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Childhood obesity is a global health concern affecting over 150 million children worldwide, with projections of a rise to 206 million by 2025. Understanding the mechanisms underlying this epidemic is crucial for developing effective interventions. In this study, we investigated circulating levels of Growth Differentiation Factor 10 (GDF10), a novel regulator of adipogenesis. Previous studies report diminished circulating GDF10 levels contribute to obesity and hepatic steatosis in mice. To further understand the role of plasma GDF10 in childhood obesity, a prospective case-control study was conducted. Using an enzyme-linked immunosorbent assay, plasma GDF10 levels were measured in children aged 5-17 years of age with normal (n = 36) and increased (n = 56) body mass index (BMI). Subsequently, plasma GDF10 levels were compared to various cardio-metabolic parameters. Children with increased BMI exhibit significantly lower levels of plasma GDF10 compared to children with normal BMI (p < 0.05). This study not only supports previous mouse data but is the first to report that lower levels of GDF10 is associated with childhood obesity, providing an important human connection for the relevance of GDF10 in obesity. Furthermore, this study revealed a significant correlation between low plasma GDF10 levels and elevated LDL-cholesterol and total cholesterol levels dependent on BMI (95% CI, p < 0.05). This study supports the hypothesis that children with obesity display lower plasma levels of GDF10, which correlates with elevated cholesterol levels. These insights shed light on potential mechanisms contributing to childhood obesity and may lead to future therapeutic interventions targeting GDF10 to mitigate adverse effects of adipogenesis in cardiometabolic health., (© 2024. The Author(s).)

Background: Studies investigating neonatal outcomes following intrapartum antibiotic exposure show conflicting results., Methods: Data were collected prospectively in pregnancy to 1-year-of-age, from 212 mother-infant pairs. Adjusted multivariable regression models estimated relationships following exposure to intrapartum antibiotics among vaginally-born, full-term infants and outcomes related to growth, atopic disease, gastrointestinal symptoms, and sleep at 1-year., Results: Intrapartum antibiotic exposure (n = 40) was not associated with mass, ponderal index, BMI z-score (1- year), lean mass index (5-months) or height. Antibiotic exposure in labour ≥4-h was associated with increase in fat mass index at 5-months (β 0.42 [95% CI: 0.03, 0.80], p = 0.03). Intrapartum antibiotic was associated with atopy in the first year (OR: 2.93 [95% CI: 1.34, 6.43], p = 0.007). Antibiotic exposure during intrapartum or day 1-7 was associated with newborn fungal infection requiring antifungal therapy (OR 3.04 [95% CI: 1.14, 8.10], p = 0.026), and number of fungal infections (IRR: 2.90 [95% CI: 1.02, 8.27], p = 0.046)., Conclusion: Intrapartum and early life exposure to antibiotics were independently associated with measures of growth, atopy, and fungal infections suggesting that intrapartum and early neonatal antibiotics be used prudently following careful risk-benefit analysis., Impact: This prospective study: Shows a shift in fat mass index at 5 months associated with antibiotic administration ≥4 h in labour; an earlier age than previously reported; Shows atopy reported less frequently among those not exposed to intrapartum antibiotics; Supports earlier research of increased likelihood of fungal infection following exposure to intrapartum or early-life antibiotics; Adds to growing evidence that antibiotics used intrapartum and in early neonatal periods influence longer-term outcomes for infants. Suggests that use of intrapartum and early neonatal antibiotics should be used prudently after careful consideration of risk and benefit., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: While the World Health Organization (WHO) developed postnatal growth standards for infants, corresponding body composition data remains scarce. This study explores growth and body composition trajectories in infants meeting the WHO Multicentre Growth Reference Study (MGRS) eligibility criteria., Study Design: Infants enrolled in this longitudinal cohort underwent anthropometric and body composition measurement by air displacement plethysmography (ADP) at 6 weeks, 12 weeks, and 5 months postnatally. Age and sex-specific growth and body composition percentiles were generated using GAMLSS, with extrapolated data at 5 months for those exceeding ADP weight limits. We evaluated which anthropometric measure (body mass index (BMI), weight for length or mid upper arm circumference) was most closely related to adiposity., Results: Of the 225 infants with body composition measures, 187 met the WHO MGRS criteria. Their length and weight curves were comparable with WHO growth curves. Trajectory curves for fat and fat-free mass were developed. Of the anthropometric measures, BMI z score was most closely related to fat mass index z score at all timepoints., Conclusion: This study presents body composition trajectories for infants meeting the WHO growth standard criteria. BMI z score is the best anthropometric metric to estimate adiposity in infants., Impact: While postnatal growth standards derived from the WHO Multicentre Growth Reference Study (MGRS) exist for the routine clinical assessment of infant growth, this study fills the previous gap in the availability of corresponding body composition data for term-born, healthy, breastfed infants meeting the MGRS criteria. Extrapolation was used to obtain body composition values for infants exceeding the weight limit of the ADP device, to avoid construction of biased body composition curves. Sex-specific growth curves for fat mass, fat-free mass, fat mass index, and fat-free mass index are presented for a population meeting the World Health Organization growth standard criteria., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Despite optimized nutrition, preterm-born infants grow slowly and tend to over-accrete body fat. We hypothesize that the premature dissociation of the maternal-placental-fetal unit disrupts the maintenance of physiological endocrine function in the fetus, which has severe consequences for postnatal development. This review highlights the endocrine interactions of the maternal-placental-fetal unit and the early perinatal period in both preterm and term infants. We report on hormonal levels (including tissue, thyroid, adrenal, pancreatic, pituitary, and placental hormones) and nutritional supply and their impact on infant body composition. The data suggest that the premature dissociation of the maternal-placental-fetal unit leads to a clinical picture similar to panhypopituitarism. Further, we describe how the premature withdrawal of the maternal-placental unit, neonatal morbidities, and perinatal stress can cause differences in the levels of growth-promoting hormones, particularly insulin-like growth factors (IGF). In combination with the endocrine disruption that occurs following dissociation of the maternal-placental-fetal unit, the premature adaptation to the extrauterine environment leads to early and fast accretion of fat mass in an immature body. In addition, we report on interventional studies that have aimed to compensate for hormonal deficiencies in infants born preterm through IGF therapy, resulting in improved neonatal morbidity and growth. IMPACT: Preterm birth prematurely dissociates the maternal-placental-fetal unit and disrupts the metabolic-endocrine maintenance of the immature fetus with serious consequences for growth, body composition, and neonatal outcomes. The preterm metabolic-endocrine disruption induces symptoms resembling anterior pituitary failure (panhypopituitarism) with low levels of IGF-1, excessive postnatal fat mass accretion, poor longitudinal growth, and failure to thrive. Appropriate gestational age-adapted nutrition alone seems insufficient for the achievement of optimal growth of preterm infants. Preliminary results from interventional studies show promising effects of early IGF-1 supplementation on postnatal development and neonatal outcomes., (© 2021. The Author(s).)

