, in spontaneous conception as eclampsia is approximately 2-fold [8].
well as in artificial reproductive techniques [2]. During pregnancy,
these women are more susceptible to pregnancy hypertensive 3. Gestational diabetes mellitus
* Corresponding author. Yariv Yogev. Perinatal Division, Department of

The association between obesity, hypertension, and insulin
Obstetrics and Gynecology, Helen Schneider Hospital for Women, Rabin resistance in type 2 diabetes is well recognized. It has been shown
Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel. that even minor degrees of carbohydrate intolerance are related to
Tel.: +972 3 9377400. obesity and pregnancy outcome [9,10]. Prepregnancy overweight
E-mail address: [email protected] (Y. Yogev). and obesity were associated with adverse pregnancy outcome
A. Aviram et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S6–S10 S7
in glucose-tolerant women [9,10]. Several studies demonstrated followed, allowing weight gain of up to 20–27 lb (9.1–12.3 kg).
a 2–10-fold increase in the rate of gestational diabetes mellitus In 1990, the Institute of Medicine (IOM) published new guidelines
(GDM) among obese patients [11–13]. A study of 6857 women based on the effects of weight gain on fetal size. The new
found a direct association between glucose screening categories, recommendations were based on prepregnancy BMI: a weight gain
obesity, and rate of GDM [14]. For patients with screening results of 28–40 lb (12.7–18.2 kg) for a BMI of 19.8 and lower; 25–35 lb
from 130–189 mg/dL, the rate of obesity was approximately 24–30%. (11.4–15.9 kg) for a BMI of 19.9–26; and 15–25 lb (6.8–11.4 kg)
Thereafter, this rate increased 2-fold. In contrast, for nonobese for a BMI of 26.1 and greater. The IOM stated that the effect of
women, the rate of GDM increased for each 10 mg increment weight gain on fetal size diminishes as the mother’s prepregnancy
in glucose screening. These data demonstrate that the rate of BMI increases [21]. This approach considered only immediate fetal
obesity and glucose tolerance are both associated with the outcomes and disregarded long-term maternal and fetal effects.
development of GDM. Additionally, fetal size and cesarean section This concept was challenged in the past 2 decades when studies
rate are associated with the degree of carbohydrate intolerance as evaluated the association between maternal weight gain, obesity,
represented by screening results. Furthermore, obesity remains a pregnancy outcome, and future development of diabetes in the
significant contributor impacting fetal size [15]. mother and the child.
To date, there is scant data on obesity and being overweight in Rooney et al. [22] evaluated a cohort of 540 women who
GDM. The few studies reporting obesity in GDM lack information had documented weight over a 5-year postpartum period. They
on the effect of achieving targeted levels of glycemic control concluded that excess weight gain and failure to lose weight after
and treatment modalities on pregnancy outcome [16–18]. Leiken pregnancy are important and identifiable predictors of long-term
et al. [16] demonstrated an independent risk for macrosomia obesity. Breastfeeding and exercise may be beneficial in controlling
among obese women with GDM. They determined that GDM had long-term weight. Edwards et al. [23] found that obese patients
a frequency of macrosomia no different than that of nondiabetic gained an average of 5 kg less during pregnancy and were more
patients. Nonobese women with GDM and fasting hyperglycemia likely to lose the weight or not gain weight at all. Obese women
treated with diet and insulin therapy also had a frequency of who lost or did not gain any weight had lower mean birth weights of
macrosomia no different than that of nondiabetic women. However, infants and higher rates of small-for-gestational-age (SGA) infants
diet and insulin did not prevent excess macrosomia in women who compared with obese women who gained 1 lb (0.45 kg) or more.
were obese.
The incidence of macrosomic fetuses increased significantly only in
These studies had small sample sizes, failed to provide
the group that gained 12 kg or more. No weight gain and weight
information on glycemic control, and only evaluated single outcome
gain up to 11.5 kg was associated with a macrosomia rate of 12.5–
variables. Maternal age, parity, and obesity are all over-represented
13.3% with a background rate of 10% in nonobese women. Therefore,
among women with GDM. These variables need to be controlled in
they recommend weight gains of 15–25 lb (6.8–11.4 kg) for obese
a study to draw accurate conclusions that also control confounding
women and 25–35 lb (11.4–15.9 kg) for normal weight women to
effects. Therefore, it is not clear if obesity, level of glycemia, or
optimize fetal growth. Neonates of obese women who gained less
treatment modality is independently or cumulatively responsible
than 6.8 kg were 3 times more likely to be SGA than neonates
for fetal growth abnormalities.
of obese women who gained at least 6.8 kg [24]. In addition, it
Langer et al. [19] found that obese and overweight GDM patients
has also been reported that obese pregnant women who gained
achieving established levels of glucose control with insulin therapy
at least 6.8 kg have been associated with increased frequency of
showed no increased risk for composite outcome, macrosomia, and
macrosomia [25].
LGA compared with normal weight GDM patients. In contrast, even
Bianco et al. [13] reported that a weight gain of more than 25 lb
when diet-treated obese patients achieved good glycemic control,
(11.4 kg) was strongly associated with the birth of LGA infants.
there was no improvement in pregnancy outcome compared
However, poor weight gain did not appear to increase the risk of
with normal weight patients. Poorly-controlled overweight and
obese patients, regardless of treatment modality, had significantly low birth weight infants. In contrast, Ratner et al. [26] found no
higher rates of composite outcome, metabolic complications, difference in fetal outcome in obese women when gaining more or
macrosomia, and LGA. Although obesity in and of itself portends less than 10 lb (4.5 kg). They concluded that limited weight gain in
potential adverse outcome in pregnancy, women with GDM treated morbidly obese women does not adversely affect fetal outcome.
with insulin and possibly oral antidiabetic drugs who achieve Luke et al. [27] reported that for every kilogram of gestational
targeted levels of glycemic control will have pregnancy outcomes weight gained, birth weight increased by 44.9 g for underweight
comparable with those of normal weight women. The improved women, 22.9 g for normal weight women, and 11.9 g for overweight
outcome in the insulin-treated overweight and obese women may women. For every kilogram of retained weight, birth weight was
be due to an unidentified effect of insulin itself on the fetus or increased by 35.6 g for underweight women, 15.9 g for normal
activation of other metabolic fuel pathways. weight women, and 5.1 g for overweight women. These findings
A recent study [20] concluded that a rise in BMI was translated suggest that beyond a certain level of weight gain, there is an
into an increased risk for GDM in consecutive pregnancy (OR 1.71 increase in birth weight at the expense of increasing maternal
for gaining 1.0–1.9 BMI units, OR 2.46 for gaining 2.0–2.9 BMI units, postpartum obesity for the woman who has gained an excessive
and OR 3.40 for gaining 3.0 or more BMI units), and that a decrease amount of weight during pregnancy.
in BMI was translated into lower risk for GDM in consecutive A systematic review published recently examined outcomes of
pregnancy, but only in overweight or obese women (OR 0.26 for pregnancies according to the IOM 1990 guidelines in terms of
losing at least 2.0 BMI units). birth weight, fetal growth, and postpartum weight retention [28].
A strong correlation between weight gain below IOM recom-
mendations and lower birth weights was demonstrated; however,
4. The impact of maternal weight change on pregnancy
only moderate correlation between weight gain in excess of
outcome
IOM recommendations and higher birth weights was found. As
The amount of weight gain recommended in pregnancy is expected, evidence suggested that weight gain in excess of IOM
controversial. Historically, obstetricians used to restrict weight gain recommendations, both total weight gain and weight gain rate, are
of up to 15 lb (6.8 kg), regardless of race, ethnicity, or prepregnancy correlated with higher incidence of weight retention postpartum in
weight. In the 1970s a more lax approach to weight gain was the short and long term.
S8 A. Aviram et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S6–S10
The IOM issued new guidelines for pregnancy weight gain in of cesarean delivery and postoperative anemia. Their infants were
2009, taking into account both maternal and fetal health [29]. For more likely to be appropriate-for-gestational-age (AGA) and be
underweight women (BMI < 18.5), a weight gain of 12.5–18 kg at a born at term. Sheiner et al. [38] found that bariatric surgery was
mean rate of 0.51 kg per week is considered adequate; for normal associated with premature rupture of membranes, labor induction,
weight women (BMI 18.5–24.9), 11.5–16 kg at a mean rate of 0.42 kg macrosomia, and obesity. No significant differences were noted
per week; for overweight women (BMI 25.0–29.9), 7–11.5 kg at a regarding pregnancy complications such as placental abruption,
mean rate of 0.28 kg per week; and for obese women (BMI 30 and labor dystocia, or perinatal complications. A systematic review by
greater) 5–9 kg with a mean rate of 0.22 kg per week. A recent study Maggard et al. [39] included 75 articles, and concluded that fewer
examined whether differences exist in infant body composition maternal complications occurred following bariatric surgery (such
based on the new IOM guidelines [30]. It was found that infants as GDM and pre-eclampsia), and that neonatal outcomes were
of obese mothers had a greater percentage of fat compared with better than in obese controls.
infants of normal weight and overweight mothers. Within the
excessive weight gain group, infants of normal weight mothers have
5. Long-term fetal and neonatal issues
less fat percentage than infants of obese or overweight mothers.
Another study by Vesco et al. [31] found that obese women Both the Barker [40,41] and fetal insulin hypotheses [42] have
gaining weight above the new IOM recommendations did not proposed that impaired adult cardiovascular health is programmed
decrease the risk for SGA but increased the risk for delivering LGA or in utero by poor fetal nutrition, or by genetically determined
macrosomic infants, and that obese women gaining weight below reduction of insulin-mediated fetal growth, which results in the
IOM recommendations had a higher risk for delivering SGA and a birth of a small infant. Low birth weight may be a significant
lower risk for LGA infants. variable for the development of the metabolic syndrome in
Bondar et al. [32] demonstrated that the prevalence of excessive adulthood. Obesity was an independent risk factor in the diabetic
gestational weight gain declined, and weight loss increased, as populations studied. Therefore, the emphasis today may need to
obesity became more severe. Generally, weight loss was associated address sedentary lifestyle and issues related to obesity upon
with an elevated risk of SGA, medically indicated and spontaneous fetal programming since undernutrition is now infrequent in high-
preterm delivery, and high weight gain tended to increase the risk resource societies.
of LGA and medically indicated preterm delivery. Hinkle et al. [33] Another study [43] reported evidence of a link between maternal
found that severity of obesity modified associations between obesity and cardiovascular disease in adult offspring, confirming
gestational weight gain and fetal growth. Compared with weight Barker’s hypothesis of higher adult death rates from coronary heart
gains of 5–9 kg, weight loss in Class I obese women significantly disease in men who were classified as low birth weight. In addition,
increased the odds of SGA, whereas a gestational weight gain of they observed a positive association between the mother’s BMI
0.1–4.9 kg was not associated with SGA and did not decrease the upon admission and future death rate from coronary heart disease
odds of macrosomia. In Class II and III women, compared with in male offspring. They concluded that the mother’s obesity may
weight gains of 5–9 kg, a gestational weight gain from −4.9 to be an independent yet additional contributing factor to infant low
4.9 kg was not associated with SGA but did decrease the odds of birth weight. Fall et al. [44] reported higher adult rates of type 2
macrosomia. diabetes in the offspring of mothers who were above average weight
In a population-based cohort, Blomberg [34] found that Class III in pregnancy.
obese women who lost weight during pregnancy had a decreased Therefore, there is an association between maternal (but not
risk of cesarean delivery (OR 0.77; 95% CI, 0.60–0.99), LGA births paternal) obesity and insulin resistance and the risk for offspring
(OR 0.64; 95% CI, 0.46–0.90), and no significantly increased risk to develop cardiovascular disease in adulthood. In a further study,
for pre-eclampsia, excessive bleeding during delivery, instrumental high maternal weight or BMI accounted for the association between
delivery, low Apgar score, or fetal distress compared with Class III birth weight and adult adiposity [45].
obese women gaining weight within the IOM recommendations. Lawlor et al. [46] found that maternal weight gain (MWG) was
There was an increased risk for SGA (OR 2.34; 95% CI, 1.15–4.76) associated with offspring BMI. In normal weight women, the
among Class III obese women losing weight, but there was no positive association between MWG and offspring BMI at age 18
significantly increased risk of SGA in the same group with low years was driven largely by shared familial risk factors for BMI,
weight gain. whereas in overweight or obese women the correlation seemed to
Getahun et al. [35] looked at whether BMI changes between be through shared familial risk factors combined with intrauterine
2 consecutive pregnancies were associated with increased risk mechanisms. In a review by Bouret [47], it is suggested that
for LGA in the second pregnancy. They found that overweight or maternal obesity and alterations in postnatal nutrition are related,
obese women in both pregnancies had an increased risk for LGA as determined by epidemiological and animal studies, to increased
infants, and that any decrease in BMI attenuated the risk. They also risks of obesity, hypertension, and type 2 diabetes in offspring.
concluded that 17.1% of LGA infants born to underweight mothers, Furthermore, several mechanisms may be responsible for the
13.2% of LGA infants born to normal weight mothers, and 7.6% of development of such diseases, such as developmental programming
LGA infants born to overweight mothers could be prevented if BMI of neuroendocrine systems by perinatal environment. As in GDM
had not increased between pregnancies. or pregestational diabetes, maternal obesity can result in fetal
Villamor and Cnattingius [36] found that compared with women growth restriction or macrosomia. Paradoxically, both are related
whose BMI changed between −1.0 and 0.9 units, women who gained to childhood metabolic syndrome [48].
3 or more units had an increased risk of pre-eclampsia, gestational Cho et al. [49] reported an association between maternal second
hypertension, GDM, cesarean delivery, stillbirth, and LGA birth [36]. and third trimester free fatty acid (FFA) concentrations (which
The associations were linearly related to weight change and were increase with maternal obesity) and diastolic blood pressure in
also noted in women who had a healthy prepregnancy BMI for both the adolescent offspring. The majority of evidence suggests a
pregnancies. relationship between low birth weight and adult disease. However,
Regarding bariatric surgery, Dell’Agnolo et al. [37] found that it is reasonable to speculate that overweight infants that are a
women who underwent bariatric surgery had less obesity-related product of both genetic and environmental factors are programmed
comorbidities such as diabetes mellitus and hypertension, and less in utero for the development of future diabetes, obesity, and
pregnancy-related hypertensive disorders, but higher prevalence metabolic syndrome. Thus, diversity (accelerated and delayed) may
A. Aviram et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S6–S10 S9
be a source for adult disease already initiated in intrauterine 6. Sibai BM, Ewell M, Levine RJ, Klebanoff MA, Esterlitz J, Catalano PM, et al. Risk
life. Given that obesity and maternal insulin resistance are not factors associated with preeclampsia in healthy nulliparous women. The Calcium
for Preeclampsia Prevention (CPEP) Study Group. Am J Obstet Gynecol 1997;
only genetic but also acquired, improvement of periconceptional
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13. Bianco AT, Smilen SW, Davis Y, Lopez S, Lapinski R, Lockwood CJ. Pregnancy
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7. Summary 20. Ehrlich SF, Hedderson MM, Feng J, Davenport ER, Gunderson EP, Ferrara A.
Change in body mass index between pregnancies and the risk of gestational
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Medicine. Nutrition during pregnancy: Part I: Weight Gain, Part II: Nutrient
mitigate pregnancy complications. Healthcare professionals and
Supplements. Washington, DC: National Academy Press; 1990.
social service providers need to actively promote a healthy lifestyle 22. Rooney BL, Schauberger CW. Excess pregnancy weight gain and long-term
to their patients and clients at every opportunity. Prepregnancy obesity: one decade later. Obstet Gynecol 2002;100(2):245–52.
clinics could provide education on healthy diet and exercise regimes 23. Edwards LE, Hellerstedt WL, Alton IR, Story M, Himes JH. Pregnancy
similar to those provided for women with diabetes. complications and birth outcomes in obese and normal-weight women: effects
of gestational weight change. Obstet Gynecol 1996;87(3):389–94.
Improving the health prospects of the mother during pregnancy
24. Parker JD, Abrams B. Prenatal weight gain advice: an examination of the recent
and the potential risk for developing complications later in life prenatal weight gain recommendations of the Institute of Medicine. Obstet
should be the focus of care. A concerted effort by public policy Gynecol 1992;79(5):664–9.
makers and the medical community could also effectively reduce 25. Johnson JW, Longmate JA, Frentzen B. Excessive maternal weight and pregnancy
healthcare costs, including those for hospitalization resulting outcome. Am J Obstet Gynecol 1992;167(2):353–70.
26. Ratner RE, Hamner LH 3rd, Isada NB. Effects of gestational weight gain in
from hypertensive disease, fetal anomalies, fetal assessment, costs
morbidly obese women: II: Fetal morbidity. Am J Perinatol 1990;7(4):295–9.
associated with the high rate of cesarean delivery, and postpartum 27. Luke B, Hediger ML, Scholl TO. Point of diminishing returns: when does
complications. gestational weight gain cease benefiting birthweight and begin adding to
maternal obesity? J Matern Fetal Med 1996;5(4):168–73.
28. Siega-Riz AM, Viswanathan M, Moos MK, Deierlein A, Mumford S, Knaack J,
Conflict of interest statement et al. A systematic review of outcomes of maternal weight gain according
to the Institute of Medicine recommendations: birthweight, fetal growth, and
The authors report no potential conflicts of interest. postpartum weight retention. Am J Obstet Gynecol 2009;201(4):339.e1–14.
29. Rasmussen KM, Yaktine AM, Committee to Reexamine IOM Pregnancy Weight
Guidelines, Institute of Medicine, National Research Council. Weight Gain During
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ARTICLE
Anemia and pregnancy: A link to maternal chronic diseases
Raja Gangopadhyay a , Mahantesh Karoshi a , Louis Keith b, *

a Barnet General Hospital, Enfield, UK
b Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL, USA
Keywords: Anemia is a global public health problem. It has serious short- and long-term consequences during pregnancy
Adverse maternal outcomes and beyond. The anemic condition is often worsened by the presence of other chronic diseases such as malaria,
Adverse fetal outcomes tuberculosis, HIV, and diabetes. Untreated anemia also leads to increased morbidity and mortality from these
Anemia chronic conditions as well. It is surprising that despite these chronic conditions (such as malaria, tuberculosis, and
Chronic anemia HIV) often being preventable, they still pose a real threat to public health. This article aims to review the current
Chronic infections understanding of the pathophysiology, risks, prevention, and treatment of anemia in the light of these chronic
Diabetes in pregnancy conditions.
HIV © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Malarial infection
Tuberculosis in pregnancy
1. Introduction In low-resource nations, iron deficiency is exacerbated by chronic

infection with hookworm, schistosomiasis, tuberculosis, HIV, and
The worldwide pandemic of anemia in pregnancy is not unlike
malaria [2]. Of these, HIV, tuberculosis, and malaria (especially
those of tuberculosis or HIV infection in that the specter of the
Plasmodium falciparum infection) represent leading contributory
problem looms so large on the care-givers’ horizon that often it
factors for anemia [5]. In contrast, in high-resource countries, the
is hard to see. At the same time, the effect of the condition is so
important contributory factors for anemia are chronic noncom-
insidious that the individual patient may not feel it until the disease municable diseases such as inflammatory bowel disease (Crohn’s/
has progressed to a most serious state. Anemia can occur at any age ulcerative colitis), malignancies (lymphoma, lung or breast carci-
and affect either gender, although it is more prevalent in pregnant noma, aplastic anemia), and malnutrition (anorexia and obesity).
women and young children [1]. It not only leads to poor outcomes In either case, chronic conditions worsen anemia, while anemia
in pregnancy and reduced work productivity among adults, but also negatively affects the progress of such longstanding conditions. The
contributes to 20% of deaths among pregnant women. In children, vicious cycle that exists between the chronic condition and anemia
it results in increased risk of morbidity as well as impaired physical is the subject of this article.
and cognitive development [2].
The data regarding the prevalence of anemia are shocking, 2. Etiology and pathophysiology of anemia related to
especially in low-resource regions. The World Health Organization nutritional deficiency
(WHO) estimates that two billion people—over 30% of the world’s
2.1. Nutritional iron deficiency and the role of other micronutrients
population—are anemic, although prevalence rates are variable
because of differences in socioeconomic conditions, lifestyles, Iron deficiency anemia (IDA) is the most common cause of nutri-
food habits, and rates of communicable and noncommunicable tional anemia. It is the only nutrient deficiency that is significantly
diseases [2]. Nearly half of all pregnant women suffer from anemia: prevalent in low-resource countries [2]. In some instances, poor
52% in low-resource countries and 23% in high-resource regions [3]. absorption of iron is aggravated by dietary contents. For example,
In the former, every second pregnant woman and about 40% of diets rich in phytates and phenolic compounds prevent absorption
preschool children are anemic [2]. of iron, thereby contributing to the anemic condition [6–9]. This
Iron deficiency is the most prevalent cause of anemia [4], but phenomenon may at least partially explain the prevalence of
only rarely does iron deficiency exist by itself. Individuals who are anemia in parts of the world with dietary predilections to foods
deficient in iron are also deficient in other important micronutri- containing large quantities of these compounds.
ents, although this important correlation is often overlooked by the Nutritional iron deficiency rarely occurs by itself; rather, it occurs
in the presence of other nutritional deficiencies, although this fact
medical profession and almost always unthought-of by the public
is frequently overlooked. For example, deficiency of micronutrients
at large.
such as folic acid, vitamins A, B12, riboflavin, and copper increase
* Corresponding author. Louis Keith. Department of Obstetrics and
the risk of anemia because these micronutrients play important
Gynecology, Northwestern University, 680 North Lake Shore Drive, roles in hemopoiesis [9]. Unfortunately, most such deficiencies
Suite 1015, Chicago, IL 60611, USA. escape detection because they are not thought about. Even if they
Tel: +1 312 432 9880; Fax: +1 312 432 4942. are, practical tests are either unavailable in most parts of the world
E-mail address: [email protected] (L. Keith). or are prohibitively expensive [3].
S12 R. Gangopadhyay et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S11–S15
2.2. Subclinical iron deficiency with asymptomatic infection and in as many as 75% to 80% of those
Figure 1 shows that iron stores are depleted over time; clinical with AIDS [17]. In pregnancy, HIV infection is associated with lower
features of anemia appear when stores are exhausted. As such, levels of serum folate and serum ferritin [18].
severe IDA represents the proverbial tip of the iceberg, related to but HIV infection can cause anemia (Fig. 2) through the changes in
removed from cases of subclinical iron deficiency [10]. Identifying
individuals within the larger community of those with subclinical
disease and taking appropriate measures to prevent progression Co-existing
to IDA is the challenge confronting physicians, although several tuberculosis
biochemical indicators (estimation of serum ferritin, transferrin

saturation, transferrin receptor, and erythrocyte protoporphyrin)
are helpful when available [8]. Nutritional deficiencies are not
gender specific, and the husband and children of the anemic mother
are likely to be in a similar nutritional state [11].
Antiretroviral Chronic wasting,
therapy, Anemia in pre-existing
e.g., HIV nutritional
zidovudine deficiency
Hepcidin
mediated
Fig. 2. Causes of anemia in HIV.

