Review

Nutritional challenges in children and adolescents with

Down syndrome
Marianne Nordstrøm, Kjetil Retterstøl, Sigrun Hope, Svein Olav Kolset

Several features and comorbidities in Down syndrome have nutritional implications and consequences. In infancy Lancet Child Adolesc Health
and early childhood, children with Down syndrome have a high risk of oral motor difficulties and pharyngeal 2020; 4: 455–64

dysphagia with aspiration, which both require systematic attention. To improve nutritional status in children who are Department of Nutrition,
Institute of Basic Medical
underweight and who have clinical signs of feeding problems, further evaluation of underlying causes is required. Sciences, University of Oslo,
Clinical interventions should promote swallowing safety and development of feeding abilities. Even from 4–5 years of Oslo, Norway
age, overweight in children with Down syndrome can be a concern. To prevent disease later in life, an urgent need (M Nordstrøm PhD,
exists for more research on nutritional aspects in the prevention and treatment of obesity in adolescents with Down Prof K Retterstøl MD,
SO Kolset PhD); Frambu
syndrome. This Review did not find any data to support the use of dietary supplementation, except when deficiency is Resource Centre for Rare
documented. Additionally, the literature reported the need for more research that uses larger study samples and Disorders, Siggerud, Norway
control groups and that addresses important nutritional challenges in children and adolescents with Down syndrome. (M Nordstrøm); and Unit for
Inborn and Hereditary
Neuromuscular Disorders,
Introduction national Danish cohort of children with type 1 diabetes, Department of Neurology
Down syndrome is caused by trisomy of the whole or a the prevalence of Down syndrome was four-times higher (M Nordstrøm), Lipid Clinic
part of chromosome 21. It is the most common cause of than in the general population.12 (K Retterstøl), and Department
mild to moderate intellectual disability and affects around Guidelines have been developed to facilitate health of Neuro Habilitation
(S Hope MD), Oslo University
one in 800 to one in 900 liveborn infants, although this supervision in this patient group. These strategies Hospital, Oslo, Norway
prevalence varies between countries because of describe nutrition and physical activity as areas that Correspondence to:
differences in maternal age and prenatal screening.1,2 require ongoing assessment throughout childhood to Prof Svein Olav Kolset,
Children with Down syndrome have characteristic, establish and maintain healthy weight.13 Children with Department of Nutrition,
phenotypic features, delays in psychomotor development, Down syndrome have an increased risk of feeding Institute of Basic Medical
Sciences, University of Oslo,
and an increased rate of congenital malformations.3 On problems and obesity.14,15 It is well known that establish­ Oslo 0316, Norway
an individual level, children with Down syndrome show ment of healthy eating habits in childhood is important s.o.kolset@medisin.uio.no
large variability because some have mild symptoms and for the prevention of disease later in life and that
complications, whereas others are more severely affected. increasing longevity in Down syndrome is likely to
This variability also applies to the risk of health problems lead to increased manifestation of lifestyle-associated
related to nutrition in this patient group. diseases.16 Obesity is known to be associated with type 2
In children with Down syndrome, attention to diabetes, cardiovascular disease, and some types of
nutritional intake and status is important because
several features and comorbidities have nutritional
implications and consequences (panel). Key messages
When assessing nutrition in children and adolescents • Increased focus on nutritional measures is important for the health and wellbeing of
with Down syndrome, clinicians should be aware of children and adolescents with Down syndrome
health conditions that might influence nutritional care • Reduced feeding abilities with increased risk of dysphagia and aspiration are
and dietary advice. Congenital heart defects are found in predominant in the first years of life, and clinical screening for feeding problems and
approximately 45% of children with Down syndrome, evaluation of children with feeding difficulties, low weight gain, or underweight is
most often in the form of atrioventricular septum defect important in this phase
and ventricular septum defect.4 Anomalies in the • Excessive weight gain is a concern for many children with Down syndrome from
