Early Childhood Body Mass Index Research Articles

Fetal and Infancy Exposure to Phenols, Parabens, and Phthalates and Anthropometric Measurements up to 36 Months, in the Longitudinal SEPAGES Cohort.

Endocrine-disrupting chemicals may play a role in adiposity development during childhood. Until now literature in this scope suffers from methodologic limitations in exposure assessment using one or few urine samples and missing assessment during the infancy period. We investigated the associations between early-life exposure to quickly metabolized chemicals and post-natal growth, relying on repeated within-subject urine collections over pregnancy and infancy. We studied the associations of four phenols, four parabens, seven phthalates, and one nonphthalate plasticizer from weekly pooled urine samples collected from the mother during second and third trimesters (median 18 and 34 gestational weeks, respectively) and infant at 2 and 12 months of age, and child growth until 36 months. We relied on repeated measures of height, weight and head circumference from study visits and the child health booklet to predict growth outcomes at 3 and 36 months using the Jenss-Bayley nonlinear mixed model. We assessed associations with individual chemicals using adjusted linear regression and mixtures of chemicals using a Bayesian kernel machine regression model. The unipollutant analysis revealed few associations. Bisphenol S (BPS) at second trimester was positively associated with all infant growth parameters at 3 and 36 months, with similar patterns between exposure at third trimester and all infant growth parameters at 3 months. Mono-n-butyl phthalate (MnBP) at 12 months was positively associated with body mass index (BMI), weight, and head circumference at 36 months. Mixture analysis revealed positive associations between exposure at 12 months and BMI and weight at 36 months, with MnBP showing the highest effect size within the mixture. This study suggests that exposure in early infancy may be associated with increased weight and BMI in early childhood, which are risk factors of obesity in later life. Furthermore, this study highlighted the impact of BPS, a compound replacing bisphenol A, which has never been studied in this context. https://doi.org/10.1289/EHP13644.

Associations of early childhood body mass index trajectories with body composition and cardiometabolic markers at age 10 years: the Ethiopian infant anthropometry and body composition (iABC) birth cohort study

BackgroundVariability in body mass index (BMI) (kg/m2) trajectories is associated with body composition and cardiometabolic markers in early childhood, but it is unknown how these associations track to later childhood. ObjectivesWe aimed to assess associations of BMI trajectories from 0 to 5 y with body composition and cardiometabolic markers at 10 y. MethodsIn the Ethiopian infant anthropometry and body composition (iABC) birth cohort, we previously identified 4 distinct BMI trajectories from 0 to 5 y: stable low BMI (19.2%), normal BMI (48.8%), rapid growth to high BMI (17.9%), and slow growth to high BMI (14.1%). At 10 y, we obtained data from 320 children on anthropometry, body composition, abdominal subcutaneous and visceral fat, and cardiometabolic markers. Associations of BMI trajectories and 10-y outcomes were analyzed using multiple linear regression. ResultsCompared with children with the normal BMI trajectory, those with rapid growth to high BMI had 1.7 cm (95% CI: 0.1, 3.3) larger waist circumference and those with slow growth to high had 0.63 kg/m2 (95% CI: 0.09, 1.17) greater fat mass index and 0.19 cm (95% CI: 0.02, 0.37) greater abdominal subcutaneous fat, whereas those with stable low BMI had −0.28 kg/m2 (95% CI: −0.59, 0.03) lower fat-free mass at 10 y. Although the confidence bands were wide and included the null value, children with rapid growth to high BMI trajectory had 48.6% (95% CI: −1.4, 123.8) higher C-peptide concentration and those with slow growth to high BMI had 29.8% (95% CI: −0.8, 69.8) higher insulin and 30.3% (95% CI: −1.1, 71.6) higher homeostasis model assessment of insulin resistance, whereas those with rapid growth to high BMI had −0.23 mmol/L (95% CI: −0.47, 0.02) lower total cholesterol concentration. The trajectories were not associated with abdominal visceral fat, blood pressure, glucose, and other lipids at 10 y. ConclusionsChildren with rapid and slow growth to high BMI trajectories before 5 y tend to show higher measures of adiposity and higher concentrations of markers related to glucose metabolism at 10 y. Clinical Trial RegistryISRCTN46718296 (https://www.isrctn.com/ISRCTN46718296).

