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Infant formula should provide the appropriate nutrients and adequate energy to facilitate healthy infant growth and development. If conclusive data on quantitative nutrient requirements are not available, the composition of human milk (HM) can provide some initial guidance on the infant formula composition. This paper provides a narrative review of the current knowledge, unresolved questions, and future research needs in the area of HM fatty acid (FA) composition, with a particular focus on exploring appropriate intake levels of the essential FA linoleic acid (LA) in infant formula. The paper highlights a clear gap in clinical evidence as to the impact of LA levels in HM or formula on infant outcomes, such as growth, development, and long-term health. The available preclinical information suggests potential disadvantages of high LA intake in the early postnatal period. We recommend performing well-designed clinical intervention trials to create clarity on optimal levels of LA to achieve positive impacts on both short-term growth and development and long-term functional health outcomes., Statement of Significance: The present work summarizes and discusses for the first time the (gaps in) available evidence on the effects of linoleic acid in an infant diet on infant health outcomes in relation to the recently adapted changes in regulations for the addition of linoleic acid to infant formula.

Limited and inconsistent evidence exists on the associations between dietary patterns and overweight during childhood. The present study describes dietary patterns of three-year-old Dutch children and associations between childhood overweight and body mass index (BMI) development between 3 and 10 years. In the GECKO Drenthe birth cohort (N = 1306), body height and weight were measured around the age of 3, 4, 5, and 10 years, and overweight was defined according to Cole and Lobstein. A validated food frequency questionnaire (FFQ) was used to measure diet at 3 years. Dietary patterns were derived using principal components analysis (PCA). Using logistic regression analyses, pattern scores were related to overweight at 3 and 10 years. A linear mixed-effect model was used to estimate BMI-SDS development between 3 to 10 years according to quartiles of adherence to the pattern scores. Two dietary patterns were identified: (1) ‘minimally processed foods’, indicating high intakes of vegetables/sauces/savory dishes, and (2) ‘ultra-processed foods’, indicating high intakes of white bread/crisps/sugary drinks. A 1 SD increase in the ‘ultra-processed foods’ pattern score increased the odds of overweight at 10 years (adjusted OR: 1.30, 95%CI: 1.08, 1.57, p = 0.006). The ‘minimally processed foods’ pattern was not associated with overweight. Although a high adherence to both dietary patterns was associated with a higher BMI-SDS up to 10 years of age, a stronger association for the ‘ultra-processed foods’ pattern was observed (p &lt, 0.001). A dietary pattern high in energy-dense and low-fiber ultra-processed foods at 3 years is associated with overweight and a high BMI-SDS later in childhood.

Background & aim: High protein intake in early life is associated with an increased risk of childhood obesity. Feeding a modified lower-protein (mLP) infant formula (1.7 g protein/100 kcal) until the age of 6 months is safe and supports adequate growth. The aim of the present study is to assess longer-term anthropometry with BMI at 1 and 2 years as primary outcome parameter and body composition in children fed mLP formula. Methods: Healthy term-born infants received mLP or control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double-blinded RCT. A breast-fed (BF) group served as a reference. Anthropometry data were obtained at 1 and 2 years of age. At the age of 2 years, body composition was measured with air-displacement plethysmography. Groups were compared using linear mixed model analysis. Results: At 1 and 2 years of age, anthropometry, including BMI, and body composition did not differ between the formula groups (n = 74 mLP; n = 69 CTRL). Compared to the BF group (n = 51), both formula-fed groups had higher z scores for weight for age, length for age, waist circumference for age, and mid-upper arm circumference for age at 1 year of age, but not at 2 years of age (except for z score of weight for age in the mLP group). In comparison to the BF group, only the mLP group had higher fat mass, fat-free mass, and fat mass index. However, % body fat did not differ between feeding groups. Conclusions: In this follow-up study, no significant differences in anthropometry or body composition were observed until 2 years of age between infants fed mLP and CTRL formula, despite the significantly lower protein intake in the mLP group during the intervention period. The observed differences in growth and body composition between the mLP group and the BF reference group makes it necessary to execute new trials evaluating infant formulas with improved protein quality together with further re-ductions in protein content. Clinical Trial Registry: This trial was registered in the Dutch Trial Register (Study ID number NTR4829, trial number NL4677). https://www.trialregister.nl/trial/4677. (c) 2021 Published by Elsevier Ltd.