Fig. 1. Gradual depletion of body iron store and development of iron deficiency
anemia (IDA). cytokine production, altered erythropoietin (EPO) response to bone
marrow, use of antiretroviral drugs (especially zidovudine) [16],
3. Chronic infections and disorders as causes of anemia and interaction with other coexisting chronic infections such as
3.1. Role of hepcidin tuberculosis [19,20].
The exact mechanism by which anemia is caused in chronic

inflammatory conditions is unknown. A common factor may be 3.4. Tuberculosis
the contribution of hepcidin, a polypeptide hormone. Chronic Anemia is a common complication of pulmonary tuberculosis
inflammatory conditions lead to release of cytokines from the with a prevalence that ranges from 16% to 76% [21]. No studies
reticuloendothelial system as a part of cell-mediated immunity. have shown that pregnant women are specifically prone to
In response to these cytokines, mainly interleukin 6 (IL-6) [12,13], develop tuberculosis, and the risk factors are similar to those of
the liver produces increased amounts of hepcidin, which in turn nonpregnant women [22]. Although the exact cause of anemia in
prevents release of iron from its stores. The process is mediated tuberculosis is not known, it is thought to be due to cytokine
by blocking iron channels (such as ferroportin). Inflammatory mediated response of chronic infection (described above) [21],
cytokines also appear to influence other important aspects of iron blood loss (as in hemoptysis in pulmonary tuberculosis), and
metabolism, such as decreasing ferroportin expression, and possibly bone marrow involvement [23] with tubercular granulomata
directly suppressing erythropoiesis by decreasing the ability of the in disseminated tuberculosis (Fig. 3). Nutritional deficiency is
bone marrow to respond to erythropoietin [14].
The chronic conditions causing anemia are summarized in
Table 1.
Hemoptysis
Table 1
Chronic conditions/diseases associated with anemia
Infections Malaria, HIV, tuberculosis, osteomyelitis, bacterial

endocarditis, pulmonary abscess
Parasitic infestations Hookworm, ascaris, schistosomiasis
Chronic noninfectious Diabetes, rheumatoid arthritis, Systemic Lupus
diseases Erythematosus, Crohn’s disease, ulcerative colitis, Tubercular Anemia in Loss of appetite,
granuloma in tuberculosis pre-existing
chronic liver disease, cirrhosis, hemoglobinopathies bone marrow nutritional
deficiency
Malignancy Carcinoma, sarcoma, lymphoma, myeloma
3.2. Malaria
Malaria is discussed separately by Christensen and colleagues in
this Supplement [15]. Hepcidin
mediated
3.3. HIV
Anemia is the most frequent hematologic abnormality associated
with HIV infection [16]. It occurs in approximately 30% of patients Fig. 3. Causes of anemia in tuberculosis.
R. Gangopadhyay et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S11–S15 S13
common, as is loss of appetite, fever, or malabsorption (as in Table 2

intestinal tuberculosis) [21]. Short-term risks of anemia
Mother
Antepartum Prone to infections, preterm labor, left ventricular failure
3.5. Co-infection of HIV and tuberculosis
Intrapartum Heart failure, postpartum hemorrhage, shock
Tuberculosis infection is commonly present in patients with HIV Postpartum Heart failure, puerperal sepsis, uterine sub-involution, increased
owing to immune suppression. Patients with HIV are 37 times more cesarean delivery morbidity
likely to develop tuberculosis compared with the HIV-negative Fetus/child Increased stillbirth and morbidity and mortality due to
population; patients living with HIV represent over 10% of annual intrauterine growth restriction, prematurity, sepsis
tuberculosis cases [24]. HIV and tuberculosis may coexist and
aggravate anemia, thereby increasing pregnancy complications and
maternal and infantile morbidity and mortality [25]. 5. Risks to pregnant women and children: Long term
The long-term risks of anemia (Table 3) are considerable and are
described as follows.
3.6. Diabetes
Anemia occurs in diabetes (Fig. 4) when the kidney is affected 5.1. Maternal
in the disease process. It can appear in the early stage of renal
Anemia leads to debilitating physical (tiredness, lethargy, reduced
disease as a key indicator of early impairment of kidney function.
exercise tolerance, dyspnea, dizziness, anginal pain, and palpitation)
Approximately one-third of people with diabetes develop kidney
and mental (impaired cognitive function) symptoms, both of which
damage, and a significant proportion of this group progresses to
negatively affect quality of life [3].
end-stage renal disease [26]. Diabetes is somewhat unique because
In terms of the effect of anemia on HIV, some studies [37,38]
of its importance in both low- and high-resource regions of the strongly suggest that adverse pregnancy events (such as low
world [27], where it has clearly been linked to the explosive birth weight, stillbirth, preterm birth, and intrauterine growth
epidemic of obesity witnessed in the past two decades. restriction) are worsened in the presence of anemia. Moreover,
The pathophysiologic mechanism of anemia in diabetes is mother-to-child transmission (MTCT) of HIV may be increased [38].
thought to be mediated through a combination of dietary iron HIV infection in pregnancy also increases anemia-related maternal
deaths [39]. Anemic condition, in turn, can result in HIV disease
progression [40,41].
Erythropoietin
deficiency Table 3
Long-term risks of anemia
Impaired quality of life

Effects on chronic infections Malaria: possible increased morbidity
Iron deficiency-
and mortality
Erythropoietin
hypo- increased urinary HIV: accelerated disease progression
responsiveness excretion, and mortality, increased
dietary
Anemia in mother-to-child transmission
diabetes
Tuberculosis: increased morbidity
Effects on chronic disease Diabetes: increased mortality, heart
failure, worsening nephropathy,
neuropathy, foot ulcer
Drug related, Economic impact
Hepcidin
e.g.,
mediated
ACE inhibitors Effects on children born to anemic women Cognitive impairment, poor growth
and development, possible adult
hypertension
Fig. 4. Causes of anemia in diabetes.
deficiency, functional iron deficiency due to IL-6 and hepcidin There is limited evidence to suggest that presence of anemia
activities, erythropoietin deficiency/hyporesponsiveness, and the accelerates tuberculosis progression or worsens its prognosis
action of ACE inhibitor and angiotensin receptor antagonists [28]. (maternal or fetal). Despite this, it is easy to presume that anemia
and other nutritional deficiencies increase maternal morbidity
because of their effects on the immune system.
4. Risks to pregnant women and children: Short term Morbidity and mortality in diabetes are aggravated by anemia
in the following manner [28]. Renal disease progresses as a
The short-term risks to women are summarized in Table 2. The
result of tissue hypoxia and reduced renal blood supply; the
exact pathophysiologic mechanisms for these complications are
same may be said for peripheral neuropathies, ocular retinopathy,
unknown. However, the propensity to infections is thought to be
and foot ulcers [42]. In diabetes with renal disease, anemia is
caused by altered cellular immunity due to iron deficiency [29,30]. considered to be an independent and modifiable risk factor for
Postpartum hemorrhage may be due to uterine atony as a result worsening hypertension, left ventricular hypertrophy, heart failure,
of impairment of uterine muscle contraction capabilities [31,32]. and cardiovascular mortality [43,44].
Cardiac failure/angina may result from increased cardiac output
secondary to a hyperdynamic circulation to meet increased
5.2. Neonates and children
demands of hypoxia at the tissue level [33,34]. Children are affected
by the increased perinatal morbidity and mortality that result from Neonates of anemic mothers are born with suboptimal iron
complications of preterm labor and prematurity [35,36]. stores and are at high risk of developing IDA [45]. Good
S14 R. Gangopadhyay et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S11–S15
evidence suggests that iron deficiency causes poor cognitive, Highly active antiretroviral therapy (HAART) treatment avoiding
motor, neurophysiological, and socio-emotional development of zidovudine and treatment of associated tuberculosis (if present)
children [46]. Studies in animals have shown the importance of are extremely important both to prevent and treat anemia in such
iron in the function of neurotransmitters and overall function of cases.
the brain [47].
7.2. Tuberculosis
6. Assessment of anemia: New technology and new possibility Recent evidence supports treatment with iron supplements in
It is well accepted that early detection and effective management of mothers with tuberculosis [21]. In mild to moderate anemia,
anemia in pregnancy can substantially reduce maternal mortality iron supplementation accelerates the normal resumption of
and improve perinatal outcomes. According to the recommenda- hematopoiesis and increases iron saturation of transferrin. How-
tions of the leading obstetric and gynecology societies, all pregnant ever, persistent improvement of anemia needs general control of
women should be offered screening for anemia. However, this tuberculosis by reducing inflammatory cytokine mediated response,
is easier said than done, primarily because of the technology improving appetite, reducing hemoptysis episodes, and intestinal
involved and its cost. Many of the classic methods to assess iron absorption of iron (intestinal tuberculosis) [21,56].
or serum ferritin levels involved venipuncture and subsequent
laboratory analysis; recently, new noninvasive technologies have 8. Conclusions
been introduced and allow massive screening opportunities
Despite a better understanding of the etiology and pathogenesis of
in low-resource countries [48–50]. Occlusion red/near-infrared
anemia, it still remains a public health challenge throughout the
spectroscopy technology is a general platform for noninvasive
world. Anemia is often worsened by chronic communicable and
detection of blood analytes. At the core of this technology
noncommunicable diseases, the most important being malaria, HIV,
is the generation of a new biophysical signal, resulting from
tuberculosis, and diabetes. When anemia occurs in pregnancy it not
temporarily occluding the blood flow to the measurement site.
only results in poor pregnancy outcome in the short term but, in the
The measurement is performed by using an annular, multi-
long term, it also leads to worsening of these chronic conditions,
wavelength probe with pneumatically operated cuffs, with which
reduced work capacity, and an impaired cognitive development
an over-systolic pressure is produced at the finger base. This new
of the child. A joint social and political approach is necessary to
biophysical signal creates the sensitivity and specificity required
control anemia in pregnancy, as it represents a life-threatening
for measuring hemoglobin. It is also capable of measuring oxygen
but preventable cause of maternal and childhood morbidity and
saturation even in cases of weak peripheral pulsation, when
mortality.
standard pulse oximeters fail. These noninvasive readings for
hemoglobin and hematocrit are accurate and measure with an
acceptable relative absolute difference (RAD) when compared with Conflict of interest statement
accepted measurement systems (complete blood count). None of the authors has a financial disclosure or a conflict of
interest.
7. Prevention and treatment of anemia in the presence of
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ARTICLE
Physiological adaption to maternal malaria and other adverse exposure:

Low birth weight, functional capacity, and possible metabolic disease in adult life
Dirk L. Christensen a , Anil Kapur b , Ib C. Bygbjerg a,b, *

a Department of International Health, Immunology and Microbiology, University of Copenhagen, Denmark
b World Diabetes Foundation, Gentofte, Denmark
Keywords: The concept of developmental origins of health and disease and the epidemic of noncommunicable diseases in
Anemia low- and middle-income countries has increased the focus on low birth weight (LBW). Most studies linking LBW to
Functional capacity future risk of metabolic diseases have focused on maternal nutrition and anemia. Several studies have shown that
Low birth weight LBW is linked to skeletal muscle insulin resistance and future risk of type 2 diabetes, possibly caused by permanent
Malnutrition modifications in skeletal muscle morphology and biochemistry leading to lowered functional capacity and physical
Maternal malaria activity in adult life. In some parts of the world, malaria infection during pregnancy is the most common cause
Metabolic diseases of anemia and LBW. By causing disruption to nutrient supply, as well as hypoxia, placental malaria and anemia
negatively impact intrauterine fetal development. Thus, in utero exposure to placental malaria and consequent
LBW may impart a higher risk of developing type 2 diabetes in early adult life. This has not been investigated
systematically. Worldwide, an estimated 125 million pregnancies occur annually in malarial areas with a vast
potential for intrauterine growth restriction, LBW, and subsequent risk of metabolic dysfunction, including type 2
diabetes; this potential link also opens an opportunity for early prevention of future metabolic diseases by paying
greater attention to malaria during pregnancy.
1. Introduction 2. Malnutrition, anemia, malaria, and low birth weight

Two decades ago Hales and Barker [1] published a review on poor In India, maternal nutritional status is the most important
fetal growth and subsequent development of type 2 diabetes and determinant of the neonate’s birth weight. Unsafe drinking water,
the metabolic syndrome: the Thrifty Phenotype Hypothesis, more lack of prenatal care, and iron deficient anemia are also significant
recently renamed the Developmental Origins of Health and Disease contributors [13]. In Sub-Saharan Africa, nearly 20% of LBW
Hypothesis [2]. Numerous studies have shown the adverse effect
deliveries are attributable to malaria in pregnancy. Malaria-induced
of low birth weight (LBW) on insulin resistance, hypertension, and
LBW is estimated to be responsible for between 62 000 and 363 000
heart disease [3–6]. There is convincing evidence that development
infant deaths every year in Africa, translating to 3–17 deaths per
in utero and in the first 2 years of life influences the risk of
1000 live births [14]. Pregnant women can be infected by all 5
noncommunicable diseases (NCDs) in later life. It is also clear that
the risk is graded across a continuum [7] and has a “U”-shaped species that cause malaria in humans, but only two, Plasmodium
relationship [8], as measured by size and birth weight, so that falciparum and P. vivax, have been studied extensively [15,16].
both low and high birth weight are associated with higher future P. falciparum sequesters in the placenta, while P. vivax does not,
risk. Maternal diet, body composition, and health determine fetal yet is still associated with LBW, which suggests that systemic
environment and are shown to affect risk factors [9]. Maternal effects also contribute to LBW [16]. During pregnancy, women in
undernutrition, infant low birth weight, and rapid postnatal growth highly endemic malaria zones—even those with partial immunity
are all associated with increased risk of diabetes and other NCDs in due to repeated exposure—show increased susceptibility to malaria
offspring, and these factors might be especially relevant to low- parasitemia [17], with parasite numbers often higher in the
resource countries [10,11]. Additionally, the offspring of women placental than in the peripheral blood [18]. The deleterious effect
who are obese or have diabetes during pregnancy are at increased of placental malaria on fetal growth has been documented for
risk of diabetes and other cardiometabolic complications [9–12]. the past 6 decades: birth weight differences ranged between 55 g
and 310 g among neonates of women with and without malaria-
* Corresponding author. Ib Christian Bygbjerg. Department of
infected placenta [19]. More recent studies have shown that the
International Health, Immunology and Microbiology, University of
proportion of LBW neonates born to mothers with placental malaria
Copenhagen, 5 Oester Farimagsgade, bd. 9, P.O.Box 2099, DK-1014
Copenhagen K, Denmark. Tel: +45 35327835, Fax: +45 35327736. infection was significantly greater [20], and the risk was more than
E-mail address: [email protected] 4-fold higher [21]; reduction in the mean birth weight of 320 g
D.L. Christensen et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S16–S19 S17
was associated with placental malaria infection compared with strength have been shown to have a positive relationship with
nonparasitized placenta. glucose tolerance [43]. Ericson and Källén [44] showed a reduction
Several mechanisms have been proposed to explain LBW in muscle strength in Swedish very LBW (<1500 g) adolescent boys.
in neonates born to women with malaria during pregnancy, Furthermore, in male and female adolescents with extremely LBW
including: (<800 g), aerobic capacity, strength, flexibility, and physical activity
• cellular infiltration of the inter-villous space leading to impaired were lower compared with age-matched adolescents born at
placental function [22]; normal birth weight [45,46]. Poor performance in cardiorespiratory
• physical limitation caused by malaria-induced damage to fitness, strength, and flexibility tests was related to the interplay
syncytiotrophoblast, the surface of the fetal villi [23]; of effects of premature birth on the motor system together with
• elevated cytokine expression limiting nutrient transfer [24]; and a more inactive lifestyle, which may result from poor fitness.
• impaired utero-placental blood flow [25]. However, the long-term effect of LBW on cardiorespiratory fitness
In addition, placental parasite sequestration may occasionally and strength needs further investigation, including to what extent
cause sufficiently severe placental hypoxia to trigger a pre- increased physical activity training is able to blunt the effects
eclampsia like process. Impaired utero-placental blood flow is caused by LBW and modify these physiological parameters.
also experienced in pregnancies at high altitude, where reduced Malaria, apart from causing an effect via LBW, might also have
fetal growth is common [26]. However, whereas the human high- direct effects on skeletal muscles. Biochemical evidence of skeletal
altitude fetus is subjected to a double insult of hypoxia due to muscle damage is common in malaria, and skeletal muscle necrosis
lowered maternal arterial partial pressure of oxygen and decreased can occur with severe infection with P. falciparum. A study on
uterine blood flow [27], placental malaria infection mainly affects malarial mice showed functional and biochemical modifications
impaired uterine blood flow, and level of hypoxia may not be in skeletal muscle [47], suggesting that there might be direct
comparable unless accompanied by severe anemia. damage caused by malarial infection to the contractile proteins.
Maternal anemia is a consequence of both malnutrition as In this context it might be worth examining the impact, if
well as malaria and has significant adverse influence on the any, of congenital or early childhood malaria on skeletal muscle
intrauterine environment and future health of the offspring. In development later in life, over and above that caused as a
Africa, the proportion of severe anemia among pregnant women consequence of LBW.
of all gravidities attributable to malaria (population-attributable
fraction) is estimated to be 26% [14]. The combined effect of
4. Implications and conclusions
malnutrition and anemia seems more detrimental than either
one. The percentage of small-for-gestational-age (SGA) neonates While we still struggle to deal with maternal and child health,
born to malnourished and anemic mothers is higher than those malnutrition, and infections such as malaria, tuberculosis, and HIV,
born to mothers who were either malnourished or anemic; the looming NCD epidemic hovers above us like a dark cloud that
these neonates have higher levels of growth hormone, prolactin, threatens to wash away any progress made toward achieving the
human placental lactogen, and insulin-like growth factor-1 (IGF-1), Millennium Development Goals (MDGs), especially Goals 4 and 5
and may be distinct from nutrient deficiency-related intrauterine that relate to women’s and children’s health. Poor nutrition and
growth restriction (IUGR) [28]. Studies on the combined effects anemia during pregnancy and early life cause a predisposition to
of malaria, malnutrition, and anemia during pregnancy on fetal hypertension, heart disease, and type 2 diabetes later in life [48].
outcomes are not available, but it is not difficult to imagine that the The rising prevalence of high blood pressure and gestational
consequences would be quite disastrous, if the babies even survived diabetes mellitus is increasing the adverse outcomes of pregnancy,
these combined insults. and maternal health and diabetes during pregnancy present serious
risks to both the woman and the baby [48]. Undiagnosed or poorly
managed diabetes or hyperglycemia during pregnancy is associated
3. Birth weight, skeletal muscle, and metabolism
with a significantly higher risk of maternal and perinatal morbidity
To understand how LBW is linked to future risk of metabolic and mortality, as well as poor pregnancy outcomes including
diseases, the relationship between LBW, lean body mass (LBM), spontaneous abortion, stillbirth, congenital anomalies, macrosomia
total fat percentage, total fat mass, and metabolic dysfunction has (large for gestational age), need for cesarean delivery, and assisted
attracted considerable attention [29,30]. Similarly, investigations deliveries [49].
on skeletal muscle morphology, physiology, and capillary density The adverse consequences of (malaria-induced) LBW have to be
in relation to LBW have been undertaken in humans and seen in the light of the growing prevalence of type 2 diabetes in
animals [31,32]. A shift toward faster, more glycolytic [33–37] populations living in the tropics where malaria infection is endemic.
muscle fiber types has been shown in association with reduced One example is Ghana, where a prevalence of type 2 diabetes in
oxidative capacity [33,37] and glucose transporter-4 (GLUT-4) Accra of just 0.4% was reported in 1958 [50] compared with a
content [38,39]. Furthermore, reduced capillary density has been prevalence of 6.6% in 2002 [51]. In the past, with poor access to
suggested as a possible LBW-induced biological adaptation [40] in care many LBW babies would not have survived long enough to
insulin resistant or glucose-intolerant individuals. Jensen et al. [32] develop diabetes and other NCDs. With improving maternal and
demonstrated that LBW adolescent males had a higher proportion child health services many of them are surviving and witnessing
of the glycolytic type IIx fibers at the expense of type IIa fibers nutrition transition and urban migration. Will this further impact
compared with age-matched normal birth weight (NBW) controls, the future burden of NCDs? Hypertension is already a huge problem
but no difference in capillary density was found between the in Africa and diabetes prevalence is expected to double in the next
2 groups. Results from these studies suggest that compromised 20 years [52].
intrauterine growth may provoke a coordinated structural and In this paper we have attempted to link NCD prevention to
functional adaptation of skeletal muscles. Earlier findings showing control of another major challenge to human health and the
that glucose-intolerant individuals have an increased size of achievement of MDG 6: control and reversal of malaria. With
type I [41] and type IIa fibers lend support to this hypothesis [42]. an estimated 125 million pregnancies threatened annually by
A consequence of change in muscle fiber morphology and malaria infection worldwide [49], there is a vast potential for
physiology is muscle strength and the ability to perform demanding IUGR, LBW, and subsequent risk of metabolic dysfunction, including
physical activity. Physical activity and cardiorespiratory fitness and type 2 diabetes. One way to understand the proposed relationship
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ARTICLE
Development of a model to assess the cost-effectiveness of gestational diabetes