Early-childhood body mass index and its association with the COVID-19 pandemic, containment measures and islet autoimmunity in children with increased risk for type 1 diabetes

Aims/hypothesisThe aim of this study was to determine whether BMI in early childhood was affected by the COVID-19 pandemic and containment measures, and whether it was associated with the risk for islet autoimmunity.MethodsBetween February 2018 and May 2023, data on BMI and islet autoimmunity were collected from 1050 children enrolled in the Primary Oral Insulin Trial, aged from 4.0 months to 5.5 years of age. The start of the COVID-19 pandemic was defined as 18 March 2020, and a stringency index was used to assess the stringency of containment measures. Islet autoimmunity was defined as either the development of persistent confirmed multiple islet autoantibodies, or the development of one or more islet autoantibodies and type 1 diabetes. Multivariate linear mixed-effect, linear and logistic regression methods were applied to assess the effect of the COVID-19 pandemic and the stringency index on early-childhood BMI measurements (BMI as a time-varying variable, BMI at 9 months of age and overweight risk at 9 months of age), and Cox proportional hazard models were used to assess the effect of BMI measurements on islet autoimmunity risk.ResultsThe COVID-19 pandemic was associated with increased time-varying BMI (β = 0.39; 95% CI 0.30, 0.47) and overweight risk at 9 months (β = 0.44; 95% CI 0.03, 0.84). During the COVID-19 pandemic, a higher stringency index was positively associated with time-varying BMI (β = 0.02; 95% CI 0.00, 0.04 per 10 units increase), BMI at 9 months (β = 0.13; 95% CI 0.01, 0.25) and overweight risk at 9 months (β = 0.23; 95% CI 0.03, 0.43). A higher age-corrected BMI and overweight risk at 9 months were associated with increased risk for developing islet autoimmunity up to 5.5 years of age (HR 1.16; 95% CI 1.01, 1.32 and HR 1.68, 95% CI 1.00, 2.82, respectively).Conclusions/interpretationEarly-childhood BMI increased during the COVID-19 pandemic, and was influenced by the level of restrictions during the pandemic. Controlling for the COVID-19 pandemic, elevated BMI during early childhood was associated with increased risk for childhood islet autoimmunity in children with genetic susceptibility to type 1 diabetes.Graphical

Early childhood adversity and body mass index in childhood and adolescence: linking registry data on adversities with school health records of 53,401 children from Copenhagen.

We examined whether childhood adversity experienced in early childhood (0-5 years) is related to body mass index (BMI) in childhood (6-7 years) and adolescence (12-15 years). This study combined data from the nationwide register-based DANLIFE study on childhood adversities with data on height and weight of school children in Copenhagen. Data were available for 53,401 children born in Denmark between 1980 and 1996. Children were divided into groups of early childhood adversity by applying group-based multi-trajectory modelling using their yearly count of childhood adversity in three dimensions (i.e., material deprivation, loss or threat of loss, and family dynamics) from 0-5 years. Direct and total associations between the early childhood adversity groups and BMI z-scores in childhood and adolescence were estimated using sex-stratified structural equation models. Five exclusive and exhaustive groups of early childhood adversity were identified, which were characterized by low adversity (51%), moderate material deprivation (30%), high material deprivation (14%), loss or threat of loss (3%) and high adversity (2%). Boys and girls exposed to moderate or high material deprivation and loss or threat of loss had a slightly higher BMI z-score, especially in adolescence, compared with those in the low adversity group, with the strongest association found for girls in the loss or threat of loss group (b (95% CI) = 0.18 (0.10, 0.26)). Additionally, boys in the high adversity group had a slightly lower BMI z-score in childhood than boys in the low adversity group (b (95% CI) = -0.12 (-0.22, -0.02)). Whereas associations with BMI were found for children and adolescents exposed to material deprivation, loss or threat of loss, and high adversity, the effect sizes were generally small. Contrary to prevailing hypotheses, weight changes in childhood is probably not a major explanatory mechanism linking early childhood adversity with later-life morbidity.