gastrointestinal tract (eg, duodenal atresia, Hirschsprung 4–5 years of age and investigations of energy requirements, nutritional intakes, and
disease, and anorectal malformations) occur in 4–6% of evaluation of clinical methods for assessment of overweight and obesity in Down
these children.5–7 The prevalence of coeliac disease is syndrome are required
increased in those with Down syndrome and has been • More in-depth studies with representative samples and controlled study designs that
shown to vary between different countries, but a use cutting edge methods and technologies are needed to develop strategies for
2018 meta-analysis showed a pooled prevalence of 5·8% evidence-based prevention and treatments of obesity in people with Down syndrome
in children and adults with Down syndrome compared • General recommendations for intakes of micronutrients in relation to age and gender
with 0·5–1% of people in the general population.8 should also be applied for children and adolescents with Down syndrome, as no
Additionally, children with Down syndrome have an evidence exists of beneficial clinical effects of intakes above these recommendations,
increased risk of comorbidities such as hypotonia and except when deficiency is reported
orofacial dysfunction that can affect the feeding ability of • The dual challenge of preventing the risk of undernutrition in the first year of living
the child,9 and thyroid disease (eg, hypothyroidism),10 and obesity in later years calls for systematic nutritional evaluations throughout
which can potentially affect energy metabolism. Auto­ childhood and adolescent years for people with Down syndrome
immunity is also increased in Down syndrome.11 In a

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 Review
Panel: Clinical features of Down syndrome with nutritional
relevance
• Hypotonia
• Oropharyngeal abnormalities
• Gastrointestinal malformations and dysmotility
• Reduced growth rate
• Hypothyroidism
• Coeliac disease
• Type 1 diabetes
• Intellectual disability
• Behavioural and psychiatric disorders
Monitoring of nutritional status
Screening
• Clinical examination of feeding ability
• Assessment of nutritional intake and use of supplementation
• Measurement of weight and length or height and monitoring of growth pattern
• Annual blood test of iron status from 1 year of age
Poor feeding ability, low weight gain, or Excessive weight gain or overweight
underweight • Evaluation of feeding behaviours and physical
• Refer infants and small children with feeding activity patterns
Examination
problems to videofluoroscopic swallow • Measure thyroid-stimulating hormone
assessment in blood
• Consider possible underlying causes such as
heart defects or gastrointestinal problems,
including gastrointestinal tract malformation,
constipation, gastro-oesophageal reflux, and
coeliac disease
Relevant interventions Relevant interventions
• Altered feeding techniques or adjustment • Education on healthy dietary choices and
Treatment
of food consistency portion sizes to parents and the child with
• Intervention to strengthen oral motor Down syndrome
function • Promote participation in regular physical
• Fortified diet or enteral nutrition activity
• In coeliac disease, gluten-free diet
Figure: Suggested nutritional assessment in children with Down syndrome
cancers. In Down syndrome, obesity is also linked to
reduced functional abilities and activities of daily
living.17 Few previous reviews have assessed nutritional
aspects in this group. To further describe and explore
nutritional challenges in children and adolescents with
Down syndrome, we searched and assessed the
scientific literature with the aim to describe feeding
abilities, nutritional intakes, and nutritional status in
this patient group and to provide some suggestions for
relevant clinical measures and interventions.
Infancy and breastfeeding
Most neonates with Down syndrome are offered human
milk, but the proportion and duration of exclusive
breastfeeding are reduced compared with neonates
without Down syndrome.5,18 The number of children with
Down syndrome who are exclusively breastfed varies
between countries from 43% in Italy,18 to 48% in the
456
Netherlands,7 55% in Israel,5 63% in Mexico,19 and 67% in
Saudi Arabia.20 In an Italian study18 that included
560 children with Down syndrome, the mean duration of
breastfeeding was 54 days (SD 111) compared with
165 days (SD 120) in controls. Congenital malform­ations,
prematurity, perceived milk insufficiency, suckling
difficulties, and maternal depression were factors found
to restrict breastfeeding.5,18,20,21 Furthermore, admission of
neonates to hospital confers a risk of reduced breast­
feeding.
