Vol 9. No 4.

October The Role of Ferritin Levels Serum

Research

The Role of Ferritin Levels Serum of Third Trimester

Obese Pregnant Women in Neonatal Outcome

Peran Kadar Feritin Serum pada Perempuan Hamil Trimester Tiga

dengan Obesitas terhadap Luaran Bayi

Rudy S. Harahap, Hasanuddin Hasanuddin, Mohd Andalas,

Rajuddin Rajuddin, Cut M. Yeni

Department of Obstetrics and Gynecology

Faculty of Medicine Universitas Syiah
Kuala Dr. Zainoel Abidin General Hospital
Banda Aceh

Abstract Abstrak
Objective: To determine relation of obesity to serum
ferritin levels in third trimester pregnant women and Tujuan: Mengetahui hubungan obesitas terhadap kadar
neonatal outcome at Rumah Sakit Umum Daerah feritin serum pada ibu hamil trimester ketiga serta neonatal
outcome di Rumah Sakit Umum Daerah (RSUD) dr.
(RSUD) dr. Zainoel Abidin Banda Aceh.
Zainoel Abidin Banda Aceh.
Methods: This was a prospective. The study was
Metode: Penelitian analitik observasional menggunakan
conducted in January-November 2019 at RSUD dr. Zainoel
desain cohort prospective. Penelitian ini dilaksanakan pada
Abidin Banda Aceh. Total of 38 patients with 34-40 weeks
Bulan Januari sampai November 2019 di RSUD dr. Zainoel
gestational age with obesity were included in the study.
Abidin Banda Aceh. Sebanyak 38 pasien dengan usia
Univariate analysis is presented in the frequency
kehamilan 34-40 minggu dengan obesitas diikutsertakan
distribution table. Bivariate analysis to test study
dalam penelitian. Analisa univariat disajikan dalam tabel
hypotheses using Spearman's Rank Correlation. P-
distribusi frekuensi. Analisa bivariat untuk menguji
values>0.05 were considered significant. The degree of
hipotesis penelitian menggunakan Spearman’s Rank
correlation is determined based on the value of the
Correlation. P-value > 0,05 dianggap signifikan. Derajat
correlation coefficient r.
korelasi ditentukan berdasarkan nilai koefisien korelasi r.
Result: Spearman test showed no correlation between Hasil: Uji hipotesis Spearman menunjukkan korelasi
obesity variables and ferritin reserve status (p: 0.068).
antara variabel obesitas dengan status cadangan ferritin
Correlation between obesity variable and the infant tidak bermakna (p: 0,068). Korelasi antara variabel
APGAR value was significant (p: 0.032) and the strength obesitas dengan nilai APGAR bayi bermakna (p: 0,032)
of correlation was weak (r: 0.349). Chi-Square test dan kekuatan korelasi lemah (r : 0,349). Hasil uji hipotesis
results showed no correlation between obesity and Chi-Square menunjukkan korelasi antara variabel obesitas
infant birth weight (p: 0.369). Relationship of serum dengan nilai berat badan lahir bayi tidak bermakna (p:
ferritin levels with APGAR no significant (p> 0.05). 0,369). Hubungan kadar serum ferritin dengan nilai
Serum ferritin levels with birth weight also did not APGAR menunjukkan hasil tidak bermakna (p >0,05).
significant (p> 0.05). Kadar serum ferritin dengan berat badan lahir bayi juga
Conclusions: This study shows that obesity in memiliki hubungan yang tidak bermakna (p>0,05).
pregnancy has an effect towords the incidence of asphyxia Kesimpulan: Penelitian ini menunjukkan bahwa korelasi
in newborns an increase in serum ferritin or the incidence antara obesitas dengan status cadangan ferritin tidak
of macrosomia in newborns. bermakna. Korelasi antara obesitas dengan nilai APGAR
Keywords: APGAR, birth weight, ferritil, obesity. bayi bermakna dan kekuatan korelasi lemah, sedangkan
dengan Berat Badan Lahir tidak bermakna. Kadar serum
ferritin dengan nilai APGAR dan BBL bayi memiliki
hubungan yang tidak bermakna.
Kata kunci: APGAR, berat badan lahir, feritin, obesitas.

