Archives de Pédiatrie 27 (2020) 53–60

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Review article

Feeding problems and gastrointestinal diseases in Down syndrome

A. Ravel *, C. Mircher, A.-S. Rebillat, C. Cieuta-Walti, A. Megarbane
Institut Jerome-Lejeune, 37, rue des Volontaires, 75725 Paris cedex 15, France

A R T I C L E I N F O A B S T R A C T

Article history: Background and method: Feeding problems and gastrointestinal disorders are the most common
Received 1st April 2019 anomalies in people with Down syndrome (DS) and have a significant impact on their daily life. This
Received in revised form 26 August 2019 study lists the various anomalies on the basis of 504 references selected from a PubMed search in
Accepted 11 November 2019
October 2018.
Available online 26 November 2019
Results: The anomalies are grouped into three categories: anatomical anomalies: duodenal atresia and
stenosis (3.9%), duodenal web and annular pancreas; aberrant right subclavian artery (12% of children
Keywords:
with DS with cardiac anomaly); Hirschsprung’s disease (2.76%); anorectal malformation (1.16%);
Down syndrome
Feeding
congenital vascular malformations of the liver; orofacial cleft, bifid uvula (4.63%), and submucous
Gastrointestinal orofacial cleft; esophageal atresia (0.5–0.9%); pyloric stenosis (0.3%); diaphragmatic hernia; malrotation
Esophageal reflux of small intestine or duodenum inversum; omphalocele, gastroschisis or anomalies of the median line,
Obesity anomalies of the umbilical vein; biological, immunological, and infectious anomalies: neonatal
Celiac disease cholestasis (3.9%); neonatal hepatic fibrosis; Helicobacter pylori infection (75.8% in institutionalized
children with DS, between 29.2 and 19.5% in non-institutionalized); non-alcoholic fatty liver disease
(NAFLD; 82% in obese and 45% in non-obese); biliary lithiasis (6.9% under 3 years); celiac disease (6.,6%);
geographical tongue (4%); hepatitis B virus sensitivity; autoimmune hepatitis and cholangitis; Crohn’s
disease, inflammatory bowel disease (IBD); pancreatitis; vitamin D deficiency (45.2% in Italy); functional
disorders: suction, swallowing and chewing disorders (13 of 19 children with DS under 4 years);
gastroesophageal reflux (47% in children with sleep apnea); achalasia (0,5% in adults); obesity (51.6% of
males and 40.0% of females in Ireland) and overweight (32.0% and 14.8%); constipation (19.0%). Based on
their practice, the authors insist on the following points: malformations are sometimes detected late
(chronic vomiting after the introduction of food pieces, resistant constipation despite appropriate
measures); prescription of preventive doses of vitamin D is advised; jaundice in a baby with DS may be
retentional; in the event of transient leukemoid reaction it is vital to monitor liver function; the patient
with geographic tongue must be reassured; for celiac serology there is no consensus on the staring age
and the frequency, we propose every year from the age of 2; we advise to test people with DS for H. pylori
infection if they are attending specialized institutions; abdominal ultrasounds must be systematic
during the first months of life; detection of NAFLD is recommended; people with DS must be vaccinated
against hepatitis B; breastfeeding is possible with maternal support; it is important to start speech
therapy very early; feeding difficulties are often overlooked by the family and educators;
gastroesophageal reflux is often pathological; preventing obesity must start from birth using body
mass index for the general population; it is necessary to do everything for their meals to be joyful.
C 2019 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

1. Introduction tinal disorders are very common in DS [2] and have a great impact
on the quality of life of people with this condition. The purpose of
Sixty years after the supernumerary chromosome was discov- this article is to compile a list of feeding and gastrointestinal
ered, the life expectancy of people with Down syndrome (DS) has disorders for practitioners.
increased [1] thanks to translational research and various
therapeutic tests. Nevertheless, feeding problems and gastrointes- 2. Method of bibliographical research

* Corresponding author. We carried out a search in October 2018 on PubMed with no

E-mail address: [email protected] (A. Ravel). start date, using the keywords [Down syndrome], [Trisomy 21],

https://doi.org/10.1016/j.arcped.2019.11.008
0929-693X/ C 2019 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.
54 A. Ravel et al. / Archives de Pédiatrie 27 (2020) 53–60