mellitus screening and lifestyle change for the prevention of type 2 diabetes
mellitus
Nicolai Lohse a, *, Elliot Marseille b , James G. Kahn c

a Global Health Partnerships, Novo Nordisk A/S, Bagsværd, Denmark
b Health Strategies International, Oakland, CA, USA
c Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco, CA, USA
Keywords: Gestational diabetes mellitus (GDM) is increasingly recognized as an opportunity for early prevention of diabetes
Cost-effectiveness and other diseases over the lifespan, and may be responsible for up to 30% of cases of type 2 diabetes. A newly
Gestational diabetes mellitus developed mathematical model (the GDModel) provides provisional estimates of the cost and health impact of
Prevention various GDM screening and management choices, and calculates averted disability-adjusted life-years (DALYs). The
Screening model was piloted in 5 different healthcare facilities in India and Israel. Universal screening of pregnant women
Type 2 diabetes followed by postpartum lifestyle management yielded net savings of US$78 per woman with GDM in India and
US$1945 per woman in Israel. The estimated DALYs averted were 2.33 in India and 3.10 in Israel. With lower
GDM prevalence, intervention efficacy, and type 2 diabetes incidence, the intervention had a net cost in India,
with a cost per DALY averted of US$11.32. This was far below the WHO definition of “very cost-effective,” set at
annual GDP per capita. The intervention in Israel remained cost-saving. GDM screening and postpartum lifestyle
management are either cost-saving or have a net cost but an attractive cost-effectiveness ratio. Some input values
are currently being refined. Nevertheless, the current findings of cost-savings or favorable cost-effectiveness are
robust to a wide range of plausible input values, including highly unfavorable values. The GDModel will be further
developed into a user-friendly tool that can guide policy-makers on decisions regarding GDM screening strategies
and guidelines.
1. Introduction criteria proposed by the IADPSG [12], and many other countries
are considering adopting them [13] although there is ongoing
Gestational diabetes mellitus (GDM) is increasingly recognized not
debate about whether to recommend universal versus selective
only as a common and serious complication of pregnancy, but also
screening [14,15]. Other countries, mainly low- and middle-income,
as an opportunity for early prevention of diabetes and other disease
are slowly introducing diabetes screening as part of the standard
over the lifespan [1,2]. GDM shares risk factors such as obesity with
prenatal care package [16] or aim to strengthen implementation of
type 2 diabetes, and the global prevalence of GDM is expected to
already-existing guidelines [17].
rise substantially [3–7] above current levels, which are in the range
It has also become clear that there is a large gap between the
of <1%–28% [8].
vast global numbers of pregnant women with GDM and the small
These growing concerns are reflected in the policy deliberations
proportion of these women who are even diagnosed, let alone able
of important official diabetes control and prevention bodies.
to access the best available treatment. In a recent survey reaching
In May 2010, the International Association of the Diabetes
173 countries, 35 out of 47 respondent countries reported having
and Pregnancy Study Groups (IADPSG) proposed new diagnostic
GDM testing and treatment guidelines, but in some countries
criteria [9] which, if implemented, will increase the prevalence
of GDM 2–3-fold [10,11]. The World Health Organization (WHO) only an estimated 10% of pregnant women receive these services.
has established an expert committee and is expected to renew Most nonresponding countries were low-income, suggesting that
its diagnostic criteria for diabetes in pregnancy in 2011 (G. inattention to GDM is greatest where the resources are scarce [8].
Roglic, personal communication, December 2010). The American The health benefits of diagnosis and proper management
Diabetes Association (ADA) is recommending the new screening of women with GDM during and after pregnancy are well-
documented [18–20]. However, neither the extent of these benefits
* Corresponding author. Nicolai Lohse. Building 6A1.079, Novo Allé, in the long term, nor the net economic implications at the health
DK-2880 Bagsværd, Denmark. Tel: +45 3079 2451. system level have been explored sufficiently. In particular, the
E-mail address: [email protected] (N. Lohse). long-term effect on type 2 diabetes incidence and thereby the
N. Lohse et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S20–S25 S21
potential to reduce the intergenerational transmission of diabetes intervention effects into a technically sound, concise, and accessible
need further investigation. A recent study from Canada estimated quantitative synthesis. The method estimates the relative reduction
that GDM may be responsible for up to 30% of the cases of type 2 in risk for mortality and morbidity for specific interventions, and
diabetes among Saskatchewan First Nations people [1]. scores the strength of evidence for each intervention from 1 to 6.
The present paper describes a computer simulation model Details on methods are available at: http://globalhealth.kff.org/
(GDModel) developed by the authors to estimate potential health GHIR/Background-Methodology.aspx.
impact, net cost, and the cost-effectiveness of various GDM
screening and management strategies. We present early results
from pilot analyses estimating the effect of long-term type 2 2.2. Gestational Diabetes Model development
diabetes reduction in India and Israel. A mathematical model for Gestational Diabetes Intervention Cost-
Effectiveness Analysis (the GDModel) was developed to estimate
2. Methods the cost and health impact of various GDM screening choices.
The GDModel aims to inform policy makers who are making
2.1. Evidence review: Efficacy decisions regarding GDM screening strategies and guidelines. The
Current evidence on the prevalence of GDM-associated risks for GDModel can compare alternative screening algorithms, prenatal
women and their offspring, and the efficacy of interventions for interventions, and postpartum preventive lifestyle interventions. It
prevention of GDM and associated complications were assessed estimates the cost per year of screening and interventions, perinatal
through a review of the literature. The latter was assessed by the complications, and cases of type 2 diabetes. It also calculates
Global Health Intervention Review (GHIR) method, developed by a averted disability-adjusted life-years (DALYs).
team including two of the authors (JK and EM), and posted in the The model is structured using a decision tree (Fig. 1). The
Kaiser Family Foundation Global Health Portal [21]. This work is tree flows from testing, to prenatal interventions and perinatal
designed to make key global health information accessible to policy outcomes, to postpartum interventions and long-term type 2
makers and health media, by translating the evidence base for diabetes outcomes. Key inputs include test sensitivity and
Fig. 1. The GDModel decision tree. Basic design of the model displaying the possible consequences of screening and treating GDM in a decision tree, in which decision nodes
are represented by squares, and chance nodes by circles. Decision nodes correspond to the mutually exclusive and collectively exhaustive set of decisions the model is able
to portray; in this case, the decision of whether and how to screen and treat GDM. Chance nodes correspond to the possible outcomes resulting from each decision, and are
depicted by lines branching from the node. This study reports cost and cost-effectiveness results for the T2DM portion of the model and does not calculate results for the
antenatal intervention and perinatal outcomes. In the base case, it ascribes 50% of the cost of GDM screening to T2DM interventions.
S22 N. Lohse et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S20–S25
specificity, health outcome risks, and intervention efficacy in the initial screening tests, the prenatal care required by GDM-
reducing those risks—all derived from the literature. A previously positive mothers, and postpartum follow-up and care. The costs
developed diabetes model, the CORE model [22,23], is used to evaluated included those entailed in direct service delivery such as
assess the costs and health effects related to type 2 diabetes that the personnel and supplies for screening tests, and the amortized
occurs after pregnancy in the mother and her offspring. For every cost of equipment (e.g. ultrasound) and training. They also included
use, the GDModel will be populated with setting-specific data on indirect costs such as the appropriately allocated portion of general
GDM prevalence and cost of GDM screening and management. The administrative activities not specific to GDM (e.g. clerical, house-
model development was advised by groups of experts and piloted keeping, reception), and other indirect costs of the facility such
in 5 different healthcare facilities in India and Israel. as utilities and telecommunications. Data were collected by a
team of two analysts who had been trained in the use of an
instrument developed for this purpose. The instrument includes
3. Review of evidence
inputs for the observed staff time for screening and counseling,
3.1. Prevalence of GDM and complications corresponding staff compensation rates, supply costs including
testing kits and glycemic control medications, and ancillary items
GDM is associated with the well-known risk of perinatal
such as syringes and indirect administrative and facility costs.
complications [19,24–29], which increase with increasing plasma
The instrument was completed through interview with program
glucose levels [24]. However, the long-term consequences for both
managers, direct observation of screening service delivery, and
mother and child are also considerable. A woman with GDM has a
abstraction of information from project records.
70% risk of type 2 diabetes in 10 years [30], a 38% risk of metabolic
Estimates of the lifetime medical cost of type 2 diabetes derive
syndrome [31], and a 1.66-fold increased risk of cardiovascular
from a literature review and use of the CORE model. All costs are
disease (CVD) in 12.3 years [32]. The adult offspring has a 21% risk
inflated to 2011 at 5% per year, yielding a median estimate of
(5-fold increased) of type 2 diabetes or pre-diabetes [33], a 4-fold
the lifetime cost of type 2 diabetes in the USA of US$88 368. We
increased risk of metabolic syndrome [34], a 2-fold increased risk of
translate this to other countries based on average annual healthcare
overweight [34], a 19% (8-fold increased) risk of impaired glucose
spending per capita, using ratios of 67:1 for USA:India and 3.3:1 for
tolerance (IGT) at age 12 [35], and a 30% increased weight at the
USA:Israel. All future costs are discounted at 3% per year.
age of 8 years [35].
5. Results from the model

3.2. GHIR review of efficacy of interventions
Table 2 shows the total costs of GDM screening and postpartum
Efficacy of prevention and treatment intervention are presented
management identified in 4 sites in India, and at a large health
in Table 1. The evidence for primary prevention of GDM is
maintenance organization in Israel.
very weak [36], whereas the evidence for secondary prevention
We examined the cost-effectiveness of testing and postpartum
(treatment and other interventions) is stronger [18,19,24,37].
lifestyle management for a base case and alternate assumptions
Lifestyle intervention studies (intensive weight reduction and
(Table 3). The values used for the base case are derived from
physical exercise) toward high-risk populations (not exclusively
the information reviewed above and summarized in note “a”
women) have reduced the incidence of future type 2 diabetes by
of Table 2. The India sites are combined for this exercise. We
58% [38–40], and in a substudy of high-risk women with GDM [20]
consider only benefits to the mother; benefits to children remain
the type 2 diabetes incidence reduction due to lifestyle intervention
speculative.
was 50%. In the postpartum period, metformin and lifestyle changes
We found that the intervention is either cost-saving or, in a few
each lower the risk of type 2 diabetes [20]. There are no data
instances, has a net cost but an attractive cost-effectiveness ratio.
on prevention of type 2 diabetes in the children of GDM-positive
In the base case, the intervention yields a net savings of US$78
mothers.
per woman in India receiving the postpartum intervention. This
reflects the relatively small chance of averting type 2 diabetes
4. Model development (31% incidence × 50% efficacy = 15%) but the large savings when this
occurs, leading to type 2 diabetes savings that on average exceed
4.1. Expert consultations
screening and intervention costs. The estimated DALYs averted are
The overall design of the GDModel was reviewed by a group of 2.33. No cost-effectiveness ratio ($/DALY) is indicated when there
international experts in mathematical modeling, health economics, are lower costs and health benefits. For Israel, the net savings are
gestational diabetes risk and management, and public health, in larger (US$1945), with similar DALYs averted (3.1) owing to greater
Stockholm, September 2010, and subsequently modified according longevity in Israel.
to their input. Results of the analyses from pilot countries were Type 2 diabetes may be more expensive to treat than we assumed
presented at conferences in Mumbai, February 2011 (6th National (our estimate based on empirical studies is below the CORE model
Conference of Diabetes in Pregnancy Study Group of India) and in estimate). Higher type 2 diabetes cost increases net savings, leaving
Salzburg, March 2011 (6th International Symposium on Diabetes DALYs unaffected. With higher GDM prevalence, the yield of a
and Pregnancy); and input from experts on model assumptions screening program is greater, decreasing the cost screening per
were sought at side meetings (in Mumbai) and at teleconferences woman receiving the postpartum intervention and thus yielding
(post-Salzburg). greater savings. If type 2 diabetes incidence is lower (empirical
evidence is limited), the intervention remains cost-saving but
with lower savings and DALYs averted. Lower intervention efficacy
4.2. Costing data collection
(half as high) sharply reduces savings and DALYs averted. If the
Data on cost and prevalence were collected in each of the two pilot intervention cost is much higher—continuing at a high level for
countries, India and Israel. Data on the incremental costs of GDM 5 years—the intervention has a net cost in India, with a cost per
were assessed from 4 service delivery sites in India. These included DALY averted of US$11.32. This is far below the WHO definition of
both public and private facilities in Chennai, Pune, and Ludhiana. “very cost-effective,” set at annual GDP per capita. The intervention
Using an ingredients-based approach, incremental costs of GDM in Israel remains cost-saving. Finally, there is some possibility that
were defined as the value of the resources needed to provide reductions in type 2 diabetes observed in clinical trials actually
Table 1
Gestational diabetes key findings a
Intervention Mortality Disease Other indicators

Maternal Infant Maternal Infant Maternal Infant
Primary prevention
Lifestyle modification
Dietary advice (low vs high glycemic index) − − − +91% (31–99%) − −
Secondary prevention
Multifaceted interventions
Package of treatment vs routine PNC (mild GDM) − + ++ +++ ++ +++

91% (−70% to 99%) 6–35% b 54–68% −31% to −512% −15% (−26% to −5%)
Diet + insulin vs usual care/routine PNC − + − +++++ ++++++ +++++

14–81% c 52–62% d 14% (−2% to 28%) 27% (−6% to 50%)
Diet + insulin vs diet alone − − − ++ − −

57% (18–78%)
Intensive vs less intensive treatment + ++++ +++++ −

10–73% e 19–66% f −4% (−34% to 20%)
Oral hypoglycemic agents
Oral hypoglycemics vs insulin therapy − − − + ++++ ++++

−575% (−5114% to 13%) 54% (23–73%) −668% (−3922% to −47%)
Glyburide vs insulin therapy − − − + − +

−4% to −7% g −24% to 5%
Metformin vs placebo (postpartum women with − − ++ − − −

history of GDM) 50% (1–75%) h
Lifestyle modification
Specific dietary advice vs routine PNC − − − +++ +++ +

7% (−97% to 56%) −190% to 15% 62% (−73% to 92%)
Exercise + diet vs diet alone − − − − − +++

2% (−87% to 49%)
Intensive lifestyle change vs placebo (postpartum − − ++ − − −

women with history of GDM) 53% (1–78%) h
Obstetric intervention
Induction of labor vs expectant management − − − − − ++

19% (−26% to 48%)
Abbreviations: PNC, prenatal care; GDM, gestational diabetes mellitus.

a Reported values are the relative reduction in risk for the listed outcomes due to the listed intervention. The Table reports the point estimates for identified reviews or
studies. The pluses represent strength of evidence (max = 6).

b Range of point estimates from two pooled data: one showed positive and significant effect and the other showed nonsignificant positive results.
c Range of point estimates from two RCTs: smaller RCT showed positive and significant effect; much larger RCT showed nonsignificant positive results.
d Three of four studies had positive statistically significant findings; one positive but nonsignificant.
e Range of point estimates from two RCTs: one showed significant positive results and the other nonsignificant positive results.
f Interquartile range (25th–75th percentile). Results of one pooled estimate and 11 single studies. All 11 single studies reported a positive effect of which 5 and the pooled
estimates were statistically significant.

g Two pooled estimates underlying this cell show no difference between glyburide and insulin, and with relatively narrow 95% CI.
h Result of one RCT (Ratner 2008 [20]) assessing the efficacy of metformin or lifestyle modification on prevention of type 2 diabetes among women with history of GDM.
The study did not provide 95% CI, we back-calculated 95% CI using specified general P value (<0.05).
represent delay rather than permanently avoiding type 2 diabetes. averted in India and Israel respectively, still “very cost-effective”
Our last two analyses in Table 3 suggest that even with a large by WHO criteria (not shown in Table 3). Finally, if in addition to
portion of “delay only,” the intervention is either cost-saving or these assumptions, the full costs of screening are ascribed to T2DM
very cost-effective. We also tested the unfavorable possibility that and none to perinatal outcomes, the cost-effectiveness results for
intervention costs are simultaneously five times the base case value, India and Israel are US$465 and US$5887 per DALY, still far below
and type 2 diabetes incidence is half of the base case value. In that the “very cost-effective” thresholds of US$3608 and US$30 347
case the cost-effectiveness ratio is US$256 and US$2584 per DALY (purchasing power parity) for India and Israel respectively [41].
Table 2
GDM cost-effectiveness model for type 2 diabetes prevention, cost input, parameter values (USD) a
Input parameter India Israel (HMO)

Site 1 Site 2 Site 3 Site 4
(Private, urban) (Private, semi-urban) (Public, urban) (Private, urban)
Screening (75 g, 2 h OGTT) $11.90 $2.51 $2.42 $2.65 $26.62

Postpartum management (year 1) $35.09 $8.24 $35.09 $25.70 $82.56
Abbreviations: HMO, health management organization; OGTT, oral glucose tolerance test; GDM, gestational diabetes mellitus.
a Sources: India sites: observed activities and local unit costs; Israel: cost-accounting system.
Table 3
Cost-effectiveness results: Base case and sensitivity analyses
India Israel
Net savings DALYs US$/DALY Net savings DALYs US$/DALY
(costs), US$ averted averted (costs), US$ averted averted
Base case a 78 2.33 n/a 1945 3.10 n/a

Type 2 diabetes is 50% more expensive 154 2.33 n/a 3471 3.10 n/a
GDM prevalence is 50% higher 94 2.33 n/a 2286 3.10 n/a
Type 2 diabetes incidence is 20% 24 1.50 n/a 862 2.00 n/a
Intervention efficacy is 25% 2 1.16 n/a 419 1.55 n/a
Intervention cost is 5 times higher (26) 2.33 11.32 1615 3.10 n/a
50% of reduced type 2 diabetes is delay only 21 1.46 n/a 810 1.95 n/a
75% of reduced type 2 diabetes is delay only (7) 1.03 7.12 242 1.37 n/a
Abbreviations: GDM, Gestational diabetes mellitus; DALY, Disability-Adjusted Life Years.