Correspondence author. Rudy S. Harahap. Department of Obstetrics and Gynecology Faculty of

Medicine Universitas Syiah Kuala Dr. Zainoel Abidin General Hospital Banda Aceh.
[email protected]

Received: july, 2020 Accepted: September,2021 Published: October,2021

 Indones
2 Harahap, Hasanuddin, Andalas et al J Obstet
Gynecol
INTRODUCTION
Patients with premature rupture of
membranes with signs of intestinal uterine
Obesity is excess fat in parts of body that
infection, preeclampsia and eclampsia,
can cause health problems, morbidity, mortality
premature rupture of premature membranes,
and has become one of the global health
fetuses with congenital abnormalities, patients
problems in the 21st century.1 Increased
with a history of diabetes mellitus and
prevalence of obesity occurs in many circles,
hypertension before pregnancy, and mothers
one of which is women in reproductive age,
with severe anemia were excluded in this
especially during pregnancy.2 Prevalence of
study.
obesity during pregnancy ranges from 1.8-
Variables used in this study were Body
25.3%.1 Prevalence of obesity in adult women
Mass Index (BMI), serum ferritin levels, and
in Indonesia increases every year to reach
Neonatal Outcomes (birthweight, and
32.9% in 2013.3
APGAR score). Univariate analysis is
Pregnancy and obesity have opposite
presented in frequency distribution table.
effects on regulation of iron homeostasis and
Bivariate analysis to test study hypotheses
nutritional status. Increased need for iron in
using Spearman's Rank Correlation. P-values
mothers occurs during pregnancy which has
>0.05 were considered significant. Degree
implications for anemia during pregnancy.
of correlation is determined based on the
Obesity changes iron homeostasis mediated
value of the correlation coefficient r. (r 0.0
by inflammatory mediators. Study showed an
- <0.2 (very weak), 0.2 - <0.4 (weak), 0.4 -
increase in ferritin serum levels in obese
<0.6
pregnant women,4 whereas a different.5
(moderate), 0.6 - <0.8 (strong) , 0.8-1.00
Obesity not only affects ferritin levels, but
(very strong).
also can have bad implications for fetus.
Increased inflammatory mediators in obese
RESULTS
mothers during pregnancy can affect
intrauterine environment and interfere with
This study was conducted in RSUD dr.
fetal development. Mothers who have a BMI
Zainoel Abidin Banda Aceh from January-
≥25 kg/m2 during pregnancy are at high risk
November 2019 and found as many as 38
for giving birth to babies with low
subjects. Characteristics of redpondents are
presented in Table 1.
Table 1. Characteristics of Study Subjects
APGAR score at minutes 1 and 5.6
The study results are in line, also found Amount (N = (%)
that obese mothers had a greater risk of 38)
giving birth to macrosomia babies which could Age (y.o)
21-25 2 5.3
increase risk of the labor complications
26-30 13 34.2
such as shoulder dystocia and perineal 31-35 13 34.2
tears.7 Based on results of studies conducted 36-40 9 23.7
above, we were interested in examining the 41-45 1 2.6
relationship of obesity to serum ferritin levels Parity Status
Primipara 7 18.4
in third trimester pregnant women and Multipara 31 81.6
neonatal outcome at RSUD dr. Zainoel Abidin Gestational Age (week)
Banda Aceh. Preterm (<37 ) 9 23.7
Early term (37-38 ) 22 57.9
Full term (39-40)
METHODS pregnancy control patients6 15.8
Late term (41) 1 2.6
and childbirth at RSUDZA,0
Post term (> 42 ) 0
We used prospective study design. This and were willing to
study uses non probability sampling participate in the study. Hemogl
obin
techniques with quota sampling. This study levels
was conducted in January-November 2019 at (gr/dL)
RSUD dr. Zainoel Abidin Banda Aceh. A total Anemia
of 38 patients were taken with inclusion (<11 )
Not
criteria 34-40 weeks gestational age with
Anemia
obesity, pregnant women in the latent and (> 11 )
active labor phase, single pregnancy,
Vol 9. No 4. October The Role of Ferritin Levels Serum
Delivery Method
Pervaginam 17
Ferritin Serum µg/L
Low (<12) 5
Normal (12-150) 30
71.1
High (>150) 3
28.9
Neonatal Outcame Apgar Score
Severely Depressed (0-3) 1
44.7
Moderately depressed (4-6) 13
13.2
78.9
7.9