In infants with Down syndrome aged 0–3 months,
most parents describe extended feeding duration
(30–60 min).21 This duration could be exhausting for both
the child and parents. In these first few months after
birth, parents of a child with Down syndrome often
experience stress and difficult emotions, such as shock
and grief, due to the diagnosis of the syndrome in their
child. These emotions can further complicate feeding
practices. Frustration and depression in mothers have
been reported as influential factors in the termination of
breastfeeding.18,20
Although some babies with Down syndrome struggle
with feeding initially, it is important to recognise that
most babies and mothers can make the transition to
breastfeeding with time and guidance from competent
health professionals.22 Thus, family-oriented support can
enhance breastfeeding practice, facilitate early parent–
child bonding, and improve long-term child outcomes.22,23
Feeding and swallowing problems
Children with Down syndrome often have reduced feeding
abilities and approximately 55–60% have problems with
feeding and swallowing.24,25 For a period, typically from age
0–3 months, 13–40% of these children require a nasogastric
tube for adequate nutrition5,21,26 and 2–5% receive gastro­
stomy.5,21 Children with an atrioventricular septal defect are
more likely to need gastrostomy.27
For the early detection of feeding problems, all children
with Down syndrome should be clinically screened for
feeding and swallowing concerns (figure). Structural and
functional oropharyngeal abnormalities, immature neuro­
motor development, and hypotonia lead to decreased
neuromotor function and are associated with suckling
problems, poor lip seal, dysphagia, and aspiration.9,21,25,28
64% of children with Down syndrome have been reported
to have oral motor difficulties and 57% have been reported
to have pharyngeal dysphagia with aspiration.25 Of those
with aspiration, almost all (90%) aspirated silently. In a
2019 study, aspiration was detected in 32% of infants with
Down syndrome before age 6 months and in 52% of
children aged 6–12 months.29 In this study, children who
had a swallowing assessment after age 6 months were
more likely to have unchanged findings on follow-up than
children assessed before age 6 months. This finding
suggests that timing of swallowing assessment could
potentially influence outcomes. High rates of pharyngeal
dysphagia were also described by O’Neill and colleagues,28
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who found that 116 (58%) of 201 children with Down
syndrome were diagnosed after videofluoroscopic
swallowing assessment. Accordingly, we suggest that
videofluoroscopic swallowing assessment should be
offered to children who present with clinical symptoms
during meals (figure).24,25 In children with pharyngeal
dysphagia, this assessment should be followed by
recommendations of feeding modifications as needed.
Relevant dietary interventions in a study of 46 children by
Jackson and colleagues25 included thickened liquids in 34
(74%) children, changed feeding procedure to control flow
rate or bolus size in 5 (11%) children, and no oral intake in
4 (9%) children.
The age at introduction to solid food is similar for both
children with Down syndrome and those without Down
syndrome, with 46% of children with Down syndrome
introduced to solids at age 6–9 months and 38% at age
9–12 months.20 Nevertheless, learning to eat solid foods
starting with pureed food and baby cereal and progressing
to regular table foods is a long process. Development of
feeding abilities and self-feeding skills is, similarly to
other developmental milestones, often delayed in
children with Down syndrome.14,30 As the required skills
become more advanced, these children are increasingly
delayed in their development and the age difference for
acquiring these skills increases between children with
and without Down syndrome.30 Feeding difficulties can
remain a challenge with problems predominantly related
to oral motor function, followed by the pharyngeal phase
and the oesophageal phase in children with Down
syndrome aged 2–7 years.14 In the oral phase, immature
chewing patterns and poor bolus control are common
concerns. In children aged 1–4 years, common difficulties
are encountered when food textures are chewy, firm, and
gummy or rubbery; whereas, creamy, soft, and purée
textures are often reported as more acceptable.31 However,
with increased age, food textures that are crispy, dry, and
hard are more likely to be managed by the child.31
Issues related to dental health are also highly relevant
in the assessment of feeding and swallowing issues in
children with Down syndrome, because these children
have an increased risk of dental abnormalities and severe
tooth wear32,33 that can also potentially affect their ability to
chew. Parents and health professionals should be aware
that extended bottle-feeding and use of a pacifier (for
>24 months) have been associated with development of
open bite and crossbite in children with Down syndrome.34
Structural training programmes that strengthen oral
motor function and adjustment of food consistency
are relevant interventions for children with poor oro­
pharyngeal motor abilities.35 In the study by Jackson and
colleagues,25 28 (20%) of 138 children with a mean age of
2·1 years (SD 3·2) also had difficulties with oral sensory
processing and could have benefited from interventions
that increased tolerance to facial and oral stimuli to
address such difficulties. Behaviour typically seen in oral
hyposensitivity includes overstuffing the mouth with
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Review
food, holding food in the mouth without chewing,
drooling, or preference for intense flavours. By contrast,
behaviours typically seen in oral hypersensitivity are food
selectivity regarding texture or temperature (often being
mistaken as being a so-called picky eater). Preference for
selected types of foods was reported as a common
behaviour related to food in children with Down
syndrome.36 Despite this patient group having higher
rates of feeding problems and often lower feeding skills
than children without Down syndrome, no association
was observed between difficult mealtime behaviours
reported by the parent and the feeding skills of the child.37
Additionally, parents of toddlers with Down syndrome
did not report more challenging mealtime behaviours
than parents of children without Down syndrome of the
same age.37
Parental feeding practices and eating
behaviours
Reports on parental feeding practices have shown that
parents put less pressure on the child to eat, had greater
weight concerns, and used more restrictions36 with the
child with Down syndrome than they did with the child’s
siblings.38 Additionally, the use of restrictions and
monitoring of food intake were more frequent among
parents of overweight children with Down syndrome
than among parents of children with Down syndrome of
a healthy weight in a study of individuals (aged 2–9 years)
with spina bifida, autism spectrum disorders, and Down
syndrome.39 In a study by Osaili and colleagues,36 47 (57%)
of 82 parents with a child with Down syndrome reported
that their child frequently continued to eat as long as
food was present. The potential effect of parental practice
on eating behaviour and the risk of overweight in young
people with Down syndrome has not been properly
investigated. Eating behaviour is an important issue to
address in future studies because it has potential
implications for both younger and older children related
to the development of obesity.