[Gastrointestinal], [Feeding], with those corresponding to each of Anorectal malformations are rather frequent among DS (1.16%
the reported disorders, such as [duodenal atresia], [biliary in Sicily [10]), and are less frequently associated with rectourethral
lithiasis], [esophageal reflux], [obesity], etc. as well as [morbidity], fistulas than among the general population. In one case, anorectal
[adults] and [ageing]. The search yielded close to 700 references. malformation was associated with cystic duplication of the
Reading the abstract or the full text of each article enabled us to rectum. Action must be taken quickly because of the risk of bowel
exclude redundant or irrelevant reports. We also added references perforation. Often, anorectal malformations are diagnosed late, at
that were cited in the relevant PubMed articles. A total of least 24 h after birth.
504 references were retained. Congenital vascular malformations of the liver have been
described: patent ductus venosus, malformations involving all
3. Anatomical anomalies three vascular systems, and anomalies of the umbilico-portal
venous system [11]. Ductus venosus was diagnosed in a 52-year-
3.1. Before birth old woman with DS, while in a young girl with DS, it was associated
with hepato-biliary-pancreatic abnormalities. Most of these
A growing number of gastrointestinal anomalies and anomalies observations were made in girls; conversely, an absence of ductus
of the diaphragm and the abdominal wall can be detected in utero; venosus was observed in two fetus with DS whose sex was not
such findings usually lead to genetic testing: duodenal atresia was specified. One case of congenital Budd–Chiari syndrome was
associated with DS in 46% of cases [3] (on fetal sonography there is published.
a characteristic double-bubble appearance with an enlarged, fluid- Children with DS represent 0.6% of cleft lip and palate cases, i.e.,
filled stomach and proximal duodenum, polyhydramnios is a slight overrepresentation [12]. Cleft uvula (4.63%) and sub-
present in 45% of these cases); the prevalence of aberrant right mucous cleft palate (0.77%) are lesser, more frequent forms [13].
subclavian artery (ARSA) is 23.6% in fetuses with DS and 1.02% in Esophageal atresia is tested at birth in every child in France. In
normal fetuses [4]; congenital diaphragmatic hernia; omphalocele DS, it is usually not associated with a tracheo-esophageal fistula. It
[5]; anorectal atresia; umbilical vein anomalies; gastroschisis; affects between 0.5 and 0.9% of infants with DS [14]. One case of
hyperechogenic bowel (chromosomal defect was identified in 13% esophageal web was reported.
of the fetuses with hyperechogenic bowel); polyhydramnios was Pyloric stenosis affects 0.3% of infants with DS [6] (compared
present in 56.3% of cases affected by esophageal atresia but with 5 in 1000 in the general population). In one case, it was
sonography alone is a poor diagnostic tool for identifying associated with duodenal atresia.
esophageal atresia prenatally; in the vast majority of fetuses Morgagni hernia is not uncommon (among 22 children with
who are diagnosed with Hirschsprung’s disease after birth, Morgagni hernia, 11 had DS) [15], and it is sometimes detected
abnormal sonographic findings of the fetal bowel are absent. late, even during adulthood. Only one case of Bochdalek hernia was
detected in an adolescent with DS.
3.2. At birth and beyond Four cases of malrotation of the small intestine were published:
two cases associated with duodenal stenosis [16], one with
Duodenal atresia and stenosis are found in about 3.9% of infants diaphragmatic hernia or annular pancreas.
with DS [6] but can be detected quite late, up to and during Table 1 shows isolated cases of some anatomical anomalies that
adolescence, or even adulthood, especially in the case of congenital have been published to date.
duodenal membrane. Atresia, usually diagnosed after bilious
vomiting, can also be detected after hematemesis or gastric or 4. Biological, immunological, and infectious anomalies
gastroduodenal pneumatosis; in some cases with distal bowel gas,
atresia is detected via an anomalous bifurcated bile duct conduct. It 4.1. At birth
is more frequent in boys and can also be associated with
Hirschsprung’s disease, pyloric stenosis, or a diaphragmatic hernia. Neonatal cholestasis occurs in a significant percentage of
Symptoms can be quite similar to the very common annular patients with DS: among 206 neonates from with DA Stockholm
pancreas (which is 430 times more frequent in cases of DS than in County, 3.9% showed cholestasis [17].
the general population) [7], whether in isolation or associated with Liver fibrosis may complicate transient myeloproliferative
duodenal stenosis or malrotation. disorder in a neonate with DS [18]; this association was also
An aberrant right subclavian artery must be sought should described in two fetuses with DS. Some biomarkers could predict
there be feeding difficulties. It can be observed in isolation or as such cases.
part of a complex vascular malformation. It is found in 12% of
children with DS with a cardiac anomaly [8]. 4.2. Beyond birth
Hirschsprung’s disease is found in 2.76% of people with DS
according to a meta-analysis [9]; the DSCAM gene seems to be The prevalence of Helicobacter pylori was higher than expected.
involved. The sex ratio of is Hirschsprung’s disease 3.6, and in the In children ranging in age from 1 to 15 years and residents of
United States it is more frequent in the Black than in the White institutes for intellectually disabled children, positive serology
population. It can be associated with anal atresia and more rarely results were found in 75.8% of children with DS, compared with
with cases of inferior vena cava interruption. It is sometimes 62.5% for children with an intellectual disability of another cause
diagnosed before birth, more often within 48 h of birth. One (ID); but the rate of seropositive cases in children younger than
complication to look out for is enterocolitis. 6 years was 52.9% in the DS group and 60% in the ID group