Background: Grip strength predicts long-term morbidity and mortality in adults. We compared grip strength in adults born with extremely low birth weight (ELBW; under 1 kg) and a normal birth weight control group (NBW) and describe change in grip strength over a 10-year period in a longitudinal cohort study of preterm birth., Methods: Grip strength, body composition, and device-measured physical activity were assessed in 95 mature adults (MA) born ELBW (age 31.6 (1.6) mean (SD) years, 59 females) and 88 born NBW (age 31.9 (1.4) years, 52 females). Regression models were used to examine the effect of perinatal factors, body composition, physical activity, and physical self-efficacy on grip strength., Results: Grip strength was lower in MA born ELBW compared to NBW (31.8 (10.0) vs. 39.8 (11.2) kg; p < 0.001). Birth weight group was associated with grip strength independent of sex, height, and lean mass index, but device-measured physical activity was not. The change in grip strength from mid-20s to MA was similar in ELBW and NBW participants., Discussion: Grip strength in MA born ELBW is low and is similar to a reference group 25-30 years older, suggesting higher risk for cardiovascular and all-cause mortality., Impact: Adults born extremely preterm have reduced grip strength compared to control participants born at full term. Reduced grip strength is a predictor of frailty and increased cardiovascular disease risk. Change in grip strength from age in mid-20s to mid-30s is similar in those born preterm and full-term-born controls. Grip strength is related to lean mass and not to device-measured physical activity-and correlates of grip strength are similar in those born preterm and term-born controls. Grip strength is a simple measure that may provide information about the health of adults born preterm.

Early life microbial colonization and succession is critically important to healthy development with impacts on metabolic and immunologic processes throughout life. A longitudinal prospective cohort was recruited from midwifery practices to include infants born at full term gestation to women with uncomplicated pregnancies. Here we compare bacterial community succession in infants born vaginally, with no exposure to antibiotics (n = 53), with infants who were exposed to intrapartum antibiotic prophylaxis (IAP) for Group B Streptococcus (GBS; n = 14), and infants born by C-section (n = 7). Molecular profiles  of the 16 S rRNA genes indicate that there is a delay in the expansion of Bifidobacterium, which was the dominate infant gut colonizer, over the first 12 weeks and a persistence of Escherichia when IAP for GBS exposure is present during vaginal labour. Longer duration of IAP exposure increased the magnitude of the effect on Bifidobacterium populations, suggesting a longer delay in microbial community maturation. As with prior studies, we found altered gut colonisation following C-section that included a notable lack of Bacteroidetes. This study found that exposure of infants to IAP for GBS during vaginal birth affected aspects of gut microbial ecology that, although dramatic at early time points, disappeared by 12 weeks of age in most infants.