Maternal stress and early childhood BMI among US children from the Environmental influences on Child Health Outcomes (ECHO) program.

We aimed to understand the association between maternal stress in the first year of life and childhood body mass index (BMI) from 2 to 4 years of age in a large, prospective United States-based consortium of cohorts. We used data from the Environmental influences on Child Health Outcomes program. The main exposure was maternal stress in the first year of life measured with the Perceived Stress Scale (PSS). The main outcome was the first childhood BMI percentile after age 2 until age 4 years. We used an adjusted linear mixed effects model to examine associations between BMI and PSS quartile. The mean BMI percentile in children was 59.8 (SD 30) measured at 3.0 years (SD 1) on average. In both crude models and models adjusted for maternal BMI, age, race, ethnicity, infant birthweight, and health insurance status, no linear associations were observed between maternal stress and child BMI. Among 1694 maternal-infant dyads, we found no statistically significant relationships between maternal perceived stress in the first year of life and child BMI after 2 through 4 years. Although existing literature suggests relationships between parental stress and childhood BMI, we found no linear associations between maternal stress in the first year of life and childhood BMI at 2-4 years of age among participants in ECHO cohorts. Higher maternal stress was significantly associated with Hispanic ethnicity, Black race, and public health insurance. Our analysis of a large, nationally representative sample challenges assumptions that maternal stress in the first year of life, as measured by a widely used scale, is associated with offspring BMI.

Infant effortful control predicts BMI trajectories from infancy to adolescence.

Effortful control, or the regulation of thoughts and behaviour, is a potential target for preventing childhood obesity. To assess effortful control in infancy through late childhood as a predictor of repeated measures of body mass index (BMI) from infancy through adolescence, and to examine whether sex moderates the associations. Maternal report of offspring effortful control and measurements of child BMI were obtained at 7 and 8 time points respectively from 191 gestational parent/child dyads from infancy through adolescence. General linear mixed models were used. Effortful control at 6 months predicted BMI trajectories from infancy through adolescence, F(5,338) = 2.75, p = 0.03. Further, when effortful control at other timepoints were included in the model, they added no additional explanatory value. Sex moderated the association between 6-month effortful control and BMI, F(4, 338) = 2.59, p = 0.03, with poorer infant effortful control predicting higher BMI in early childhood for girls, and more rapid increases in BMI in early adolescence for boys. Effortful control in infancy was associated with BMI over time. Specifically, poor effortful control during infancy was associated with higher BMI in childhood and adolescence. These findings support the argument that infancy may be a sensitive window for the development of later obesity.

Associations of Gestational Perfluoroalkyl Substances Exposure with Early Childhood BMI -Scores and Risk of Overweight/Obesity: Results from the ECHO Cohorts.