Nutritional status
The mean weight and length at birth is reduced in
neonates with Down syndrome, with mean birthweight
closer to the mean of unaffected children than birth
length.6 Reduced growth rate leading to final short stature
is a well known characteristic of people with Down
syndrome.
Growth charts for people with Down syndrome from
birth to age 18–20 years have been developed on the basis
of several national cohorts.40–46 Traditionally, growth
curves can be useful in children without Down syndrome
to monitor growth and nutritional status. For children
with Down syndrome, weight-for-length charts that are
specific to their diagnosis can be used to screen for
growth faltering and wasting, but might be less precise
in determining overweight than for those without Down
syndrome.40
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As a consequence of the increased risk of overweight
and obesity, the mean body-mass index (BMI) percentile
for the age of children with Down syndrome increases
during childhood when plotted on curves developed for
the general population. Based on data from a French
Down syndrome cohort,41 mean BMI was in the
25th percentile in girls and boys aged 0–1 year.
Furthermore, mean BMI was in the 50th percentile in
girls aged 3 years and in boys aged 4 years and, thereafter,
in the 75th percentile for girls aged 5 years and boys aged
12 years of age. In adolescents aged 18 years, mean BMI
was in the 80th percentile for girls and above the
75th percentile for boys with Down syndrome.41 Therefore,
when BMI curves are used that are specific to Down
syndrome, recognising that these curves only describe
the normal distribution of BMI values in the cohort and
do not necessarily represent an ideal weight status is
important.40,41 Plotting an individual on a BMI curve that
is specific to Down syndrome only provides information
about weight status in comparison with other people who
have Down syndrome. Subsequently, this type of curve
can classify a person with Down syndrome to be a healthy
weight, although they would otherwise be classified as
overweight or obese with standard curves.47 However,
because individuals with Down syndrome tend to have a
shorter stature, the curves and cutoffs developed for
children without Down syndrome have been found to
overestimate obesity and body fat percentage as meas­
ured by dual-energy x-ray absorptiometry.48 Therefore,
additional examin­ations might be required to screen for
overweight and obesity and associated health outcomes.
Measuring skinfolds at four locations (triceps, biceps,
subscapular, and suprailiac) is an alternative method to
assess adiposity and equations have been developed for
children with reduced growth.49 Compared with the body
fat percentage measured by dual-energy x-ray absorptio­
metry, the prediction equation for reduced growth, which
was specifically developed for groups with health
conditions affecting growth, did well in children with
Down syndrome.49 Another option might be the use of
waist circumference. A strong correlation (r=0·85)
between waist circumference measurements and body fat
percentage measured by bioelectical impedance analysis
has been described in a small study of 19 children and
adolescents with Down syndrome.50 Even though these
results indicate that bioelectical impedance analysis and
waist circumference could be promising methods in
clinical practice, additional validation is required before
such methods could be recommended.
The prevalence of iron deficiency anaemia was
investigated in an uncontrolled study of 149 children and
adolescents with Down syndrome (aged 0–20 years).
This study found that 4 (5%) of 83 children who were
younger than 10 years and 7 (14%) of 51 children aged 10
years or older had iron deficiency anaemia.51 This study
further described an association between a haemoglobin
concentration that was lower than average and delays in
458
motor milestones, such as starting to walk after the age
of 2 years.51 By contrast, in a larger cohort study of
856 children with Down syndrome who had a mean age
of 8·8 years (SD 6·5), iron deficiency was more common
(10% [18 children]) in children younger than 36 months
than in those older than 3 years (4% [28 children]).52 In
this study, in addition to haemoglobin parameters, other
parameters are suggested, like ferritin and red cell
distribution width. An Italian study showed that children
with Down syndrome had a high risk of low 25-hydroxy-
vitamin D levels compared with controls, with 24 (77%)
of 31 children having vitamin D deficiency.53 These
studies suggest that blood tests for iron deficiency and
vitamin levels could be of clinical importance.
