Fat mass and fat-free mass track from infancy to childhood:New insights in body composition programming in early life

OBJECTIVE: Early life is a critical window for adiposity programming. This study investigated whether fat mass percentage (FM%), fat mass index (FMI), abdominal fat, and fat‐free mass (FFM) in early life track into childhood and whether there are sex differences and differences between infant feeding types. METHODS: Detailed body composition was longitudinally measured by air‐displacement plethysmography, dual‐energy x‐ray absorptiometry, and abdominal ultrasound in 224 healthy, term‐born children. Measurements were divided into tertiles. Odds ratios (OR) of remaining in the highest tertile of FM%, FMI, abdominal subcutaneous and visceral fat, and FFM index (FFMI) were calculated from early life to age 4 years. RESULTS: High FM% and FMI tracked from age 3 and 6 months to age 4 years (OR = 4.34 [p = 0.002] and OR = 6.54 [p < 0.001]). High subcutaneous abdominal fat tracked from age 6 months to age 4 years (OR = 2.30 [p = 0.012]). High FFMI tracked from age 1, 3, and 6 months to age 4 years (OR = 4.16 [p = 0.005], 3.71 [p = 0.004], and 3.36 [p = 0.019]). In non‐exclusively breastfed infants, high FM% tracked from early life to age 4 years, whereas this was not the case for exclusively breastfed infants. There was no tracking in visceral fat or sex differences. CONCLUSIONS: Infants with high FM%, FMI, subcutaneous abdominal fat, and FFMI in early life are likely to remain in the highest tertile at age 4 years. Exclusive breastfeeding for 3 months is potentially protective against having high FM% at age 4 years

Prenatal and Neonatal Characteristics of Children with Prader-Willi Syndrome

Objective: Prader-Willi syndrome (PWS) is a rare genetic syndrome with a wide spectrum of clinical features in early life. Late diagnoses are still present. We characterized the perinatal and neonatal features of PWS, compared them with those of healthy newborns and assessed the prenatal and neonatal differences between the genetic subtypes. Design: A cohort study in children with PWS. The prevalence of variables was compared with healthy infants (PLUTO cohort) and to population statistics from literature. Patients: 244 infants with PWS and 365 healthy infants. Measurements: Data on prenatal and neonatal variables in both cohorts. Population statistics were collected through an extensive literature search. Results: A higher prevalence of maternal age >35 years was found in PWS compared to healthy infants and population statistics, and the highest maternal age was found in the mUPD group. Higher prevalence of polyhydramnios, caesarean section, labour induction and breech presentation, and lower birth weight SDS was found in PWS compared to healthy infants. High prevalences of decreased fetal movements (78.5%), hypotonia (100%), cryptorchism (95.9%) and poor sucking/tube feeding (93.9%) were found in PWS. Conclusions: This study presents an overview of prenatal and neonatal variables in infants with PWS compared to healthy infants. Our findings may increase clinical awareness of the early perinatal signs of PWS by obstetricians, neonatologists and all those involved in infant care, enabling early diagnosis and start of multidisciplinary treatment

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00394-021-02533-z

Metabolomics in early life and the association with body composition at age 2 years

Funder: Danone Nutricia Research; Id: http://dx.doi.org/10.13039/100015766Summary: 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 (Q2 = 0.322) than girls (Q2 = 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

Early life poly- and perfluoroalkyl substance levels and adiposity in the first 2 years of life

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%; &gt;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.</p

Body composition and bone mineral density by Dual Energy X-ray Absorptiometry: Reference values for young children