a Base case: Type 2 diabetes incidence in GDM is 31%, cost US$1322 India and US$26 457 Israel, efficacy of intervention is 50% reduction
in type 2 diabetes, all reduced type 2 diabetes is permanent (not just delayed). GDM prevalence is 10% in India and 2.6% in Israel. Half of
screening costs are assigned to type 2 diabetes prevention, and half to prevention of perinatal complications (not in this analysis). Intervention
uptake is 50%.
*NOTE: World Health Organization standard for “very cost-effective” = US$/DALY averted < than annual GDP per capita. Per capita GDP (in
2010) = US$3400 (India) and US$29 500 (Israel).
6. Limitations and further development conducted in additional countries, the expanded database will
facilitate extrapolation to other, similar healthcare systems. Finally,
The GDModel is, to our knowledge, the first to assess the cost-
continuous monitoring of the literature, including results from long-
effectiveness of GDM screening and interventions, and also the
term prospective studies [16], and assessing the cost and impact of
first to collect detailed GDM costing data in low-income settings.
policy changes already taking place, will inform improvement of
However, our effort has clear limitations. First, data on intervention
the tool in the coming years.
effectiveness were weak. The model had to be based on a
combination of efficacy data and expert judgments, which could
be imperfect. Second, uptake as well as content of postpartum Acknowledgements
interventions varied between sites and differed from published
Thanks to Rajkumar Channabasavaiah and Somya Gupta for
trials, making it difficult to assess their long-term effect. Third,
collecting the costing data in India, and to Dr Nicky Lieberman and
an analysis of just two countries inhibits confident extension of
his team for providing costing data from Israel. Thanks to Professor
results to other countries. Finally, our focus on T2DM prevention
V Seshiah, Dr Madhura Balaji, Professor V Balaji, Professor CS Yajnik,
did not account for the effects of screening and antenatal
and Dr G Arora for facilitating the data collection process at their
treatment on perinatal outcomes. In spite of these limitations, the
respective facilities.
sensitivity analyses, including the highly unfavorable set of input
values we explored, suggest that the study’s central finding, that
GDM screening and treatment can be highly cost-effective, is likely Conflict of interest statement
to hold following further refinements to the model.
The development of the GDModel was funded by Novo Nordisk
It is our intention to further develop the model into a user-
A/S. Authors EM and JGK were contracted by Novo Nordisk A/S
friendly tool that can guide policy-makers via the inclusion of local
to conduct this work. They have no other connection to Novo
data on prevalence and costs. The model will permit analysis of
Nordisk. Author NL works for Novo Nordisk A/S. Novo Nordisk
current practice patterns versus adopting new practice guidelines.
A/S manufactures and markets drugs to treat diabetes. Expanded
The tool will be able to compare different screening strategies
interest in gestational diabetes could possibly increase the demand
(universal, selective, or none), diagnostic criteria (“old” versus
for Novo Nordisk’s products.
“new”), intervention intensity (low versus high), risk populations,
and age groups. These input options would make the tool useful for
both high-resource settings aiming to optimize the current strategy, References
and low-resource settings considering whether to introduce GDM
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ARTICLE
Matching diagnosis and management of diabetes in pregnancy to local priorities

and resources: An international approach
H. David McIntyre a, *, Jeremy J.N. Oats b , Willibald Zeck c,d,e , V. Seshiah f , Moshe Hod g
a University of Queensland, Mater Health Services and Mater Medical Research Institute, South Brisbane, Australia
b Department of Obstetrics and Gynecology, University of Melbourne, Victoria, Australia
c United Nations Children’s Fund (UNICEF), Regional Office, Kathmandu, Nepal
d Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria
e Duke Global Health Institute, Duke University, Durham NC, USA
f Dr V. Seshiah Diabetes Research Institute and Dr Balaji Diabetes Care Centre, Chennai, India
g Division of Maternal Fetal Medicine, Helen Schneider Hospital for Women, Rabin Medical Center, Petah-Tiqva, Israel
Keywords: The International Association of the Diabetes and Pregnancy Study Groups’ (IADPSG) criteria for the diagnosis and
Diagnosis classification of hyperglycemia in pregnancy are described and application of these in differing healthcare contexts
Gestational diabetes on a worldwide basis is reported. Existing local protocols and known epidemiologic and clinical data regarding
Hyperglycemia the detection and management of overt diabetes and gestational diabetes in the context of human pregnancy are
IADPSG considered. Although the IADPSG criteria are uniform, their introduction poses a variety of practical and technical
Low-income countries challenges in differing healthcare contexts, both between and within countries. Knowledge of local factors will
Pregnancy be vital in the implementation of the new guidelines and will require extensive liaison with local clinical and
health policy groups. Resource availability will be critical in determining the type of treatment available in this
context. The IADPSG criteria offer an important opportunity for a uniform approach to diabetes in pregnancy.
Scaled implementation of these criteria adapted to a variety of local healthcare contexts should improve both
research endeavors and patient care.
1. Introduction contexts, broadly divided into high-/middle-/low-income countries

as defined by the World Bank [3]. It is acknowledged that differing
The International Association of the Diabetes and Pregnancy Study
healthcare contexts may also exist within countries, but such local
Groups (IADPSG) has recently published a suggested diagnostic
variations are beyond the scope of this paper.
pathway and criteria for diabetes in pregnancy [1], based on
the epidemiologic findings of the Hyperglycemia and Adverse
2. IADPSG recommendations
Pregnancy Outcome (HAPO) study [2] and other available data.
These recommendations allow for pragmatic local variations in The published IADPSG recommendations for diagnosis and
implementation of revised diagnostic protocols, in particular classification of hyperglycemia in pregnancy [1] propose the
in relation to early pregnancy screening designed to detect following diagnostic pathway:
undiagnosed type 2 diabetes. 1. Early pregnancy
Whilst wishing to emphasize the importance of diabetes in Test with any of: random plasma glucose (RPG), fasting plasma
pregnancy across a variety of healthcare contexts, the IADPSG glucose (FPG), or HbA1c (for all or only for high-risk women
recognizes that pregnancy healthcare priorities may vary according depending on local circumstances) to detect overt diabetes. FPG
to local factors, including available resources for both diagnosis ≥7.0 mmol/L or HbA1c ≥6.5% are considered as overt diabetes
and management and the relative frequency and importance requiring immediate therapy. RPG ≥11.1 mmol/L indicates likely
of hyperglycemia compared with other health risks in different overt diabetes and requires FPG or HbA1c for confirmation.
countries or areas. FPG 5.1–6.9 mmol/L is accepted as gestational diabetes mellitus
This article aims to consider the issues involved in detection (GDM).
and management of diabetes in pregnancy across a range of 2. 24–28 weeks of gestation
Diagnostic 75 g oral glucose tolerance test (OGTT) including
* Corresponding author. David McIntyre. University of Queensland, Mater fasting, 1- and 2-h samples for all women not previously found to
Health Services and Mater Medical Research Institute, South Brisbane, have abnormal results. Glucose thresholds for diagnosis of GDM:
QLD 4101, Australia. Tel +61 7 3163 6358; Fax + 61 7 3163 2510. fasting ≥5.1 mmol/L (92 mg/dL); 1 h ≥10.0 mmol/L (180 mg/dL);
E-mail address: [email protected] (D. McIntyre). 2 h ≥8.5 mmol/L (153 mg/dL).
H. D. McIntyre et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S26–S29 S27
Owing to lack of evidence and lack of international consensus, The dropout rate is very high when a pregnant woman is asked
the IADPSG document does not make a specific recommendation to come again for the glucose tolerance test. In South Asians,
regarding early pregnancy testing for GDM and allows some both HbA1c and fasting glucose show poor sensitivity in the
flexibility for local implementation of these recommendations. diagnosis of overt diabetes in the nonpregnant population [14],
leading to reservations about their use in pregnancy. Further,
HbA1c measures are currently difficult to standardize, expensive,
3. High-income countries
and require equipment and trained technical staff not routinely
Most high-income countries are in the vanguard of the dual available in middle-income countries. Optimal detection of overt
epidemics of obesity and diabetes, with resultant morbidity diabetes and lesser degrees of hyperglycemia in the South Asian
and healthcare costs rising due both to higher prevalence context may require a formal OGTT in early pregnancy. Current
and demographic shifts toward an ageing population [4]. Both guidelines in India endorse a pragmatic, convenient, 75 g glucose
obesity and diabetes contribute substantially to major pregnancy challenge in either fasting or nonfasting state irrespective of the
complications including stillbirth [5] and congenital anomalies [6]. last meal timing and with a single venous blood sample drawn
In populations where early onset type 2 diabetes is common, its after 2 hours [15]. Published findings from the Chennai group have
pregnancy prevalence appears to be growing more rapidly than that shown that 2-hour post load glucose values are similar irrespective
of GDM [7], demonstrating that local conditions must be taken into of fasting status [16], but this study did not incorporate fasting
account when devising appropriate testing programs for diabetes in glucose in the diagnostic algorithm. The relative merits of this
pregnancy. approach versus the IADPSG recommendations and formal OGTT
We recommend that high-income countries implement the may be partly examined using existing datasets. However, definitive
IADPSG recommendations as part of routine prenatal care. Some data are likely to come only from well-designed prospective trials.
form of routine early testing for overt diabetes is recommended In some regions/countries, the IADPSG approach represents a
and prospective trials should be undertaken to ascertain the substantial change from long-established practices, which have
relative merits of RPG, FPG, and HbA1c as part of this detection gained government recognition and endorsement after many years
strategy. A recent study by Agarwal et al. [8] has suggested possible of persistent work. Countries that have been following the WHO
simplification of GDM diagnosis using initial fasting glucose testing criteria or local criteria are likely to take several years to consider
and this warrants further evaluation. In women with known risk and ultimately implement IADPSG recommendations. In future
factors for diabetes (including obesity, advanced maternal age, first clinical practice we hope that simpler, more cost-effective strategies
degree family history of diabetes, high-risk ethnic groups, polycystic may be developed and validated, eliminating the requirement for
ovarian syndrome, and previous gestational diabetes), detailed the OGTT in most pregnant women.
evaluation of glycemic status, either as part of preconception care
or in early pregnancy, seems desirable. However, formal trials in
5. Low-income countries
this area are lacking.
Detailed recommendations regarding treatment of diabetes in Paradoxically, both obesity and undernutrition pose health risks
pregnancy are beyond the scope of this article, but we note that key in low-income countries, both on a societal level [17] and even
elements of current treatment strategies [9], supported by available within individual households [18]. Diabetes and obesity are more
trial evidence [10,11], include dietary and exercise therapy, use prevalent in urban areas of low-income countries [17] owing to
of self-monitoring of blood glucose, close obstetric monitoring, rapid nutritional, lifestyle, and socioeconomic transitions. Poverty
and careful attention to the detection and treatment of potential also clusters with metabolic syndrome and cardiovascular risk
diabetes complications, particularly retinopathy and nephropathy. factors in urban slums [19].
Postnatal follow-up of women diagnosed with diabetes in Reliable data regarding diabetes in pregnancy in most low-
pregnancy is also recommended, given the well-described risk income countries, particularly those in Africa, are lacking and
of progression to permanent (mostly type 2) diabetes [12] and research in this area is urgently needed [20]. The IADPSG criteria
the available evidence regarding prevention of type 2 diabetes in offer a potential uniform approach to epidemiologic studies and
“at risk” patients [13]. Postnatal follow-up should include lifestyle we propose that a standardized global survey of the pregnancy
and behavior change counseling, incorporating appropriate physical prevalence of overt diabetes and GDM should be conducted,
activity, and dietary modifications. including both urban and rural areas of low-income countries.
Technical personnel and equipment are likely to be in short supply
in low-income countries and new glucose assay technologies that
4. Middle-income countries
are robust and suitable for use under demanding climatic conditions
Middle-income countries are a diverse group, covering a wide range would be of great value. Another article in the present Supplement
of economic circumstances. Universal early testing for diabetes by Agarwal et al. [21] addresses in more detail the unmet need for
in populations with a high prevalence of type 2 diabetes (e.g. low-resource regions.
Asian Indians) is recommended [1]. Increasing diabetes prevalence In everyday practice, detection and treatment of diabetes in
also poses major problems in the middle-income countries of pregnancy in some low-income countries must compete with
South America. Local health service implementation of the IADPSG other pressing threats such as armed conflict and famine. Many
recommendations poses some specific challenges. countries also face severe maternal health problems due to
Factors to be considered for recommending a diagnostic poor or absent birth attendant care and the risks posed by
procedure are ethnic diversity, population specific problems, immediate life-threatening complications including hemorrhage
developmental index, and availability of infrastructure facilities and infection, which lead to persistently high risks of maternal [22]
including equipment and skilled technical staff. The most important and perinatal [23] mortality. The scope of other fundamental
factors are the initial costs involved and the cost-effectiveness of Millennium Development Goals such as reduction of extreme
diagnostic tests as healthcare delivery is government funded in poverty, provision of at least primary education, and equality for
most of these countries. women [24] outlines the broad and demanding nature of the
In particular, fasting glucose testing may be difficult to integrate societal challenges facing any new program.
with standard prenatal care in middle-income countries. Attending Resources for treatment of diabetes in pregnancy are also scarce
the first prenatal visit in the fasting state poses logistic problems. in low-income countries. Insulin is a costly drug in short supply
S28 H. D. McIntyre et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S26–S29
Table 1
Summary of recommendations for detection and treatment of diabetes in pregnancy in various healthcare contexts
Recommendation High-income countries Middle-income countries Low-income countries
Early pregnancy testing Random venous plasma glucose (VPG), Random VPG Variable – depending on local diabetes prevalence
for overt diabetes fasting VPG or HbA1c Evaluate early oral glucose tolerance and resources.
test (OGTT) in relevant populations Formal prevalence studies recommended
Diagnosis of gestational Universal 75 g OGTT at 24–28 weeks of Universal 75 g OGTT at 24–28 weeks Variable – depending on local resources
diabetes (GDM) gestation of gestation
Treatment of diabetes in Urgent medical evaluation and treatment of Urgent medical evaluation and Urgent medical evaluation and treatment of newly
pregnancy newly detected overt diabetes. treatment of newly detected overt detected overt diabetes.
GDM: Dietary and lifestyle measures, diabetes. GDM: Dietary and lifestyle measures, increased use
pharmacologic treatment based on GDM: As for high-income countries, of oral antidiabetic agents, insulin depending on
maternal glycemia and fetal growth pattern depending on local resources availability
Follow-up post pregnancy Repeat OGTT in most cases. Re-evaluation of glycemic status Develop strategies to detect and treat ongoing overt
Encourage breastfeeding depending on local resources. diabetes.
Dietary and lifestyle behavior change Encourage breastfeeding. Encourage breastfeeding.
counseling Dietary and lifestyle behavior Develop personal and population measures to
change counseling reduce prevalence of obesity and diabetes.
and beyond the resources of many people in low-resource regions. References

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ARTICLE
Gestational diabetes screening: The low-cost algorithm
Mukesh M. Agarwal a , Bernhard Weigl b , Moshe Hod c, *

a Department of Pathology, Faculty of Medicine, UAE University, Al Ain, United Arab Emirates
b NIBIB Center for POC Diagnostics for Global Health, PATH (Program for Appropriate Technology in Health), Seattle, WA, USA
c Division of Maternal Fetal Medicine, Rabin Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
Keywords: The American Diabetes Association has endorsed the demanding recommendation by the International Association
Fasting glucose of the Diabetes and Pregnancy Study Groups (IADPSG) that every pregnant woman should undergo the oral glucose
Gestational diabetes tolerance test (OGTT) for the screening of gestational diabetes mellitus (GDM). The aim of this study was to find
Low-resource countries out if the fasting plasma glucose (FPG) and newer emerging technologies could simplify the cumbersome IADPSG
Screening algorithm. Two FPG thresholds (of the OGTT) were used to rule in and rule out GDM in the Hyperglycemia and
Adverse Pregnancy Outcome (HAPO) cohort (n = 23 316) and a population at high risk for GDM (n = 10 283). For
the HAPO cohort and the high-risk population, respectively, FPG thresholds of: (a) ≥5.1 mmol/L (specificity 100%)
independently ruled in GDM in 1769 (8.3%) women and 2975 (28.9%) women; and (b) ≤4.4 mmol/L ruled out
GDM in 11 526 (49.4%) women (84.1% sensitivity) and 2228 (21.7%) women (95.4% sensitivity). Use of the FPG
independently could have avoided 13 295 (57.0%) and 5203 (50.6%) OGTTs in the 2 groups. The initial FPG—by
significantly reducing the number of cumbersome OGTTs needed—can make the IADPSG recommendations more
acceptable worldwide. The number of GDM women missed is population dependent. For low-resource countries,
alternative newer and cheaper tests in development hold an exciting future.
1. Introduction OGTT; the use of universal OGTT, i.e. that every pregnant woman
undergo an OGTT, was limited to high-risk populations [3].
Despite 4 decades of research, the screening and diagnosis of One such high-prevalence country is the United Arab Emirates
gestational diabetes mellitus (GDM) have remained controversial. (UAE), a multiethnic society where the prevalence of type 2 diabetes
The different international obstetric, health, and endocrine (approximately 20.1%) is the second highest in the world [4]. The
associations often support markedly disparate schemes for GDM, prevalence of GDM in the UAE varies from 7.9% to 24.9%, depending
resulting in an array of algorithms [1]. To unify this diversity, on the criteria used for the diagnosis [5]. A decade of experience
the International Association of the Diabetes and Pregnancy in this population confirms that trying to screen every pregnant
Study Groups (IADPSG) proposed a one-step approach for GDM woman with the OGTT is difficult, if not impossible. Despite no
worldwide [2]. In January 2011, this approach was endorsed by the dearth of financial resources in the UAE, the laboratory has grappled
American Diabetes Association (ADA) and all international diabetes with the physical demands of making every pregnant woman
and global health organizations are expected to follow suit. undergo the OGTT; these ADA recommendations have appeared
The unified IADPSG approach utilizes the 75 g oral glucose to be an ivory tower approach [6]. The danger of the IADPSG
tolerance test (OGTT) with diagnostic thresholds based on the approach is similar: poorer countries may abandon screening for
prodigious Hyperglycemia and Adverse Pregnancy Outcome (HAPO) GDM altogether, while more affluent nations may find it a logistic
study; however, each and every pregnant woman would need to nightmare.
undergo the OGTT. This approach, although validated by extensive This paper outlines an alternative approach, which is practical
research and endorsed by experts, is extremely demanding. The and user friendly; furthermore, and most crucial, it does not
OGTT is a costly and cumbersome test, both for the patient and the compromise health care with data corroborated by the HAPO
health provider. Before January 2011, the ADA recommended that study. Poorer countries may use this algorithm out of compulsion;
populations at low risk for GDM should use clinical or laboratory the more affluent countries would find it cost-effective, patient-
screening (the glucose challenge test, GCT) to avoid the demanding friendly, and convenient. It also looks at alternate, practical new
technologies for low-resource settings that are available and in
* Corresponding author. Moshe Hod. Division of Maternal Fetal Medicine, development.
Helen Schneider Hospital for Women, Rabin Medical Center, Petah-Tiqva,
49100, Israel. Tel: 972 3 937 7400; Fax: 972 3 937 6897.
E-mail address: [email protected] (M.Hod).
M.M. Agarwal et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S30–S33 S31
Table 1
Data from the United Arab Emirates circumventing use of the OGTT
No. of OGTTs Thresholds (lower and higher), OGTT Diagnostic Comments Reference
circumvented, % mmol/L criteria
50.9 4.4 and 5.3 100 g ADA Biased sampling: Preselected by clinical/GCT [10]
30.1 4.7 a and none 75 g WHO FPG performance poor with WHO criteria [13]
68.5 4.9 and 7.0 75 g ADA Glucometer used for FPG [12]
63.8 4.9 75 g ADA FPG screening criteria dependent [14]
50.1 4.7 and 7.0 75 g ADA Fasting capillary glucose used [9]
50.6 4.4 and 5.1 75 g IADPSG Data from four studies [15]
Abbreviations: GCT, glucose challenge test; OGTT, oral glucose tolerance test; ADA, American Diabetes Association; IADPSG, International Association of the Diabetes and
Pregnancy Study Groups.
a Only lower threshold used.
2. Problems of the OGTT for universal screening of GDM: The lower threshold of 4.4 mmol/L is based on the findings of
Experience of high-risk populations the HAPO study [11]. After reviewing the HAPO study, the IADPSG
agreed that the risks of adverse outcomes were low when the FPG
The OGTT is a test with multiple problems. It is nonphysiologic,
was ≤4.4 mmol/L. However, the IADPSG has admonished that using
unpleasant with poor reproducibility, expensive, and time-
the FPG to potentially identify pregnancies at very low risk for
consuming [7]. Without an alternative diagnostic test, all major
adverse outcomes (in GDM) would need further evaluation [2].
diabetes and health organizations endorse the OGTT for the
diagnosis of GDM. The diagnosis is further compounded by the
different thresholds—for the same OGTT test result—advocated by 5. The number of OGTTs circumvented
these organizations.
For high-risk populations such as the UAE (similar to the 5.1. HAPO data
current IADPSG recommendations), the ADA (before January 2011) FPG thresholds of: (a) ≥5.1 mmol/L (specificity 100%) independently
and the American College of Obstetricians and Gynecologists ruled in GDM in 1769 (8.3%) women; and (b) ≤4.4 mmol/L ruled
(ACOG) [8] recommended screening all pregnant women (i.e. out GDM in 11 526 (49.4%) women (84.1% sensitivity). The initial
universal screening) with the one-step OGTT as early in pregnancy FPG independently could have avoided 13 295 (57.0%) OGTTs. Nearly
as possible. All women testing negative need to repeat the OGTT one-quarter of women with GDM would be missed using this
between 24–28 weeks of pregnancy to exclude GDM. This approach, approach.
though conceptually sound, is taxing and difficult to follow [9].
Hence, one can extrapolate that applying the IADPSG criteria, since
it also recommends the universal OGTT approach for all pregnant 5.2. UAE data
women, would face similar problems. A decade of experience confirms that the initial FPG result (of
the OGTT) can help to decide the need to proceed with the
3. The two threshold approach: Fasting plasma glucose as a OGTT [9,10,12–14] (Table 1). The number of OGTTs avoided is
screening test for GDM dependent on the criteria used for GDM diagnosis [14]. In a study
Despite doubts about its value as a screening test for GDM [9],
fasting plasma glucose (FPG) can be used to limit the number of
OGTTs. A two threshold rule-in and rule-out algorithm has been
used for this purpose [10]. Briefly, two (instead of one) cut-off
values are used for a screening test (FPG, in this case). The higher
cut-off, which has an inherently increased specificity, is used to
rule in the disease (GDM); while the lower cut-off with its innately
increased sensitivity is used to rule out the disease. Patients
who have FPG values in between these two selected thresholds
are considered indeterminate and would require the OGTT. The
pregnant woman, after her fasting glucose is drawn, should wait
for the FPG result, which the laboratory performs on a stat basis.
Based on the result, the decision to stop or proceed with the OGTT
can be made. Thus, initial testing by FPG can significantly decrease
the number of OGTTs needed for the diagnosis of GDM.
4. Rationale for use of the higher (5.1 mmol/L) and lower