2.6
34.2
 Indones
4 Harahap, Hasanuddin, Andalas et al J Obstet
Gynecol
Excellent Condition (7-10) 24 63.2 Most age groups in this study are 26-30
Baby Birth Weight (gr)
Low (< 2500) and 31-35 years. Majority of respondents
22 57.9
Normal (2500-4000 ) 11 28.9
included in multipara (81.6%). Gestational
More (> 4000) 5 13.2 age at time of delivery in the majority of
Stage of respondents was 37-38 weeks (57.9%) with the
Obesity 11 28.9
Obesitas stg I highest number of labor methods (55.3%).
22 57.9
Obesitas stg II Majority of study respondents had anemia
5 13.2
Obesitas stg III (71.1%).
Spearman hypothesis test results showed
no correlation between obesity variables and
ferritin reserve status (p: 0.068).
Table 2. Results of Correlation Obesity Analysis and Serum Ferritin Levels

Ferritin Serum
Low Normal High Total
Obesitas P-value
n % n % n % n %
Stage I 0 0 10 26.3 1 2.6 11 28.9
Stage II 3 7.9 17 44.7 2 5.3 22 57.9 0.068
Stage III 2 5.3 3 7.9 0 0 5 13.2
Total 5 13.2 30 78.9 3 7.9 38 100

Spearman hypothesis test results showed

a correlation between the obesity variable
with a significant infant APGAR value (p:
0.032) and weak correlation strength (r:
0.349).
Table 3. Results of Obesity Correlation Analysis and Infant APGAR Value
Apgar Score
Excellent Moderately Severely
Total
Condition Depressed Depressed
Obesitas R P-value
n % n % n % n %
Stage I 9 23.6 2 5.3 0 0 11 28.9
Stage II 14 36.9 7 18.4 1 2.6 22 57.9 0.349 0.032
Stage III 1 2.6 4 10.6 0 0 5 13.2
Total 24 63.1 13 34.3 1 2.6 38 100

