Early Nutrition and Its Effect on Growth, Body Composition, and Later Obesity (N&G 2024)

Early Nutrition and Its Effect on Growth, Body Composition, and Later Obesity

Introduction

Healthy nutrition during the first years of life is critical for optimal growth and development in the short and long term. Growth patterns in infancy are influenced by feeding practices and have been investigated extensively. Papers examining early nutrition and its effects on growth, body composition, and later obesity cover a range of topics including maternal diet, breast milk (BM) components, formula and especially the protein content in formula, and complementary feeding (CF) with studies conducted in low- and middle-income countries as well as high-income countries. This year we have focused on BM composition, protein content in formula, and sources of protein in CF in relation to growth and risk of later obesity. The studies are mainly from high-income countries, but a study from a middle-income country is also included. We have selected 10 publications published between July 1, 2022 and June 30, 2023, which we find of special interest. The original articles comprise randomized controlled trials, observational studies, and reviews and have been grouped into three categories: BM composition and infant growth (two studies), protein content of infant formula and infant growth (four studies), and CF and growth (four studies).

Breast Milk Composition and Infant Growth

Metabolizable energy content of breastmilk supports normal growth in exclusively
breastfed Icelandic infants to age 6 months

Comments: It is inevitable that energy content of breast milk (BM) contributes to infant growth. The content is often assessed by the bomb calorimetry technique or by adding energy contributions from each macronutrient. These methods do not take into account that not all energy is utilized as energy for the infant, i.e., a fraction of the energy goes to bacterial growth, maturation of gut and immune function or is simply not absorbed in the infant’s gut. Thus, energy availability through BM may be overestimated when used in assessments of infant growth.

The study by Thorisdottir et al. uses data from an Icelandic prospective longitudinal study investigating breastfeeding and BM content among infants exclusively breastfed (EBF) for 6 months. The authors used the doubly labeled water (DLW) technique to estimate both metabolizable energy content of BM, BM intake, and infant body composition to assess whether energy content in BM is sufficient to support infant growth up to 6 months. Using this method, total energy expenditure and subsequently BM intake, BM content of metabolizable energy, and fat mass (FM) and fat free mass (FFM) were assessed. The authors estimated the metabolizable energy to 2.61 kJ/g BM, which they concluded is in accordance with current literature (2.56–2.60 kJ/g). Importantly, the comparable literature uses either bomb calorimetry or direct measurements of macronutrient contributions to estimate BM content without consideration of absorption. Thus, these methods may be considered valid for estimation of energy availability for the infant through BM. Furthermore, Thorisdottir et al. estimated a mean BM intake of 983 ± 169.7 g per day at 6 months, which was also considered comparable to current literature using the same method. However, a recent systematic review and meta-analysis investigating BM intake throughout lactation reported a mean BM intake of 729 mL per day (95% confidence interval: 713–745) at 6 months [1]. Considering a density of BM of 1.03 g/mL [2], the 983 g per day corresponds to 954 mL per day, which is higher than the intake reported in the systematic review and meta-analysis. However, this review included studies using the 24-h test weighing method (n = 113), deuterium dilution (n = 49), and/or both (n = 5). These methods have their limitations and especially the most used 24-h test weighing may underestimate BM intake due to underreporting of feeds. In this regard, another strength of the study by Thorisdottir et al. is the avoidance of a BM sample normally
used to determine energy content. The method of milk sample collection influences
the composition of BM especially with regard to macronutrient such as fat. Hindmilk samples, in comparison to foremilk samples, have higher fat concentration, which increases energy content and may overestimate the total energy availability for the infant. A recent systematic review investigating BM composition and later risk of obesity emphasized that (1) the protocol of BM sample collection and analyses as well as (2) estimation of BM intake are essential methodological challenges to consider in order to end up with representable and comparable data [3]. Despite using the DLW technique which is a strength to the present study, comparing the results with results from other studies using a BM sample and/or other BM intake assessments may be difficult due to the abovementioned challenges.

Regarding infant growth and body composition, infants in the present study showed weight, length, and body mass index Z-scores within the normal range compared to the WHO reference. This supports that EBF for 6 months and the BM content were sufficient to support healthy growth. Furthermore, FFM Z-score was 0.22, while FM Z-score was 0.78, with only the latter being significantly different from 0. This further indicates that EBF up to 6 months increased fat deposition, but not FFM accretion, compared to a reference population from the United Kingdom. 

