Growth Patterns of 11-29-Month-Old Children Consuming Young Child Formula: Secondary Analysis of a Randomized, Controlled Study.

INTRODUCTION: The impact of young child formula (YCF) consumption on children's growth, particularly under suboptimal conditions, has scarcely been studied. In the current study, weight-for-age (WAZ), length-for-age (LAZ), and BMI-for-age (BAZ) z-score development was evaluated in children from five different countries (n = 668) who participated in a double-blind, randomized, controlled trial. METHODS: The children (1-3 years old) were randomized to one of two intervention YCFs (with presence or absence of prebiotics and n-3 LCPUFAs) during 52 weeks of intervention. Additional stratified analyses evaluated the growth patterns of underweight, overweight, or stunted children. RESULTS: No apparent differences in anthropometric measurements were observed between the intervention groups. In both YCF intervention groups, mean WAZ, LAZ and BAZ development was indicative of adequate growth during the intervention period. Stratified analyses showed stable WAZ and BAZ development among children with a healthy weight or overweight at baseline. Among underweight and stunted children, normalization in mean weight (∼1 SD) and length (∼0.8 SD) gain, respectively, was observed. CONCLUSION: The current study suggests that consumption of YCF, either or not containing prebiotics and n-3 LCPUFAs, is associated with adequate growth among young children. This association may depend on the child's baseline nutritional status. Future studies to assess the potential role of YCF in supporting adequate weight/length gain among children at risk for undernutrition are warranted.

Early infancy growth, body composition and type of feeding in late and moderate preterms.

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.

Appetite-regulating hormone trajectories and relationships with fat mass development in term-born infants during the first 6 months of life.

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 < 0.001), while PYY decreased (p < 0.001), resulting in increasing ghrelin/PYY ratio. Leptin decreased. Leptin at 3 months was higher in girls, other ARH were similar between sexes. Leptin at 3 and 6 months correlated with FM% at both ages(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.

Feeding patterns and BMI trajectories during infancy: a multi-ethnic, prospective birth cohort.

BACKGROUND: Milk feeding type (exclusive breastfeeding [EBF], formula feeding or mixed feeding) and timing of complementary feeding (CF) have been associated with infant growth. However, studies evaluating their combined role, and the role of ethnicity, are scarce. We examined associations of feeding patterns (milk feeding type combined with timing of CF) with infant body mass index (BMI) trajectories and potential ethnic-specific associations. METHODS: Infant feeding and BMI data during the 1st year of life from 3524 children (Dutch n = 2880, Moroccan n = 404 and Turkish n = 240) from the Amsterdam Born Children and their Development (ABCD) cohort were used. Six feeding patterns were defined: EBF/earlyCF, EBF/lateCF (reference), formula/earlyCF, formula/lateCF, mixed/earlyCF and mixed/lateCF. A covariate adjusted latent class mixed model was applied to simultaneously model BMI trajectories and associations with feeding patterns. Potential ethnic differences in the associations were studied in a separate model where interactions between ethnicity and feeding patterns were included. RESULTS: Four distinct BMI trajectories (low, mid-low, mid-high and high) were identified. Feeding pattern of formula/earlyCF was associated with lower odds for low (OR: 0.43; 95% CI: 0.25, 0.76) or mid-high (0.28; 0.16, 0.51) (ref: high) trajectory compared with EBF/lateCF pattern (ref). An ethnic-specific model revealed that among Dutch infants, formula/earlyCF pattern was associated with lower odds for low trajectory (0.46; 0.24, 0.87), whereas among Turkish/Moroccan infants almost all feeding patterns were associated with lower odds for the low trajectory (ref: high). CONCLUSION: Infant feeding patterns are associated with early BMI trajectories with specific ethnic differences. Future studies should take the role of ethnicity into account in the associations between infant feeding and growth.

Growth and Clinical Variables in Nitrogen-Restricted Piglets Fed an Adjusted Essential Amino Acid Mix: Effects of Partially Intact Protein-Based Diets.

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 × Yorkshire × 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 (∼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 < 0.05, relative to O-75). 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.

Growth and Clinical Variables in Nitrogen-Restricted Piglets Fed an Adjusted Essential Amino Acid Mix: Effects of Free Amino Acid-Based Diets.

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 × Yorkshire × 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 ∼15 g · kg-1 · d-1), whereas ST-50 had a markedly lower weight gain relative to all groups (all P < 0.05). Relative to ST-100, all groups with reduced AA intake showed ∼16% reduction in plasma albumin and ∼30% reduction in plasma urea (both P < 0.05). The absolute leucine oxidation rate was ∼30% lower for O-80 than for ST-100 piglets (P < 0.05). 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.

Impact of Early Infant Growth, Duration of Breastfeeding and Maternal Factors on Total Body Fat Mass and Visceral Fat at 3 and 6 Months of Age.

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.

Associations of Infant Subcutaneous Fat Mass with Total and Abdominal Fat Mass at School-Age: The Generation R Study.

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/height(3) ), 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.

Partly Fermented Infant Formulae With Specific Oligosaccharides Support Adequate Infant Growth and Are Well-Tolerated.

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.

Serum Visfatin and Leptin in Relation to Childhood Adiposity and Body Fat Distribution: The PIAMA Birth Cohort Study.