Gestational per- and polyfluoroalkyl substances (PFAS) exposure may be associated with adiposity and increased risk of obesity among children and adolescents. However, results from epidemiological studies evaluating these associations are inconsistent. We estimated the associations of pregnancy PFAS concentrations with child body mass index (BMI) -scores and risk of overweight/obesity in eight U.S. cohorts. We used data from 1,391 mother-child pairs who enrolled in eight Environmental influences on Child Health Outcomes (ECHO) cohorts (enrolled: 1999-2019). We quantified concentrations of seven PFAS in maternal plasma or serum in pregnancy. We measured child weight and height between the ages of 2 and 5 y and calculated age- and sex-specific BMI -scores; 19.6% children had more than one BMI measurement. We estimated covariate-adjusted associations of individual PFAS and their mixture with child BMI -scores and risk of overweight/obesity using linear mixed models, modified Poisson regression models, and Bayesian approaches for mixtures. We explored whether child sex modified these associations. We observed a pattern of subtle positive associations of PFAS concentrations in pregnancy with BMI -scores and risk of overweight/obesity. For instance, each doubling in perfluorohexane sulfonic acid concentrations was associated with higher BMI -scores (; 95% CI: 0.01, 0.12). Each doubling in perfluroundecanoic acid [; 95% CI: 1.04, 1.16] and -methyl perfluorooctane sulfonamido acetic acid (; 95% CI: 1.00, 1.12) was associated with increased risk of overweight/obesity, with some evidence of a monotonic dose-response relation. We observed weaker and more imprecise associations of the PFAS mixture with BMI or risk of overweight/obesity. Associations did not differ by child sex. In eight U.S.-based prospective cohorts, gestational exposure to higher levels of PFAS were associated with slightly higher childhood BMI -score and risk of overweight or obesity. Future studies should examine associations of gestational exposure to PFAS with adiposity and related cardiometabolic consequences in older children. https://doi.org/10.1289/EHP11545.

Invited Perspective: PFAS and the Childhood Obesity Phenotype-Challenges and Opportunities.

Invited Perspective: PFAS and the Childhood Obesity Phenotype-Challenges and Opportunities.

In utero exposure to perfluoroalkyl substances and early childhood BMI trajectories: A mediation analysis with neonatal metabolic profiles

BackgroundIn utero perfluoroalkyl substances (PFAS) exposure has been associated with childhood adiposity, but the mechanisms are poorly known. ObjectiveTo investigate the potential mediating role of neonatal metabolites in the relationship between prenatal PFAS exposure and childhood adiposity trajectories in the first four years of life. MethodsWe analyzed the data for 1671 mother-child pairs from the Shanghai Birth Cohort study. We included those with PFAS exposure information in early pregnancy, neonatal metabolites data and at least three child anthropometric measurements at 6, 12, 24 and/or 48 months. Body mass index (BMI) z-score trajectories were identified using latent class growth mixture modeling. The associations between PFAS concentrations and trajectory classes were assessed using multinomial logistic regression. Screening and penalization-based selection was used to identify neonatal amino acids and acylcarnitines with significant mediation effects. ResultsThree BMI z-score trajectories in early childhood were identified: a persistent increase trajectory (Class 1, 2.2 %), a stable trajectory (Class 2, 66 %), and a transient increase trajectory (Class 3, 32 %). Increased odds of being in Class 1 were observed in association with one log-unit increase in concentrations of perfluorooctane sulfonate (odds ratio [OR], 1.76 [95 % CI, 0.96–3.23], Class 2 as reference; OR, 2.36 [95 % CI, 1.27–4.40], Class 3 as reference), perfluorononanoic acid (OR, 1.90 [95 % CI, 0.97–3.72], Class 2 as reference; OR, 2.23 [95 % CI, 1.12–4.42], Class 3 as reference) and perfluorodecanoic acid (OR, 1.95 [95 % CI, 1.12–3.38], Class 2 as reference; OR, 2.14 [95 % CI, 1.22–3.76], Class 3 as reference). The effect of prenatal PFAS exposure on being in Class 1 was significantly but partly mediated by octanoylcarnitine (2.64 % for perfluorononanoic acid and 3.70 % for sum of 10 PFAS). ConclusionsIn utero PFAS exposure is a risk factor for persistent growth in BMI z-score in early childhood. The alteration of neonatal acylcarnitines suggests a potential molecular pathway.