Despite a low sample size of n = 27 infants and only n = 22 infants included in the final analyses, the study uniquely investigates energy sufficiency in BM up to 6 months
postpartum using the DLW technique. The results support WHO recommendations of
EBF up to 6 months with regard to infant growth and body composition. The study uses techniques for assessing both infant body composition and BM composition with high accuracy, which strengthens the study conclusions. However, the results should be compared to infants EBF up to 4 months or a group of infants receiving infant formula or mixed fed to further investigate the influence of infant feeding mode on growth. In addition, the Icelandic study was conducted in a high-income setting with participants highly motivated to breastfeed, and thus, the study should be replicated in other settings in order to improve generalizability of the results.

Associations between breast milk intake volume, macronutrient intake and
infant growth in a longitudinal birth cohort: the Cambridge Baby Growth and
Breastfeeding Study (CBGS-BF)

Comments: The study by Olga et al. investigates whether breast milk (BM) intake and/or BM composition are associated with measures of infant growth (weight, length) and adiposity (skinfold thickness) within the first year of life. The study includes 94 mother-infant dyads, although only 46 pairs had complete data. BM intake was assessed using the dose-to-mother deuterium method, BM composition (triglycerides [fat], lactose [carbohydrate], and protein) was assessed in postfeed (i.e., hindmilk) samples collected 6 weeks postpartum, and anthropometry was assessed repeatedly up to 12 months of age. The main findings of the present study include positive associations between BM carbohydrate and protein and early (0–6 weeks) adiposity gains, while an inverse association was found between BM carbohydrate and protein and late (3–12 months) adiposity gains. The authors did not find any association with BM fat concentration or intake and suggest that BM carbohydrate and protein may be a stronger predictor for later growth and adiposity.

The study highlights an important challenge within the research area of breastfeeding and BM composition, namely whether to use nutrient concentrations or intakes in associations with infant outcomes. The choice of exposure may rely in the research question being asked. However, using BM nutrient intakes may be more prone to reverse causality as it is more plausible that infant growth outcomes predict BM intakes (i.e., a larger infant drinks more milk) compared to BM concentrations (i.e., a larger infant changes BM composition). Thus, it is worth to consider adjusting for the total energy intake as this might confound the results when using BM intake as exposure. This is rarely described in the literature and should be considered in future studies. In line with the discussion of the previous study, the method of milk sample collection in the present study has limitations, which is also highlighted by the authors. The postfeed samples have higher concentrations of fat, and possibly protein, compared to prefeed samples or samples from full expressions [4]. As a result, concentrations might be overestimated, which could result in the lack of associations for fat. For protein, an overestimation of protein concentration could explain the inverse association seen during 3–12 months. As mentioned above, the method of BM sample is one of the main challenges within BM research, and standardized protocols are needed to align studies for comparison of results.

Regarding infant growth assessment, weight is potentially influenced by hydration status and/or weight loss shortly after birth, where infants born with a higher birth weight seem more prone to a higher weight loss compared to infants with normal or low birth weight [5]. In addition, length measurements are less accurate at earlier ages, e.g., birth length. Furthermore, positive associations between BM nutrient intakes and infant growth during 0–6 weeks might reflect breastfeeding practice, i.e., successful breastfeeding establishment early on compared to problematic breast feeding establishment. In summary, assessment of very early growth (0–6 weeks) maybe less accurate to estimate adiposity, whereas assessment from 3 to 12 months
might be more reliable as the inaccuracy has likely been evened out.

As the authors emphasize, the long-term consequences of more rapid versus slower growth within the first 12 months are yet unestablished. Generally, it is recognized that a high weight gain or adiposity among EBF infants is not a concern, while overweight among infants receiving formula can be concerning. Although the evidence is sparse, high protein concentration in formula has been associated with rapid weight gain and thus contributes to the risk of later overweight in certain studies. In this regard, accurate assessment of BM protein concentration becomes highly important to either support or reject these findings.

One of the main strengths of the study is the use of dose-to-mother deuterium method to assess BM intake. The authors argue that a correlation between BM protein concentration and BM intake is not confounding the results of the positive association between BM protein intake and infant growth. While this argument seems valid in relation to the results, several other factors such as infant age and/or sex may influence the correlation between BM macronutrient concentration and BM intake. As most statistical approaches combine few variables of interest, many more seem to influence the complete picture of BM composition, BM intake, and infant outcomes. Novel statistical approaches such as machine leaning techniques could be interesting when exploring this area.