BACKGROUND/AIMS: Visfatin has been suggested as a marker of visceral adiposity. We hypothesized that visfatin, but not leptin, would be specifically associated with visceral adiposity. We investigated the relation of serum visfatin and leptin with measures of adiposity and body fat distribution in children. METHODS: Serum leptin and visfatin levels were measured in 1,022 12-year-old children participating in the PIAMA birth cohort. BMI, waist, hip and upper arm circumference were available for all children. Multiple linear regression analyses were conducted to study associations between different anthropometric indices and log serum visfatin and leptin levels. RESULTS: All anthropometric indices showed positive and strong dose-response relationships with serum leptin. Visfatin was increased only in children with a high waist-to-hip ratio. The effect size was small compared to those observed for leptin and the association was present in overweight children (n = 133) but not in normal weight children. CONCLUSION: Serum leptin levels strongly increased with increasing adiposity, but were not related to a specific type of fat distribution. In contrast, serum visfatin was associated only with high waist-to-hip ratio in overweight children. Based on our study we would currently not recommend visfatin as a marker of visceral adiposity in the general population of children.

Effect of dietary lipid structure in early postnatal life on mouse adipose tissue development and function in adulthood.

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.

Infant fat mass and later child and adolescent health outcomes: a systematic review.

OBJECTIVE: Obesity and excess adiposity are leading causes of metabolic and cardiovascular morbidity and mortality. Early identification of individuals at risk is key for preventive strategies. We examined the relationship between infant body composition (0-2 years of age) and later (>2 years) health outcomes using a systematic review. DESIGN: We preregistered the study on PROSPERO (ID 288013) and searched Embase, PubMed and Cochrane databases for English language publications using the Medical Subject Headings (MeSH) terms 'infant' and 'body composition' and 'risk' between January 1946 and February 2022. We included studies which assessed infant body composition using predetermined in vivo methods other than body mass index (BMI). RESULTS: We identified 6015 articles. After abstract screening to assess eligibility, we reviewed 130 full text publications. 30 were included in the final assessment and narrative synthesis. Meta-analysis was not possible due to heterogeneity of results. All 30 studies were of high quality and reported associations between infant body composition and 19 different health outcomes after 2 years of age. Outcome measurements ranged from 2 years to 16 years. The strongest associations were found between infant fat mass and later fat mass (7 studies), and later BMI (5 studies). For 11 of the outcomes assessed, there was no relationship to infant adiposity detected. CONCLUSIONS: Current evidence, from a small number of studies, suggests a positive association between infant adiposity and future adiposity or BMI, but the validity of infant body composition as a biomarker of future health remains inconclusive. Carefully designed, standardised studies are required to identify the value of infant body composition for predicting later health. TRIAL REGISTRATION: PROSPERO: 288013.

Infant Milk Formula with Large, Milk Phospholipid-coated Lipid Droplets Enriched in Dairy Lipids Affects Body Mass Index Trajectories and Blood Pressure at School Age: Follow-up of a Randomized Controlled Trial.

BACKGROUND: Human milk comprises large fat globules enveloped by a native phospholipid membrane, whereas infant formulas contain small, protein-coated lipid droplets. Previous experimental studies indicated that mimicking the architecture of human milk lipid droplets in infant milk formula (IMF) alters lipid metabolism with lasting beneficial impact on later metabolic health. OBJECTIVES: To evaluate in a follow-up (FU) study of a randomized, controlled trial whether a Concept IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids beneficially impacts long-term body mass index (BMI in kg/m2) trajectories and blood pressure at school age. METHODS: Fully formula-fed infants were randomly assigned to Concept IMF (n = 115) or Control IMF with conventional, small lipid droplets containing vegetable oils (n = 108) for the first 4 mo of age. A group of 88 breastfed infants served as a reference. During FU, anthropometrics were collected at 1, 3, 4, and 5 y of age, and blood pressure only at the last visit. RESULTS: Compared to Control, Concept group children had consistently lower mean BMI values during FU, with the most marked difference at 1 y of age (difference in means -0.71 kg/m2, 95% confidence interval (CI): -1.13, -0.29; P = 0.001); mean values were close to the breastfed group (P > 0.05). Contrary, the mean BMI values of the Control group were higher compared with the breastfed group during FU from 1 to 5 y of age (differences in means from 0.59 to 0.96 kg/m2, respectively; P < 0.02). At 5 y of age, the Concept group had a lower mean diastolic and arterial blood pressure compared with the Control group; -4.3mm Hg (95% CI: -7.3, -1.3; P = 0.005) and -3.7 mm Hg (95% CI: -6.5, -0.9; P = 0.01), respectively. CONCLUSIONS: Early life feeding of an innovative IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids results in a BMI trajectory closer to breastfed infants and a lower blood pressure at school age. This trial was registered at the Dutch Trial Register as NTR3683 and NTR5538.

Complementary Feeding Practices among Young Children in China, India, and Indonesia: A Narrative Review.

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.

An Infant Formula with Large, Milk Phospholipid-Coated Lipid Droplets Supports Adequate Growth and Is Well-Tolerated in Healthy, Term Asian Infants: A Randomized, Controlled Double-Blind Clinical Trial.

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.

An Observational Cohort Study and Nested Randomized Controlled Trial on Nutrition and Growth Outcomes in Moderate and Late Preterm Infants (FLAMINGO).

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.

Infant Feeding and Ethnic Differences in Body Mass Index during Childhood: A Prospective Study.

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.

Dietary Patterns in Early Childhood and the Risk of Childhood Overweight: The GECKO Drenthe Birth Cohort.

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 < 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.

Evaluation of an Infant Formula with Large, Milk-Phospholipid Coated Lipid Droplets on Long-Term Growth and Development of Singaporean Infants: Randomized Controlled Trial Protocol.

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.

A partially hydrolyzed formula with synbiotics supports adequate growth and is well tolerated in healthy, Chinese term infants: A double-blind, randomized controlled trial.

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.