Prospective Association Patterns for the Physical Activity Intensity Spectrum With Body Mass Index and Lower Body Muscle Strength in Norwegian Children Aged 3–9 Years

Limited evidence exists regarding prospective associations for physical activity (PA) and sedentary time (SED) with body mass index (BMI) and muscle strength in young children. We aimed to determine prospective associations for PA and SED with change in BMI and standing long jump over 2 and 4years in children aged 3-5years at baseline. A sample of 262 Norwegian children (50% girls) was followed from 2015 to 2017 and/or 2019. PA and SED (hip-worn ActiGraph GT3X+) were measured at baseline and BMI and standing long jump at baseline and at follow-ups. Multivariate pattern analysis was used to determine prospective associations between the triaxial PA intensity spectrum (0-99 to ≥15,000 counts per minute) and the change in outcomes. We found significant prospective associations between the PA intensity spectrum and standing long jump at 2- (explained variance = 5.8%-7.7%) and 4-year (explained variance = 4.8%-5.6%) follow-ups. Associations were negative for SED and positive for all PA intensities. We found no associations between PA/SED and BMI. Our findings suggest that PA and SED can predict future lower body muscle strength but not BMI in early childhood.

Maternal obesity, gestational weight gain, and offspring asthma and atopy

BackgroundMaternal obesity may affect offspring asthma and atopic disease risk by altering fetal immune system development. However, few studies evaluate gestational weight gain (GWG). ObjectiveTo evaluate relationships between maternal body mass index (BMI), GWG, and persistent wheeze, eczema, allergy, and asthma risk in offspring through middle childhood. MethodsA total of 5939 children from Upstate KIDS, a population-based longitudinal cohort of children born in upstate New York (2008-2019) were included in the analysis. Persistent wheeze or asthma, eczema, and allergy were maternally reported at multiple study time points throughout early and middle childhood. Poisson regression models with robust SEs were used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for offspring atopic outcomes by maternal prepregnancy BMI and GWG. ResultsPrepregnancy BMI was associated with increased risk of persistent wheeze by 3 years of age even after adjustments for maternal atopy (class I obesity: aRR, 1.58; 95% CI, 1.13-2.20; class II or III obesity: aRR, 1.69; 95% CI, 1.22-2.35). Associations with reported asthma in middle childhood did not reach statistical significance. Furthermore, no associations were found between prepregnancy BMI and atopic outcomes in either early or middle childhood. GWG was not associated with higher risk of early childhood persistent wheeze or middle childhood asthma. ConclusionMaternal prepregnancy BMI was associated with increased risk of offspring wheeze, whereas excessive GWG was generally not associated with childhood asthma or atopy.

Characterization of the genetic architecture of infant and early childhood body mass index.

Early childhood obesity is a growing global concern; however, the role of common genetic variation on infant and child weight development is unclear. Here, we identify 46 loci associated with early childhood body mass index at specific ages, matching different child growth phases, and representing four major trajectory patterns. We perform genome-wide association studies across 12 time points from birth to 8 years in 28,681 children and their parents (27,088 mothers and 26,239 fathers) in the Norwegian Mother, Father and Child Cohort Study. Monogenic obesity genes are overrepresented near identified loci, and several complex association signals near LEPR, GLP1R, PCSK1 and KLF14 point towards a major influence for common variation affecting the leptin-melanocortin system in early life, providing a link to putative treatment strategies. We also demonstrate how different polygenic risk scores transition from birth to adult profiles through early child growth. In conclusion, our results offer a fine-grained characterization of a changing genetic landscape sustaining early childhood growth.

Early childhood body mass index trajectory and overweight/obesity risk differed by maternal weight status.