Table 1
Anatomical anomalies: isolated cases.
Gastroschisis 1 case with a congenital diaphragmatic hernia Inoue S et al. [50]
Omphalocele 1 case with midline developmental anomalies Kieslich M et al. [51]
Duodenum inversum 1 case in a 1-month-old infant Kim ME et al. [52]
 A. Ravel et al. / Archives de Pédiatrie 27 (2020) 53–60 55

[19]. Two studies among non-institutionalized children with DS Geographic tongue is found in 4% of children with DS [27]. In the
found 29.2 and 19.5% seropositivity rates. Another study found overall population it is often associated (much like Crohn’s disease
positive serology results in 25% of adults with T21, suggesting or celiac disease) with psoriasis. Usually asymptomatic, it can be
insufficient screening in adults. The most common indicative associated with some burning sensation, especially if associated
clinical signs are: failure to thrive, abdominal pains, and iron- with fungal infection.
deficiency anemia. In the general population, H. pylori infection The high prevalence of the hepatitis B virus (HBV) in people
seems to be associated with numerous extragastric complica- with DS has been known for a while. In 2008 in the United States,
tions—particularly neurological complications. In 2016, the 5% of adults with DS under 50 years of age and 13% of adults over
European and the North American Societies for Paediatric 50 years of age were HBV carriers [28]. A longitudinal study
Gastroenterology Hepatology and Nutrition updated their Guide- confirmed the sensitivity of people with DS to this virus, and their
lines for the management of H. pylori in children and adolescents. marked propensity to develop chronic HB antigenemia. We should
Screening is based on serology and diagnosis on gastric tissue note the possibility of abnormal T cells. Vaccination is highly
biopsy, but the consensus group recommended that invasive recommended. In cases where someone bites a patient, the mode
diagnostic testing be performed only if treatment would be offered of transmission is never specified, but health and safety measures
should the test results be positive. There is no recommendation for lower the levels present in institutional facilities. These chronic
screening in DS children. HBV infections are anicteric. A correlation between chronic HBV
Cirrhosis associated with non-alcoholic fatty liver disease and autoimmune thyroiditis was found in people with DS (but not
(NAFLD) is found in 82% of obese children with DS and in 45% in controls) [29]. Long-term monitoring aims at detecting early
of non-obese children with DS [20]. High aspartate aminotransfe- hepatocellular carcinoma.
rases (ASAT) is almost persistently found in the latter. It was There was no increased frequency of hepatitis A [30]. Two
suggested that in the non-obese DS population, it might be studies were carried out of children with DS infected with hepatitis
stimulated by sleep apnea. Among adults of the general popula- C [31], probably during cardiothoracic surgery for congenital heart
tion, non-alcoholic steatohepatitis (NASH) may cause complica- disease.
tions of obesity, especially in the event of celiac disease or diabetes Associations between Crohn’s disease and DS have been
but, oddly, it has never been found in the DS population, suggesting reported, although very rarely. Only six cases have been published
insufficient diagnosis. [32]. It can be preceded by or associated with primary sclerosing
Cholelithiasis and biliary sludge are very frequent, and most cholangitis. The known association with hidradenitis suppurativa,
often asymptomatic; they are detected during systematic ultra- often seen in people with DS, should be noted. The three main
sound examinations. Lithiasis may be congenital; it is often suggestive symptoms are abdominal pain, weight loss, and chronic
diagnosed in the first 12 months of life. Among children with DS diarrhea; there is no consensus on how to confirm the diagnosis.
who are under 3 years of age, 6.9% showed biliary lithiasis and 2.1% Two cases of nonspecific inflammatory bowel disease inflamma-
biliary sludge [21]. tion (IBD) were reported, including one in France [33].