Background & aims: Childhood obesity is a global public health threat, with an alarming rise in incidence. Obesity at young age has short-term and long-term morbidity. It is, therefore, important to accurately assess body composition throughout infancy and childhood to identify excess adiposity. However, reference values for age 2–5 years, needed to interpret measurements and identify young children at risk, are lacking. Our primary objective was to fill the current gap in reference values by constructing sex-specific body composition reference values and charts for fat mass (FM), fat mass percentage (FM%), fat mass index (FMI), lean body mass (LBM), lean body mass index (LBMI) and total body less head bone mineral density (BMDTBLH) for children aged 2–5 years using Dual-Energy X-ray Absorptiometry (DXA). Methods: We performed 599 accurate DXA-measurements in 340 term-born children aged 2–5 years, using Lunar Prodigy with Encore software (V14.1). Using GAMLSS, sex-specific reference values and charts were created for FM, FM%, FMI, LBM, LBMI and BMDTBLH. Results: Sex-specific body composition reference values and charts for age 2–5 years were constructed. In boys and girls, FM and LBM increased from age 2–5 years (all p ≤ 0.001), but body size-corrected FM% and FMI decreased (all p ≤ 0.023). LBMI remained similar between 2 and 5 years of age. Girls had higher FM, FM% and FMI and lower LBM and LBMI compared to boys. BMC and BMDTBLH increased with age between 2 and 5 years of age (all p < 0.001) and were similar for boys and girls. Conclusions: We present sex-specific reference values and charts for body composition and total body bone mineral density measured by DXA, based on a large cohort of healthy children aged 2–5 years. These longitudinal references can be used for clinical practice and research purposes to monitor body composition and bone mineral density development and identify children at risk for excess adiposity

Body Composition Assessment by Air-Displacement Plethysmography Compared to Dual-Energy X-ray Absorptiometry in Full-Term and Preterm Aged Three to Five Years

It is important to monitor body composition longitudinally, especially in children with atypical body composition trajectories. Dual-energy X-ray absorptiometry (DXA) can be used and reference values are available. Air-displacement plethysmography (ADP) is a relatively new technique, but reference values are lacking. In addition, estimates of fat-free mass density (Dffm), needed in ADP calculations, are based on children aged >8 years and may not be valid for younger children. We, therefore, aimed to investigate whether DXA and ADP results were comparable in young children aged 3–5 years, either born full-term or preterm, and if Dffm estimates in the ADP algorithm could be improved. In 154 healthy children born full-term and 67 born < 30 weeks of gestation, aged 3–5 years, body composition was measured using ADP (BODPOD, with default Lohman Dffm estimates) and DXA (Lunar Prodigy). We compared fat mass (FM), fat mass percentage (FM%) and fat-free mass (FFM), between ADP and DXA using Bland–Altman analyses, in both groups. Using a 3-compartment model as reference method, we revised the Dffm estimates for ADP. In full-term-born children, Bland–Altman analyses showed considerable fixed and proportional bias for FM, FM%, and FFM. After revising the Dffm estimates, agreement between ADP and DXA improved, with mean differences (LoA) for FM, FM%, and FFM of −0.67 kg (−2.38; 1.04), −3.54% (−13.44; 6.36), and 0.5 kg (−1.30; 2.30), respectively, but a small fixed and proportional bias remained. The differences between ADP and DXA were larger in preterm-born children, even after revising Dffm estimates. So, despite revised and improved sex and age-specific Dffm estimates, results of ADP and DXA remained not comparable and should not be used interchangeably in the longitudinal assessment of body composition in children aged 3–5 years, and especially not in very preterm-born children of that age

Skinfold-based-equations to assess longitudinal body composition in children from birth to age 5 years

Background & aims: In order to identify children at risk for excess adiposity, it is important to determine body composition longitudinally throughout childhood. However, most frequently used techniques in research are expensive and time-consuming and, therefore, not feasible for use in general clinical practice. Skinfold measurements can be used as proxy for adiposity, but current anthropometry-based-equations have random and systematic errors, especially when used longitudinally in pre-pubertal children. We developed and validated skinfold-based-equations to estimate total fat mass (FM) longitudinally in children aged 0–5 years. Methods: This study was embedded in the Sophia Pluto study, a prospective birth cohort. In 998 healthy term-born children, we longitudinally measured anthropometrics, including skinfolds and determined FM using Air Displacement Plethysmography (ADP) by PEA POD and Dual energy X-ray Absorptiometry (DXA) from birth to age 5 years. Of each child one random measurement was used in the determination cohort, others for validation. Linear regression was used to determine the best fitting FM-prediction model based on anthropometric measurements using ADP and DXA as reference methods. For validation, we used calibration plots to determine predictive value and agreement between measured and predicted FM. Results: Three skinfold-based-equations were developed for adjoined age ranges (0–6 months, 6–24 months and 2–5 years), based on FM-trajectories. Validation of these prediction equations showed significant correlations between measured and predicted FM (R: 0.921, 0.779 and 0.893, respectively) and good agreement with small mean prediction errors of 1, 24 and −96 g, respectively. Conclusions: We developed and validated reliable skinfold-based-equations which may be used longitudinally from birth to age 5 years in general practice and large epidemiological studies