The discovery of brown adipose tissue (BAT) in adults has sparked interest in its role as a therapeutic target in metabolic disorders. Infrared thermography is a promising way to quantify BAT; however, a standardized methodology has not been established. This study aims to establish a standardized and reproducible protocol to measure thermal response to cold in the supraclavicular area using thermographic imaging. In Phase 1, we compared the thermal response to 12 °C cold after acclimation at either 32 °C or room temperature using thermographic imaging. Repeatability of the 32 °C acclimation trial was studied in a second group in Phase 2. Phase 1 included 28 men (mean age 23.9 ± 5.9 y; mean BMI 25.2 ± 3.9 kg/m 2 ) and Phase 2 included 14 men (mean age 20.9 ± 2.4 y; mean BMI 23.6 ± 3.1 kg/m 2 ). The thermal response was greater after 32 °C than after room temperature acclimation (0.22 ± 0.19 vs 0.13 ± 0.17 °C, p = 0.05), was not related to outdoor temperature (r = -0.35, p = 0.07), did not correlate with supraclavicular fat (r = -0.26, p = 0.21) measured with dual-energy x-ray absorptiometry and was repeatable [ICC 0.69 (0.14-0.72)]. Acclimation at 32 °C followed by cold generates a reproducible change in supraclavicular skin temperature measurable by thermal imaging that may be indicative of BAT metabolic activity.

The contribution of polymorphisms associated with adult lipids in early life is unknown. We studied 158 adult lipid polymorphisms in 1440 participants (544 children, 544 mothers and 324 fathers) of the Family Atherosclerosis Monitoring In early life (FAMILY) birth cohort. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) measurements were collected at birth, 3 and 5 years of age. Polymorphisms were genotyped using the Illumina Cardio-Metabochip array. Genotype scores (GS) were calculated for TC, HDL-C, LDL-C and TG. Linear and mixed-effects regressions adjusted for sex, age and population stratification were performed. The GS was associated with LDL-C level at 3 and 5 years (β = 0.017 ± 0.003, P = 2.9 × 10 -8 ; β = 0.020 ± 0.003, P = 5.7 × 10 -9 ) and from birth to 5 years (β = 0.013 ± 0.003, P = 2.6 × 10 -7 ). The GS was associated with TC level at 3 and 5 years (β = 0.009 ± 0.002, P = 9.1 × 10 -7 ; β = 0.009 ± 0.002, P = 7.7 × 10 -6 ). CETP rs3764261 was associated with the HDL-C level from birth to 5 years (β = 0.064 ± 0.014, P =  7.4 × 10 -6 ). AMPD3 rs2923084 was associated with the HDL-C level at 5 years (β = 0.096 ± 0.024, P = 9.7 × 10 -5 ). Known loci associated with blood lipids in adults are associated with TC, LDL-C and HDL-C, but not TG in early life. Genetically predisposed children may benefit from early lipid lowering preventative strategies.

Premature birth in conjunction with extremely low birth weight (<1 kg, ELBW) is associated with insulin resistance and increased cardiometabolic health risk compared to birth at full term with normal birth weight (NBW). However, little is known regarding the biologic mediators of these effects. Abdominal and ectopic lipid accumulation is linked to insulin resistance and metabolic dysfunction, yet whether ELBW survivors are predisposed to aberrant lipid deposition in adulthood is unknown. We used magnetic resonance imaging in a cohort of 16 NBW and 29 ELBW participants to determine if ELBW survivors have differences in pancreatic, hepatic, subcutaneous and visceral fat distribution compared to NBW participants. ELBW individuals had a higher proportion of liver and pancreatic fat compared to NBW subjects (P < 0.05). Abdominal subcutaneous fat, but not visceral fat, area was higher in ELBW survivors compared to NBW individuals. In multivariate analyses, tissue fat measures were most highly related to BMI and sex, but not preterm birth. This work highlights that fat deposition is enhanced in adults born preterm and suggests that ectopic fat accretion driven by their relatively greater adiposity may contribute to the higher rates of metabolic dysfunction seen in ELBW survivors.