To evaluate the associations of maternal prepregnancy body mass index (pp-BMI) and gestational weight gain (GWG) with the childhood BMI z-score (BMI-z) trajectories from birth to 2 years old and the risk of overweight/obesity (OWO) at 2 years of age. Mother-child dyads (23,617) were involved in the analysis. They were followed up from early pregnancy to 2 years postpartum with their healthcare data recorded in the Wuhan Maternal and Child Health Management Information System (WMCHMIS). The OWO in children was defined as BMI-z > 1. Linear mixed models (LMM) and unconditional logistic regression were used to evaluate the independent and joint associations of pp-BMI and GWG with the BMI-z trajectory of children per their anthropometric measurements at 0, 1, 3, 6, 9, 12, 18, and 24 months old and the risk of OWO at 2 years of age. Maternal overweight/obesity and excessive GWG independently and jointly increased the risks of their offspring falling into high BMI-z trajectories of birth to 2 years (p < 0.001). In addition, the children whose mothers were overweight/obese before pregnancy and gained excessive weight during pregnancy independently and jointly increased the OWO risk in children at age 2, with adjusted odds ratios (adjOR) of 1.36 (95% CI, 1.22-1.53), 1.28 (95% CI, 1.18-1.39), and 1.76 (95% CI: 1.52-2.03), respectively. Maternal prepregnancy overweight/obesity and excessive GWG can independently and jointly increase the risks of their children falling into high BMI-z trajectories from birth to 2 years of age and becoming overweight/obese at age 2. Maternal overweight/obesity and excessive gestational weight should be the prime targets for early obese prevention efforts.

Inequalities in early childhood body-mass index Z scores in Victoria, Australia: a 15-year observational study

Early childhood overweight and obesity increased substantially in high-income countries throughout the 1980s and 1990s. The flattening or reversal of this trend since the early 2000s might conceal widening inequalities. This study aimed to identify trends in body-mass index Z score (BMIz) among children aged 1-3·5 years in Victoria (Australia), by socioeconomic status and geographical location. This repeated, cross-sectional study used deidentified records of height, weight, and demographic information from electronic databases in the Victorian Maternal and Child Health system. Data from the consultations for children aged 1, 2, and 3·5 years were included in this analysis. We removed duplicate records; records with missing data for sex, age, weight, height, or postcode; and records with postcodes that were outside of Victoria. The coprimary outcomes were trends in mean BMIz (continuous linear models) and prevalence of high BMIz (>+1; generalised linear models), estimated for six independent age-sex groups. Secondary analysis was done for the prevalence of BMIz greater than 2. Effect modification by socioeconomic status and remoteness was evaluated. Electronic data were available for 48 local government areas collected between Jan 1, 2003, and Dec 31, 2017, representing approximately 63% of the Victorian population. Overall, 1 329 520 measurements from 675 991 children were included in the analysis. There were small, significantly decreasing trends in mean BMIz across all six age-sex groups, overall and in major cities. Similar patterns were observed for some subgroups in prevalence of high BMIz. These decreasing trends appear to be partly explained by migration. Conversely, in regional areas the trends in BMIz were consistently increasing in all age-sex groups and across socioeconomic strata, although not all groups were statistically significant. Inequalities in BMIz according to socioeconomic status persisted throughout the study period, such that the children from more advantaged areas had lower mean BMIz. This study showed that at a state level, mean BMIz and prevalence of high BMIz decreased in children aged 1, 2, and 3·5 years in Victoria between 2003 and 2017. We found metropolitan-regional differences to be key source of inequality in early childhood BMIz trends, alongside area-level socioeconomic status. These findings highlight the risk that analysis of overall trends in childhood BMIz might obscure important inequalities according to, for example, remoteness, socioeconomic status, and ethnicity. Future research requires monitoring data with large population samples to adequately examine differences in prevalence and trends between population subgroups. None.

Rapid BMI Increases and Persistent Obesity in Small-for-Gestational-Age Infants.

