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Importance: Poly- and perfluoroalkyl substances (PFASs) are nondegradable, man-made chemicals. They accumulate in humans with potential harmful effects, especially in susceptible periods of human development, such as the first months of life. We found that, in our cohort, exclusively breastfed (EBF) infants had 3 times higher PFAS plasma levels compared with exclusively formula-fed (EFF) infants at the age of 3 months. Thus, PFASs could potentially reduce the health benefits of breastfeeding., Objective: We investigated the associations between PFAS levels at the age of 3 months and accelerated gain in fat mass during the first 6 months of life, body composition at 2 years, and whether these associations differ between EBF and EFF infants., Setting: In 372 healthy term-born infants, we longitudinally assessed anthropometrics, body composition (by air-displacement plethysmography and dual-energy X-ray absorptiometry), and visceral and subcutaneous fat (by abdominal ultrasound) until the age of 2 years., Measures: The plasma levels of 5 individual PFASs were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry at the age of 3 months., Main Outcomes: We studied associations between PFAS levels and outcomes using multiple regression analyses., Results: Higher early life plasma perfluorooctanoic acid and total PFAS levels were associated with an accelerated gain in fat mass percentage [FM%; >0.67 SD score (SDS)] during the first 6 months of life. Higher early life PFAS levels were associated with lower fat-free mass (FFM) SDS at the age of 2 years, but not with total FM% SDS at 2 years. Furthermore, we found opposite effects of PFAS levels (negative) and exclusive breastfeeding (positive) at the age of 3 months on FFM SDS at 2 years., Conclusion: Higher PFAS levels in early life are associated with accelerated gains in FM% during the first 6 months of life and with lower FFM SDS at the age of 2 years, which have been associated with an unfavorable body composition and metabolic profile later in life. Our findings warrant further research with longer follow-up times., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Background & Objectives: Early life is a critical window for adiposity programming and metabolic profile may affect this programming. We investigated if plasma metabolites at age 3 months were associated with fat mass, fat free mass and abdominal subcutaneous and visceral fat outcomes at age 2 years in a cohort of healthy infants and if these associations were different between infants receiving exclusive breastfeeding (EBF) and those with exclusive formula feeding (EFF)., Methods: In 318 healthy term-born infants, we determined body composition by Dual Energy X-ray absorptiometry (DXA) and visceral fat by abdominal ultrasound at 2 age years. High-throughput metabolic profiling was performed on blood samples collected at age 3 months. Tertiles were generated for each body composition outcome and differences in plasma metabolite levels at age 3 months between infants with high and low body composition outcomes at age 2 years were evaluated in general, as well as separately in EBF- and EFF-infants., Results: Distinct plasma metabolite variables identified at age 3 months were associated with body composition at 2 years. These metabolites included several classes of lyso-phospholipids. Associations between the metabolites at age 3 months and fat mass index, fat mass percentage, fat free mass index and visceral fat at 2 years were predominantly found in EBF-infants., Conclusion: Associations between plasma metabolite levels at age 3 months and high body fat mass at 2 years depend on infant feeding type. These findings contribute to our insight into the importance of infant feeding on adiposity programming in early life., Competing Interests: Conflict of interest None of the authors declare conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Early life is a critical window for adiposity programming. Metabolic-profile in early life may reflect this programming and correlate with later life adiposity. We investigated if metabolic-profile at 3 months of age is predictive for body composition at 2 years and if there are differences between boys and girls and between infant feeding types., Methods: In 318 healthy term-born infants, we determined body composition with skinfold measurements and abdominal ultrasound at 3 months and 2 years of age. High-throughput-metabolic-profiling was performed on 3-month-blood-samples. Using random-forest-machine-learning-models, we studied if the metabolic-profile at 3 months can predict body composition outcomes at 2 years of age., Results: Plasma metabolite-profile at 3 months was found to predict body composition at 2 years, based on truncal: peripheral-fat-skinfold-ratio (T:P-ratio), with a predictive value of 75.8%, sensitivity of 100% and specificity of 50%. Predictive value was higher in boys (Q 2  = 0.322) than girls (Q 2  = 0.117). Of the 15 metabolite variables most strongly associated with T:P-ratio, 11 were also associated with visceral fat at 2 years of age., Conclusion: Several plasma metabolites (LysoPC(22:2), dimethylarginine and others) at 3 months associate with body composition outcome at 2 years. These results highlight the importance of the first months of life for adiposity programming., (© 2021 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

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., (© 2021. The Author(s).)