Summary Background & aims Breastfeeding is the gold standard infant feeding. Data on macronutrients in relation to longitudinal body composition and appetite are very scarce. The aim of this study was to investigate longitudinal human milk macronutrients at 1 and 3 months in association with body composition and appetite during early life in healthy, term-born infants. We hypothesized that infants receiving higher caloric human milk would have more body fat mass and satiate earlier. Methods In 133 exclusively breastfed infants (Sophia Pluto Cohort), human milk samples at 1 and 3 months were analyzed for macronutrients (fat, protein, carbohydrate) by MIRIS Human Milk Analyzer, with appetite assessment by Baby Eating Behavior Questionnaires. Fat mass (FM) and fat-free mass (FFM) were measured by PEA POD and DXA, and abdominal FM by ultrasound. Results Milk samples showed large differences in macronutrients, particularly in fat content. Protein and energy content decreased significantly from 1 to 3 months. Fat and carbohydrate content tended to decrease (p = 0.066 and 0.081). Fat (g/100 ml) and energy (kcal/100 ml) content at 3 months were associated with FM% at 6 months (β 0.387 and 0.040, resp.) and gain in FM% from 1 to 6 months (β 0.088 and 0.009, resp.), but not with FM% at 2 years. Carbohydrate content at 3 months tended to associate with visceral FM at 2 years (β 0.290, p = 0.06). Infants receiving higher caloric milk were earlier satiated and finished feeding faster. Conclusions Our longitudinal data show decreasing milk protein and energy content from age 1 to 3 months, while fat and carbohydrate tended to decrease. Macronutrient composition, particularly fat content, differed considerably between mothers. Milk fat and energy content at 3 months associated with gain in FM% from age 1 to 6 months, indicating that higher fat and energy content associate with higher gain in FM% during the critical window for adiposity programming. As infants receiving higher caloric breastfeeding were earlier satiated, this self-regulatory mechanism might prevent intake of excessive macronutrients. Online trial registry NTR, NL7833.

Background The first 6 months of life are a critical window for adiposity programming. Appetite-regulating hormones (ARH) are involved in food intake regulation and might, therefore, play a role in adiposity programming. Studies examining ARH in early life are limited. Purpose To investigate ghrelin, peptide YY (PYY) and leptin until 6 months and associations with fat mass percentage (FM%), infant feeding and human milk macronutrients. Procedures In 297 term-born infants (Sophia Pluto Cohort), ghrelin (acylated), PYY and leptin were determined at 3 and 6 months, with FM% measurement by PEAPOD. Exclusive breastfeeding (BF) was classified as BF ≥ 3 months. Human milk macronutrients were analyzed (MIRIS Human Milk Analyzer). Main findings Ghrelin increased from 3 to 6 months (p p R ≥ 0.321, p ≤ 0.001) and gain in FM% from 1 to 6 months(R ≥ 0.204, p = 0.001). In BF infants, also ghrelin and ghrelin/PYY ratio correlated with this gain in FM%. Exclusively BF infants had lower ghrelin and higher PYY compared to formula fed infants at 3 months (p ≤ 0.039). ARH did not correlate with macronutrients. Conclusions Increasing ghrelin and decreasing PYY, thus increasing ghrelin/PYY ratio, suggests an increasing orexigenic drive until 6 months. ARH were different between BF and FF infants at 3 months, but did not correlate with human milk macronutrients. Ghrelin and leptin, but not PYY, correlated with more FM development during the first 6 months, suggesting that they might be involved in adiposity programming.

Background: Late and moderate preterm (LMPT) infants are at risk for adverse later life outcomes. We determined the association between feeding method at enrolment and growth and body composition of LMPT infants until 3 months corrected age (3mCA). Methods: Infants born between 32+0 and 36+6 weeks of gestation (n = 107) were enrolled up to 4 weeks corrected age and stratified according to feeding at enrolment. We performed anthropometric measurements at enrolment, term equivalent age (TEA) and 3mCA, including skinfold measurements and body composition using dual X-ray absorptiometry (DEXA). Results: Feeding method at enrolment was associated with fat mass (FM) (breast 554.9 g, mixed 716.8 g, formula 637.7 g, p = 0.048), lean body mass (LM) (2512 g, 2853 g, 2722 g, respectively, p = 0.009) and lean mass index (LMI) (10.6 kg/m2, 11.6 kg/m2,11.2 kg/m2 respectively, p = 0.008) at TEA, but not 3mCA. Breastfed infants demonstrated greater increase in LM (breast 1707 g, mixed 1536 g, formula 1384 g, p = 0.03) and LMI (1.23 kg/m2, 0.10 kg/m2, 0.52 kg/m2, respectively, p = 0.022) between TEA and 3mCA. Conclusions: Breastfed LMPT infants have lower FM and greater LM increase and LMI increase up to 3mCA compared to formula or mixed-fed infants. These findings stress the importance of supporting breastfeeding in this population. Impact: Infants born late and moderate preterm age who are exclusively breastfed soon after birth gain more lean mass up to 3 months corrected age compared to mixed- or formula-fed infants.Breastfed infants have lower lean and fat mass at term equivalent age compared to mixed- and formula-fed infants.This is the first study exploring this population’s growth and body composition in detail at 3 months corrected age.Our results underline the importance of supporting mothers to initiate and continue breastfeeding at least until 3 months corrected age.