Purpose: In order to compensate for the early intrauterine growth restriction, small-for-gestational age (SGA) infants have “catch-up growth” after birth. Increased caloric intake has been suggested for SGA infants conventionally. It is important to determine if the early growth rate of body mass index (BMI) is associated with risk of persistent obesity later in life. In this longitudinal cohort study, we assessed the BMI of a large cohort of children who were SGA at birth to determine their risk of persistent obesity at school age (6–7 years) due to excessive weight gain in the first 3 years of life.Methods: We collected the height and weight data of 23,871 SGA babies. A polynomial function was used to fit the BMI-for-age z-score (BAZ) values of 0–6 years old SGA children and interpolate their growth trajectory. In addition, we screened out 6,959 children from 23,871 children to further evaluate the dynamic changes of early childhood BMI. We divided the school-age children into groups as non-obese (BAZ < 2) and obese (BAZ > 2), and determined the association between changes in BMI and school-age obesity.Results: From the perspective of BMI distribution, the interpolated growth trajectory indicated that SGA children reaching overweight status or developing obesity by 3 years of age, continued to have obesity until school age (R2, 0.65; R2, 0.21). The retrospective analysis showed that children who were overweight and had obesity during school age had a high BMI from early age. By analyzing the changes in early BMI, we found that the fastest growth of SGA children occurred in the early infancy before 6 months and they continued to grow rapidly for a period of time. Interestingly, former SGA children who maintained a near overweight (1 < BAZ < 2) status before the age of 2 maintained an appropriate growth rate and usually did not develop obesity.Conclusions: A rapid increase in BMI during early infancy in former SGA newborns leads to a persistent risk of obesity. The energy intake of SGA infants should appropriately meet the infants' growth needs and early BMI changes should be closely monitored for an optimal integrated management.

Associations of prenatal metabolomics profiles with early childhood growth trajectories and obesity risk in African Americans: the CANDLE study.

ObjectivePrenatal metabolomics profiles, providing measures of in utero nutritional and environmental exposures, may improve the prediction of childhood outcomes. We aimed to identify prenatal plasma metabolites associated with early childhood body mass index (BMI) trajectories and overweight/obesity risk in offspring.MethodsThis study included 450 African American mother-child pairs from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study. An untargeted metabolomics analysis was performed on the mothers’ plasma samples collected during the second trimester. The children’s BMI-z-score trajectories from birth to age 4 [rising-high- (9.8%), moderate- (68.2%), and low-BMI (22.0%)] and overweight/obesity status at age 4 were the main outcomes. The least absolute shrinkage and selection operator (LASSO) was used to select the prenatal metabolites associated with childhood outcomes.ResultsThe mothers were 24.5 years old on average at recruitment, 76.4% having education less than 12 years and 80.0% with Medicaid or Medicare. In LASSO, seven and five prenatal metabolites were associated with the BMI-z-score trajectories and overweight/obese at age 4, respectively. These metabolites are mainly from/relevant to the pathways of steroid biosynthesis, amino acid metabolism, vitamin B complex, and xenobiotics metabolism (e.g., caffeine and nicotine). The odds ratios (95% CI) associated with a one SD increase in the prenatal metabolite risk scores (MRSs) constructed from the LASSO-selected metabolites were 2.97 (1.95–4.54) and 2.03 (1.54–2.67) for children being in the rising-high-BMI trajectory group and overweight/obesity at age 4, respectively. The MRSs significantly improved the risk prediction for childhood outcomes beyond traditional prenatal risk factors. The increase (95% CI) in the area under the receiver operating characteristic curves were 0.10 (0.03–0.18) and 0.07 (0.02–0.12) for the rising-high-BMI trajectory (P=0.005) and overweight/obesity at age 4 (P=0.007), respectively.ConclusionsPrenatal metabolomics profiles advanced prediction of early childhood growth trajectories and obesity risk in offspring.

Maternal Oxidative Stress Biomarkers in Pregnancy and Child Growth from Birth to Age 6.