Obesity
Prevention and treatment of obesity are important issues
for children and adolescents with Down syndrome. In a
review addressing overweight and obesity in children
and adolescents with Down syndrome, decreased energy
expenditure at rest, increased leptin levels, untreated
hypothyroidism, unhealthy diet, and low physical activity
were described as factors that were likely to contribute to
excessive weight gain.15 In line with this hypothesis, a
2018 study on total energy expenditure that used doubly
labelled water in nine children with Down syndrome
(mean 10·0 years [SD 3·9]) found that children with the
condition required 500–800 fewer calories per day than
children without Down syndrome.54 However, studies on
nutritional intake did not find a decreased energy intake
in children with Down syndrome compared with
controls, but rather an increased energy intake55 or no
difference in energy intake between children with and
without Down syndrome.56
Reduced cognitive abilities might influence food choices
and activity levels in children. However, Jankowicz-
Szymanska and colleagues57 found no clear correlation
between the degree of intellectual disability and nutritional
status when adolescents with Down syndrome and mild
intellectual disability were compared with other adolescents
with Down syndrome and moderate intellectual disability.
Poor knowledge of healthy foods has been described in
children and adolescents with Down syndrome aged 11–18
years.58 Even so, an intervention study that consisted of an
18-session education programme on physical activity,
healthy eating, and motivational skills only resulted in a
shift towards a decrease in the frequency of consumption
of sweets, with no other changes in dietary habits
observed.59
To date, most interventions for obesity in children and
adolescents with Down syndrome have been based on
exercise, with mixed and inconclusive effects on weight
loss.15 However, some studies have involved multi­
component interventions. In a small, 6-month nutrition
and exercise intervention study (n=21), no weight loss
was observed in the group that received a 16-session
nutrition and exercise education programme with
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Study design Age (years)
Magenis et al Case-control study (Down 5–18
(2018)55 syndrome group n=19 and
control group n=19)
Samarkandy et al Case-control study (Down 5–12
(2012)56 syndrome group n=108
and control group n=113)
Grammatikopoulou Cross-sectional study (child 2–18 (child
et al (2008)61 Down syndrome group group aged 2–9
n=11 and adolescent Down and adolescent
syndrome group n=23) group aged
10–18)
RDA=recommended dietary allowances.
Table 1: Studies on nutritional intake in children with Down syndrome
individualised plans for diet and exercise.60 Never­theless,
in the group where parents also received education in
behavioural strategies, such as diet and activity
monitoring, short-term goal setting, and positive
reinforcement, participants lost an average of 2·7 kg. At
the 1-year follow-up visit, mean weight loss was 1·9 kg
from baseline weight.60 This study indicates the potential
importance of family-oriented interventions and
education for successful weight loss and maintenance,
but needs to be further evaluated in larger samples.
Nutritional intake and assessment
Assessment of nutritional intake is an essential component
in the prevention and treatment of abnormal weight status
and micronutrient deficits. However, few studies have
addressed dietary intakes in children and adolescents with
Down syndrome and no specific dietary pattern in this
group has been shown to be associated with an increased
risk of overweight.15 Intakes below recommended dietary
allowances of various micro­nutrients were found in some
individuals.55,61 Compared with siblings, reduced intakes of
protein and particular micronutrients have also been
documented (table 1).56 Parents of young children are most
often able to present an accurate picture of their child’s
typical dietary habits and nutritional intake. Because of the
widespread use of dietary supplements in children with
Down syndrome,62 all assessments of nutritional intake in
this population should include questions about use of
herbal and dietary supplements. As children with Down
syndrome grow older, additional methods might be
required to provide adequate dietary data. Technology-
based methods like image-based food records accessible by
mobile phone have been found to be accepted, feasible,
and promising for nutritional assessment in adolescents
with Down syndrome.63,64
Dietary supplementation studies
Vitamins, minerals, and antioxidants from the diet are
important cofactors in many biochemical processes
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Review
Country Method Results
Brazil Parent completed Higher intakes of energy, protein, and carbohydrates in Down syndrome group than
3-day food record in control group; proportions of participants with intakes below RDA:
vitamin D 14 (74%), nicotinic acid 4 (21%), folic acid 5 (26%), pantothenic acid
7 (37%), calcium 5 (26%), and thiamine 2 (11%); no significant difference in
proportions with suboptimal intakes of micronutrients between Down syndrome
group and control group
Saudi Arabia Parent completed No significant difference in energy intake between Down syndrome group and
3-day food record sibling control group; significantly lower intakes of protein, vitamin A, riboflavin,
calcium, and potassium in Down syndrome group than in controls
Greece Parent completed Highest intakes in total energy and macronutrients in adolescent group (as
3-day food record expected); suboptimal intakes of micronutrients for children with Down syndrome
(presented as mean percentage of RDA): folic acid 81%, vitamin D 70%, vitamin E
35%, vitamin K 49%, and iron 76%; suboptimal intakes of micronutrients for
adolescents with Down syndrome (presented as mean percentage of RDA): folic acid
84%, biotin 60%, vitamin D 94%, vitamin E 87%, vitamin K 43%, and calcium 90%
throughout the body. To ensure short-term and long-
term health, most countries have developed recom­
mendations for daily intakes. A study by Reza and
colleagues65 found that exercise, with and without intake
of calcium and vitamin D from enriched milk, had a
positive effect on bone mineral density in children with
Down syndrome (table 2). The interventions in this
study mimic the general recommendations of physical
activity and intakes of calcium and vitamin D from foods
and provide some evidence that adherence to these
recommendations also has positive effects on bone
health in children with Down syndrome.65 Likewise, in a
study by Stagi and colleagues,53 a positive but inadequate
effect was shown when children and adolescents with
Down syndrome who had low baseline levels of
25-hydroxy vitamin D were supplemented with
10 µg/day of vitamin D3. This study did not investigate
total intake of vitamin D in the diet, but described a
reduced intake of vitamin D from fortified milk in the
group of participants with Down syndrome (table 2).
The study indicates the importance of adequate
vitamin D intake to prevent low vitamin D status and
that adherence to general recommendations might be
inadequate in people with Down syndrome who already
have a deficiency.
The presence of an extra copy of chromosome 21 causes
an overexpression of genes located on this chromosome
and further metabolic alterations that lead to increased
levels of oxidative stress and abnormalities in zinc metab­
olism.72,73 Subsequently, dietary interventions involving
higher intakes of supplements of selected antioxidants,
vitamins, and minerals than general recommendations
have been hypo­­thesised to contribute to the normalisation
of biochemical processes. Consequently, the effect of the
syndrome on the nervous system and intellectual ability
might be ameliorated.
Although several studies involving dietary sup­
plements have reported improvements in biochemical
markers, no study to date has been able to translate
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Study design Age Country Intervention Daily* intervention Measurements Results

duration
Before intervention After intervention
Stagi et al Controlled 4–19 years Italy 6 months 10 µg oral cholecalciferol Plasma 25(OH) D levels, Significantly lower 25(OH) Increased plasma 25(OH) D
(2015)53 intervention (November to serum calcium and D levels in Down syndrome levels in Down syndrome
study (Down May) phosphate, bone specific group than in control (but not control) group, but
syndrome alkaline phosphate, and group; 14 (45%) children still significantly lower than
group n=31 and parathyroid hormone; in Down syndrome group control group; 8 (29%)
control group evaluation of dietary had deficient (<20 ng/mL) children in Down syndrome
n=99) vitamin D intake by 25(OH) D levels and 10 group had deficient 25(OH)
interview with parents on (32%) had severe D levels and 7 (22%) had
use of vitamin D fortified deficiency (≤10 ng/mL); severe deficiency;
milk higher parathyroid parathyroid hormone levels
hormone levels in Down still higher in Down
syndrome group than in syndrome group than in
control group; less control group
vitamin D fortified milk
consumed by Down
syndrome group than by
control group
Reza et al Four-arm 7–12 years Iran 4 months Group A: exercise (45 min Bone mineral density at Approximately 430 mg Significantly higher bone
(2013)65 randomised weight-bearing activities right proximal femur neck per day dietary calcium mineral density in all groups;
controlled trial three times per week) and by dual-energy x-ray intake in all groups; similar combined exercise and
(Down calcium (daily intake of absorptiometry physical activity pattern in calcium group: 14·6%
syndrome 500 mL of cow’s milk all groups increase; exercise group:
group n=48) enriched with vitamin D 8·6% increase; calcium
containing 200 mg calcium group: 3·5% increase; no
per serving); group B: intervention: 1·3% increase
calcium; group C: exercise;