Lipids are essential for healthy infant growth and development. The structural complexity of lipids in human milk is not present in infant milk formula (IF). A concept IF was developed mimicking more closely the structure and composition of human milk fat globules. The current study evaluates whether a concept IF with large, milk phospholipid-coated lipid droplets (mode diameter 3 to 5 μm) is equivalent to standard IF with regard to growth adequacy and safety in healthy, term Asian infants. In this randomized, double-blind, controlled trial, infants were randomized after parents decided to introduce formula. Infants received a standard IF with (Control) or without the specific prebiotic mixture scGOS/lcFOS (9:1 ratio; Control w/o prebiotics), or a Concept IF with large, milk phospholipid-coated lipid droplets and the prebiotic mixture. A group of 67 breastfed infants served as a reference. As a priori defined, only those infants who were fully intervention formula-fed ≤28 days of age were included in the equivalence analysis (Control n = 29; Control w/o prebiotics n = 28; Concept n = 35, per-protocol population). Primary outcome was daily weight gain during the first four months of life, with the difference between the Concept and Control as the key comparison of interest. Additionally, adverse events, growth and tolerance parameters were evaluated. Equivalence of daily weight gain was demonstrated between the Concept and Control group after additional correction for ethnicity and birthweight (difference in estimated means of 0.1 g/d, 90%CI [−2.30, 2.47]; equivalence margin +/− 3 g/d). No clinically relevant group differences were observed in secondary growth outcomes, tolerance outcomes or number, severity or relatedness of adverse events. This study corroborates that an infant formula with large, milk phospholipid-coated lipid droplets supports adequate growth and is well tolerated and safe for use in healthy infants.

Under- and overnutrition are co-existing health issues in several countries across Asia. Poor complementary feeding (CF) is a significant determinant of malnutrition in children and a major cause of morbidity and mortality. The purpose of this narrative review is to summarize the most recent evidence regarding the CF practices in 3 countries with a high prevalence of stunting and overweight, and currently undergoing rapid economic and nutritional transition: China, India, and Indonesia. We focused particularly on the adequacy of CF, based on the WHO feeding indicators (2021) regarding timing, frequency, diversity, as well as the consumption of specific food groups. According to the findings, the majority of infants in the 3 countries are introduced to CF at an inappropriate time: either too early (particularly in urban/rural areas of China and Indonesia) or too late (India) compared with the WHO recommendation. Furthermore, in all countries, diets are characterized by a low variety and frequency of CF and consist mainly of staple foods with poor nutritional quality, such as rice, cereals, or noodles. Nutrient-dense and protein-rich foods, such as foods of animal origin, are either inadequately consumed (rural areas of China and India) or introduced too late (urban areas of China and Indonesia) in the diets of children. In all countries, the consumption of fruit and vegetables, especially during the early CF period, is poor. In contrast, a significant proportion of both urban and rural children, particularly in Indonesia and India, are consuming energy-dense/nutrient-poor snacks and sugary drinks during the CF period. The described practices may pose a significant risk for the development of energy and/or nutrient gaps, magnifying the double and triple burden of malnutrition present in these countries. Further research is warranted to understand the significance of the observed practices for stunting and/or overweight/obesity risk. A large proportion of world's malnourished children live in Asia. This article summarizes the complementary feeding practices in China, India and Indonesia and discusses the relevance for health outcomes.

A concept infant formula (IF) was developed with physical properties of lipid droplets mimicking more closely those in human milk. This paper describes the unique design of a randomised controlled trial evaluating the impact of the concept IF on infant growth and body composition development whilst applying a cohort-like recruitment approach that fully supports breastfeeding practices of the study population. Subjects entered the study between birth and 1 months of age, and whenever parents decided to introduce formula were randomised to one of three study formulas, the concept IF comprising large lipid droplets coated by milk phospholipids and containing a specific mixture of prebiotics, a standard IF with the specific prebiotic mixture or a standard IF without the prebiotic mixture. The primary objective was to evaluate the impact of the concept IF on growth and body composition outcomes during the first year of life with a follow-up at 2, 3, 4 and 5 years of age. In addition, stool, saliva and buccal smear samples and parameters assessing safety, gastrointestinal tolerance and cognitive outcomes were collected. The applied cohort-like enrolment approach is distinctly different from standard clinical safety or efficacy studies and may provide valuable insights on trial design for the evaluation of IF while carefully considering breastfeeding practices.