(4.4 mmol/L) FPG thresholds
In the 75 g OGTT, any value of FPG ≥5.1 mmol/L (as per the IADPSG)
confirms the diagnosis of GDM. This is irrespective of the threshold
of the 1- or 2-hour values. Thus, any FPG over this threshold has
a specificity of 100%, i.e. no false positives. If this value exceeded
the cut-off, the other values would be superfluous. That was not Fig. 1. Histogram of women with and without gestational diabetes mellitus (IADPSG
the case earlier when the ADA needed two or more values (of the criteria) with suggested fasting plasma glucose thresholds. Key: FPG, fasting plasma
OGTT) for GDM diagnosis [3]. glucose; GDM, gestational diabetes mellitus.
S32 M.M. Agarwal et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S30–S33
using the new IADPSG criteria [15], 10 283 women underwent the is evaluating an instrument-free, rapid strip test for GAlb in low-
OGTT. Of these, 2975 (28.9%) were over a threshold of 5.1 mmol/L, resource settings.
while 2228 (21.7%) were below the threshold of 4.4 mmol/L Other markers for GDM screening include cytokines, chemokines,
with a sensitivity of 95.4% (Fig. 1). Thus, the FPG could have hormones, transcriptional factors stimulated by the AGE/RAGE
circumvented the OGTT in 5203 (50.6%) women. GDM would be signaling pathway, and soluble RAGE (Receptor for Advanced
missed in just 4.6% of the 3875 (37.7%) women with GDM. This Glycation Endproducts) [22]. However, more studies will be needed
approach has been supported by independent reviewers (http:// before any of these markers become feasible alternatives for GDM
plus.mcmaster.ca/evidenceupdates/Default.aspx). screening.
The variation in the women in the 2 cohorts shows that this
approach is population dependent; presumably, the ethnic mix of 10. Urinalysis and integrated screening devices
Arab and South Asians (in the UAE data) had a higher mean FPG
Microalbuminuria is elevated in women with GDM without type 2
than the HAPO cohort.
diabetes [23]. Low-cost urine dipsticks for glucose and albumin,
although displaced in wealthier settings, may have a place in low-
6. Shortcomings of the two threshold approach resource settings. A multiplex urine dipstick with glucose and
microalbumin could be a powerful initial screening tool in a low-
One limiting factor for this approach is laboratory turnaround time
resource setting prenatal clinic.
for the initial FPG result, which is the time the pregnant woman
An alternative approach is multivalent platforms that screen
has to wait in a fasting state. This time would vary from laboratory
for several prenatal parameters such as malaria, syphilis, anemia,
to laboratory. To decrease the turnaround time, a glucometer has
HIV, and GDM. Such platforms are costly, but their concomitant
been used to measure the fasting venous glucose instead of the
effectiveness may justify the expense and potential complexity.
hospital laboratory [12]. Nevertheless, all women would still have
Platforms under evaluation include a blood test that can detect all
to undergo a venipuncture for the FPG. Another alternative is fasting
these parameters based on a reagent-free multiple light assay [24].
capillary glucose (FCG) measured by a glucometer. It is much easier
Noninvasive techniques based on “occlusion spectroscopy” enable
to perform, and more patient-friendly than the venous FPG. The
multiparameter screening; these have been used for measuring
FCG has been found to be as good as the FPG with excellent clinical
hemoglobin and glucose [25].
concordance (k = 0.95) for GDM diagnosis [9].
The HAPO data are not a microcosm of all populations of the
world. In some Asian populations, the FPG is very low but the 11. Conclusions
postprandial is very high [16]. Thus, the suggested approach, in The IADPSG recommendation that every pregnant woman should
many populations, may not circumvent as many OGTTs as indicated undergo the OGTT is onerous. It would (a) severely pressurize the
by this report. laboratories in high-resource settings; and (b) prove challenging in
low-resource settings; however, many new tests and technologies
are under development. An urgent, initial FPG result can avoid the
7. GDM in low-resource countries: Alternative approaches and
need for many OGTTs. Until a simpler, low-cost, more user-friendly
new candidate technologies
test or newer methodology becomes available, the FPG could help to
The key to screening for GDM in low-resource countries lies in simplify the demanding algorithm for the screening and diagnosis
a new generation of minimally invasive, rapid diabetes screening of GDM.
technologies that measure new biomarkers of hyperglycemia.
An ideal GDM screening tool for low-resource settings must fulfill Conflict of interest statement
many requirements: it should: (1) be cheap; (2) not need elaborate
preparations (e.g. fasting); (3) have a high sensitivity and specificity; The authors have no conflicts of interest to declare.
(4) have a short turnaround time; (5) be administrable by minimally
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ARTICLE
Integrating noncommunicable disease prevention into maternal and child health

programs: Can it be done and what will it take?
William K. Maina *
Division of Non-communicable Diseases, Ministry of Public Health and Sanitation, Nairobi, Kenya
Keywords: Noncommunicable diseases (NCDs) are the leading cause of mortality worldwide. However, these diseases have not
Disease prevention been adequately addressed by health systems, especially in low-resource countries. Similarly, there is no equitable
Noncommunicable disease allocation of global resources for health commensurate with the burden of diseases occasioned by NCDs. This has
Maternal and child health programs resulted in poor access to care for women, girls, and other vulnerable groups affected by NCDs. Owing to their
position in most societies, women lack control over resources and, hence, cannot afford quality care to treat NCDs.
Women also face sociocultural, geographic, and economic barriers to access to care. They are less recognized and
catered for in terms of accessibility, comprehensiveness, and responsiveness of healthcare systems. Considering
that NCDs affect women more than the general population, tackling them as part of an integrated program for
women’s health will improve the coverage of the most vulnerable groups. This paper describes how NCD prevention
and control could be integrated into maternal and child health programs to improve access to NCD services. It
presents the effectiveness, benefits, and challenges of this approach when applied at the primary healthcare level.
1. Introduction As a result, women with NCDs may conceal their problems, which
may lead to long-term suffering.
The world is experiencing an upward trend in the burden of
As the primary care givers in families, women and girls tend
noncommunicable diseases (NCDs) such as cardiovascular diseases,
to bear the greatest burden of NCDs when family members are
diabetes, cancers, and chronic respiratory diseases. Often thought
affected. Women are more likely to discontinue their employment,
to be diseases of high-resource countries or of the affluent in low-
while girls are withdrawn from school to play an active role in
resource nations, NCDs are now ravaging the poorest of the poor
taking care of the sick in the family [2]. Globally, women account
in many low-resource regions [1,2]. These diseases cause 60% of
for more than half of the poor. Women also suffer high levels of
mortality worldwide, with 80% of these deaths occurring in low-
illiteracy and poor access to information on NCDs. Women lack
and middle-income countries [3].
control over resources and, hence, cannot afford quality care to treat
The rising trends in NCDs are driven by modifiable risk factors
NCDs. Women often face sociocultural, geographic, and economic
such as tobacco use, harmful use of alcohol, unhealthy diets, and
barriers to access to care. They are less recognized and catered
physical inactivity. The exposure of the population to these risk
for in terms of access, comprehensiveness, and responsiveness of
factors is directly influenced by rapid urbanization, globalization of
healthcare systems [5].
markets, and economic development. In low- and middle-income
As the burden of NCDs increases worldwide, new approaches to
countries, women and girls are disadvantaged in their capacity to
prevention and control of these diseases become apparent. Barr
protect themselves from exposure to these risk factors.
et al. [6] have suggested the expanded chronic care model: a
NCDs combined are the leading cause of death in women
combined approach that integrates population health promotion
worldwide, accounting for 65% of all deaths [2]. Half of all people
with improved clinical care. The practice of this model of care may
with diabetes are women and 1 in every 25 pregnant women
serve to reorientate care delivery toward more proactive behavior
is likely to get gestational diabetes mellitus (GDM), which is
and improvements in patient health outcomes [7].
associated with complications during labor that endanger the life
Women can be key agents of change in adoption of healthier
of the mother and offspring [4]. Unlike men, women with NCDs are
lifestyles and, therefore, play a key role in the prevention of NCDs.
likely to suffer more stigma and discrimination from their families
The integration of NCD prevention and control into programs for
and society, and the potential for divorce and loss of employment.
women’s health would empower women to control NCDs in their
* Corresponding author. William K. Maina. Division of Non-communicable families and better safeguard their own health.
Diseases, Ministry of Public Health and Sanitation, PO Box 30016–00100 This paper explores how the principle of integrated services
Nairobi, Kenya. Tel: +254 722 334 365. could be applied to improve access to care for women with
E-mail address: [email protected] (W.K. Maina). NCDs. It describes how NCD prevention and control could be
W.K. Maina / International Journal of Gynecology and Obstetrics 115S1 (2011) S34–S36 S35
integrated within maternal and child health (MCH) programs. The 4. Ensuring successful integration of services
paper describes the effectiveness, benefits, and challenges of this
For an integrated program to work successfully, planning must be
approach when applied at the primary healthcare level.
done in an integrated manner. All entities in the program must be
operating at the same level of efficiency. An integrated planning and
2. Integration of services budgeting process will give rise to an integrated program. Funds
must be allocated in a manner that allows them to be distributed
Integration of services is the process of merging two or more to all activities in an integrated way. This calls for greater flexibility
services or management components together to meet the needs from managers not to hold on to their funds, staff, and even physical
of the individual with the co-occurring conditions. The basic aims infrastructure.
of integration of services are to promote the use of one or both Within an integrated service, staff roles and responsibilities
services, to reduce costs, and to improve efficiency of delivery change. Healthcare providers will be called upon to take on
of these services. Integration of services recognizes that two or expanded responsibilities. It is therefore important that staff are
more integrated services have a frequent tendency to co-occur, that accorded equal status including salary, allowances, and position as
there is always a relationship between the outcomes of inadequate long as they are performing the same function within the integrated
management of each condition, and that the responses to these program. In the past, we have witnessed healthcare providers
conditions are compatible for all of the conditions [8]. working in HIV/AIDS, malaria, tuberculosis, and reproductive health
Given the relationship between certain NCDs (such as diabetes, programs earning higher salaries and allowances, as well as
hypertension, and cardiovascular diseases) and maternal health, being accorded higher status, than those working in less lucrative
failure to address them in an MCH set-up may lead to failure to programs such as immunization, diabetes, or trauma care.
provide comprehensive care. Integration of services yields benefits When an NCD program is being integrated into MCH services and
to the recipient and to the care giver. It improves patient outcomes, organization charts are being redrawn, it is important to reallocate
improves adherence to treatment, and improves efficiency because staff according to where they are needed most. Inappropriate
services are sourced from one delivery point. It provides integrated deployment may lead to poor motivation, diminished performance,
information without contradicting messages and improves access and failure of the program. Decentralization of planning and
to care. Integration also provides an opportunity for organization services helps to streamline the central bureaucracy while
and individual care-provider growth in terms of skills development strengthening the regional or district management capabilities,
and job satisfaction [9]. which eventually improve the performance of the overall program.
The addition of new health services to existing MCH programs Training programs are necessary for existing staff; in some
provides an opportunity to prevent exposure of vulnerable people cases, multitasking should be applied when additional staff are
to risk factors, while providing early detection of co-occurring unavailable. Adequate time is required to plan and create an
illness and prompt treatment. These services often include integrated training program that teaches providers to assess each
diagnosing, treating, and providing information on how to prevent patient and provide the appropriate services. When developing the
health risks, providing pre- and postnatal health services, and training curriculum, it is also important to identify the combination
providing contraceptive services tailored specifically to women with of skills that staff and supervisors will need to support each other,
coexisting NCDs. so that together the entire staff at a service facility can deliver high-
quality services to their patients.
Programs should only be integrated if they are operating at the
3. Integration of NCD services into MCH programs same or similar level of efficiency. It is paramount that the less
efficient program is improved before integration begins. This will
The prevalence of NCDs, such as type 2 diabetes, is increasing
ensure that the efficiency of the more efficient systems does not
globally. With increasing numbers of pregnancies and deliveries
deteriorate.
in most low-resource countries, the prevalence of GDM is also
expected to increase [10]. This increases the pool of people at risk
of developing type 2 diabetes since GDM increases the risk of the 5. Challenges to integration
disease in the mother and the offspring [11]. Although it is commonly believed that integrating different services
Integrated services at primary level have been applied with results in improved delivery of care, reduced costs, and improved
proven success. Traditionally, most low-resource countries have patient satisfaction, a dissenting opinion exists that integration
provided maternal health, child health, and family planning dilutes focus of services [13]. It is also difficult to integrate services
in an integrated setting. A program integrating child health, that are not operating at the same efficiency. Integration is not
immunization, prenatal care, and cancer screening in women was possible where systems have failed and it is not a substitute for
implemented in Cearà, a poor state in Brazil [12]. This program this.
allowed community and primary level healthcare providers to Integration of services requires changes to health systems and
provide and expand access to care. implementation of reforms that need policy, and administrative
At prenatal care clinics, mothers are advised to ensure that they and technical support. In most cases, such changes may generate
make a minimum of 4 visits during their pregnancy. The prenatal resistance among health workers and managers, or prompt fears of
visits provide the necessary opportunity for routine screening losing prioritization and resources.
of mothers at risk of GDM, hypertension, heart diseases, and Most programs are funded by different funding agencies
kidney diseases, and can be done at every patient contact. The that have strict guidelines on specific targets and outcomes.
family planning clinics that are already integrated into MCH Integrated services give rise to integrated programs if only an
services provide an opportunity for health promotion of NCD risk integrated budget is applied. “Verticalization” of donor funding
factors such as smoking, alcohol abuse, diet, and physical activity. enhances vertical programs and prevents efforts toward integration.
These clinics are also a good entry point for breast and cervical Historically, programs for NCDs have received little funding support
cancer screening among women of reproductive age. Reinforcement and other resource allocations. This may render such programs
of lifestyle modifications that target the prevention of the 4 vulnerable to marginalization, or the view that they are diluting
major NCDs, namely cardiovascular diseases, diabetes, cancers, and the prominence of other MCH programs within an integrated care
chronic respiratory diseases, can be provided in these settings. system.
S36 W.K. Maina / International Journal of Gynecology and Obstetrics 115S1 (2011) S34–S36
6. Conclusion 5. World Health Organization. Women and health: Today’s evidence, to-
morrow’s agenda. www.who.int. http://whqlibdoc.who.int/publications/2009/
The burden of NCDs is increasing and impacts heavily on women’s 9789241563857_eng.pdf. Published 2009.
health. Women will continue to carry the heaviest burden of 6. Barr VJ, Robinson S, Marin-Link B, Underhill L, Dotts A, Ravensdale D, et al. The
NCDs while they remain in vulnerable positions in society for expanded Chronic Care Model: an integration of concepts and strategies from
population health promotion and the Chronic Care Model. Hosp Q 2003;7(1):
both risk-factor exposure and poor access to care. Women can 73–82.
influence the prevention and control of NCDs because they often 7. Piatt GA, Orchard TJ, Emerson S, Simmons D, Songer TJ, Brooks MM, et al.
determine family food production, nutrition, and lifestyle. They are Translating the chronic care model into the community: results from a
key partners in the fight against NCDs; therefore, NCD programs randomized controlled trial of a multifaceted diabetes care intervention.
Diabetes Care 2006;29(4):811–7.
must be integrated into MCH programs within health systems.
8. World Health Organization. Innovative care for chronic conditions: building
blocks for action. www.who.int. http://www.who.int/diabetesactiononline/
about/icccglobalreport.pdf. Published 2002.
Conflict of interest statement 9. Etz RS, Cohen DJ, Woolf SH, Holtrop JS, Donahue KE, Isaacson NF, et al. Bridging
primary care practices and communities to promote healthy behaviors. Am J
The author declares that he has no conflict of interest.
Prev Med 2008;35(5 Suppl):S390–7.
10. Foreman M. The Challenges of Integrating Family Planning and Mater-
nal/Child Health Services. www.prb.org. http://www.prb.org/Articles/2011/
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www.wpro.who.int/NR/rdonlyres/1FC8050D-36F2–40D4–88A4–45E819EEF0FB/ diabetes. Br Med Bull 2001;60:183–99.
0/poverty_ncd.pdf. Published 2006. 12. Cufino Svitone E, Garfield R, Vasconcelos MI, Araujo Craveiro V. Primary health
2. World Health Organization. Global burden of disease 2004. www.who.int. http:// care lessons from the northeast of Brazil: the Agentes de Saúde Program. Rev
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full.pdf. Published 2008. 13. Dehne KL, Snow R, O’Reilly KR. Integration of prevention and care of sexually
3. World Health Organization. The global status report on non-communicable dis- transmitted infections with family planning services: what is the evidence for
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full_en.pdf. Published 2010.
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2011_women_ncd_report.pdf.pdf. Published 2011.

ARTICLE
Designing feasible interventions for healthy pregnancies in low-resource settings
Shane A. Norris *
MRC/Wits Developmental Pathways for Health Research Unit, Department of Pediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Keywords: In low-resource settings there is a need for effective interventions targeting women before and during pregnancy
Healthy pregnancy to improve their health outcomes and provide the best start to life for their infants. The aim of this paper is
Interventions; Implementation to provide an overview for designing, implementing, and evaluating such interventions. Drawing upon published
Low-resource settings literature and case studies, several key steps in the process of intervention design, implementation, and evaluation
are identified. Pregnancy intervention studies in low-resource settings are challenging. Essential intervention
process steps include: (1) selecting the optimal setting to pilot the intervention; (2) forming strong stakeholder
collaborations; (3) identifying, understanding, and prioritizing community health problems; (4) facilitating the
demand for intervention research and evidence utilization; (5) effectively implementing and evaluating the
prototype intervention to provide evidence of effectiveness; and (6) planning with stakeholders for sustainability.
Fundamental to any intervention for healthy pregnancies is the understanding that the process does not end with
an evaluation study, but rather the end goal is to ensure successful interventions are sustainable, scalable, and
integrated into health services.
1. Introduction creating infrastructure around HIV/AIDS services. Other solutions

may include intervening before and during pregnancy by improving
The statistics are startling. Annually, up to 500 000 women die
micronutrient status, promoting the access to prenatal care early
from causes related to pregnancy and childbirth [1,2], and 3.7
and more regularly during pregnancy, and providing community
million children die before they are 1 month old worldwide [3].
health worker disseminated health education [8].
Hemorrhage, HIV, infection, and hypertensive disorders account
Whatever the intervention, designing and testing new ones
for over half of maternal deaths among women aged 15–44 years
targeted at pregnant women and their offspring, getting support
in low-income countries [4]. Preterm birth, asphyxia, and sepsis
account for two-thirds of newborn deaths [5]. from the local community, adhering to ethical standards,
Most maternal deaths stem from emergencies that do not receive maintaining high participant retention rates, being able to measure
the rapid and adequate interventions they need. Younger mothers the effect, and ensuring integration into existing services is not an
are particularly at risk. Compared with women aged 20–24 years, effortless task in any setting, and may be more exigent in low-
girls aged 12–14 years have a 5-fold increase in the likelihood of resource countries. The aim of this paper is to provide a practical
death; those aged 15–19 years are at twice the risk [6]. Improved overview to designing and implementing pregnancy interventions.
maternal, newborn, and child health are essential for families to
break out of crippling cycles of ill health that may otherwise 2. Intervention planning and development models
continue across generations. New transgenerational cycles of risk
Intervention models, for example the PRECEDE-PROCEED and
are being understood; mothers who were stunted in childhood
Intervention Mapping models, provide explicit procedures to guide
and later are obese may place themselves and their offspring at
intervention conceptualization and development. In essence, the
risk when they become pregnant because they are more likely to
procedural steps include: (1) problem identification; (2) under-
develop gestational diabetes, have obstructive labor, and confer risk
standing the root causes of the health problem(s); (3) selecting
for type 2 diabetes to their offspring [7].
which of these determinants should be translated into intervention
These stark realities may seem insurmountable, but they
highlight opportunities for interventions to save lives. Promoting or change goals; (4) mapping out the intervention objectives into
the integration of programs may be one solution; for example, specific and explicit activities; and (5) intervention implementation
unifying maternal, newborn, child health initiatives within and evaluation [9–15].
reproductive health and HIV/AIDS programs may be sensible,
particularly in settings where resources have been ploughed into 3. Identifying the problem
Health challenges may or may not exist, depending on the
* Corresponding author. Shane Norris. MRC/Wits Developmental
Pathways for Health Research Unit, Room 4L16, Medical School, 7 York perceptions of key informal and formal stakeholders. Often in rural
Road, Parktown, 2146, South Africa. areas, cultural beliefs, traditions, practices, poor education, and lack
E-mail address: [email protected] (S. Norris). of data may hamper recognition of a health problem. Frequently
S38 S.A. Norris / International Journal of Gynecology and Obstetrics 115S1 (2011) S37–S40
Table 1
Checklist of actions to help define the problem
Action Task
Understand the evidence Conduct a scientific literature review so as to identify local information and data within the community of interest.
Collect additional formative data to supplement and fill in missing information highlighted by the literature review.
Identify possible intervention opportunities Select a standard/reference population (regional, national, or international) for comparison with the local community/setting.
Compare local data to the standard so as to identify health concerns and the intervention possibilities.
Understand the local setting Describe the health concern according to who is affected, where, and why?.
Scrutinize the root causes (medical, social, cultural, behavioral) so as to better inform the intervention.
Consensus Come to a consensus with key stakeholders about which health concern is important and a priority with the aid of evidence
from quantitative epidemiological data and qualitative community narratives.
Source: Lawn et al. The healthy newborn. A reference manual for program managers [17].
Table 2
Stakeholders: Who are they and why are they important to pregnancy interventions?
Informal/community sector Intersectoral sector Formal sector
Who? Traditional village leaders Teachers Community health workers, nurses, doctors
Youth group leaders Local government officials District/regional medical officers
Religious leaders Department of Transport Department of Health (regionally and nationally)
Women’s groups Department of Education
National Treasury
Academic institutions
NGOs and CBOs
Funders
Why? To understand what stakeholders consider to be critical To mobilize resources to support the To understand clinic staff perceptions of barriers and
community concerns. study. opportunities.
To promote ownership of the problem and provide To foster demand for evidence that can To access local data to assist with problem
potential solutions. drive policy. identification and review of health service statistics.
To mobilize community resources and support for an To provide information on planned To promote ownership of the problem.
intervention and evaluation study. projects that may be relevant to the To create a demand for the study and the data.
study (for example, new roads). To enable stakeholders to drive policy based on
evidence.
How? Community forums Focus groups Collect data to address the gaps in understanding
Focus groups In-depth interviews the problem.
In-depth interviews Provide data analysis support and feedback forums.
Provide financial and logistic support.
Barriers? Health problem may not be seen as a priority by the Intersectoral stakeholders not identified. Overburdened clinic staff.
community. No established links with intersectoral Poor motivation and negative attitudes.
Conflict with traditional practices/beliefs. sector stakeholders. No strong links with local government.
Lack of trust and support for the study in the community.
Lack of resources and infrastructure to implement an
intervention study.
Source: Lawn et al. The healthy newborn. A reference manual for program managers [17].
referred to as a “needs assessment,” drawing upon available services (Table 2). Indeed, the community may in itself be a core
data, evidence from other interventions [16], and identifying gaps component of the intervention to effect change and address a health
between what is observed and what is happening elsewhere problem [18].
(standard/reference population) can help identify opportunities
for intervention priorities. Actual measurement of the magnitude 5. Evaluation of the intervention
of the problem is needed to harness recognition of the health All the formative work (the evidence base) in the preceding steps is
problem within a community and among stakeholders; also, an used to prioritize and support the development of an intervention
understanding of the underlying cultural, social, and behavioral prototype. Selecting the pilot community where the intervention
causes is also essential to formulate the pilot intervention. Health prototype will be tested and evaluated is another crucial decision.
problems need to be defined by both observed evidence and from Partnering with academic entities that have cohorts, demographic
a stakeholder and community perspective. Interventions based and health surveillance sites, or access to hospitals and clinics can
exclusively on either will not be effective in the long term (Table 1). prove useful in identifying the pilot community. Academic partners
are often able to provide established and trusted relationships
with communities and stakeholders, in depth understanding of
4. Stakeholders
community barriers and solutions, infrastructure, skilled staff,
Collaborating with stakeholders and the community early on, ethics application support and compliance with local guidelines
and throughout the intervention design and implementation and processes, and a platform that may be economical for nesting
process, can help increase demand for the study, foster shared intervention studies within.
ownership, assist with the identification of existing resources, and The foundation for developing an evaluation framework is to
open opportunities for sustainability and integration into health ensure that the study team can articulate precisely and simply
S.A. Norris / International Journal of Gynecology and Obstetrics 115S1 (2011) S37–S40 S39
Table 3
Making Pregnancy Safer (MPS) intervention in Uganda
Intervention design and What the MPS intervention did Key learning point
implementation step
Stakeholders Community forums Partnerships were built early on so as to