Longitudinal poly- and perfluoroalkyl substances (PFAS) levels in Dutch infants

Background and aims: Per- and polyfluoroalkyl substances (PFAS) are a potential hazard for public health. These man-made-chemicals are non-degradable with an elimination half-life of multiple years, causing accumulation in the environment and humans. Rodent studies demonstrated that PFAS are harmful, especially when present during the critical window in the first months of life. Because longitudinal data during infancy are limited, we investigated longitudinal plasma levels in infants aged 3 months and 2 years and its most important determinants. Methods: In 369 healthy term-born Dutch infants, we determined plasma PFOS, PFOA, PFHxS, PFNA and PFDA levels at age 3 months and 2 years, using liquid chromatography-electrospray-ionization-tandem-mass-spectrometry (LC-ESI-MS/MS). We studied the associations with maternal and child characteristics by multiple regression models. Results: At age 3 months, median plasma levels of PFOS, PFOA, PFHxS, PFNA and PFDA were 1.48, 2.40, 0.43, 0.23 and 0.07 ng/mL, resp. Levels decreased slightly until age 2 years to 1.30, 1.81, 0.40, 0.21 and 0.08 ng/mL, resp. Maternal age, first born, Caucasian ethnicity and exclusive breastfeeding were associated with higher infant's plasma levels at age 3 months. Levels at 3 months were the most important predictor for PFAS levels at age 2 years. Infants with exclusive breastfeeding during the first 3 months of life (EBF) had 2–3 fold higher levels throughout infancy compared to infants with exclusive formula feeding (EFF), with PFOA levels at 3 months 3.72 ng/mL versus 1.26 ng/mL and at 2 years 3.15 ng/mL versus 1.22 ng/mL, respectively. Conclusion: Plasma PFAS levels decreased only slightly during infancy. Higher levels at age 3 months were found in Caucasian, first-born infants from older mothers and throughout infancy in EBF-infants. Our findings indicate that trans-placental transmission and breastfeeding are the most important determinants of PFAS exposure in early life

Poly- and perfluoroalkyl substances (PFAS) exposure through infant feeding in early life

Background and aims: Per- and polyfluoroalkyl substances (PFAS) are non-degradable, man-made-chemicals with an elimination half-life of multiple years, causing accumulation in the environment and humans with potential harmful effects. However, longitudinal PFAS levels in human milk, daily PFAS intake and the association with infant plasma PFAS levels have never been reported. We investigated longitudinal PFOA and PFOS levels in human milk and the daily PFAS intake through infant feeding in the first 3 months of life, the most important determinants and the correlation with PFAS plasma levels at age 3 months and 2 years. Methods: In 372 healthy term-born Dutch infants, we determined PFOA and PFOS levels in human milk given at age 1 and 3 months, in 6 infant formula brands and in infant plasma at 3 months and 2 years, using liquid-chromatography-electrospray-ionization-tandem-mass-spectrometry(LC-ESI-MS/MS). We studied the associations between daily PFAS intake and predictive characteristics by multiple regression models. Results: PFOA and PFOS levels in human milk decreased between 1 and 3 months after delivery, regardless whether breastfeeding was given exclusively(EBF) or in combination with formula feeding. PFOA and PFOS could not be detected in any formula feeding. Daily PFAS intake(ng/kg) was highest in EBF-infants. Higher amount of human milk, older maternal age, lower parity and first-time breastfeeding were associated with higher daily intake. Daily PFAS intake in early life was strongly correlated with PFAS plasma levels at age 3 months and 2 years(R = 0.642–0.875, p < 0.001). Conclusions: Human milk contains PFOA and PFOS, in contrast to formula feeding. Daily PFOA and PFOS intake in early life is highest in exclusively breastfed infants and it is highly correlated with infant's plasma levels throughout infancy. Our findings show that breastfeeding is an important PFAS exposure pathway in the first months of life, with unknown but potential adverse effects. Knowing the important health benefits of breastfeeding, our findings warrant more research about the health outcomes in later life