This study investigated ethnic differences in childhood body mass index (BMI) in children from Dutch and Turkish descent and the role of infant feeding factors (breastfeeding duration, milk feeding frequency, as well as the timing, frequency and variety of complementary feeding (CF)). We used data from 244 children (116 Dutch and 128 Turkish) participating in a prospective study in the Netherlands. BMI was measured at 2, 3 and 5 years and standard deviation scores (sds) were derived using WHO references. Using linear mixed regression analyses, we examined ethnic differences in BMI-sds between 2 and 5 years, and the role of infant feeding in separate models including milk or CF factors, or both (full model). Relative to Dutch children, Turkish children had higher BMI-sds at age 3 (mean difference: 0.26, 95%CI: 0.04,0.48) and 5 (0.63, 0.39,0.88), but not at 2 years (0.08, −0.16,0.31). Ethnic differences in BMI-sds were somewhat attenuated by CF factors at age 3 (0.16, −0.07,0.40) and 5 years (0.50, 0.24,0.77), whereas milk feeding had a minor impact. Of all factors, only CF variety was associated with BMI-sds in the full model. CF factors, particularly CF variety, explain a small fraction of the BMI-sds differences between Dutch and Turkish children. The role of CF variety on childhood BMI requires further investigation.

Background: High protein intake in early life is associated with an increased risk of childhood obesity. Dietary protein intake may be a key mechanistic modulator through alterations in endocrine and metabolic responses. Objective: We aimed to determine the impact of different protein intake of infants on blood metabolic and hormonal markers at the age of four months. We further aimed to investigate the association between these markers and anthropometric parameters and body composition until the age of two years. Design: Term infants received a modified low-protein formula (mLP) (1.7 g protein/100 kcal) or a specifically designed control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double blinded RCT. The outcomes were compared with a breast-fed (BF) group. Glucose, insulin, leptin, IGF-1, IGF-BP1, -BP2, and -BP3 levels were measured at the age of 4 months. Anthropometric parameters and body composition were assessed until the age of 2 years. Groups were compared using linear regression analysis. Results: No significant differences were observed in any of the blood parameters between the formula groups (n = 53 mLP, n = 44 CTRL) despite a significant difference in protein intake. Insulin and HOMA-IR were higher in both formula groups compared to the BF group (n = 36) (p &lt, 0.001). IGF-BP1 was lower in both formula groups compared to the BF group (p &lt, 0.01). We found a lower IGF-BP2 level in the CTRL group compared to the BF group (p &lt, 0.01) and a higher IGF-BP3 level in the mLP group compared to the BF group (p = 0.03). There were no significant differences in glucose, leptin, and IGF-1 between the three feeding groups. We found specific associations of all early-life metabolic and hormonal blood parameters with long-term growth and body composition except for IGF-1. Conclusions: Reducing protein intake by 20% did not result in a different metabolic profile in formula-fed infants at 4 months of age. Formula-fed infants had a lower insulin sensitivity compared to breast-fed infants. We found associations between all metabolic and hormonal markers (except for IGF-1) determined at age 4 months and growth and body composition up to two years of age.

Background: Over the past decades, the preterm birth rate has increased, mostly due to a rise in late and moderate preterm (LMPT, 32–36 weeks gestation) births. LMPT birth affects 6–7% of all births in the United Kingdom and is associated with increased morbidity risk after birth in infancy as well as in adulthood. Early life nutrition has a critical role in determining infant growth and development, but there are limited data specifically addressing LMPT infants, which was the rationale for the design of the current study.Objective: The Feeding Late and Moderate Infants and Growth Outcomes (FLAMINGO) study aims to improve understanding of the longitudinal growth, nutritional needs, and body composition of LMPT infants as well as their microbiome development and neurodevelopment. In addition, having a nested non-inferiority trial enables evaluation of the nutritional adequacy of a concept IMF with large milk phospholipid-coated lipid droplets comprising dairy and vegetable lipids. The primary outcome of this RCT is daily weight gain until 3 months corrected age.Methods: A total of 250 healthy LMPT infants (32+0–36+6 weeks gestational age) with birth weight 1.25–3.0 kg will be recruited to the cohort, of which 140 infants are anticipated to be enrolled in the RCT. During six visits over the first 2 years of life, anthropometry, body composition (using dual energy X-Ray absorptiometry), feeding behavior, and developmental outcomes will be measured. Saliva and stool samples will be collected for oral and gut microbiota assessment.Discussion: The FLAMINGO study will improve understanding of the longitudinal growth, body composition development, and feeding characteristics of LMPT infants and gain insights into their microbiome and neurodevelopment.Study Registration:www.isrctn.com; Identifier ISRCTN15469594.