Importance: A rapid increase in weight in early life is associated with an increased risk for adiposity and cardiovascular diseases at age 21 years and beyond. However, data on associations of early change in measured fat mass percentage (FM%) with adiposity development are lacking., Objective: To investigate whether a rapid increase in FM% in the first months of life is associated with higher trajectories of body fat mass during the first 2 years of life., Design, Setting, and Participants: A birth cohort consisting of 401 healthy, term-born infants of the Sophia Pluto Cohort Study was analyzed. Participants were born between January 7, 2013, and October 13, 2017. Data were analyzed from February 1, 2020, to May 20, 2020., Interventions: Longitudinal measurements of FM% by air-displacement plethysmography and dual-energy x-ray absorptiometry, and abdominal subcutaneous and visceral fat mass (FM) by ultrasonography in infants at ages 1, 3, 6, 9, 12, 18, and 24 months. A rapid increase in FM% was defined as a change in FM% of greater than 0.67 standard deviation scores (SDS)., Main Outcomes and Measures: Associations between change in FM% SDS in the first and second 6-month period of life with body composition at age 2 years and whether a rapid increase in FM% SDS during the first 6 months leads to higher body FM and abdominal FM trajectories during the first 2 years of life., Results: Of the 401 participants, 228 infants (57%) were male. Change in FM% SDS from age 1 to 6 months was positively associated with FM% (β, 0.044; 95% CI, 0.017-0.068), FMI (β, 0.061; 95% CI, 0.032-0.091), and abdominal subcutaneous FM (β, 0.064; 95% CI, 0.036-0.092) at age 2 years, but not with visceral FM. In contrast, no associations were found within the 6- to 12-month period. Infants with a rapid increase in FM% of greater than 0.67 SDS in the first 6 months of life had higher trajectories of FM%, FM index, and subcutaneous FM during the first 2 years of life (all P≤.001), but visceral FM index was not significantly different compared with infants without a rapid increase (P = .12)., Conclusions and Relevance: In this study, only the change in FM% in the first 6 months of life was associated with more adiposity at age 2 years. Infants with a rapid increase in FM% had higher trajectories of FM% and FM index during the first 2 years of life. These findings appear to support a critical window for adiposity programming in early life.

Introduction: 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 < 0.001, p = 0.098, respectively). Girls had higher FM% than boys at 1 and 6 months (p = 0.05, p < 0.001 respectively) and less FFM than boys at 1, 3 and 6 months (p = 0.02, p = 0.02, p < 0.001, respectively). There was a large variation in FM% at all ages even between infants with similar weight standard deviation scores. Visceral fat and abdominal subcutaneous fat did not change between 3 and 6 months. FM% was highly correlated with abdominal subcutaneous fat but not with visceral fat., Conclusion: Changes in FM% occur mainly in the first 3 months of life, and FM%, visceral and abdominal subcutaneous fat do not change between 3 and 6 months, supporting the concept of a critical window for adiposity development in the first three months of life. In addition, our study provides longitudinal reference data of FM%, FFM, visceral fat and abdominal subcutaneous fat during the first 6 months of life., (© 2016 World Obesity Federation.)

Background: The predisposition for obesity is suggested to originate in the prenatal period. Prenatal markers are needed to identify foetuses at risk for neonatal adiposity, as early marker of childhood obesity., Objective: The aim of this study is to assess the association between foetal fractional thigh volume (TVol) and neonatal percentage fat mass from mid-gestation onward., Methods: In this perinatal cohort study, singleton pregnancies with term born infants were included. Foetal TVol was measured on three-dimensional ultrasound scans (3D US) obtained at 22, 26 and 32 weeks of gestation. Neonatal body composition measurement (percentage body fat (%BF)) was planned between 42 +0 and 42 +6 -week postmenstrual age. Cross-sectional and longitudinal linear regression analyses were performed., Results: Seventy-nine mother-child pairs were included. Median (interquartile range) TVol increased from 7.6 (7.1; 8.5) cm 3 at 22 weeks to 36.5 (33.8; 40.9) cm 3 at 32 weeks. Median neonatal %BF was 14.3% (11.7; 17.0). TVol at 22 weeks (β = -1.58, 95% CI -2.45; -0.70, explained variance 31%) was negatively associated with %BF, but no associations were found at 26 and 32 weeks of gestation. TVol growth between 22 and 32 weeks of gestation (explained variance 18%) was also statistically significantly negatively associated with %BF., Conclusions: Foetal TVol is a promising 3D US marker for prediction of neonatal adiposity from mid-gestation onward., (© 2017 World Obesity Federation.)

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., (© 2017 S. Karger AG, Basel.)