The Effect of Protein Content and Quality of Infant Formula on Infant Growth

Low-protein infant formula and obesity risk

Comments: This review by Kouwenhoven et al. provides a very detailed and interesting discussion about many relevant aspects of how low-protein infant formula may influence obesity risk in the infants. Although the paper does not include a systematic review, the authors conclude that there is a need for new trials examining protein quality and effects of a further reduction in protein content. Also, there is a need to explore the possible underlying mechanisms behind how early protein intake can influence infant growth and later health.

The level of protein intake is of course a key issue, but they conclude that it is only when the protein intake is very high, that there is an effect on obesity risk. They mention the very high protein content of 4.4 g per 100 kcal given from age 6–12 months in the high-protein group in the European ChildHood Obesity Project (CHOP) study, whereas the content in the control group in other studies was 2.7 g per 100 kcal or lower [6]. At the 6-year follow-up, the high-protein group had considerably higher body mass index and a risk of obesity, which was more than two times higher than the low-protein group [7]. The systematic review by Milani et al., which is discussed below, also supports that only very high protein intake has an effect on growth. An important methodological aspect is also mentioned in the review. Macronutrient
content of the infant formula may influence intake of formula. A low-protein content may result in a higher intake, as the infant may compensate for the lower protein content. Therefore, it is important to measure volume intake, if possible, by using stable isotopes.

It is also mentioned that a high protein intake early in life might have a negative effect on kidney function. In the CHOP study, kidney size was increased in the high-protein group compared to the groups with lower protein formula or breastfeeding at 6 months [8]. Interestingly, a new study followed up a subgroup from the CHOP study, including participants from Spain and Poland, at the age of 11 years. They examined the long-term effect of high protein intake on kidney volume [9]. Those in the high-protein group still had higher kidney volume, which could have negative long-term effects as pointed out by the authors. Furthermore, those in the high-protein group also had a higher systolic blood pressure, which was partially mediated by the kidney volume. However, at the age of 11 years, there was no difference in weight, length, and body mass index.

In the review, it is mentioned that a higher content of plant proteins in infant formula will benefit the environment. However, it is also underlined that using plant-based protein in infant formula involves lower protein quality and possibly impaired digestibility, which have to be addressed.

At the end of the review, there is a brief description of an intervention study the authors were planning. It is a large multicenter long-term randomized controlled trial of infants born to overweight or obese mothers, as these infants have an increased risk of adiposity. The main outcomes are growth and body composition. The protein level of the new formula will be closer to that of BM and part of the protein will be plant based to support environmental sustainability.

Protein and growth during the first year of life: a systematic review and meta-
analysis

Comments: This systematic review and meta-analysis by Milani et al. provides a good overview of the current status within the field of protein intake and infant growth. They compared the growth effect of interventions with cow’s milk formulas with different protein content during the first year of life. In the meta-analysis they included intervention studies which compared infant formula with a high (>2.0 g/100 kcal) versus low (≤2.0 g per 100 kcal) protein content. They identified 12 papers for the systematic review and 5 of them were also included in the meta-analysis. There was considerable heterogeneity, and the overall conclusion of the systematic review with the 12 studies was that there were no clear-cut effects of protein intake on growth. The conclusion from the meta analysis of the five studies with formula interventions was also that it does not support an effect of protein intake on growth. Interestingly, the ChildHood Obesity Project (CHOP) study, which showed major differences in growth up to the age of 6 years [7], was not included in the meta-analysis because one of the inclusion criteria was that the intervention with formula should have started before 30 days after birth. In the CHOP study, start of intervention was allowed until the age of 2 months.

Infant feeding choices during the first post-natal months and anthropometry at
age seven years: follow-up of a randomized clinical trial

Comments: This paper is a 7-year follow-up of the Belgrade-Munich Infant Milk Trial (BeMIM)
study. In this study, healthy term infants were randomized to protein-reduced infant formula with alfa-lactalbumin-enriched whey and long-chain polyunsaturated fatty acids (1.89 g protein/100 kcal) or a control formula with 2.30 g protein/100 kcal. The formula was given from 30 to 120 days after birth and a breastfed group was included as reference. At 4 months of age, infants in the low-protein formula group had a higher length gain compared to the control group, which could be because of the enrichment. At follow-ups at 4 and 7 years, there were no differences in anthropometry between the groups. So, this result is in line with most of the studies comparing formulas with a relatively small difference in protein content. However, of special interest was that the insulin-like growth factor 1 (IGF-1) values at 4 months were significantly associated with weight, height, and body mass index Z-scores at 7 years. Thus, how early diet influences IGF-1 levels might have a long-term programming effect on growth.