Background: Although a longer duration of breastfeeding has been associated with a lower risk of childhood obesity, the impact on specific organ fat depots is largely unknown.Objective: We examined the associations of any breastfeeding, duration and exclusiveness of breastfeeding, and of age at introduction of solid foods with measures of general, visceral, and organ adiposity at 10 y.Design: In a population-based prospective cohort study in 4444 children, we obtained information on infant feeding by questionnaires. At the mean age of 9.8 y, we estimated body mass index from height and weight; fat mass index and fat-free mass index by dual-energy X-ray absorptiometry; and visceral fat index, pericardial fat index, and liver fat fraction by MRI. MRI scans were performed in a subgroup of 2646 children.Results: After adjustment for age and sex, we observed associations of infant feeding with all general, visceral, and organ fat outcomes, except for pericardial fat index, at the age of 10 y. After further adjustment for family-based sociodemographic, maternal lifestyle-related, and childhood factors, only the associations of shorter breastfeeding duration and nonexclusive breastfeeding with a lower fat-free mass index remained significant (P Conclusion: Our results suggest that the assoiations of any breastfeeding, duration and exclusiveness of breastfeeding, and age at the introduction of solid foods with general, visceral, and organ fat measures at the age of 10 y are largely explained by family-based sociodemographic factors.

Objectives The aim of this study was to evaluate growth and gastrointestinal tolerance in infants fed a partially hydrolyzed protein formula (pHF) with a synbiotic mixture of short-chain galacto-oligosaccharides and long-chain fructooligosaccharides (scGOS/lcFOS; 9:1) and Bifidobacterium breve M-16V (test formula) compared with an intact protein infant formula (IF) with scGOS/lcFOS (control formula). Methods This randomized, double-blind, controlled, multicenter trial enrolled healthy, fully formula-fed Chinese infants (≤44 d) who received either the test (n = 112) or control formula (n = 112) until 17 wk of age. Fully breastfed infants served as a reference (n = 60). Anthropometrics, gastrointestinal symptoms, and adverse events were assessed monthly. Primary outcome was weight gain in grams per day from baseline to 17 wk of age. Results Equivalence in daily weight gain (primary outcome) was demonstrated between the test and control groups (estimated mean difference [SE]: –0.36 [0.93] g/d, 90% confidence interval [CI], –1.90 to 1.18) as well as between each IF group and the breastfed reference group (test: 0.02 [1.05] g/d, 90% CI, –1.71 to 1.75; control: 0.36 [1.04] g/d, 90% CI, –1.35 to 2.08). There were no clinically relevant differences in gastrointestinal tolerance or adverse events between the formula groups. Conclusion A pHF with synbiotics supports adequate growth and is well tolerated in healthy, term-born Chinese infants. Additionally, infant growth and gastrointestinal tolerance measures of both IF groups were comparable to the breastfed group and can be considered suitable and well tolerated for use.

SummaryIntroduction Body composition in early life influences the development of obesity during childhood and beyond. It is, therefore, important to adequately determine longitudinal body composition during the first months of life. Patients and methods In 203 healthy term infants, we investigated longitudinal body composition, including fat mass percentage (FM%) and fat-free mass (FFM), by air-displacement plethysmography, at 1, 3 and 6 months of age and abdominal visceral fat and abdominal subcutaneous fat, by ultrasound, at 3 and 6 months. Results We found a significant increase in FM% between 1 and 3 months but not between 3 and 6 months (p

Maternal hyperglycemia alters an offspring’s metabolic health outcomes, as demonstrated by the increased risk for obesity, impaired glucose handling and diabetes from early childhood onwards. Infant growth patterns are associated with childhood adiposity and metabolic health outcomes and, as such, can be used as potential markers to detect suboptimal metabolic development at an early age. Hence, we aimed to assess whether gestational diabetes mellitus (GDM) has an impact on offspring growth trajectories. Outcomes included weight gain (WG), body mass index (BMI), and skin fold thickness (SFT) measured at least at two time points from birth to later childhood. In addition, we explored the role of early life pre- and post-natal nutritional modifiable factors on longitudinal growth in infants of mother with GDM (GDM–F1). Despite the large heterogeneity of the studies, we can still conclude that GDM seems to be associated with altered growth outcomes in the offspring. More specifically, these alterations in growth outcomes seem to be rather time-specific. Increased SFT were reported particularly at birth, with limited information on reporting SFT between 2–5 y, and increased adiposity, measured via SFT and BMI, appeared mainly in later childhood (5–10 y). Studies evaluating longitudinal growth outcomes suggested a potential role of early life nutritional modifiable factors including maternal nutrition and breastfeeding. These may impact the cycle of adverse metabolic health by attenuating growth outcome alterations among GDM–F1. Conclusions: Timely diagnoses of growth deviations in infancy are crucial for early identification of GDM–F1 who are at risk for childhood overweight and metabolic disease development.