The overall prevalence of celiac disease, according to a meta- Only three cases of pancreatitis in children with DS have
analysis, among children with DS is estimated at 6.6% and at 5.1% in been published [34] but not all cases have necessarily been
adults, which are grounds for systematic screening [22]. It is often published (we are following up a patient and have not yet
not associated with any digestive disorders. The most common published this case) and they are most probably under-
signs are abdominal pain and constipation. It is most probably diagnosed. Diagnosis is based on the presence of two of the
under-diagnosed, and must be screened systematically. In Sweden, following criteria: abdominal pain, levels of amylase and/or
the frequency of celiac disease in children with DS, when proved by lipase at least three times greater than the upper limit of normal,
villous atrophy, is six times higher than in the general population; imaging findings consistent with acute pancreatitis. We reported
in that research, the average age at diagnosis was 7 years, with one case of pancreatic fibrosis associated with a prenatal
1:1.8 boy:girl ratio [23]. In the United States, among 114 people leukemoid reaction and liver fibrosis.
with DS of all ages in whom anti-tissue transglutaminases Isolated cases of autoimmune chronic active hepatitis and
antibodies (tTG-IgA) coupled with total immunoglobulin A (IgA) autoimmune primary sclerosing cholangitis were reported associ-
were found, 13 screened positive for celiac disease; among those, ated with other autoimmune anomalies (Table 2). The symptoms
eight underwent duodenal biopsy and three were diagnosed with are often insidious (fatigue, nausea, weight loss, pruritus); it has to
villous atrophy [24]. In The Netherlands, an author suggested that be monitored in people with DS who are at risk of autoimmunity.
every individual with DS should undergo HLA-DQ testing once in The diagnosis is based on the existence of chronic biliary retention
their life, since there is a strong correlation between the and magnetic resonance angiography (MRA).
DQA1*0501/DQB1*02 combination and villous atrophy. A recent Table 2 presents isolated cases of biological, immunological,
study researching HLA-DQ2 and DQ8 antigens in buccal swabs and infectious anomalies that have been published.
from children with DS found a prevalence of 5.2% and the authors
recommend carrying out these tests at the age of 3 years [25]. For 4.3. Vitamin D deficiency
the American College of Gastroenterology [26], screening from the
age of 2 years is based on anti-tissue transglutaminases antibody Despite the importance of vitamin D, there are few articles
tests coupled with total IgA tests; in the event of low or deficient regarding this topic in children with DS. An American study reported
IgA levels, IgG-deaminated gliadin should be tested. Should there that administering vitamin D and minerals versus a placebo did not
be suspicion of celiac disease, even if the serology result is make any difference in terms of IQ, education, language, and motor
negative, a biopsy should be performed; serological testing can skills; however, since the milk sold in the United States is enriched
only be performed on patients on a gluten-containing diet. Before with vitamin D, deficiencies are rare. A Spanish study found few cases
the age of 2 years, anti-tissue transglutaminases antibody tests and of vitamin D deficiencies, whereas an Italian study found a higher
IgG-deaminated gliadin tests should be combined. The French frequency of hypovitaminosis D, especially in cases of obesity and
National Authority for Health (Haute Autorité de santé [HAS]) autoimmunity. In India, 26.8% of children were found to have a
recommended in 2007 to use anti-tissue transglutaminases 25(OH) vitamin D level below 10 ng/mL [35].
antibody tests for celiac disease detection and gluten-free diet Adults with DS have a lower bone density than the general
survey. population but vitamin D is not the only relevant factor.
56 A. Ravel et al. / Archives de Pédiatrie 27 (2020) 53–60