The effect of goat-milk-based infant formulas on growth and safety parameters:
a systematic review and meta-analysis

Comments: There has been an increasing interest in the use of goat milk infant formula, and it has been approved as an infant formula by the European Food Safety Authority. In the present review, it is stated that production of goat milk requires lower feeding requirements and lower production cost compared to cow milk. There is also some evidence that there is an increased rate of gastric emptying compared to cow milk, which could influence stool frequency. Using strict inclusion criteria, 4 randomized controlled trails where a goat milk formula was compared to a cow milk-based formula were included. All four studies were funded by industry. There were no significant differences in weight, length, or head circumference between the groups. In the review, there are no information on or discussion of the amount of protein content in the formulas. Going through the 4 papers included, there were no major difference in the amount of protein comparing goat and cow milk formula in three of the studies. However, in the largest study, the protein content in the goat formula was about 20%
higher corresponding to 1.7 versus 1.35 g/100 kcal in the cow milk formula [10]. In that study, the weight gain in the goat milk group tended to be higher. However, it was not discussed in the original paper if the difference could be caused by the higher protein content. Based on the four studies in the meta-analysis, it is concluded that goat milk formula is safe and well tolerated. Stool frequency was not different between the groups.

Complementary Feeding and Growth

A randomized, controlled trial of a Nordic, protein-reduced complementary diet in
infants: effects on body composition, growth, biomarkers, and dietary intake at 12
and 18 months

Quantity and source of protein during complementary feeding and infant growth:
evidence from a population facing double burden of malnutrition

Comments: There is a growing interest in plant-based foods worldwide, especially plant protein due to environmental concerns and possible health benefits. A report by the EAT-Lancet Commission on healthy foods and sustainable food production recommend a predominantly plant-based diet and low amount of animal source foods for reduction of green house gases and preventing noncommunicable diseases [11]. The protein intake is very critical for growth and should be balanced. During the complementary feeding (CF) period, the protein intake increases typically from 5% to about 15% percent of energy (%PE). In high-income countries (HICs), the protein intake is often of animal origin and, according to the “early protein hypothesis,” high amounts of early protein would stimulate growth, especially fat tissue, which could lead to later increased risk of later obesity [12]. In low- and middle-income countries (LMICs), there is a risk of undernutrition and stunting due to a low intake of high-quality protein. The effect of different protein sources, e.g., plant-based protein, dairy protein, and meat protein, on growth is not widely investigated during the CF period. We have selected two publications examining the association between the source and quantity of protein intake and growth during in-fancy and early childhood in a HIC (Sweden) and LMIC (Thailand). The papers contribute substantially to the understanding of the importance of protein sources, which is becoming more and more crucial because of sustainability.