This study evaluated the effect of a partly fermented infant formula (using the bacterial strains Bifidobacterium breve C50 and Streptococcus thermophilus 065) with a specific prebiotic mixture (short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS, 9:1)) on the incidence of gastrointestinal symptoms, stool characteristics, sleeping and crying behaviour, growth adequacy and safety. Two-hundred infants &le, 28 days of age were assigned either to experimental infant formula containing 30% fermented formula and 0.8 g/100 mL scGOS/lcFOS or to non-fermented control infant formula without scGOS/lcFOS. A group of breastfed infants served as a reference. No relevant differences in parent-reported gastrointestinal symptoms were observed. Stool consistency was softer in the experimental versus control group with values closer to the breastfed reference group. Daily weight gain was equivalent for both formula groups (0.5 SD margins) with growth outcomes close to breastfed infants. No clinically relevant differences in adverse events were observed, apart from a lower investigator-reported prevalence of infantile colic in the experimental versus control group (1.1% vs. 8.7%, p &lt, 0.02). Both study formulae are well-tolerated, support an adequate infant growth and are safe for use in healthy term infants. Compared to the control formula, the partly fermented formula with prebiotics induces stool consistencies closer to breastfed infants.

Background: Accelerated gain in fat mass in the first months of life is considered to be a risk factor for adult diseases, given the tracking of infancy fat mass into adulthood. Our objective was to assess the influence of early growth, type of feeding and maternal variables on fat mass in early life. Methods: In 300 healthy term infants, we longitudinally measured fat mass percentage (FM%) by air-displacement-plethysmography at 1, 3, and 6 months and abdominal visceral and subcutaneous fat measured by ultrasound at 3 and 6 months. Results: Both gain in FM% and weight-for-length in the first 3 months were positively associated with FM% at 6 months of age and visceral fat at 3 months of age. Gain in FM% and weight-for-length between 3 and 6 months were both positively associated with visceral fat at 6 months. Breastfeeding duration associated positively with subcutaneous fat but not with visceral fat at 3 and 6 months. Maternal characteristics did not associate with FM% or visceral fat at 3 or 6 months. Conclusion: Higher gain in FM% or in weight-for-length in the first postnatal months leads not only to higher FM% but also more to accumulation of visceral fat. Exclusive breastfeeding appears to promote subcutaneous but not visceral fat in the first 6 months.

Background: Excess protein intake in early life has been linked to obesity and metabolic syndrome in later life. Yet protein, and in particular the essential amino acids (EAAs), need to be present in adequate quantity to support growth.Objective: With the use of a piglet model restricted in dietary amino acids (AAs), we compared the efficacy and safety of a standard formula with a low-AA formula containing an adjusted AA composition.Methods: Female piglets (3-7 d old; Landrace x Yorkshire x Duroc) were fed 1 of 4 isoenergetic AA-based formulas for 14 d (700 kJ . kg body weight(-1).d(-1)). The formulas contained a set control amount (44 g/L) and AA compositions referred to as the experimental standard (ST-100, n = 22), or 20% or 50% lower total AAs (respectively, ST-80, n = 19 and ST-50, n = 13), or 20% lower total AAs with an optimally adjusted EAA composition (O-80, n = 17). A series of clinical and paraclinical endpoints were measured.Results: Growth rates were similar for ST-100, O-80 and ST-80 piglets (all similar to 15 g.kg(-1).d(-1)), whereas ST-50 had a markedly lower weight gain relative to all groups (all P Conclusions: These data show that a 20% reduction in total AA intake for both the control (ST-80) and the adjusted AA (O-80) formula did not have any short-term adverse effects on growth in artificially reared, AA-restricted piglets. The lower absolute leucine oxidation rate observed in O-80 supports the development of an infant formula with an improved AA composition and a moderate reduction in total protein to support adequate growth in healthy infants.

Background: Current recommendations for protein levels in infant formula are intended to ensure that growth matches or exceeds growth of breastfed infants, but may provide a surplus of amino acids (AAs). Recent infant studies with AA-based formulas support specific adjustment of the essential amino acid (EAA) composition allowing for potential lowering of total protein levels. With the use of a combination of intact protein and free EAAs, we designed a formula that meets these adjusted EAA requirements for infants.Objective: Our objective was to test whether this adjusted formula is safe and supports growth in a protein-restricted piglet model, and whether it shows better growth than an isonitrogenous formula based on free AAs.Methods: Term piglets (Landrace x Yorkshire x Duroc, n = 72) were fed 1 of 4 isoenergetic formulas containing 70% intact protein and 30% of an EAA mixture or a complete AA-based control for 20 d: standard formula (ST-100), ST-100 with 25% reduction in proteinaceous nitrogen (ST-75), ST-75 with an adjusted EAA composition (O-75), or a diet as O-75, given as a complete AA-based diet (O-75AA).Results: After an initial adaptation period, ST-75 and O-75 pigs showed similar growth rates, both lower than ST-100 pigs (similar to 25 compared with 31 g . kg(-1) . d(-1), respectively). The O-75AA pigs showed further reduced growth rate (15 g . kg(-1) . d(-1)) and fat proportion (both P Conclusions: Formula based partly on intact protein is superior to AA-based formula in this experimental setting. The 25% lower, but EAA-adjusted, partially intact protein-based formula resulted in similar weight gain with a concomitant increased AA catabolism, compared with the standard 25% lower standard formula in artificially reared, protein-restricted piglets. Further studies should investigate if and how the specific EAA adjustments that allow for lowering of total protein levels will affect growth and body composition development in formula-fed infants.