Soroti district local government leverage funds to conduct the
District health team and hospitals intervention, but also to share goals,
Ministry of Health resources, roles, and responsibilities.
Development partners
NGOs
World Health Organization
UNICEF
UNFPA
Community assessment Reproductive Health Needs Survey The survey aided the identification of gaps
and needs in responding to the problem of
high maternal mortality in the district at
both community and health facility level.
The health problem Soroti MMR ratio was 885 per 100 000. Identified reasons included: failure to implement the They compared local data with the MMR
policy of delivery of integrated Reproductive Health services, inadequacy of second line drugs for national average (504 per 100 000), which
management of sepsis and malaria, understaffing in remote rural health units, poor knowledge was able to assist with reaching
on danger signs during pregnancy, and poor access to maternity services. consensus that maternal mortality was an
opportunity gap and a priority.
Evaluation MMR was halved to 221 per 100 000, which was 50% below the 2006 national MMR. The success was largely due to the
Time taken for patients to reach referral hospitals was reduced from an average of 2 h to 30 min. different stakeholder sectors working
The percentage of deliveries at health facilities increased from 19% to 41.4%. together on a common challenge and
Attendance of prenatal care by pregnant women increased. pooling resources that enabled
Reproductive health awareness increased. cost-savings.
More men accompanied wives for maternity services.
Logistics, supplies, and training improved.
the goal, objectives, what interventions will achieve the objectives, understanding responsible fatherhood. The information campaign
where the interventions will be delivered, by whom, when, and also tackled cultural barriers and practices that hinder safe
how. Ensuring that each objective contributes to the overall goal pregnancy practices such as over-reliance on Traditional Birth
and is linked to specific tasks and deliverables will assist the Attendants, use of herbs, and delays in seeking skilled medical
evaluation process [14]. It is important that the evaluation study attention when in labor (Table 3) [19].
also examines the cost-effectiveness, feasibility, and sustainability The case study highlights that a pregnancy intervention in a low-
of the prototype. resource setting can be successfully designed and implemented,
Embedded in the evaluation is monitoring, which will entail but it also brings to the fore the enormous challenge of
the ongoing collection of data to reflect project progress, sustainability. Despite the effectiveness of the interventions and the
quality assurance, budget expenditure, and provide process data commitment of the local government, equipment running expenses
(quantitative and qualitative) that will contribute to the impact and replacement costs, ongoing staff training needs, community
evaluation. For successful monitoring and evaluation, selecting key engagement costs, and scale-up barriers, pose real threats to the
indicators that will be measured is useful as it will assist with sustainability of the interventions. Furthermore, MPS monitoring
identifying the data sources for the indicators, how often they need and evaluation highlighted new health concerns, in particular, high
to be collected and by whom, and the data analysis and reporting infant mortality [19].
requirements. After the prototype intervention has been tested
and evaluated, data reviewed by study partners and stakeholders, 7. Conclusion
and the intervention improved, the process of implementation
Good collaboration to facilitate data demand, stakeholder involve-
begins [14,16].
ment, evidence utilization, and sound research practice can be
invaluable in designing and implementing pregnancy interventions.
6. Case study: Making Pregnancy Safer (MPS) intervention, Fundamental to an intervention is the understanding that the
Uganda process does not end with an evaluation study, but rather the end
goal is to ensure successful interventions are sustainable, scalable,
The Soroti district in the eastern region of Uganda implemented and integrated into health services amid limited resources and
a 5-year pregnancy intervention in 2001 that aimed to reduce the emerging health challenges that may become prioritized.
exceedingly high maternal mortality ratio (MMR) through improved
access and utilization of quality reproductive health services.
The intervention equipped doctors, nurses, and midwives with
enhanced obstetric skills. The referral system from communities to The author has no conflict of interest to disclose.
Health Centers (HCs) to hospitals was improved. Communities were
equipped with bicycle ambulances, HCs with radio transmission References
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ARTICLE
Gestational diabetes mellitus: Advocating for policy change in India
Anand Madhab a, *, Vishwa Mohan Prasad a , Anil Kapur b

a Jagran Pehel, New Delhi, India
b World Diabetes Foundation, Gentofte, Denmark
Keywords: A multimedia awareness and advocacy campaign for mainstreaming gestational diabetes mellitus (GDM) in the
Gestational diabetes mellitus public health domain is described. The multimedia campaign has created awareness about the relevance of GDM
India to women’s health and the health of future generations through direct contact, reaching out to over half a million
Information education communication people in 7 districts of 4 states in northern India. Using mass media, over 3.7 million people have received
Low-resource country information on GDM. Through multistakeholder forums, more than 1000 key stakeholders have been encouraged
Multimedia campaign to mainstream GDM into the existing health delivery system. The Indian Ministry of Health has introduced free
Policy advocacy screening for GDM among the 5 services offered to pregnant women below the poverty line in the National Rural
Health Mission (NRHM) program. In addition, several state governments, such as in Bihar, Delhi, Jharkhand, and
Punjab, have pledged similar initiatives addressing GDM; the Government of Tamil Nadu is already implementing
such a policy. Policy development is a complex process that requires action on many fronts. By showcasing
evidence, raising awareness, creating public opinion through dialogue and discussion, media can help build a
positive environment and momentum for effective policy creation as well as service utilization.
1. Introduction estimated that the overall prevalence of diabetes, hypertension,

ischemic heart diseases (IHD), and stroke in India is 62.5, 159.4,
The need for public awareness campaigns is well recognized and
37.0, and 1.5, respectively, per 1000 people [1]. NCDs also account
extensively implemented in the context of communicable diseases;
for a sizeable loss in national income and productivity. In a country
however, this approach is less utilized for noncommunicable
with inadequate social security, low health insurance penetration,
diseases (NCDs).
and poor public health facilities, out-of-pocket expenses for health
Awareness and advocacy campaigns related to health require
care can be as high as 75% and the risk of catastrophic spending or
careful consideration of the medium, message, and audience;
impoverishment is 2–5-fold higher in people with NCDs compared
the use of multimedia ensures segmentation, synergy, and
with those without NCDs within the same socioeconomic strata [2].
optimization. The large number of illiterate people limits the reach
In July 2010, India launched a National Programme for Prevention
and applicability of the print media; increasing availability of radio
and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke
among the poor offers opportunities, but none can replace direct
(NPCDCS) to be implemented in 100 Districts across 15 States and
interpersonal engagement.
Union Territories. The program has a resource allocation of only
Along with informing and educating, media provides an
US$273 million. An Economist Intelligence Unit report in 2007
opportunity for dialogue to shape public opinion. Engaging decision
stated that if all the known people with diabetes in India were
makers and elected representatives in dialogue through advocacy
forums gives them the opportunity to understand the evidence, treated, even with the country’s low-cost medicine, it would cost
gauge its importance, and get a sense of public opinion. Decisions on US$13.8 billion annually, nearly one-quarter of its overall current
political actions are not merely based on rational facts, but require healthcare spending. Diabetes alone costs India 2.1% of its GDP, 0.2%
backing of popular public opinion, especially when resources are in costs of treatment and 1.9% in lost productivity [3].
limited. In 2007, India spent US$40 per capita, i.e. 4.1% of its GDP on
Owing to their insidious nature and the complex interplay of health services, 26% of which was government funding. With a
risk factors linked to their development—as well as the mistaken per capita gross national income of only US$460, 86% of the 1.2
assumption that they are diseases of the rich—NCDs have until billion population surviving on less than US$2 per day, and 70%
recently failed to attract political attention despite accounting for living in rural areas, the healthcare delivery challenges in India are
a significant health burden and many premature deaths. It is phenomenal [4]. Recent developments in addressing rural health
through the National Rural Health Mission (NRHM) program are yet
* Corresponding author. Anand Madhab. Jagran Pehel, 84 Okhla Industrial to bear fruit. Improving maternal and child health, and reducing the
Estate Phase III, New Delhi-110 020, India. high maternal and infant mortality and morbidity are key objectives
E-mail address: [email protected] (A. Madhab). of the NRHM.
S42 A. Madhab et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S41–S44
Hyperglycemia during pregnancy due to unrecognized or the problem. The proportion of mothers attending all 3 prenatal
unmanaged gestational diabetes mellitus (GDM) increases the risk checkups in Jharkhand, UP, Punjab, and Delhi was 26.3%, 36.1%,
of poor pregnancy outcomes, and enhances the likelihood of both 72.8%, and 74.4%, respectively.
mother and offspring developing type 2 diabetes in the future [5]. Key issues that emerged from the survey were: (1) gaps in service
Data from India indicate high prevalence of GDM; fortunately, up delivery; (2) low demand or access to services; and (3) lack of health
to 90% of cases require diet and physical activity alone and the information. Women were identified as the primary target group.
remainder may require insulin to achieve control [6]. Addressing Adolescent girls attending schools and colleges, and young women
GDM has multifaceted positive outcomes—in terms of immediate are targeted as future mothers and spokespersons for the issue.
benefits, the direct link to maternal and child health, a national Health service providers are targeted to mainstream GDM in their
priority, and in the long term, prevention of NCDs (another national existing services, and policy level stakeholders are targeted to take
priority)—and would intuitively seem attractive to the planners appropriate action for mainstreaming GDM into existing policies
and policy makers; however, existing programs are competing for and programs.
meager resources and initiating new activities is not easy. Besides,
the National Family Health Survey 3 (NFHS-3) data show that only
52% of mothers have 3 or more prenatal visits, only 47% of births are
assisted by professional health service providers, and only 40.8% are
institutional births [7]. An intervention addressing GDM requires
engagement at multiple levels from the top decision makers to the
grass-root community health workers.
Jagran Prakashan Limited (JPL), a leading media conglomerate
in India, is engaged in extensive advocacy and public education
campaigns on issues as diverse as HIV/AIDS, banning sex
determination of the unborn child, mother and child care,
women’s empowerment, and diabetes through different structured
interventions. Fig. 1. Minister of Health and Family Welfare, Government of India, reiterating his
In 2007/2008, Jagran Pehel—a strategic social initiative of JPL— commitment to GDM.
in collaboration with and co-funded by the World Diabetes
Foundation, implemented a multimedia campaign to generate
awareness and advocacy for prevention and care of diabetes. The
campaign reached 96 Districts of 14 States in northern India,
covering more than 350 000 people through direct interpersonal
communication and around 60 million people through mass media,
i.e. radio, mobile SMS, and print. A total of 114 027 people at high
risk volunteered to be screened and 13.8% were found to have
diabetes [8]. The campaign generated positive action on policy at
various levels with commitments to mainstream diabetes in the
future—some already achieved.
With this background, a new intervention on GDM has been
initiated that is currently ongoing. This article describes the Fig. 2. Screening and consultation camps organized with the support of public and
structure of, and preparations for, the GDM campaign, its initial private health providers during the IEC campaign.
rollout, and its expected outcome and impact.
2. Method and plan of action

The project “Awareness, sensitization, and advocacy to mainstream
GDM in the health delivery system” is planned around a two-
pronged strategy: (1) public education through sensitization and
community awareness is centered on promoting screening for GDM
and a healthy lifestyle among pregnant women; and (2) advocating
supportive public policies, as well as identifying, motivating, and Fig. 3. A wall painting on a community center with key messages about GDM.
training local providers to deliver the services. The awareness
component of the project is targeted primarily at the community 4. Creating a resource pool
at large and the grass-root level health service providers, whereas
the advocacy initiatives are intended to sensitize and convince To assist with information, validation, and guidance, a technical
the policy-level decision makers and key players involved in advisory group was created with specialists representing different
implementation of health programs. fields of specialization. Knowledge about specific issues related to
GDM has been consolidated in the form of resource articles. The
role of the technical advisory group is to approve the Information
3. Identifying issues, needs, and key target groups
Education and Communication (IEC) tools and promotion material,
Seven project districts from 4 States were selected: Jharkhand, develop training material, and provide training for district level
Uttar Pradesh (UP), Punjab, and Delhi (National Capital Region). panels of doctors and project teams.
A baseline survey was conducted to assess issues, needs, and key
target groups among 1394 respondents, 25% of whom were health
5. Key messages and synchronization of multimedia
professionals. Awareness about GDM is poor, not only among lay
people, but also among health professionals. The study revealed To create a sense of continuity, the awareness campaign is built
that only 40.6% of respondents recognized the term or understood around “screening saves life,” which was used in the 2007/2008
A. Madhab et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S41–S44 S43
diabetes awareness project. The campaign on GDM revolves around spokespersons. At the events held in schools and junior colleges a
the slogan “Janch Se Bache Do Jan,” which means “screening saves film about GDM is shown, followed by a talk by a local gynecologist
two lives.” The slogan reiterates the importance of screening to and a Q&A session. Later, the young women are encouraged to
detect diabetes during pregnancy, which benefits both the mother participate in short essay writing and poster competitions to
and unborn child, and highlights the seriousness of the condition internalize the key learning points.
that could threaten two lives.
Messages have been designed to promote 3 levels of action on
7. Creating forums for dialogue
the part of the community and service providers:
1. Three mandatory prenatal checkups for pregnant women. The project organizes forums at different levels—district, state,
2. Screening of diabetes among pregnant women. and national—to sensitize different stakeholders. At such meetings,
3. Appropriate action taken through diet, physical exercise, or policy makers are invited; they are informed about the issues, sense
treatment as advised by the doctor. their relevance, and realize the consensus around the desired action.
In addition, 3 key messages for policy advocacy are: Political vetting and the commitments made at the forums are then
1. Diabetes is a huge public health problem with economic and followed-up to ensure implementation.
social implications for the nation.
2. Attention and focus on GDM offers the opportunity to address
8. Results and outcomes
prevention and reduce the future burden.
3. Well-equipped health delivery systems to address GDM help The project has been running for just over 1 year and has already
strengthen overall maternal care and reduce maternal and achieved important results, even before completion of the project
prenatal morbidity and mortality. time frame. A total of 1009 different stakeholders participated in
These key messages are disseminated through a multimedia ap- national and district level workshops and forums. An IEC van brings
proach including print, radio, wall paintings, mobile SMS, internet, education and information material to the communities and has
and a van with IEC materials and trained community mobilisers; reached 496 626 people from 473 different communities with an
this approach reaches out to different target groups. Because of awareness campaign and interpersonal messages. An SMS service
low literacy levels, radio and interpersonal communications provide has been developed where people can send a message and receive
better impact for community education in rural areas. Media information about GDM, including its risk factors, implications for
such as IEC vans, wall paintings, mobile SMS, and websites are the mother and child, the screening or diagnosis test, and diet. The
utilized in coherence so that each reinforces the messages of the service is announced by the IEC van that travels the selected district
other, to establish a bidirectional communication with the target according to a prescheduled plan, and also by posters and wall
population. paintings that are put up in the districts. More than 2 million mobile
users are sent messages regarding GDM and 56 000 users replied
with further enquiries. A subsection on the popular website portal
“onlymyhealth.com” has been created to provide information on
GDM in both English and Hindi. Videos containing interviews with
doctors giving relevant information as well as the possibility for
online Q&As with a doctor are also offered. The GDM site is visited
by more than 300 000 unique users.
A radio campaign with jingles on GDM, interviews with doctors,
coverage from stakeholder workshops, and a fictional character,
“Dr Mantra,” who provides useful tips, is running on Radio Mantra
and is aired in two of the participating districts. Radio Mantra
has around 158 000 listeners in these two districts and caters
Fig. 4. Women in a tribal village of Jharkhand watching an AV presentation on GDM. particularly for people in the 18–35 age group.
A close relationship with the Jagran group ensures good coverage
in the various newspapers it publishes. With more than 90 000 cm2
6. Building and leveraging partnerships
of allocated editorial space, it has the power to ensure that the issue
To create empirical evidence for positive outcomes in the targeted is always high on the agenda. Various activities are announced and
areas, multistakeholder engagement is essential because the receive coverage in the newspapers. Other competing newspapers
evidence will be required to trigger further policy initiatives at the also cover the initiatives and activities.
state and national level. To leverage their technical expertise and To date, over 74 086 female students from 219 schools and 58
influence, key stakeholders—senior members of local professional colleges have participated in awareness sessions and activities on
organizations—were invited to be part of the initiative from the GDM. The district level project team in Jalandhar, in association
start of the project. Similarly, local NGOs were engaged to utilize with the NRHM, organized a sensitization program for 2000
their outreach in the local communities for mass mobilization. Local Accredited Social Health Activists (ASHAs) on GDM. The ASHAs visit
public and private health service providers assisted by leveraging pregnant women, counsel them, and accompany them to primary
their human and physical resources for screening and treatment healthcare centers. Screening was not part of the initial project
facilities. By ensuring their participation, these providers are being plan; however, with help from local healthcare providers, screening
sensitized to the issue and provide a platform for recognition; at has taken place at 143 of the community centers and around 9500
the same time the communities have been introduced to the service women have been screened.
providers for future access. In many intervention districts, religious At the national level workshop to launch the program, the
leaders and places of worship are helping ensure maximum Minister of Health and Family Welfare, Government of India,
participation of the community. Similarly, engagement of the local although unaware of the gravity of the issue at that point in
health department ensures the participation of grass-root health time, promised to investigate and initiate action on the subject.
service providers and health workers. Subsequently, screening for GDM has been added to the list of free
Local educational institutions are now also part of the initiative services to be provided to women below the poverty line on the
as school and college-going women are engaged and prepared as maternal and child healthcare card used in the NRHM Program.
S44 A. Madhab et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S41–S44
Similar facilities are provided under the National Program for support of a media house. Logistics, mobilization, and participation
Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases of decision makers were certainly secured because of the power and
and Stroke (NPCDCS) [9]. The state governments of Delhi [10] influence that media exert. Commitment made at a forum organized
and Punjab announced that screening for diabetes in pregnant by a large media house has a greater chance of positive outcome
women would become mandatory in their respective states. The simply because of better accountability. Greater involvement and
government of Bihar (a nonproject state that was part of the participation of the media in issues of public relevance such
earlier diabetes initiative) has made GDM screening mandatory in as health seem relevant and crucial for better governance and
its public health facilities [11] and should be seen as a multiplier accountability.
effect.
AM and VMP are employed by Jagran Pehel, a social initiative wing

of Jagran Prakashan Ltd. AK has no conflict of interest to report.
References
1. National Programme for Prevention and Control of Cancer, Diabetes,
Cardiovascular diseases and Stroke (NPCDCS) approved [news release]. Press
Information Bureau, Ministry of Health and Family Welfare, Government of
India; July 8, 2010. http://pib.nic.in/newsite/erelease.aspx?relid=63088
2. Mahal A, Karan A, Engelgau M. The Economic Implications of Non-
Communicable Disease for India. Health, Nutrition and Population (HNP) Discus-
Fig. 5. Engaging adolescent girls on GDM at Lucknow Public College. sion Paper. Washington: World Bank; 2010. http://siteresources.worldbank.org/
healthnutritionandpopulation/Resources/281627–1095698140167/
EconomicImplicationsofNCDforIndia.pdf
9. Discussion 3. Economist Intelligence Unit. The silent epidemic. An economic study of
diabetes in developed and developing countries. http://viewswire.eiu.com/
Policies and programs have their priorities. Initiating new priorities report_dl.asp?mode=fi&fi=1882281973.PDF&rf=0. Published June, 2007.
requires evidence and assessment both in terms of immediate 4. World Health Organization. World Health Statistics 2010. Geneva: WHO; 2010.
returns via incremental value to existing strategy and the long-term 5. World Diabetes Foundation, Global Alliance for Women’s Health. Diabetes,
implications. The advocacy messages in this initiative ensure that Women, and Development. Meeting summary, expert recommendations for
policy action, conclusions, and follow-up actions. Int J Gynecol Obstet
both short- and long-term aspects are covered. Enhanced demand 2009;104(Suppl):S46–S50.
for services at the community level acts as an important lever 6. Seshiah V, Balaji V, Balaji MS, Paneerselvam A, Kapur A. Pregnancy and diabetes
for positive action. The project ensures that both the demand and scenario around the world: India. Int J Gynecol Obstet 2009;104(Suppl):S35–
supply side are addressed. S38.
7. International Institute for Population Sciences (IIPS) and Macro International.
The sensitization of policy level institutions and implementation
National Family Health Survey (NFHS-3), 2005–06: India: Volume I. Mumbai:
mechanism are ensured through their active participation at IIPS; 2007. http://www.nfhsindia.org/NFHS-3%20Data/VOL-1/India_volume_I_
different forums, workshops, and in one-to-one dialogue. The corrected_17oct08.pdf
commitment to support the initiative made by the decision makers 8. Media campaign for prevention and care of diabetes, India. http://
www.worlddiabetesfoundation.org/composite-1860.htm
and program implementing agencies is publicized through mass
9. Azad Launches Diabetes, Hypertension Screening Campaign for Delhi’s Urban
media and creates a platform for further concrete actions. Slums [news release]. Press Information Bureau, Ministry of Health and
In a dynamic environment where multiple initiatives—some Family Welfare, Government of India; June 28, 2011. http://pib.nic.in/newsite/
complementary, others antagonistic—take place, it is not prudent erelease.aspx?relid=72915
to make undue claims about the success of one initiative. In this 10. Diabetes test a must for pregnant women in Delhi. iGovernment; January
10, 2011. http://www.igovernment.in/site/diabetes-test-must-pregnant-women-
case, however, it is difficult to imagine that the initiatives would
delhi-39065
have made such significant progress and achieved such clear impact 11. Private firm to help state fight diabetes. The Telegraph, Calcutta, India. March 9,
within such a short time without the active engagement and 2011. http://www.telegraphindia.com/1110309/jsp/bihar/story_13684554.jsp