In the study by Johansson et al., the Nordic diet with reduced protein intake was investigated in a randomized controlled trial. The Nordic diet is characterized by a high intake of plant-based foods including fruit, vegetables, legumes, and whole grains and a reduced intake of red meat, meat products, and saturated fat [13]. They included 250 healthy term-born infants between 4 and 6 months of age (baseline). They were randomized to either a Nordic diet group (NG) or a conventional group (CG), which followed the Swedish dietary guidelines. Children in the NG received taste portions of Nordic fruit, berries, and vegetables following a schedule from 4 to 6 months. From 6 to 18 months, the parents were offered recipes on Nordic homemade baby food and protein-reduced baby food products. Measurements were performed at baseline, 12, and 18 months including body composition by deuterium dilution as primary outcome, anthropometry, biomarkers, and dietary intake. They found no difference between groups regarding body composition, growth, or energy intake, but lower levels of insulin-like growth factor 1 (IGF-1) and blood urea nitrogen, used as an adherence biomarker, and higher levels of folate, also an adherence biomarker in the NG group compared to the
CG. The biomarkers complied with the dietary intake. For both groups, weight-for-age
and BMI-for-age Z-scores were around 0.6–0.8 at 12 and 18 months, which seemed to support healthy growth. The protein intake at 12 and 18 months was 9.2 and 12.4 %PE for the NG group and 12.5 and 14.6 %PE for the CG group, respectively. Intake of fruit and vegetables were 42 and 45% higher in the NG group at 12 and 18 months though it declined in both groups by 14–16% over time. The energy intake was the same in both groups. It is notable that the protein intake is rather low for both groups. At 12 months, it is just below the Nordic nutrition recommended range of 10–15 %PE for the NG group and below 15% for the CG, which has previously been reported as an upper limit for protein intake in early childhood to avoid altered growth [14]. The authors suggest that the low protein intake in the CG may partly explain why no difference in body composition or growth was found. Another issue is higher attrition in the NG (24%) compared to the CG (12%), which may reduce the power. Furthermore, the high dropout rate in the NG underlines that adopting new and unfamiliar foods and eating habits even in highly educated, motivated, and well-resourced families is not straightforward, and the study illustrates that this should be addressed in the transition to a more plant-based and sustainable diet. Nevertheless, this well-conducted randomized controlled trial suggests that reducing protein intake and increasing plant-based foods during the CF period are safe and do not compromise growth. It seems beneficial to introduce local
and plant-based foods during the CF period as this age is important for accepting new
flavors and textures and thus may contribute to favor a more plant-based diet later in life in HIC. Future studies should examine the long-term health effects of protein-reduced diets with more plant-based protein in early childhood and how it can be implemented in the daily life.

The other study by Kittisakmontri et al. focused on protein intake during CF in relation to the double burden of malnutrition (DBM), describing the coexistence of under- and overnutrition, which is often present at different time points. Optimizing CF might contribute to overcome this problem. From a prospective cohort, 145 healthy term infants between ages 4 and 6 months mainly from middle-class families in Thailand were included. Infant growth and dietary assessments took place at 6, 9, and 12 months and a blood sample was taken at 12 months. Households with underweight infants and overweight/obese parents indicating DBM were present in 6.2% of the families. The protein intake increased markedly from 6 to 12 months, i.e., PE% was 7.8, 12.6, and 15.6% at 6, 9, and 12 months, respectively. Furthermore, protein intake was positively associated with weight and BMI Z-score, but not associated with length.
The main protein sources were animal based and mostly from infant formula. The protein sources differed in associations with growth. While plant-based protein showed no associations, dairy protein showed stronger associations with weight-related growth outcomes than nondairy animal-based protein. Also, dairy protein intake was positively correlated with IGF-1 levels.

It is interesting that the protein intake at 12 months in this study is actually higher than in the Swedish study mentioned above, both compared to the NG and the CG, and as the authors note also above the recommendations in Thailand and by WHO [15, 16]. This indicates that CF in some middle-income countries is altered toward a more Western diet with higher intake of animal source protein. This may also challenge the transition to a more sustainable diet globally. The authors suggest an upper limit of protein intake for international recommendations taking the increase of overweight in childhood in many LMICs into consideration. The Thai study lacks a more detailed description of the plant-based protein consumed at this age. It is mentioned that is was mainly cereals, which may be of lower nutritional quality than protein from legumes and grains, which was part of the Nordic diet in the Swedish study. Shifting toward a more plant-based diet during CF should comprise high-quality protein and adequate micronutrients to secure optimal growth and development. The follow-up time for the Thai study is very short and therefore information on long-term effects of amount and source of protein are lacking. These studies illustrate the different kind of problems middle- and high-income settings may experience in relation to achieving high-quality and sustainable foods during the CF period. Finally, future studies should be conducted or repeated in diverse settings regarding socioeconomic conditions to be able to assess if the findings are valid in general.

Impact of complementary feeding on obesity risk

Comments: This review is distinguished by giving a short and accurate overview of the latest literature regarding various aspects of complementary feeding (CF) on obesity risk including timing, composition, and feeding methods. The authors have preferably included systematic reviews; however, the majority of studies are observational, implying the risk of confounding. Whereas the timing of introduction of CF does not seem to influence the risk of later obesity, the content seems more critical. Most evidence concerns protein consumption in Western populations. The protein content especially in formula, which constitutes a large part of the diet particularly in the beginning of the CF period, may contribute to rapid weight gain and later risk of obesity [17, 18].