Results of bivariate analysis of the

relationship of serum ferritin levels with infant
birth weight showed no significance (p> 0.05).
Data analysis results can be seen in full in
Table 4.
Table 4. Results of Correlation Analysis of Serum Ferritin Levels and Infant Birth Weight
Birth Weight
Low Normal High Total
Ferritin Serum P-value
n % n % n % n %
Low 4 10.5 2 5.3 0 0 6 15.8
Normal 17 44.7 7 18.4 4 10.5 28 73.7 0.673
High 2 5.3 2 5.3 0 0 4 10,5
Total 1 60.5 13 29 24 10.5 38 100
Vol 9. No 4. October The Role of Ferritin Levels Serum
DISCUSSION hepsidin is feedback regulated by iron
concentration, erythropoietic processes, and
Pregnant women with iron deficiency inflammation. Chronic low-level inflammation
can experience increased maternal and fetal associated with obesity can increase the
mortality during prenatal and perinatal periods.8
Pregnancy in obese women can have bad
implications for their health during pregnancy
and even fetuses in the womb.9 The results of
this study found 38 respondents were
trimester pregnant women third who
underwent labor in the delivery room and
operating room RSUDZA with the category of
obesity nutritional status.
The average age of study respondents was
25- 35 years with multigravida parity status
(81.6%), the results of this study are 6.558
samples, 17% of them were obese and the
average age was
30.5 (+5.8).10 The average gestational age of
the study respondents was 37-38 weeks, this
result of 4.438 pregnant women respondents
with the category of overweight and obese
the majority giving birth to babies at 38
weeks gestation.11 Different which
shows that 28% of mothers with a BMI
>30.0 give birth prematurely on medical
indications and 18% spontaneously give birth.12
According to the American College of
Obstetricians and Gynecologyst (ACOG) obesity
increases the risk during pregnancy one of
which is frequent premature birth occur due
to an increased incidence of preeclampsia in
obesity.13 The mean of study respondents had
anemia (Hb <11 mg/dl). To assess whether
Body Mass Index or BMI in early pregnancy
can affect the risk of anemia in respondents
in the form of pregnant women from
Indonesia and Ghana with prospective
cohort study methods, found that in
comparison In both of the study groups, a
higher weight in early pregnancy affected higher
Hb levels so that the risk of anemia was
lower. Meanwhile, if the initial weight is low
or the BMI under the category of underweight
reflects poor nutritional intake, including
intake of various important micronutrients
that play a role in the
haematopoiesis process.14
Majority of respondents in this study had
normal ferritin serum. This can occur due
to an increase in the regulation of hepsidin
which is induced by IL-6 as one of the
inflammatory mediators that is triggered due
to excess adipose tissue in obese patients.15
Hepsidin is a hormone that regulates cellular
iron exports, where the expression of
 Indones
6 Harahap, Hasanuddin, Andalas et al J Obstet
regulation of hepsidin, and inhibit the complicated by obesity can increase the risk of
Gynecol
absorption of iron in the intestine and umbilical cord twisting.20
release of iron from both the liver and Environmental placental lipotoxicity is
spleen macrophage storage, thereby reducing influenced by obesity that occurs in mothers
circulating iron concentration which is
characterized by an increase in sTfr and a
decrease in serum iron, whereas ferritin can
increase or remain in normal concentration.16
A total of 55.3% of respondents in this
study gave birth using the method of
Mandarin. This can happen because
respondents of this study are pregnant