ARTICLE
Global adaptation of IADPSG recommendations: A national approach
Nicky Lieberman a, *, Ofra Kalter-Leibovici b , Moshe Hod c

a Community Medicine Division, Clalit Health Services, Israel
b Unit of Cardiovascular Epidemiology, Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Israel
c Helen Schneider Hospital for Women, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Petah-Tiqva, Israel
Keywords: The current practice for diagnosing gestational diabetes mellitus (GDM) in Israel employs a two-step screening
Cost-effectiveness approach using a 50 g glucose challenge test (GCT) followed by a 3-hour 100 g oral glucose tolerance test (OGTT).
Gestational diabetes The overall adherence to this process is more than 90%. Recently, the International Association of the Diabetes and
IADPSG Pregnancy Study Groups (IADPSG) recommended changing this practice to a single-step GDM screening, employing
Screening a 75 g OGTT. New plasma glucose cutoffs were recommended. To make recommendations for a new screening
and diagnosis policy for GDM in Israel, a committee was assembled, including representatives of professional
medical organizations, health maintenance organizations (HMOs), health policy makers, epidemiologists and
biostatisticians. There was agreement that a consensus can be achieved only by clinical evidence and that consensus
is a key factor for changing health policy. It was also realized that the availability of local data on the annual rates
of GDM, its complications, and cost-effectiveness of screening and treatment are suboptimal. This generated two
studies: the first provided additional analyses of data concerning Israeli women participating in the Hyperglycemia
and Adverse Pregnancy Outcome (HAPO) study, and the second was a cost-effectiveness analysis based on Clalit
Health Service’s (the largest HMO in the country) database. We found that the prevalence of GDM in Israel is
approximately 6% and is expected to increase to 9% by adopting the new IADPSG recommendations. The conclusion
was that a one-step approach is presumed to be not only cost-effective but cost-saving, even under conservative
estimates. We recommend such a process for other countries debating whether to change their GDM screening
and diagnostic approach.
1. Introduction macrosomia, birth trauma, primary cesarean delivery, neonatal

hypoglycemia, hyperbilirubinemia, hypocalcemia, and erythremia;
Gestational diabetes mellitus (GDM) was first defined in 1964 as
and an increase in neonatal intensive care unit (NICU) admissions
the onset or first recognition of abnormal glucose tolerance during
and perinatal mortality. Long-term complications of GDM also
pregnancy. This condition can be identified by the 3-hour oral
include a greater risk for type 2 diabetes, with an estimated annual
glucose tolerance test (OGTT) [1]. In 2000, the American Diabetes
incidence of 10% per year. This risk varies by the diagnostic criteria
Association (ADA) revised the recommendations for the diagnosis
used, race, and ethnicity. Long-term adverse neonatal outcomes
of GDM and adopted lower plasma glucose cutoffs as suggested
include increased risk of childhood obesity and type 2 diabetes,
by Carpenter and Coustan [2]. The glucose cutoffs selected were
impaired motor functions, and higher rates of inattention and
chosen according to their association with the risk of developing
hyperactivity [4].
type 2 diabetes during follow-up. Since 1998, the diagnosis of GDM
The Hyperglycemia and Adverse Pregnancy Outcome (HAPO)
in Europe has been based on the World Health Organization (WHO)
study results showed a continuous increase in the risk of poor
criteria, defining GDM as either impaired glucose tolerance or
pregnancy outcomes with increasing fasting and postload plasma
frank diabetes diagnosed by a 2-hour OGTT [3]. These diagnostic
glucose levels, with no obvious thresholds at which risks increase.
criteria endorsed by the ADA [2] and WHO [3] increased the
Pregnant women with increased plasma glucose levels that do not
number of women diagnosed with GDM. The prevalence of GDM
fall into the category of overt diabetes have a higher risk for adverse
has increased further with the increasing prevalence of maternal
maternal and fetal outcomes [5]. These results were the main drive
obesity, older age at pregnancy, and increasing prevalence of a
sedentary lifestyle [4]. GDM is associated with poor maternal for the reassessment of the currently employed plasma glucose
and fetal outcomes, including pre-eclampsia, polyhydramnios, fetal thresholds for the diagnosis and treatment of GDM.
To complicate matters further, little data exist on the impact
* Corresponding author. Nicky Lieberman. Community Medicine Division, of various interventions on pregnancy outcomes at lower plasma
Clalit Health Services, Arlozorov str. 101, Tel Aviv, Israel. glucose levels. In the study by Crowther et al. [6], treatment of GDM
Tel: +972 3 6923311; fax: +972 3 6923376; mobile: +972 506 263050. reduced adverse perinatal outcomes, and the number-needed-to-
E-mail address: [email protected]; [email protected] (N. Lieberman). treat (NNT) to avoid one adverse outcome was 43. Landon et al. [7]
S46 N. Lieberman et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S45–S47
showed that treatment of mild GDM cases also reduced perinatal GDM and the cost-effectiveness of a one-step screening process are
adverse outcomes. needed. One of the main issues raised was whether fasting plasma
Another important issue that affects cost-effectiveness of GDM glucose (FPG) can suffice for the diagnosis of GDM.
interventions is the prevalence of GDM that varies between
countries and different populations [8]. In a recent survey it 4. Improving the database regarding a one-step screening
was found that only 18 countries conducted national prevalence approach in Israel
assessments of GDM. In the USA the estimated prevalence of GDM
The dialogue initiated by the committee and the realization that
was 2–15%. The prevalence was higher among African Americans,
local data are urgently needed created the momentum for two
Latinos, Native Americans, and Asian women. Prevalence rates in
important studies, the first provided additional analyses of data
other countries ranged from 1% to 38%. In India the prevalence of
from the Israeli women participating in the HAPO study and the
GDM was as high as 19%, whereas in Germany it was less than 1%.
second generated data regarding the presumed cost-effectiveness
As a consequence of the results of the HAPO study and a
of the different screening methods, relying on Clalit’s database.
lack of consensus concerning the diagnostic criteria for GDM, the
International Association of the Diabetes and Pregnancy Study
Groups (IADPSG) [4] recommended that for the diagnosis of GDM 5. Prevalence of GDM
a single test using 75 g of oral glucose should be used during weeks Of 19 370 women, 501 (2.6%) were diagnosed as having GDM
24–28 of pregnancy, using new plasma glucose thresholds that according to the two-step procedure; a large number of women
were chosen based on their association with adverse pregnancy do not complete this unpleasant and complicated combined test,
outcomes. especially the 100 g OGTT part. A substantial number of those who
do not complete the test will get a correct GDM diagnosis anyway,
but some will not. Therefore, one of the benefits of switching
2. Current situation in Israel
to the single-step 75 g OGTT is that some pregnant women who
To understand the advantages and limitations of implementing would have gone undiagnosed and untreated, or who would start
a one-step screen in Israel it is important to be familiar with treatment only at a later stage in their pregnancy, will now receive
the structure of the healthcare system in Israel. Health insurance more timely treatment. Accordingly, we believe that the real GDM
is provided to all Israeli citizens by law. Health services are prevalence may be much higher: 6% or even as high as 9%, rather
provided by 4 health maintenance organizations (HMOs): Clalit than the 2.6% positively identified in the study cohort. If we assume
Health Services, Maccabi Health Services, Meuhedet, and Leumit. that all those women who did not complete testing would meet
Clalit Health Services is the largest HMO and provides health GDM criteria, the prevalence in our study cohort would rise from
services to more than 4 million Israeli citizens, accounting for 54% 2.6% to 8.0%. We also learned that by applying the new criteria
of the Israeli population. GDM screening and diagnosis have been for diagnosing GDM, we will encounter about 50% more GDM
universally employed by the 4 Israeli HMOs since the 1970s. The pregnancies, and this will present a substantial challenge to the
screening program, employed in all HMOs, is a two-step approach. public medical system. On the other hand, we speculate that this
All pregnant women undergo a first screening with a 50 g oral new approach can prevent or at least delay the transformation of
GCT at 24–28 weeks of pregnancy. Further testing with a 100 g the GDM episode into full blown type 2 diabetes.
3-hour OGTT is performed for women with a 1-hour glucose level
greater than or equal to 140 mg/dL at GCT. There are no data on the 6. Cost-effectiveness data
sensitivity, specificity, and cost-effectiveness of this approach. The
We invited Dr Elliot Marseille, Health Strategies International, and
estimated adherence of Israeli women to the first screening step is
Professor Jim G. Kahn, University of California San Francisco, to
greater than 90% [8].
use data from the Clalit Health Service’s database to pilot the
The information on the prevalence of GDM in Israel stems from
GDModel. This mathematical model, which is currently under
the database of one HMO (Maccabi Health Services), which shows
development, can estimate the cost and health impact of various
that the age-adjusted rate of GDM is about 6% of all pregnancies [9].
GDM screening choices [10]. The GDModel aims to inform policy
Using this rate, the estimated number of pregnancies diagnosed
makers who are making decisions regarding GDM screening
with GDM using the current screening practice is about 9700 per
strategies and guidelines. An analysis was conducted to assess
year.
the cost-effectiveness of a change in the Israeli recommendations.
Using a cohort of all women who underwent screening for
3. A unique approach to creating a policy change GDM during 2009 with a two-step procedure it was possible to
estimate the costs and savings of the current Israeli approach as
The new recommendations of the IADPSG, as well as additional data
well as prospective costs and savings of a change in screening
regarding screening and effectiveness of interventions to reduce
recommendations. The uniqueness of this model is that it applies
GDM and type 2 diabetes, created a debate regarding the implica-
true rates and real glucose level data supplied by Clalit’s registry
tions of the endorsement of the new recommendations. To create a
and thus goes beyond the currently available calculations. The
productive dialogue that all participating parties would be able to
preliminary results were very illustrative and encouraging in that
endorse it was crucial to join efforts with the medical professional
they suggested that switching to a one-step approach would be
organizations, the various HMOs, health policy makers, epidemi-
cost-saving, even with the low GDM prevalence of 2.6%. The savings
ologists, and biostatisticians. A committee was appointed that
would come from a combination of delaying future type 2 diabetes,
included representatives from the Israeli Society of Obstetrics and
and from preventing perinatal complications. Please note that the
Gynecology, the National Diabetes Council, The Gertner Institute
GDModel is undergoing further refinement, and that the purpose
for Epidemiology and Health Policy Research, Clalit Health Services,
of this article is to illustrate the effect of these preliminary results
Maccabi Health Services, and the Ministry of Health. The aim of this
on the policy discussions.
committee was to formulate recommendations for GDM screening
that were based on evidence. The importance of local data was
7. Lessons learned and recommendations
emphasized because variations in the prevalence of GDM between
countries regardless of the chosen definition are significant. It was The results generated by these preliminary studies contribute
soon realized that additional local data addressing the prevalence of significantly to the Israeli debate on whether to adopt a one-step
N. Lieberman et al. / International Journal of Gynecology and Obstetrics 115S1 (2011) S45–S47 S47
screening for GDM in Israel. Differences between the local dataset References
and available data throughout the world were significant. Despite 1. O’Sullivan JB, Mahan CM. Criteria for the oral glucose tolerance test in pregnancy.
this, the one-step approach seems to remain cost-effective—and Diabetes 1964;13:278–85.
even cost-saving—for the diagnosis and management of GDM. The 2. American Diabetes Association. Diagnosis and classification of diabetes mellitus.
presentation of local data analysis created a sense of assurance Diabetes Care 2009;32(Suppl 1):S62–7.
3. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes
and mitigated a large proportion of the criticism regarding the mellitus and its complications. Part 1: diagnosis and classification of
appropriateness of the universal recommendations to the local diabetes mellitus provisional report of a WHO consultation. Diabet Med
diabetic scene. It also enabled the discussions to remain evidence- 1998;15(7):539–53.
based rather than emotion-based. We plan in the coming months 4. International Association of Diabetes and Pregnancy Study Groups Consensus
to gather further data and analyze these in a refined version of the
GDModel, and then present it to the professional associations and recommendations on the diagnosis and classification of hyperglycemia in
national councils; it is hoped that, by the beginning of 2012, formal pregnancy. Diabetes Care 2010;33(3):676–82.
recommendations regarding the screening process of GDM in Israel 5. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR,
Trimble ER, Chaovarindr U, et al. Hyperglycemia and adverse pregnancy
will be finalized and adopted by the Ministry of Health.
outcomes. N Engl J Med 2008;358(19):1991–2002.
The process described here may serve as a model for other 6. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS, et al. Effect
countries contemplating a change in their GDM screening approach. of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J
We recommend that such decisions should be made based on Med 2005;352(24):2477–86.
local figures of prevalence and costs. The great variations between 7. Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, et al.
A multicenter, randomized trial of treatment for mild gestational diabetes.
countries and ethnic groups regarding the prevalence of GDM may N Engl J Med 2009;361(14):1339–48.
affect the appropriateness of general recommendations for each 8. Jiwani A, Marseille E, Lohse N, Damm P, Hod M, Kahn JG. Gestational diabetes
country and a cut and paste approach may not necessarily yield the mellitus: results from a survey of country prevalence and practices. J Matern
best local solutions. Another important lesson is that incorporating Fetal Neonatal Med 2011. In press.
9. Chodick G, Elchalal U, Sella T, Heymann AD, Porath A, Kokia E, et al. The risk of
all the relevant parties involved in the treatment of these women overt diabetes mellitus among women with gestational diabetes: a population-
is crucial for gaining a consensus and that the political arena is as based study. Diabet Med 2010;27(7):779–85.
important as the medical one. It is noteworthy that such a process 10. Lohse N, Marseille E, Kahn JG. Development of a model to assess the
is feasible within a reasonable time frame. cost-effectiveness of gestational diabetes mellitus screening and lifestyle
change for the prevention of type 2 diabetes mellitus. Int J Gynecol Obstet
2011;115(Suppl 1):S20–5.
The authors have no conflicts of interest to declare.

COMMENTARY
FIGO—A professional nonprofit organization: Reproductive, maternal, and child

health policy and programs to address noncommunicable childhood disease
Gamal I. Serour a , Luis Cabero Roura b, *

a President of FIGO (2009–2012); Professor of Obstetrics and Gynecology and Director of the International Islamic Centre for Population Studies and Research, Al Azhar University;
Clinical Director, The Egyptian IVF and ET Centre, Maadi, Egypt
b Chair of the FIGO Committee for Capacity Building in Education and Training; Professor of Obstetrics and Gynecology, Autonomous University of Barcelona, Hospital Universitari
Vall Hebron, Barcelona, Spain
The International Federation of Gynecology and Obstetrics (FIGO) offspring. Nutritional disturbances that occur early in development
is a professional organization dedicated to the improvement of tend to damage more elementary systems, such as those associated
women’s health and rights, and to the reduction of disparities with nutritional balance, adiposity, blood coagulation, and
in health care available to women and newborns. Traditionally, atherogenic lipid profile, whereas nutritional insults during later
FIGO’s focus was the high maternal mortality ratio (MMR) in low- gestational periods disrupt higher-order systems, causing problems
resource countries and measures to reduce it. Recently there has with kidney function (microalbuminuria) and the respiratory
been a reduction in maternal mortality to 350 000 maternal deaths system. Furthermore, infants exposed to poor environments and
annually, which represents a 34% decline. However, reduction of given poor maternal attention shortly after birth have been found
maternal mortality in Sub-Saharan Africa is far below optimum to have disruptions in cognitive and emotional development.
for achieving Millennium Development Goal (MDG) 5 target A: Appropriate nutrition reduces these complications, including
to reduce the MMR by three quarters. The Countdown to 2015 GDM, and also reduces the incidence of chronic diseases for both
initiative (www.countdown2015mnch.org) has shown that only the mother and the next generation. Ensuring optimal health during
5 of the 68 countries are on track to achieve this target. The pregnancy and in the early childhood years not only provides the
leading causes of maternal mortality are preventable and include best chance for a healthy start, but also reduces suffering and
postpartum hemorrhage (PPH), pre-eclampsia, obstructed labor, the cost to society of chronic diseases over decades of life. The
infections, and other causes such as undernutrition, anemia, and preconceptional state can be crucial. Many parental effects on the
unsafe abortion. developing offspring occur even before pregnancy.
Noncommunicable diseases (NCDs) are the leading causes of FIGO is developing different programs to address these concerns.
death in women and account for an estimated 18 million deaths For example, the FIGO Saving Mothers and Newborns Initiative
annually [1]. NCDs such as diabetes, obesity, and undernutrition are (SMNH), aims to increase women’s access to new, cost-effective,
responsible for maternal conditions that have an important impact and evidence-based technology for the reduction of maternal and
on maternal mortality [2]. Diabetes (pre and gestational) can newborn mortality in 10 low-resource countries in Asia, Africa,
cause macrosomia, obstructed labor, PPH, and neonatal mortality Latin America, and Eastern Europe. FIGO works with communities
(prematurity, respiratory distress syndrome, hypoglycemia, etc). and promotes utilization of interventions to reduce maternal and
In addition, pregnant women with gestational diabetes mellitus newborn morbidity and mortality. Another example is the FIGO
(GDM) are over 7 times more likely to develop type 2 diabetes later Adolescent Sexual and Reproductive Health (ASRH) Initiative, which
in life, and their children are at 4–8 times greater risk of developing
focuses on strengthening the capacity of FIGO member associations
the disease [3].
at the national level and promotes access to information and
Many aspects of health are determined before birth, not only
quality services in ASRH. The Leadership in Obstetrics and Gynecology
by genes, but also by the uterine environment [4]. The mother’s
for Impact and Change in Maternal and Newborn Health Initiative
nutritional status, stress levels, and overall health have impacts
(LOGIC) is another program that has an impact on the diagnosis
on the health of the fetus and infant, as well as on the health
and treatment of NCDs. FIGO received a substantial grant from the
of the adult. Undernutrition in utero and low birth weight can
Bill and Melinda Gates Foundation for capacity building of member
be responsible for an increased risk of cardiovascular disease
associations in 8 low-resource countries in Asia and Africa. The
or diabetes in adult life. Maternal undernutrition and disrupted
project will enable member associations to play a leadership role
macronutrient intake early in life have been linked to permanent
and influence policy and practices in maternal and newborn health.
changes in gene expression patterns, and it has been proven that
Improving maternal and newborn health in low-resource countries
maternal dietary, endocrine, or other stresses can induce long-
by strengthening the role of national obstetric and gynecologic
term changes in the cardiovascular and metabolic functioning of
associations will help to achieve MDGs 4 and 5 to reduce child
* Corresponding author. Luis Cabero Roura. Department of Obstetrics and and maternal mortality and morbidity.
Gynecology, Hospital Universitari Vall de Hebron, Universitat Autónoma The close link between child and maternal health and the
de Barcelona, Passeig Vall Hebron 119, 08035 Barcelona, Spain. importance of early-life origin of NCDs requires that preventive and
E-mail address: [email protected] (L. Cabero Roura). healthcare interventions related to such diseases be integrated into
G.I. Serour, L. Cabero Roura / International Journal of Gynecology and Obstetrics 115S1 (2011) S48–S49 S49
reproductive, maternal, and child health programs, especially at the References

primary healthcare level [5]. Many of these preventive strategies
1. World Health Organization. Global status report on noncommunicable diseases
are effective for reducing both maternal and infant mortality and 2010. Geneva: WHO; 2011. Available at: http://www.who.int/nmh/publications/
later chronic diseases. In addition, it will also be important to ncd_report_full_en.pdf
demonstrate that cost-effective interventions are possible. It may be 2. Keeling A. Halting the rise of non-communicable diseases: an urgent priority for
helpful to emphasize the benefits of an alliance bringing together women’s health. Diabetes Res Clin Pract 2011;92(1):143–4.
new advocates to each cause. In general, the NCD field is not 3. International Association of Diabetes and Pregnancy Study Groups Consensus
addressing maternal health, and the maternal health field has not
et al. International Association of Diabetes and Pregnancy Study Groups
established a place for itself in the push for greater attention paid recommendations on the diagnosis and classification of hyperglycemia in
to NCDs. We have a unique opportunity for a change and we should pregnancy. Diabetes Care 2010;33(3):676–82.
not miss it. 4. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-
life conditions on adult health and disease. N Engl J Med 2008;359(1):61–73.
5. World Health Organization. 2008–2013 Action plan for the global strategy
Conflict of interest statement for the prevention and control of non-communicable diseases. Geneva: WHO;
2008. Available at: http://www.who.int/nmh/publications/9789241597418/en/
The authors declare that they have no conflicts of interest. index.html