Item does not contain fulltext Context: Higher infant growth rates are associated with an increased risk of obesity in later life. Objective: We examined the associations of longitudinally measured fetal and infant growth patterns with total and abdominal fat distribution in childhood. Design, Settings and participants:We performed a population-based prospective cohort study among 6,464 children. We measured growth characteristics in second and third trimester of pregnancy, at birth, and at 6, 12, and 24 months. Main Outcomes Measures: Body mass index, fat mass index (body fat mass/height2), lean mass index (body lean mass/height2) and android/gynoid fat ratio measured by Dual-energy X-ray Absorptiometry, and subcutaneous and preperitoneal abdominal fat measured by ultrasound at the median age of 6.0 years (90% range 5.7 – 7.4). Results: We observed that weight gain in second and third trimester of fetal life, and in early, mid and late infancy were independently and positively associated with childhood body mass index (p-values

Obese individuals have more (hyperplastic) and larger (hypertrophic) adipocytes in their white adipose tissue (WAT) than normal-weight individuals. The difference in cell number emerges early in childhood, suggesting that this is a critical period for being susceptible to obesity. Breast-feeding has been shown to be protective against obesity, and we have previously shown in mice that the physical structure of lipids in human milk may contribute to this protective effect. In the present study, we investigated how differences in the physical structure of lipids in the early diet may modulate adipose tissue development. Male mice were fed a diet containing control infant milk formula (Control IMF; Danone Research) or Nuturis®(Concept IMF with large phospholipid-coated lipid droplets; Danone Research) from postnatal day (PN)16 to 42. Subsequently, mice were challenged with a moderate Western-style diet (WSD) until PN98, and body composition was monitored by dual-energy X-ray absorptiometry. Epididymal WAT was analysed for adipocyte size, number and gene expression of metabolic transcription factors. Early Concept IMF exposure reduced fat accumulation during the WSD challenge by 30 % compared with the Control IMF. It reduced adipocyte size without affecting adipocyte number in adult mice. The Concept IMF decreased the expression of PPARγ, CCAAT/enhancer-binding protein and retinoid X receptor α in WAT in adulthood, key regulators of metabolic activity. In conclusion, Concept IMF exposure in early life reduced susceptibility to obesity in adult life, by preventing adipocyte hypertrophia upon adult dietary challenge without affecting adipogenesis. These data emphasise the importance of the physical properties of dietary lipids in early life in obesity risk later in life.

Background Skinfold thickness enables the measurement of overall and regional subcutaneous fatness in infancy and may be associated with total and abdominal body fat in later childhood. We examined the associations of subcutaneous fat in infancy with total and abdominal fat at school-age. Methods In a population-based prospective cohort study among 821 children, we calculated total subcutaneous fat (sum of biceps, triceps, suprailiacal, and subscapular skinfold thicknesses) and central-to-total subcutaneous fat ratio (sum of suprailiacal and subscapular skinfold thicknesses/total subcutaneous fat) at 1.5 and 24 months. At 6 years, we measured fat mass index (total fat/height3), central-to-total fat ratio (trunk fat/total fat), and android-to-gynoid fat ratio (android fat/gynoid fat) by dual-energy X-ray absorptiometry and preperitoneal fat mass area by abdominal ultrasound. Results Central-to-total subcutaneous fat ratio at 1.5 months was positively associated with fat mass index and central-to-total fat ratio at 6 years, whereas both total and central-to-total subcutaneous fat ratio at 24 months were positively associated with all childhood adiposity measures. A 1-standard-deviation scores higher total subcutaneous fat at 24 months was associated with an increased risk of childhood overweight (odds ratio 1.70, 95% confidence interval 1.36, 2.12). These associations were weaker than those for body mass index and stronger among girls than boys. Conclusions Subcutaneous fat in infancy is positively associated with total and abdominal fat at school-age. Our results also suggest that skinfold thicknesses add little value to estimate later body fat, as compared with body mass index.