group D: no intervention
Parisotto Case-control 3–14 years Brazil 6 months in 400 mg vitamin E and Antioxidant enzymatic ·· Significant differences in
et al study (Down Down 500 mg ascorbic acid activity from whole blood, antioxidant enzymatic
(2014)66 syndrome syndrome haemolysates, and in activity between Down
group n=21 and group only serum samples syndrome and control group;
control group more normalised antioxidant
n=18) enzymatic activity values in
Down syndrome group;
increased vitamin E levels in
whole blood of Down
syndrome group
Lakshmi Case-control 5–16 years India 6 months in 1 mg/kg bodyweight zinc, Serum Lower acetylcholinesterase Increased and more
et al study (Down Down 1·5 mg vitamin A, 17 mg acetylcholinesterase and and butyrylcholinesterase normalised values of
(2008)67 syndrome syndrome vitamin E, 100 mg ascorbic butyrylcholinesterase values in Down syndrome acetylcholinesterase and
group n=40 group only acid, 10 mg thiamine, 10 mg group than in control butyrylcholinesterase in
and control riboflavin, 3 mg pyroxidine, group Down syndrome group than
group n=40) 5 µg cyanocobalamin, 50 mg in control group
nicotinic acid, 1 mg folic
acid, 12·5 mg calcium
pantothenate, 2·5 mg
copper, 60 µg selenium,
1·4 mg manganese, and 5 µg
chromium
Ellis et al Four-arm 0–7 UK 18 months Group A: antioxidants Antioxidant enzymatic ·· No clinically or statistically
(2008)68 single-blinded months (10 µg selenium, 5 mg zinc, activity in red blood cells; significant outcomes
randomised 0·9 mg vitamin A, 100 mg lipid peroxidation
controlled trial vitamin E, and 50 mg biomarker in urine; clinical
(Down ascorbic acid) and 0·1 mg improvements by
syndrome folic acid (n=41); group B: quotient on Griffiths
group n=156) antioxidants (n=40); mental developmental
group C: 0·1 mg folic acid scale and MacArthur
(n=36); group D: placebo communicative
(n=39) development inventory
(Table 2 continues on next page)

these findings into improvements in clinical outcomes any description of clinical outcome measures. The
(table 2). An important limitation of research is that randomised controlled trial by Ellis and colleagues68 had
most studies include small samples and do not include a stricter study design than most Down syndrome

460 www.thelancet.com/child-adolescent Vol 4 June 2020

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Study design Age Country Intervention Daily* intervention Measurements Results

duration
Before intervention After intervention
(Continued from previous page)
Nachvak Three-arm 7–15 years Iran 4 months in Group A: 268 mg d-alpha Serum thiobarbituric acid ·· Higher levels of oxidative
et al randomised Down tocopherol; group B: 100 mg reactive substances and stress markers in Down
(2014)69 controlled trial syndrome thioctic acid; group C: urinary 8-hydroxy-2- syndrome group than in
(Down group only placebo deoxyguanosine oxidative sibling control group; no
syndrome stress markers change in thiobarbituric acid
group n=93 and reactive substances after any
sibling control intervention in all groups;
group n=26) significantly lower urinary
8-hydroxy-2-
deoxyguanosine in d-alpha
tocopherol group than in
placebo group
Marreiro Uncontrolled 10–19 Brazil 4 weeks 30 mg zinc Measures of zinc-related ·· Increased zinc concentration
et al intervention years nutritional status in in plasma and decreased
(2009)70 study (Down plasma and erythrocytes; concentration in
syndrome serum concentration of erythrocytes; no difference in
group n=16) thyroid hormones serum thyroid hormone
(thyroxine and concentration
tri-iodothyronine)
Gualandri Uncontrolled 1–14 years Italy 30 days in 200 mg thioctic acid and Thiol groups, septic ·· 13 children withdrew so
et al intervention children with 200 mg cysteine reactive oxygen species, results based on
(2003)71 study (Down compromised and total antioxidant 20 participants; significant
syndrome redox balance status in serum increase in serum thiol
group n=33) at baseline groups and antioxidant
capacity in serum; significant
decrease in serum total and
septic reactive oxygen
species
*Unless otherwise indicated.

Table 2: Dietary intervention studies in children with Down syndrome

studies to date and included a relatively large sample of
156 infants with Down syndrome with a mean age of
4 months at enrolment. The researchers investigated
the effect of antioxidants and folic acid supplementation
and did not find any improvements on oxidative stress,
which was biochemically measured, or cognitive
functions, which were measured by the development of
major motor milestones and language development
(table 2).68 Furthermore, a systematic review from 2002
by Michael Salman74 did not find evidence that cognitive
function or psychomotor development were affected by
any combination of supplement with vitamins or
minerals. We did not identify any studies on the safety
of dietary supplements, which is a concern because
some of the doses that have been used in
supplementation studies have been high (table 2).