COMMENTARY
Pregnancy: A window of opportunity for improving current and future health
Anil Kapur *
Managing Director, World Diabetes Foundation, Gentofte, Denmark
1. Early-life origins of noncommunicable diseases 2. NCDs impact pregnancy outcomes

Cardiovascular diseases, diabetes, cancers, and chronic respiratory Hemorrhage, hypertensive disorders, obstructed labor, and in-
diseases are the most common noncommunicable diseases (NCDs), fection/sepsis are among the leading global causes of maternal
accounting for 63% of global deaths (36 million) in 2008 and mortality [13]. High blood pressure and GDM are linked directly or
projected to claim 52 million lives by 2030. Almost 80% of indirectly to all of them. The rising prevalence of high blood pres-
these deaths occur prematurely in low- or low/middle-income sure and GDM is increasing the adverse outcomes of pregnancy and
countries [1]. NCDs become burdensome, costly, and debilitating maternal health [1]. Undiagnosed or poorly managed diabetes or
over time, negatively impacting productivity and family income. hyperglycemia during pregnancy is associated with a significantly
They are, however, largely preventable with focus on lifestyle higher risk of maternal and perinatal morbidity and mortality, as
interventions in adult life, targeting adults at high risk—a strategy well as poor pregnancy outcomes including spontaneous abortion,
fraught with implementation difficulties [2]. still birth, congenital anomalies, macrosomia, need for cesarean
Mounting evidence shows that prenatal and early-life develop- delivery, and assisted deliveries [14].
ment influence the risks of NCD in later life [3–5] and might be The occurrence of hypertensive disorder or hyperglycemia
especially relevant to low-resource countries [5–8]. A mother’s diet, during pregnancy is a strong marker of a high future risk for
body composition, and health determine fetal environment and are hypertension and diabetes, and thus offers opportunities for
shown to affect risk factors. instituting preventive strategies early on.
Improvements in access to care in many low- and middle-income
countries have led to improved survival for even the “at risk” small
3. Pregnancy: a window of opportunity
for gestational age (SGA) babies born to undernourished mothers
in rural settings. These babies continue to be malnourished and The concept of fetal programming and its consequences are
stunted during childhood, but remain at relatively low risk for paradigm changing. It highlights that pregnancy offers a window of
NCDs in adult life as long as they have a subsistence lifestyle. opportunity to provide maternal care services, not only to reduce
With even minor changes towards improved living conditions as the traditionally known maternal and perinatal morbidity and
a consequence of economic development or migration to towns mortality indicators, but also great potential for intergenerational
or cities, these individuals manifest the risk of diabetes and other prevention of several chronic diseases, such as diabetes, arterial
NCDs at much lower body mass index (BMI) and central adiposity hypertension, cardiovascular disease, and stroke. Thus, with one
threshold [9]. Transition in lifestyle in this population seems to high-quality intervention related to maternal and child health
produce rapid adverse changes favoring development of diabetes services, it is now possible to achieve several objectives with far-
and cardiometabolic disorders [10]. reaching health and economic benefits [14].
In young women, adverse changes may present early in The international health community, including donors and
pregnancy, resulting in gestational diabetes and/or pregnancy- national governments, cannot afford to continue with their “silo”
induced hypertension. Seshiah et al. [11] reported prevalence rates short-term approach of fixing certain health and development
of 8–10% for gestational diabetes mellitus (GDM) among women indicators while continuing to ignore the long-term overall health
of low socioeconomic status who had a prepregnancy BMI of less and economic benefits that would accrue from an integrated health
than 19, and significantly higher prevalence rates at higher BMIs system approach. While this approach saves many vulnerable lives,
and in urban environments [11]. Estimates based on data from the it does not address the root cause of the vulnerability and, in fact,
International Diabetes Federation’s Diabetes Atlas [12] show that may increase the vulnerability of future generations. Having saved
approximately 76 million women in the 20–39 years’ reproductive a mother with GDM and eclampsia and her large-for-gestational-
age group have diabetes or impaired glucose tolerance/pre-diabetes, age baby, or a mother with anemia and her low birth weight baby,
and thus are potentially at risk of diabetes during pregnancy; this what can we do to ensure their future good health and prevent or
link creates a vicious cycle of diabetes begetting diabetes. While significantly delay the onset of hypertension or type 2 diabetes? To
maternal undernutrition and its links to future NCDs in offspring get it right will require strengthening of health systems to further
have been more widely studied, similar mechanisms may apply to reinforce maternal and child care services at primary care level
other conditions, such as maternal malaria and HIV/AIDS that also and integrating elements of NCD prevention and health promotion.
result in low birth weight and SGA babies. It will also require investments in information technology to
identify and track high-risk individuals to enlighten, empower, and
* E-mail address: [email protected] (A. Kapur). encourage them to adopt healthy living throughout life. Monitoring
A. Kapur / International Journal of Gynecology and Obstetrics 115S1 (2011) S50–S51 S51
women during pregnancy and their offspring may be the most 6. Yajnik CS, Deshmukh US. Maternal nutrition, intrauterine programming and
appropriate place to begin this health system transformation. We consequential risks in the off spring. Rev Endocr Metab Disord 2008;9(3):
203–11.
have the evidence, we also have the technology, and we know it is
7. Ma RC, Chan JCN. Pregnancy and diabetes scenario around the world: China. Int
feasible, but do we have the willingness to work together to get it J Gynecol Obstet 2009;104(Suppl 1):S42–5.
done? 8. Tam WH, Ma RC, Yang X, Ko GT, Tong PC, Cockram CS. Glucose intolerance
and cardiometabolic risk in children exposed to maternal gestational diabetes
mellitus in utero. Pediatrics 2008;122(6):1229–34.
Conflict of interest statement 9. Ramachandran A, Snehalatha C, Baskar AS, Mary S, Kumar CK, Selvam S, et al.
Temporal changes in prevalence of diabetes and impaired glucose tolerance
The author declares that he has no conflict of interest. associated with lifestyle transition occurring in the rural population in India.
Diabetologia 2004;47(5):860–5.
10. Snehalatha C, Ramachandran A. Cardiovascular risk factors in the normo-
References glycaemic Asian-Indian population—influence of urbanisation. Diabetologia
2009;52(4):596–9.
1. United Nations. Prevention and control of non-communicable diseases. Report
11. Seshiah V, Balaji V, Balaji MS, Paneerselvam A, Kapur A. Pregnancy and diabetes
of the Secretary General. UN General Assembly, 19 May 2011. Avail-
scenario around the world: India. Int J Gynecol Obstet 2009;104(Suppl 1):
able at: http://www.un.org/ga/search/view_doc.asp?symbol=A/66/83&referer=/
S35–8.
english/&Lang=E
12. International Diabetes Federation. http://www.diabetesatlas.org/. Accessed
2. Hanson MA, Gluckman PD. Developmental origins of noncommunicable disease:
10 June, 2011.
population and public health implications. Am J Clin Nutr 2011. doi:10.3945/
13. Khan KS, Wojdlya D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes
ajcn.110.001206.
of maternal death: a systematic review. Lancet 2006;367(9516):1066–74.
3. Godfrey KM. Maternal regulation of fetal development and health in adult life.
14. World Diabetes Foundation, Global Alliance for Women’s Health. Diabetes,
Eur J Obstet Gynecol Reprod Biol 1998;78(2):141–50.
Women, and Development. Meeting summary, expert recommendations for
4. McCance DR, Pettitt DJ, Hanson RL, Jacobsson LT, Knowler WC, Bennett PH. Birth
policy action, conclusion, and follow-up actions. Int J Gynecol Obstet
weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype,
2009;104(Suppl 1):S46–50.
or surviving small baby genotype? Br Med J 1994;308(6934):942–5.
5. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-
life conditions on adult health and disease. N Engl J Med 2008;359(1):61–73.

ARTICLE
Taking on the challenge of noncommunicable diseases: We all hold a piece of the

puzzle
Nicolai Lohse *, Charlotte Ersbøll, Lise Kingo

Corporate Relations, Novo Nordisk A/S, Bagsværd, Denmark
Keywords: Two out of 3 deaths globally are attributable to noncommunicable diseases (NCDs), with 80% occurring in low-
Health systems strengthening resource countries. The “cost of inaction” is estimated to be US$35 trillion between 2005 and 2030. We need to get
Noncommunicable diseases behind the societal root causes of this global health challenge; we need a life-course approach to respond to the
Prevention increasing evidence of intergenerational transmission of NCDs; and we need to focus on strengthening of health
Public–private partnerships systems and integration of services for prevention, screening, and management across disease groups. There is
a growing understanding that all actors, private or public, for-profit or not-for-profit, can make substantial and
positive contributions as long as they maintain transparency in their agenda, motivation, and actions. Effective
and sustainable global public–private partnerships require trust between partners, a safe space for talks and
negotiations, and a framework for governance and accountability. We need a neutral global convener to unite
us all behind shared visions for a healthier future, where each player is encouraged to commit and contribute
to the common cause and be recognized or held accountable for their respective commitments. Creation of
such a platform could be a direct outcome of the United Nations High Level Meeting on NCDs to be held in
September 2011.
1. Introduction globally are attributable to NCDs, 80% of which occur in low- and
middle-income countries [9], and 75% of people with diabetes now
Health is a life-long resource that needs to be nurtured. A
live in these countries [6]. Preliminary health economic analyses
healthy population is a prerequisite for well-being, productivity,
carried out by the Harvard School of Public Health estimated the
prosperity, and growth in any society. Tremendous progress has “cost of inaction” (global loss of economic output) to be US$35
been made during the past century, most notably by reducing trillion during the 25-year period 2005–2030, and “the cost of
the incidence and prevalence of infectious diseases. Success action” (implementing a package of public health interventions) to
stories include the eradication of smallpox and near-eradication be several orders of magnitude less [10].
of polio through immunization programs [1], implementing simple To create another success story will not be easy [9]. We need
hygienic measures such as hand washing and tooth brushing, and to address the social determinants of NCDs [11–17] to get behind
most recently the advent and accessibility of effective and life- the societal root causes of this global health challenge. We need
saving antiretroviral drugs for HIV treatment and prevention [2,3]. a life-course approach to respond to the increasing evidence of
However, new and possibly greater challenges to public health are intergenerational transmission of NCDs [18,19]. And we need an
emerging. Globalization, urbanization, and economic development approach that focuses on strengthening of health systems and
lead to changes in lifestyle and climate that can have a negative integration of services for prevention, screening, and management
impact on our health and environment if we do not take relevant across disease groups. This article describes how the factors above
and timely precautions [4]. By 2030, between 1.9 and 3.3 billion could be addressed in a whole-of-systems response that is broader
people will be overweight or obese, up from 1.3 billion in 2005 [5]. and more inclusive than if confined to the healthcare system.
Some 552 million people will be living with diabetes, compared
with 366 million today [6]. And contrary to common belief, 2. The need for new collaboration
noncommunicable diseases (NCDs) are not diseases of the rich [7].
The burden of NCDs—principally cardiovascular diseases, dia- Public health has traditionally been the domain of the public sector,
betes, cancers, chronic respiratory disease, and mental diseases—is represented by governments and intergovernmental organizations
increasing in low- and middle-income countries, and people who (IGOs) [20]. The not-for-profit part of the private sector, repre-
are poor are disproportionately affected [8]. Two out of 3 deaths sented by nongovernmental organizations (NGOs), has increasingly
gained economic power and therefore a seat around the table
* Corresponding author. Nicolai Lohse. Building 6A1.079, Novo Allé, when decisions are made. The for-profit part of the private sector
DK-2880 Bagsværd, Denmark. Tel: +45 3079 2451. has not been allowed in because of perceived lack of legitimacy
E-mail address: [email protected] (N. Lohse). (not representing a large group), and because their accountability
toward shareholders renders them suspicious. But as the landscape focus areas such as maternal health, child and adolescent health,
is changing, there is a growing understanding that no actor can and NCDs. Under the umbrella of the Every Women Every Child
claim to be totally unbiased, and that all actors can make substantial initiative launched by the UN Secretary-General in 2010, this
and positive contributions as long as they maintain transparency in partnership will combine the strengths of multiple partners to
their agenda, motivation, and actions [20–22]. We must recognize identify and test interventions directed toward improving the
that we are all part of the problem and therefore should all be lifestyle, health, and well-being of adolescents, pregnant women,
part of the solution: governments, intergovernmental organizations, and their children in the short term, with the long-term goal of
nongovernmental organizations, businesses, and the people we decreasing the risk of NCDs in the adult population and thereby
serve [23,24]. The private sector provides products and services the transgenerational transmission of NCDs. When fully established,
of which some may contribute to the problem while others offer the partnership will include other corporations, foundations,
solutions to solve the problem, and hence all must be engaged in intergovernmental organizations, academia, and implementing
dialogue to find solutions. organizations. We will build on our experience from public–
private partnerships building capacity for diabetes management
at national level in low- and middle-income countries [38,39].
3. Interaction between public and private sectors
Through this Early Origins of Health partnership, we hope to
We all hold a piece of the puzzle, but can all sectors work toward contribute our collective experience and expertise to shape a new
a shared objective despite vested interests that conflict with the framework for partnerships as part of the UN Global Compact LEAD
overall goal? The answer has to be yes. If we all believe so, it can initiative [40].
be done. Every sector needs to promote sustainable development
starting with its core capabilities, asking itself, what can we change 6. A need for global governance
today? Each point of interaction between the private and public
sectors entails an opportunity to drive aligned agendas toward We are in a transition from international to global health
common goals and create synergistic outcomes. Examples are governance. Civil society groups, nongovernmental organizations,
joint decision making; advocacy and fund raising; seconding of social movements, foundations, and private companies that operate
personnel from private to public sector; use of logos or product at supranational levels are more eager than ever to play active
endorsement; collaboration on sales or marketing promotions; roles [20,28]. We need a neutral global convener to unite us all
or private sector donations for activities or publications [25]. behind shared visions for a healthier future, where each player is
Other opportunities could arise from leveraging private sector core encouraged to commit and contribute to the common cause and be
capabilities such as innovation of new technologies, creating chains recognized or held accountable for their respective commitments.
for effective distribution of life-saving and life-changing products, A Global Health Index, for example building on the next version of
the MDGs, could hold us accountable and serve as a stretch target
and improvement of health literacy through education and creation
for nations, companies, and other parties to move toward and use
of awareness. All of this would contribute to the much needed
to stand out positively. Such a platform does not exist today, but
strengthening of health systems.
could be a direct outcome of the UN High Level Meeting on NCDs
to be held in September 2011.
4. Public–private partnerships
Effective and sustainable global public–private partnerships 7. A systems-wide approach
(GPPP) [26] require trust between partners, a safe space for All government sectors must collaborate in a coordinated fashion
talks and negotiations, and a framework for governance and that creates maximum health impact of new legislation and
accountability [27]; and they must have long-term horizons and initiatives; it is not just the health sector, but also the sectors of
be built on existing infrastructures. The Millennium Development agriculture, food, urban planning, education, and development that
Goals (MDGs) have served as a catalyst for successful GPPPs can play a major role toward improving the long-term health of
in communicable diseases. However, only few GPPPs have so their populations and nations. Companies must look closely at their
far been established in the field of NCDs [28]. The Oxford products, manufacturing, distribution, and marketing practices, and
Health Alliance was created in 2003 “as an alliance between the move toward a pro-health approach, not for the few but for the
University of Oxford and Novo Nordisk A/S to foster a co-ordinated many, not least the growing middle classes in low- and mid-
approach, involving all stakeholders, with the aim of preventing income countries who are at high risk. An accountability framework
epidemic chronic disease” [29], while the Global Alliance for must be established, with IGOs and NGOs leading the way, but
the Prevention of Obesity and Related Chronic Disease brings at the same time being willing to engage in partnerships and
together 5 international NGOs with the goal of supporting the channel resources toward horizontal programs and finding new
implementation of the WHO Global Strategy on Diet, Physical solutions [22]. Inclusion of intergenerational prevention of diseases
Activity and Health [30]. However, more GPPPs on NCDs are needed in the coming version of the MDGs would not only be extremely
with partners from multiple sectors and a scope beyond the health important, but also an ambitious goal that could inspire parties to
sector [31], and multiple initiatives are likely to emerge as the come together.
global response to NCDs matures [31,32].
8. Sustainability
5. GPPPs to address Early Origins of Health
Former Director-General of the WHO and chair of the World
Novo Nordisk wishes to address the NCD epidemic through Commission on Environment and Development, Gro Harlem
formation of a GPPP focusing on healthy pregnancies and early Brundtland, defined sustainable development as “development that
childhood. The epidemic of childhood obesity is fuelling morbidity meets the needs of the present without compromising the ability
such as hormonal disturbances, cardiovascular disease, and cancer of future generations to meet their own needs” [41]. Yet, we are
in adolescents and adults [33], and the origins may have begun presently stress-testing the resilience of the health of our planet
in utero [34–37]. Thus, addressing the earliest roots of disease and the people who inhabit it. At the current crossroads in global
might hold the key to a thorough improvement of life-long health. health, there is an urgent need for new leadership that can show
We acknowledge the challenge of combining traditionally separate the way for nations as well as companies.
Novo Nordisk and many other pharmaceutical companies have 12. Unwin N, Whiting D, Roglic G. Social determinants of diabetes and challenges
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Volume 115 Supplement 1 November 2011 ISSN 0020-7292

Early Origins of Health:

Official publication of FIGO Guest Editors:

Volume 115, Supplement 1 (2011)

President: G. Serour (Egypt)

FIGO Chief Executive

Argentina N.C. Garello France B. Carbonne Palestine S.S. Jaber

International Editions and Collaborations

Giornale Italiano di Ostetricia e Ginecologia

For information about The Secretariat of FIGO is at FIGO House, Suite 3,

Editor: T. Johnson (USA)

Editor Emeritus: J. Sciarra (USA)

Associate Editor: W. Holzgreve (Germany)

Managing Editor: C. Addington (UK)

Honorary Editor: H. Kaminetzky (USA)

Symposia and Supplements: G. Benagiano (Italy)

Ethical and Legal Issues R. Cook (Canada)

Averting Maternal Death and

FIGO Staging of Gynecologic

Contemporary Issues in R. Adanu (Ghana)

Evidence Based Obstetrics

Surgery and Technology: A. Advincula (USA)

Statistical Consultant: A. Vahratian (USA)

Editorial Office: FIGO Secretariat, FIGO House

Early origins of health:

Luis Cabero Roura, Moshe Hod, Anil Kapur, Nicolai Lohse

Electronic Storage or Usage

Printed by Henry Ling, Dorchester

N. Lieberman, O. Kalter-Leibovici, Global adaptation of IADPSG recommendations: A national approach S45

Contents lists available at ScienceDirect

International Journal of Gynecology and Obstetrics

Conﬂict of interest statement

Contents lists available at ScienceDirect

International Journal of Gynecology and Obstetrics

Developmental origins of health and disease: Moving from biological concepts to

Mark A. Hanson a, *, Peter D. Gluckman b,c

article info abstract

Contents lists available at ScienceDirect

International Journal of Gynecology and Obstetrics

Amir Aviram, Moshe Hod, Yariv Yogev *

article info abstract

1. Introduction disorders, gestational diabetes, respiratory complications, and

* Corresponding author. Yariv Yogev. Perinatal Division, Department of

Contents lists available at ScienceDirect

International Journal of Gynecology and Obstetrics

Anemia and pregnancy: A link to maternal chronic diseases

Raja Gangopadhyay a , Mahantesh Karoshi a , Louis Keith b, *

article info abstract

1. Introduction In low-resource nations, iron deﬁciency is exacerbated by chronic

biochemical indicators (estimation of serum ferritin, transferrin

Fig. 2. Causes of anemia in HIV.

The exact mechanism by which anemia is caused in chronic

Infections Malaria, HIV, tuberculosis, osteomyelitis, bacterial

common, as is loss of appetite, fever, or malabsorption (as in Table 2

Impaired quality of life

Contents lists available at ScienceDirect

International Journal of Gynecology and Obstetrics

Physiological adaption to maternal malaria and other adverse exposure:

Dirk L. Christensen a , Anil Kapur b , Ib C. Bygbjerg a,b, *