women who have risk factors, namely
obesity. The majority of respondents in this
study gave birth to babies with excellent
condition (63.2%). Yeşilçiçek Çalik study (2018)
in Turkey, from 27 study samples with
obesity category (BMI> 30) 16 of them
(59.3%) gave birth to babies with APGAR
score 7-10.16.17
Based on the results of this study, if we
look at the correlation of obesity variables
and the status of ferritin reserves which
were tested using Spearman's Rank showed
no significant correlation (p: 0.068 and r:
0.063). Pregnancy and obesity have
opposite effect on hepsidin which is a
hormone regulator of iron levels in the
body and consequently affects regulation on
iron homeostasis and nutritional status.
Increase in adipose tissue activity of chronic
low-level inflammation and involves the removal
of cytokines as mediators of information, one
of which is interleukin 6 (IL-6) and leptin,
thus affecting the effectiveness of the
ferroportin membrane which causes
internalization and degradation of ferroportin
and iron resistance in enterocytes. This
causes the absorption and mobilization of
iron from the liver and macrophages as
storage will decrease.18
Influence of obesity on Apgar Score in
this study has a significant value with weak
correlation strength. Obesity in pregnant
women can affect the neonatal condition in
various ways.10 Obesity in pregnancy increases
the incidence of morbidity in the fetus, thereby
affecting the baby's outcome (APGAR and
birth weight). Obese female placenta has
more lipids that can affect placental
pathogenesis through inflammation and
oxidative stress.19 Placental dysfunction
disrupts the health condition of the fetus in
the womb due to changes in metabolism,
inflammation, and endothelial dysregulation in
placental tissue which contribute to an
increased risk of asphyxia. Pregnancy
Vol 9. No 4. October The Role of Ferritin Levels Serum
with a metabolic profile that can increase looking at other variables such as
inflammation and oxidative stress, as well as complications of placental disorders,
a decrease in angiogenesis regulators. This inflammatory markers and other variables.
can cause intrauterine growth restriction
(IUGR) or intra uterine fetal growth
disturbance.21 Mechanisms that can affect
neonatal outcome are pathomechanisms of
anemia that occur due to increased levels of
hepsidin which can reduce the amount of iron
available to be released into the circulation,
thereby affecting the synthesis of hemoglobin
and production of erythrocytes. 22 Decreased
hemoglobin levels cause a decrease in oxygen
transport and treatment of the fetus, thereby
supporting the occurrence of hypoxic
conditions in the fetus.23
Direct evidence for the effect of lipotoxicity
in pregnancy with obesity on neonatal
outcomes is directly lacking, studies are
currently only linking lipotoxicity to
dysfunction in the placenta. The placenta can
cause metabolic abnormalities to the fetus
through intra utero, so the consequences can
affect the health of children widely. Because of
its considerable potential to harm both
mother and baby, studies of the level, causes
and effects of lipotoxicity in obese
pregnancies continue.13
Based on an article review study, of about
34 articles that examined the relationship
between maternal BMI and infant birth
weight, around
15 studies evaluated the relationship
between maternal BMI and LBW. The total
of subjects included in the study metanalyst
review was around 313.569 and using the
reference category of mothers with normal
BMI, it was found that no relationship was
found between the incidence of infants with
low birth weight with obese mothers. 24