Gastrointestinal distress has been reported as a side-
effect of dietary sup­ plementation.62,68 No association
between the use of vitamin supplements and the risk of
leukaemia has been found in children with Down
syndrome.75
Despite minimal evidence of the effect of various
dietary supplementations, their use remains common in
children with Down syndrome. In a survey of
1167 parents with a child with Down syndrome from
the USA, 49% reported that they gave or had given
supplements to their child, with antioxidants and
vitamins being the most popular supplement
categories.62 On average, the children used three
supplements (range 1–18). 87% of these parents reported
improve­ ments in language, immunity, and attention.
This finding shows a discrepancy between scientific
literature and opinions of the parents that needs to be
systematically addressed.
Dietary issues related to coeliac disease and
type 1 diabetes
As previously mentioned, children with Down syndrome
have an increased risk of coeliac disease8 and type 1
diabetes.12 The only available treatment for coeliac disease
is a gluten-free diet (figure). In a small study of nine people
(aged 12–50 years) with Down syndrome who were
diagnosed with coeliac disease, clinical improvements in
anaemia and diarrhoea and improved, less irritable
behaviour were observed at 1 year of follow-up in
participants who had good diet compliance.76 Apart from
this observation, we did not identify any other studies that
described aspects related to diet or determinants of diet
compliance in children with both Down syndrome and
coeliac disease or type 1 diabetes.

www.thelancet.com/child-adolescent Vol 4 June 2020 461

 Review
Search strategy and selection criteria
We searched Ovid MEDLINE for articles using the following
search terms “Down syndrome” AND (“nutrition” OR
“nutritional” OR “feeding” OR “diet” OR “dietary”). We limited
our search to articles published in English from Jan 1, 2000, to
Aug 19, 2019. We considered this period relevant for health-
care practice because of the increased survival rate of children
with Down syndrome who are born with congenital
malformations and improvements in medical and nutritional
treatment. Our search identified 351 articles. We assessed
titles and abstracts for studies in children and adolescents
with Down syndrome. We included original studies that used
various descriptive and intervention designs and the most
recent review articles that were nutritionally relevant. We
excluded case reports, adult population studies, and studies
in animal models. Additionally, guidelines for health
supervision in children with Down syndrome were assessed
and included. We identified 57 articles that matched our
criteria. We did a supplementary search for the identification
of diagnosis-specific growth curves.
Limitations and future perspectives
Little research has been done on the nutritional
challenges in children and adolescents with Down
syndrome, with few published intervention studies.
Several studies include small numbers of participants
with wide age distributions and inadequate descriptions
of health status. Additionally, many studies include
cohorts that were followed up at specialist clinics
and could, therefore, be selective populations. More
in-depth studies with representative samples and
controlled study designs are needed that use cutting-
edge methods and technologies. This Review shows that
an urgent need exists for studies that address energy
requirements and nutritional intakes and status that
should be the basis for the development of targeted,
randomised clinical interventions. Knowledge on
relevant health issues in Down syndrome in general,
and nutritional issues in this patient group in particular,
is needed for such studies to be of high quality and
relevance for doctors and clinical dietitians who work
with this group.
Conclusions
Increased focus on nutritional measures is important
for the health and wellbeing of children and adolescents
with Down syndrome. Specific clinical features of Down
syndrome have nutritional relevance and need to be
addressed systematically. There are different nutritional
implications in various age groups, with feeding
problems predominant in the first years of life. Clinical
screening for feeding problems and evaluation of
children with feeding difficulties and low weight gain is
important. Excessive weight gain is a concern for many
children with Down syndrome aged 4–5 years and
462
above. This concern calls for early prevention to avoid
later comorbidities. The switch between preventing the
risk of undernutrition in the child’s first year of life and
obesity in later life is a challenge to treatment. Clearly, a
need exists for more research on nutritional aspects in
the prevention and treatment of obesity in Down
syndrome.
Contributors
MN did the literature search, identified relevant articles, read included
studies, drafted, and finalised the Review and tables. MN also made
the figures and participated in discussions and revision of the Review.
SH contributed to the planning of the first draft of the manuscript
with clinical cases and relevant pathology linked to nutrition and
commented on the Review. KR contributed to the planning of the
literature search, the use of selection criteria, and the first draft of
the Review with clinical examples and relevant pathology linked to
nutrition. KR also contributed to finalising and revising the Review.
SOK contributed to the planning of the literature search, the use of
selection criteria, and did the literature search. SOK also contributed
to the outline of the Review, preliminary drafting and finalising of
the manuscript, and participated in discussions and revision of
the Review.
Declaration of interests
All authors declare no competing interests.
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