Table 2
Biological, immunological, and infectious anomalies: isolated cases.
Autoimmune chronic active hepatitis A 29-year-old male, associated with Hashimoto’s disease McCulloch AJ et al. [53]
and alopecia aerata
Autoimmune primary sclerosing cholangitis A 21-year-old male, with myxedema coma after ablative Mehta DI et al. [54]
radioiodine therapy for Graves’ disease, recurrent alopecia
aerata and pancytopenia
Congenital liver fibrosis An 8-year-old boy Cinquetti M et al. [55]
Lethal hemochromatosis A neonate with DS related to maternal autoimmunity Collardeau-Frachon S et al. [56]

5. Functional disorders with stricture is a long-term complication of untreated GERD as is,

sometimes, esophageal adenocarcinoma of which only two cases
5.1. Feeding disorders in DS have been published [40], although it may be under-
diagnosed as these patients suffer from two other risk factors:
In the few months following birth, children with DS often have obesity and H. pylori infection.
low suction tone and swallowing disorders [36]. Breastfeeding is
possible if appropriate support is provided; in addition to the usual 5.2.3. Achalasia
benefits, it is reported to lower the risk of leukemia in these Achalasia is more frequent in the DS population than in the
children. An English author studying children between the age of general population. Two cases were published of young children. A
9 and 36 months states that feeding disorders are not due to prospective study found achalasia in 0.5% of 58 adults with DS
delayed relevant skills but to an abnormal development and to the showing no sign or history of gastrointestinal disorders [41]. About
fact that meals are less cheerful occasions than for normal children. 15 cases were published on patients of any age showing various
The use of a feeding bottle and a pacifier after 24 months could disorders: dysphagia, regurgitation, vomiting, poor growth,
improve open bite and posterior crossbite. inhalation, and respiratory infections. One author suggested it
Masticatory dysfunction [37] and aspiration are frequent was associated with a defect in the enteric nervous system.
during feeding, which delays the introduction of solid food.
Studies of children show that parents need support and that they 5.3. Obesity and overweight
underestimate their children’s feeding disorders; therefore, meals
should be monitored. In adults, feeding disorders are often ignored. A big part of the literature is dedicated to this subject.
Thickening liquids are often useful. Meals of aging relatives should Prevalence varies quite a lot but the criteria used (body mass
be monitored. index [BMI], skin fold, bioelectrical impedance analysis, or dual-
Food reflux through the nose is not uncommon in the first few energy absorptiometry) are not consistent, the dates of studies
months if life, and may be amplified by frequent velopharyngeal vary (obesity prevention is relatively recent), and the countries and
insufficiency, which seems to be related to the shape of the palate lifestyles are different.
that prevents full contact with the back of the tongue. In adults,
insufficiencies of the velum result in changes in the voice. 5.3.1. Measuring method
In most studies, diagnosis relies on the BMI. BMI is more
5.2. Gastroesophageal reflux disease and achalasia efficient for the detection of obesity in young people with DS. In
this case one must use the BMI chart published by the CDC in
5.2.1. Gastroesophageal reflux disease among children Atlanta for the general population and not specific charts for DS,
Gastroesophageal reflux disease (GERD) has long been known since one would overlook a large part of the obese population
to be frequent in children with DS displaying respiratory [42]. Waist circumference and chest-to-hip ratio are also excellent
infections. Several studies measured its prevalence in children indicators. Skin fold thickness can also be used. However,
with DS hospitalized for atrioventricular canal defect (AVCD) Bergman’s body adiposity index does not seem to be relevant
treatment, in those who had come for dental treatment, and in for the body fat of people with DS. Bioelectrical impedance analysis
children with DS displaying subglottic stenosis or laryngomalacia. is not suitable for patients with DS as it underestimates their body
GERD is found in 47% of those experiencing sleep apnea [38]. In this fat. Authors have suggested an equation to calculate body fat from
population, the clinical presentation of sleep apnea and reflux is anthropometric data.
often difficult to detect. GERD is more frequent in cases of celiac
disease. It is constant in cases of anal atresia. It was suggested that 5.3.2. Prevalence and occurrence in European studies
additional screening must be performed to detect GERD in children Table 3 shows the prevalence (in percentage) of morbid obesity,
with DS experiencing regurgitation, vomiting, feeding disorders, or obesity, and overweight in some European countries; the
cough and, as is true in the general population, unmonitored comparison is drawn either with the general population (GP) or
asthma and recurrent respiratory infections, especially in young with ID people, with or without a breakdown by gender and age.
children. The treatment is based on the same recommendations as
for the general population. When GERD is responsible for 5.3.3. Factors mentioned to explain the tendency toward obesity and
respiratory complications, it is recommended to continue pro- overweight
ton-prompt inhibitors until the patient can walk unaided (which The common explanation is that people with DS are very drawn
happens on average during the 30th month of life in children with to food and exercise too little. Today, we tend to consider that the
DS). This extended prescription may cause small intestinal key factors are sleep apnea and their limited walking activities
bacterial overgrowth (SIBO). [43]. Let us look at these parameters.
Several studies (except one that relates the BMI to body surface
5.2.2. Gastroesophageal reflux disease among adults area) indicate that the resting metabolism rate of people with DS is
Among adults, the frequency of GERD is estimated at 9%, which lower regardless of their age. But this lower rate is not enough to
is quite likely an underestimation [39]. Severe peptic esophagitis justify an increase in body fat.
 A. Ravel et al. / Archives de Pédiatrie 27 (2020) 53–60 57