CONCLUSION

This study shows that the correlation

between obesity and ferritin reserve status is
not significant. The correlation between
obesity with a baby's APGAR value is
significant and the strength of the correlation
is weak, whereas with BBL it is not
significant. Serum ferritin levels with APGAR
and BBL values of infants have no
significant relationship.

SUGGESTION

This study is expected to be continued by

 Indones
8 Harahap, Hasanuddin, Andalas et al J Obstet
ACKNOWLEDGEMEN G, et al. Patterns of GestationalGynecol
Weight Gain in
Women with Overweight or Obesity and Risk of Large
T for Gestational Age. Obes Facts. 2019;12(4):407–
15.
The author is very thankful to the Obstetrics
and Gynecology and Internal Medicine
Department of Faculty of Medicine in Syiah
Kuala University, Dr. Zainoel Abidin General
Hospital and also to the staff of Prodia Clinic
in Banda Aceh for their help and
collaboration on this study. This study does
not have any conflict of interest.

REFERENCES
1. World Health Organization. Global database on
Body Mass Index: BMI Classification. 2013.
http://app.who. int/index.jsp?
2. Simko M, Totka A, Vondrova D, Samohyl M,
Jurkovicova J, Trnka M, et al. Maternal body
mass index and gestational weight gain and
their association with pregnancy complications
and perinatal conditions. Int J Environ Res Public
Health. 2019;16(10):1–11.
3. Euro-Peristat Project. Core indicators of the health
and care of pregnant women and babies in Europe
in 2015. Eur Perinatal Health Rep. 2018:180.
www.europeristat. com.
4. Flores-Quijano ME, Vega-Sánchez R, Tolentino-
Dolores MC, López-Alarcón MG, Flores-Urrutia
MC, López-Olvera AD, et al. Is associated with
changes in iron nutrition status and its
homeostatic regulation in pregnancy. Nutrients.
2019;11(3):1–19.
5. Eftekhari MH, Mozaffari-Khosravi H, Shidfar F.
The relationship between BMI and iron status in
iron- deficient adolescent Iranian girls. Public
Health Nutr. 2009;12(12):2377–81.
6. Shaukat S, Nur U. Effect of prepregnancy maternal
BMI on adverse pregnancy and neonatal outcomes:
Results from a retrospective cohort study of a
multiethnic population in Qatar. BMJ Open.
2019;9(9):1–11.
7. Liu L, Ma Y, Wang N, Lin W, Liu Y, Wen D. Maternal
body mass index and risk of neonatal adverse
outcomes in China: A systematic review and meta-
analysis. BMC Pregnancy Childbirth.
2019;19(1):1–12.
8. Jayanth Kumar P, Ravi Kiran Suri S, Phanindra Babu
K. Serum Ferritin and Haematological Levels in
Non- Pregnant and Pregnant Women. J Evol Med
Dent Sci. 2016;5(50):3181–4.
9. Papazian T, Tayeh GA, Sibai D, Hout H, Melki I,
Khabbaz LR. Impact of maternal body mass index and
gestational weight gain on neonatal outcomes
among healthy Middle-Eastern females. PLoS One.
2017;12(7):1–13.
10. HÅberg SE, Stigum H, London SJ, Nystad W,
Nafstad
P. Maternal obesity in pregnancy and
respiratory health in early childhood. Pediatr
Perinatal Epidemiol. 2009;23(4):352–362.
11. Garcia- JJ, Henriquez-sanchez P, Alema N,
Bautista- castan I, Gonzalez-quesada A, Garcı
JA. Maternal Obesity in Early Pregnancy and
Risk of Adverse Outcomes. 2013;8(11):1–6.
12. Zheng W, Huang W, Zhang Z, Zhang L, Tian Z, Li
 Vol 9. No 4. October The Role of Ferritin Levels Serum
13. Marrs CC, Moussa HN, Sibai BM, Blackwell SC.
The relationship between primary cesarean 19. Stephen J M, Zhuoyang L, Jennifer J K, Elizabeth S,
delivery skin incision type and wound Marian K. Maternal and perinatal outcomes in pregnant
complications in women with morbid obesity. Am J women with BMI >50: An international collaborative
Obstet Gynecol . 2014;210(4):319. study. PLoS One. 2019;1–11.
14. Parker MG, Ouyang F, Pearson C, Gillman MW, 20. Raguž MJ, Brzica J. Does Body Mass Index in
Belfort MB, Hong X, et al. Prepregnancy body Pregnant Women Affect Laboratory Parameters in the
mass index and risk of preterm birth: Association Newborn? AJP Rep. 2016;6(2):e155–9.
heterogeneity by preterm subgroups. BMC 21. Aigner E, Feldman A, Datz C. Obesity as an
Pregnancy Childbirth. 2014;14(1):1–10. emerging risk factor for iron deficiency. Nutrients.
15. Jones AD, Zhao G, Jiang YP, Zhou M, Xu G, Kaciroti 2014;6(9):3587– 600.
N, et al. Maternal obesity during pregnancy is 22. McDonald SD, Han Z, Mulla S, Beyene J. Overweight
negatively associated with maternal and neonatal iron and obesity in mothers and risk of preterm birth
status. Eur J Clin Nutr. 2016;70(8):918–24. and low birth weight infants: Systematic review
16. Rahma H, Lumbanraja SN, et al. Hepcidin and and meta- analyses. BMJ. 2010;341(7765):187.
Feritin Levels in Obese Pregnant Women and 23. Figueiredo ACMG, Gomes-Filho IS, Batista JET,
Normal Body Weight before Pregnancy. Indones J Orrico GS, Porto ECL, Cruz Pimenta RM, et al. Maternal
Med. 2018;3(1):22– 6. anemia and birth weight: A prospective cohort study.
17. Yeşilçiçek Çalik K, Korkmaz Yildiz N, Erkaya R. Effects PLoS One. 2019;14(3):e0212817.
of gestational weight gain and body mass index 24. Stubert J, Reister F, Hartmann S, Janni W. The
on obstetric outcome. Saudi J Biol Sci. Risks Associated With Obesity in Pregnancy. Med
2018;25(6):1085–9. (United States). 2018;115(16):276–83.
18. Kim JW, Kim DH, Roh YK, Ju SY, Nam HY, Nam GE,
et al. Serum ferritin levels are positively associated
with metabolically obese normal weight:A
nationwide population-based study. Med (United
States). 2015;94(52):1–6.