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.

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.

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

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.

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.

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.

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.

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.

Longitudinal telomere length and body composition in healthy term-born infants during the first two years of life.

OBJECTIVE: Leukocyte telomere length (LTL) is one of the markers of biological aging as shortening occurs over time. Shorter LTL has been associated with adiposity and a higher risk of cardiovascular diseases. The objective was to assess LTL and LTL shortening during the first 2 years of life in healthy, term-born infants and to associate LTL shortening with potential stressors and body composition. STUDY DESIGN: In 145 healthy, term-born infants (85 boys), we measured LTL in blood, expressed as telomere to single-gene copy ratio (T/S ratio), at 3 months and 2 years by quantitative PCR technique. Fat mass (FM) was assessed longitudinally by PEAPOD, DXA, and abdominal FM by ultrasound. RESULTS: LTL decreased by 8.5% from 3 months to 2 years (T/S ratio 4.10 vs 3.75, p<0.001). LTL shortening from 3 months to 2 years associated with FM%(R = 0.254), FM index(R = 0.243) and visceral FM(R = 0.287) at 2 years. LTL shortening tended to associate with gain in FM% from 3 to 6 months (R = 0.155, p = 0.11), in the critical window for adiposity programming. There was a trend to a shorter LTL in boys at 2 years(p = 0.056). LTL shortening from 3 months to 2 years was not different between sexes. CONCLUSION: We present longitudinal LTL values and show that LTL shortens considerably (8.5%) during the first 2 years of life. LTL shortening during first 2 years of life was associated with FM%, FMI and visceral FM at age 2 years, suggesting that adverse adiposity programming in early life could contribute to more LTL shortening.

Early weight gain trajectories and body composition in infancy in infants born very preterm.

BACKGROUND: Concerns are raised about the influence of rapid growth on excessive fat mass (FM) gain in early life and later cardiometabolic health of infants born preterm. OBJECTIVES: To study the association between postnatal weight gain trajectories and body composition in infancy in infants born very preterm. METHODS: In infants born <30 weeks gestation, we evaluated associations between weight Z-score trajectories for three consecutive timeframes (NICU stay, level-II hospital stay and at home) and body composition, measured at 2 and 6 months corrected age by air-displacement plethysmography. RESULTS: Of 120 infants included, median gestational age at birth was 27+5 (interquartile range 26+1 ;28+5 ) and birth weight 1015 g (801;1250). The majority of infants did not make up for their initial loss of weight Z-score, but growth and later body composition were within term reference values. Weight gain during NICU stay was not associated with fat mass (absolute, %FM or FM index) in infancy. Weight gain during NICU and level II hospital stay was weakly associated with higher absolute lean mass (LM), but not after adjustment for length (LM index). Weight gain in the level-II hospital was positively associated with fat mass parameters at 2 months but not at 6 months. Strongest associations were found between weight gain at home and body composition (at both time points), especially fat mass. CONCLUSIONS: Weight gain in different timeframes after preterm birth is associated with distinct parameters of body composition in infancy, with weight gain at home being most strongly related to fat mass.

Longitudinal human milk macronutrients, body composition and infant appetite during early life.

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 (ß 0.387 and 0.040, resp.) and gain in FM% from 1 to 6 months (ß 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 (ß 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.

Association Between Fat Mass in Early Life and Later Fat Mass Trajectories.

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% (ß, 0.044; 95% CI, 0.017-0.068), FMI (ß, 0.061; 95% CI, 0.032-0.091), and abdominal subcutaneous FM (ß, 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.

Longitudinal body composition assessment in healthy term-born infants until 2 years of age using ADP and DXA with vacuum cushion.

OBJECTIVES: Accelerated gain in fat mass (FM) in early life increases the risk for adult diseases. Longitudinal data on infant body composition are crucial for clinical and research use, but very difficult to obtain due to limited measurement tools and unsuccessful measurements between age 6-24 months. We compared FM% by dual-energy X-ray absorptiometry (DXA), with cushion to reduce movement artifacts, with FM% by air-displacement plethysmography (ADP) and evaluated the reliability of this cushion during DXA by comparing FM% with and without cushion. Subsequently, we constructed sex-specific longitudinal body composition charts from 1-24 months. METHODS: In 692 healthy, term-born infants (Sophia Pluto Cohort), FM% was measured by ADP from 1-6 months and DXA with cushion from 6-24 months. At 6 months, FM% was measured in triplicate by ADP and DXA with and without cushion(n = 278), later on in smaller numbers. RESULTS: At 6 months, mean FM% by DXA with cushion was 24.1 and by ADP 25.0, mean difference of 0.9% (Bland-Altman p = 0.321, no proportional bias). Mean FM% by DXA without cushion was 12.5% higher compared to ADP (Bland-Altman p < 0.001). DXA without cushion showed higher mean FM% compared to DXA with cushion (+11.6%, p < 0.001) at 6 months. Longitudinally, FM% increased between 1-6 months and decreased from 6-24 months(both p < 0.001). CONCLUSIONS: In infants, DXA scan with cushion limits movement artifacts and shows reliable FM%, comparable to ADP. This allowed us to construct longitudinal body composition charts until 24 months. Our study shows that FM% increases from 1-6 months and gradually declines until 24 months.

[A boy with a painful tumour of his skull]. / Een jongen met een pijnlijke zwelling op zijn hoofd.

A 12-year-old boy presented with an increasing painful swelling of the skull. Physical examination revealed in the left parieto-occipital region a skin-coloured solid mass of 2-3 cm in diameter. The X-ray of the skull was highly suspicious for Langerhans cell histiocytosis. Histopathology of a biopsy of the lesion confirmed the diagnosis.