Table 3
Prevalence in percentage of morbid obesity (MOb), obesity (Ob), and overweight (OW) in some European countries, without or with dementia (Dem).

Country Year Age With DS Without DS (GP* or ID**) First author

MOb Ob OW MOb Ob OW

England 1995 Adults M 48 31 Prasher [57]

F 47 22
Scotland 2005 Adults M 1.5 20.0 37.7 6.2** 18.4** 22.3** Melville et al. [58]
F 6.8 33.3 37.6 2.6** 29.9** 29.5**
Netherlands 2012 Children M 4.2 25.5 1.8* 13.3* van Gameren-Oosterom
et al. [59]
F 5.1 32.0 2.2 14.3
Scotland 2017 Adults 56.5 37** Kinnear et al. [60]
Ireland 2018 Children M 51.6 32.0 O’Shea et al. [61]
and teenagers F 40.0 14.8
England 2018 Ageing adults 47.7 without Dem Hithersay et al. [62]
53.19 with Dem

Much like in the general population, there is a correlation obese people with DS than in those without DS but with the same
between mothers’ overweight and obesity and that of young adults BMI. In women with DS, levels of leptin in the blood are
with DS, which suggests the impact of food habits and obstacles to significantly lower after 10 weeks of physical exercise.
physical activity. A study conducted by the Cincinnati Children’s Hospital
Parents are reported to be less strict regarding food with their Medical Center seems to indicate that sleep apnea may precede
children who have DS than with their brothers and sisters. Hence, a obesity, since 62% of obese children had a higher prevalence of
study showed that when the parents of children with DS give them large lingual tonsils and, more often than not, had undergone
smaller rations than normal rations for their age, their weight suits palatine tonsillectomy.
their height. An Irish study highlighted low-quality food intake, The degree of obesity and amount of body fat bear no relation to
with daily intakes mostly made up of sugar, fat, and saturated fat. A the degree of intellectual deficiency in adolescents. A study found a
Norwegian study found no difference between the three following strong correlation between periodontitis and obesity. GH secretion
groups: DS, Prader–Willi syndrome, and Williams’s syndrome if is normal in young adults with DS despite a higher BMI and body
one correlates BMI and walking capacity (distance covered in fat. It seems that oxygen consumption in lymphocytes is lower.
6 min). In comparing the food intake of these three groups, we can There was mention of possible mitochondrial disorders in people
see that Prader–Willi patients eat more fruit and vegetables, and with DS.
Williams patients more fish, while people with DS do not eat much
fruit, fish, or vegetables. 5.3.4. Complications due to obesity
A study showed that physical activity patterns are not Obesity increases the risk of sleep apnea in children with DS
significantly different between infants with DS and those [45]: In an American cohort of children with DS, 74% experienced
developing typically during the first year of life. After learning sleep apnea, 85.2% of obese children and 64.6% of non-obese
to walk, physical activity as measured with a podometer is lower children. In the DS population, there is a correlation between BMI
in children with DS. It seems that obesity is the consequence of and the apnea hypopnea index (AHI).