Objective: Fermented formulae (FERM) and a specific mixture of 90% short-chain galacto-oligosaccharides and 10% long-chain fructo-oligosaccharides (scGOS/lcFOS; 9:1) have a potential beneficial effect on gastrointestinal function and microbiota development in infants. The present study assessed the safety and tolerance of the combination of partly fermented infant milk formulae and scGOS/lcFOS compared with either 1 feature, in healthy term infants. Methods: Four hundred thirty-two infants were enrolled before 28 days of age and followed up to 17 weeks of age and assigned to 1 of the 4 groups: (i) formula with scGOS/lcFOS, (ii) scGOS/lcFOS + 15% FERM, (iii) scGOS/lcFOS + 50% FERM, or (iv) 50% fermented formula (50% FERM). Primary outcome was daily weight gain during intervention (equivalence criterion: difference in daily weight gain ≤3 g/day). Infants’ anthropometrics, formula intake, number, and type of (serious) AEs were monitored monthly. Stool samples were collected at baseline and after 17 weeks for analysis of physiological and microbiological parameters. Results: Equivalence of weight gain per day was demonstrated in both the intention-to-treat and per-protocol population, with a mean weight gain (SD) of 29.7 (6.1), 28.2 (4.8), 28.5 (5.0), and 28.7 (5.9) g/day for the groups i to iv respectively. No differences were observed in other growth parameters, formula intake, and the number or severity of AEs. In all scGOS/lcFOS-containing formulae, a beneficial effect of scGOS/lcFOS was observed, indicated by the lower pH, lower Clostridium difficile levels, and higher secretory immunoglobulin A levels. Conclusions: The partly fermented infant milk formulae containing the specific mixture scGOS/lcFOS were well-tolerated and resulted in normal growth in healthy infants.

Summary Background The increasing incidence of childhood obesity in Asia could be a reflection of early life programming in which environmental/nutritional challenges during pregnancy and first two years of life (the so-called first 1000 days) influence later health. Objective of narrative review To assess differences/similarities of anthropometric measures in early life and their influences on metabolic health risk in later life among children in Asia. Methods Literature search for publication in English using selected key words from Medline (PubMed), Scopus, Science Direct and Google Scholar published from 1994 to October 2014. Some comparisons with Caucasian setting were made when relevant. Results From 152 publications selected for this narrative review, differences in foetal growth and birth weight were deducted between Asian and Caucasian children. Infants in India and Hong Kong had increased fat mass at birth and early infancy as compared to those from other parts of the world. Pre- and during pregnancy conditions influenced birth weight; feeding practices and gender influenced post-natal growth and body composition development. High and low birth weights followed by rapid postnatal growth were linked to increased risks of obesity, insulin resistance and high blood pressure in later life. Conclusion Foetal and postnatal growth trajectories are different between countries within and outside Asia. Extremes in birth weight followed by rapid postnatal growth were linked to increased risks of metabolic health of children in this region. As there is limited evidence in Asia, it is important to conduct thorough investigations by using longitudinal studies on early life programming.

Item does not contain fulltext Breastfeeding may have a protective effect on the development of obesity in later life. Not much is known about the effects of infant feeding on more-specific fat measures.We examined associations of breastfeeding duration and exclusiveness and age at the introduction of solid foods with general and abdominal fat outcomes in children.We performed a population-based, prospective cohort study in 5063 children. Information about infant feeding was obtained by using questionnaires. At the median age of 6.0 y (90\% range: 5.7\%, 6.8\%), we measured childhood anthropometric measures, total fat mass and the android:gynoid fat ratio by using dual-energy X-ray absorptiometry and preperitoneal abdominal fat by using ultrasound.We observed that, in the models adjusted for child age, sex, and height only, a shorter breastfeeding duration, nonexclusive breastfeeding, and younger age at the introduction of solid foods were associated with higher childhood general and abdominal fat measures (P-trend < 0.05) but not with higher childhood body mass index. The introduction of solid foods at a younger age but not breastfeeding duration or exclusivity was associated with higher risk of overweight or obesity (OR: 2.05; 95\% CI: 1.41, 2.90). After adjustment for family-based sociodemographic, maternal lifestyle, and childhood factors, the introduction of solid food between 4-4.9 mo of age was associated with higher risks of overweight or obesity, but the overall trend was not significant.Associations of infant breastfeeding and age at the introduction of solid foods with general and abdominal fat outcomes are explained by sociodemographic and lifestyle-related factors. Whether infant dietary composition affects specific fat outcomes at older ages should be further studied.

We thank Dr Hosaka et al1 for sharing their observation that breastfeeding is associated with blood pressure (BP) when measured at home, but not when measured at the survey center. We specifically studied the n-3 long-chain polyunsaturated fatty acids in human milk and formula feeding because this may be the underlying mechanism for the association between breastfeeding and BP. Children who received human milk with an n-3 long-chain polyunsaturated fatty acids content above the median (ie, 0.51 weight percentage) had a 4.79-mm Hg lower systolic (95% confidence interval, −7.64 to −1.94) and a 2.47-mm Hg lower diastolic (95% confidence interval, −4.45 to −0.49) BP at the age of 12 years than never-breastfed children.2 In addition, we conducted analyses on BP with breastfeeding as the main determinant. The mean systolic BP of children who were ever breastfed (114.4 mm Hg; SD, 9.1) was 2.17 …