Studies on the effects of other sources of protein, both plant-based and nondairy animal-based protein, are limited and need to be investigated further. Likewise, there is limited evidence for the effect of sugar and sugar-sweetened beverage, but as the authors conclude, the intake should be low as there is no nutritional requirement. The authors also include studies on methods of CF. Regarding baby-led weaning, there is limited evidence of the effect on growth and obesity risk, and findings from the studies are inconclusive. On the other hand, responsive feeding, which includes education of the parents to respond adequately to the infant’s signs for appetite and satiety, seems to support healthy growth in some studies. However, the duration of the studies was relatively short and studies with longer follow-up are warranted.

Another strength of the review is that it also underlines the shortcomings of the present knowledge and the need for high-quality studies conducted in both high-income countries and low- and middle-income countries. As commented above, the double burden of malnutrition in low- and middle-income countries should be given special attention in relation to CF.

Do vegetarian diets provide adequate nutrient intake during complementary
feeding? A systematic review

Comments: The WHO recommends exclusive breastfeeding for the first 6 months of life and partly breastfeeding to continue up to 2 years or beyond. After 6 months, the breast milk no longer contains enough energy and nutrients to support optimal growth and development of most infants. The infant needs, in addition to milk, food with a higher nutrient content in this important age with high growth and development. The complementary feeding (CF) period where the infant starts to get solid food is a critical period with a high demand of nutrients and the WHO strongly recommends a healthy diet during infancy containing all essential nutrients [19]. 

In the last decades, vegetarianism has become more popular in many Western countries. However, only few reliable studies on the prevalence in Western countries exist. Children tend to follow their family’s dietary pattern, and it is expected that the prevalence of infants, children, and adolescents eating vegetarian diets will increase.

The attitudes among nutrition societies in Western countries have been very different, where many support the use of vegetarian diets at all life stages if nutrient supplements are taken when needed. Contrary, other countries recommend that diet should include all food groups, including animal-based food especially during pregnancy, lactation, and childhood. In cases where vegetarian or vegan diet is followed in children, supplementation and medical monitoring are recommended to discover any nutrient deficiency. With growing interest for vegetarian and vegan diets, more pediatricians are asked by parents if these diets are safe.

The first 1,000 days are especially vulnerable and important for later metabolic and
neurodevelopmental outcomes. The authors therefore consider a systematic review of literature on the outcomes of vegetarian/vegan diet during CF of paramount importance. The aim of this systematic review was to examine the findings on the influence of vegetarian diets during CF on different outcomes like growth, neurodevelopment, risk of wasting and/or stunting, overweight, and obesity. Additional outcomes are risk of deficiency of vitamins and micronutrients, infections, development of type 2 diabetes, and hypertension later in life. The authors planned to include (1) intervention and observational studies from industrialized countries, (2) studies where intervention or exposure was present during the CF period (6–24 months of age), and (3) studies comparing vegetarian diets (lacto-ovo vegetarian, vegan, macrobiotic, and others, completely free of animal protein) and healthy diets (e.g., Mediterranean diet). The authors underline that the comparator/control should be healthy CF including food of animal origin.

Only four studies (one guideline, one systematic review, and two studies) were included, indicating that there are very few studies with infants/children during the CF period evaluating vegetarian and vegan diets. For obvious ethical reasons, there were no intervention studies assessing the impact of nonsupplemented vegetarian/vegan diets. However, there are several observational or case studies investigating the influence on individual nutrient deficiency. Especially, deficiency in vitamin B12, DHA, and iron can cause irreversible damage of the neurosystem. Furthermore, vegetarian and vegan diets during CF period have no documented positive effects on noncommunicable disease. The authors concluded that current evidence suggests that risks of critical micronutrient deficiency or insufficiency and growth retardation are high when exposed to vegetarian or vegan diets and these are therefore not considered
safe.

Consequently, vegetarian and vegan diet cannot be recommended during the CF period. Following the authors’ conclusion, pediatricians and nutritionists should be very aware of infants where parents insist to give their child vegetarian diets with very little or no food of animal origin. This is also in accordance with an ESPGHAN Position Paper from 2017 [20] stating that these children should have supplementation ensuring sufficient supply of vitamin B12, vitamin D, iron, zinc, folate, n-3 long-chain unsaturated fatty acids, and protein, and their growth and neurodevelopment should be monitored close. It should be ensured that parents understand the serious consequences of not following these advices.

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