low physical activity and not the other way around. Research In children with DS, even non-obese children with DS, overall
shows that at similar activity levels, the BMI of people with DS is cholesterol, triglyceride, and low-density lipoprotein (LDL) levels
not higher than that of those without DS. Adults also exercise less. are higher than in their siblings and their high-density lipoprotein
A study showed that adults with DS have a steeper response of (HDL) levels are lower.
VO2 (rate of oxygen uptake, i.e., energy expenditure) to increased Among young adults of both sexes, whether with DS or not, the
walking speed, and their VO2 is higher compared with adults comparison of fat distribution and muscle mass shows that in
without DS, especially at fast speeds [44]. Among the possible women with DS, excess body fat and insufficient lean body mass
explanations are: less precise control of body dynamics and greater are more significant on the trunk and less so on the limbs than in
difficulty in maintaining balance during walking, which may result women without DS. In men with DS there is more lean body mass
from the documented deficits of the cerebellum, muscle hypotonia on their upper limbs and less lean body mass on the whole body
and ligamentous laxity of persons with DS; coactivation of and lower limbs compared with non-DS men. Increased fat on the
agonist—antagonist muscle groups; mitochondrial dysfunction; trunk in women with DS suggests a higher risk of metabolic
and very low aerobic fitness. The oxygen uptake efficiency slope— syndrome.
which assesses one’s aptitude for physical exercise—is lower. This Adolescents seem to be insulin-resistant. A study finds no
poor adaptation to exercise could be related to dysautonomia. difference between lipid profile and insulin resistance in adults
Arterial resistance in response to maximum physical exercise is with or without DS. But in another study the same authors find
blunted in people with DS. DS seems to curb the effect of obesity on higher insulin resistance in people with DS and abdominal obesity.
the peak heart rate and peak oxygen consumption; however, if Women with DS have lower fasting blood glucose levels and
obesity is associated with lower peak oxygen consumption in systolic blood pressure, which suggests that they are at lower risk
adults, this is not the case in children. of becoming insulin-resistant; men have lower systolic and
Leptin levels are higher in children with DS than in their siblings diastolic blood pressure, which suggests that both groups have
and this rise is steeper than suggested by the percentage of body reduced risks of atherosclerosis. Furthermore, lower levels of
fat. This could explain the increased risk of obesity. Leptin levels plasminogen activator inhibitor-1 (PAI-1) would explain the low
are higher in children with DS than in those without DS but with incidence of atherosclerosis. The reduced risk of atherosclerosis
the same BMI, regardless of obesity; this suggests leptin resistance can also be explained by the overexpression of cystathionine-beta-
in DS. According to research in adults, leptin levels are lower in synthase.
58 A. Ravel et al. / Archives de Pédiatrie 27 (2020) 53–60

Obesity impacts walking capabilities particularly on the hips. the elderly. This suggests insufficient diagnosis of dietary and
Being overweight puts additional pressure on the arches of the digestive pathologies in both the adult and the elderly.
foot; therefore, in obese people, feet must be regularly checked.
In elderly people with DS, chronic kidney disease is more 6.1. Regarding anatomic disorders
common and is associated with obesity.
Chronic vomiting occurring after the introduction of larger
5.3.5. Care dietary volumes or the introduction of food pieces should suggest
There are scales to assess feeding behavior, sedentary behavior, duodenal stenosis. In a patient who does not eat solid food in
and sleep patterns for children under 5 years, which are also usable pieces, one must always suspect gastrointestinal tract obstruction.
for children with DS. Resistant constipation despite appropriate hygiene–dietary
Because of the risk of obesity, one must address feeding during measures should lead to the search for a terminal form of
each consultation with a child with DS as early as in the first year. A Hirschsprung’s disease.
study of children and adolescents with DS showed that, overall, in
the younger population overweight is slight but during their 6.2. Regarding biological, immunological, and infectious disorders
childhood, as they become more autonomous and choose their
food and eat excessive amounts of proteins and carbohydrates and Since vitamin D deficiency is common in ID people, vitamin D
insufficient amounts of vegetable fibers, obesity is promoted. should be prescribed in preventive doses at any age.
Preventing obesity requires more exercise. An American study In the presence of jaundice in an infant with DS, one must
shows that with comprehensive care (pediatrician, dietician, always wonder whether it may be conjugated bilirubin retentional
psychological support, physiotherapist, and sports instructor) jaundice.
involving families, the results are the same between intellectually In the event of a transient leukemoid reaction, it is vital to
deficient and non-intellectually deficient children. Some children monitor liver function.
with DS reduced their body fat in 12 weeks of physical activity. The The patient with geographic tongue must be reassured and
Nintendo Wii game console can be a good way to encourage uncomfortable sensations should be examined to detect secondary
physical activity. The benefits of exercising remain up until fungal infections.
3 months after the end of practice but disappear afterwards. This There is no consensus on the starting age or the frequency at
shows that physical activity should not be stopped. Other studies which serological testing for celiac disease should be performed in
have reached less compelling results. patients with DS (longitudinal studies showed that serology results
Some authors suggest that the frequency of dyslipidemia is can be positive at any age). In our consultation, we chose the
cause for monitoring blood lipids on a regular basis. following empirical approach: from the age of 2, every year—along
The HAS published good practice guidelines for the general with the annual thyroid test—then in adults every 3–4 years or
population that also apply to DS. In children, they recommend when witnessing behavioral degradation. Villous atrophy must be
monitoring the BMI from birth, two or three times a year. The detected to start a gluten-free diet. We monitored children whose
French Society of Pediatrics (SFP) suggested guidelines on children biopsy was normal despite positive serology test results and the
and adolescents’ carbohydrate intake. presence of HLA antigens.
We advise systematic testing of people with DS who do not
5.4. Constipation always express pain for H. pylori infection if they are attending
specialized institutions or in contact with higher-risk communi-
Constipation is one of the most frequent symptoms found ties.
during consultations with children and adolescents with DS When people with DS express acute abdominal pain, to the
[46]. One must always keep in mind both Hirschsprung’s disease point of lying flat on the floor, one should suspect possible
and intolerance to gluten, for which constipation is one of the most pancreatitis.
frequent signs. Its association with mictional disorders is debated. When facing abdominal pain with weight loss and diarrhea,
In one case, severe constipation and severe urinary problems were Crohn’s disease should be considered and the patient should be
associated with tethered spinal cord syndrome. Constipation, often referred to a specialist for consultation.
found in ID patients with behavioral disorders, must be looked for The frequency of biliary lithiasis is cause for systematic
before the prescription of psychotropic drugs. abdominal ultrasound examinations during the first months of
life, especially since there can be various kidney disorders.
For obese patients, it is recommended to monitor the liver and
6. Some useful points for practitioners the gallbladder by ultrasounds in search of biliary lithiasis.
To detect NAFLD, it is recommended to use liver ultrasound for
Key information for the doctor to take into consideration is the obese people with DS and regular ASAT monitoring for non-obese
complexity that people with DS encounter in expressing pain. people.
According to their parents, children with DS are ‘‘tough.’’ This is People with DS must be systematically vaccinated against
also true of adults and the elderly. Therefore, when diagnosis or hepatitis B.
severity criteria include pain, one should be very wary. Pain often One must consider hepatitis or autoimmune cholangitis when
resembles behavioral disorders. When a patient with DS expresses facing quite unspecific but lingering symptoms: fatigue, nausea,
pain it must be taken seriously knowing that it may be located weight loss, pruritus.
elsewhere. For instance, most youths who complained about their
‘‘teeth’’ were in fact suffering from erosive esophagitis or gastritis. 6.3. Regarding functional disorders
On the other hand, in our practice, we sometimes discover
serious medical conditions in adults that have been ignored for Breastfeeding is possible if the mother is given appropriate
years, probably because relatives end up losing sight of what is guidance and support.
normal or not. Frequent chewing disorders and aspiration are cause for early
Finally, this review of the literature shows that most of the speech therapy rehabilitation. It is important to start speech
publications concern the child, very little the adult, and even less therapy very early, even in the first days of life. Thickening the
 A. Ravel et al. / Archives de Pédiatrie 27 (2020) 53–60 59

content of baby bottles may prove useful. Later on, thickening References
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