Maternal oxidative stress in pregnancy can arise through a multitude of sources and may have lifelong consequences for the child. Animal studies suggest that prenatal oxidative stress may contribute to metabolic dysfunction and excessive weight gain in the offspring. However, this relationship has been studied minimally in humans. Determine the association between prenatal oxidative stress biomarkers and child weight and body mass index (BMI) z-scores from birth to age 6. Within The Infant Development and the Environment Study (TIDES) prospective pregnancy cohort, we calculated age- and sex-specific Z-scores for child weight and BMI, measured between birth and age 6 (N = 736). Three oxidative stress biomarkers were quantified in third-trimester urine, including 8-iso-prostaglandin F2α (8-iso-PGF2α), its primary metabolite, and prostaglandin F2α (PGF2α). We examined associations between each biomarker and Z-scores using linear regression as well as group-based trajectory modeling. Prenatal 8-iso-PGF2α and its metabolite were associated with lower birth weight and higher weight at age 4. For example, an ln-unit increase in 8-iso-PGF2α was associated with 0.17 SD higher weight at age 4 (95% CI 0.01, 0.33). These biomarkers were also associated with higher BMI at age 4. Finally, within 4 unique weight trajectories (low, normal, high, and low-high), children of mothers with higher 8-iso-PGF2α were 2.56 times more likely (95% CI 1.22, 5.41) to be in the low-high trajectory than children in the normal group. We observed associations between third-trimester oxidative stress and lower birth weight as well as higher early childhood weight and BMI. These findings have important implications for understanding the developmental origins of childhood weight gain and metabolic disease.

Prenatal Stress and Early Childhood Body Mass Index: A Path Analysis Approach.

Stress experienced by mothers during the prenatal period can have negative impacts on offspring development. Elevated BMI in childhood in response to early stress experience is a particularly critical outcome of interest since high BMI in childhood is associated with diabetes, heart disease and stroke in later life. The primary objective of this study was to analyze pathways between prenatal stress and early childhood BMI at 54-months of age and to begin to explore ethnic variations in these pathways. This study used the Growing Up in New Zealand (GUiNZ) dataset, which is a longitudinal, representative birth cohort study that began with recruiting pregnant women in 2009 and 2010 in Auckland, New Zealand. Path analysis modeling was used to explore risk and protective pathways between prenatal maternal stress and early childhood body mass index (BMI) at 54-months of age and differences by ethnicity (n = 5510). Prenatal stress was positively associated with early childhood BMI at 54-months and maternal nutrition behaviors and length of exclusive breastfeeding mediated this direct relationship (χ2 (1) = 0.83, p = 0.36; AIC = 50,496). Mediation and moderation paths varied by ethnicity. These findings contribute to the understanding of the intergenerational transmission of stress with respect to early childhood obesity. Reducing early stress exposure and/or addressing mediating and moderating factors linking stress experience with obesity development may prove to be more effective than attempting to alter health behaviors and trajectories in adulthood.

Associations Between Delivery Mode and Early Childhood Body Mass Index Z-Score Trajectories: A Retrospective Analysis of 2,685 Children From Mothers Aged 18 to 35 Years at Delivery

Objective: To investigate the association between cesarean delivery (CD) and trajectory patterns of age- and sex-specific body mass index (BMI) z-score in early childhood.Methods: A retrospective cohort study was conducted among 2,685 children whose maternal age at the time of birth was between 18 and 35 years, and birth data and anthropometric measurement data during their ages 3–60 months were collected. A group-based trajectory modeling approach was used to identify distinct BMI z-score trajectories, and multinomial logistic regressions were applied to estimate the associations among CD (both elective and non-elective combined), elective and non-selective CD, and BMI z-score trajectory classes.Results: Of the 2,685 participants, 46.5% (N = 1,248) were born by vaginal delivery (VD), 20.7% (N = 556) by elective CD, and 32.8% (N = 881) by non-elective CD. Five BMI z-score trajectory patterns were identified, and they were “increasing from moderate to high” (10.1%, n = 270), “increasing from mild to moderate” (34.2%, n = 919), “increasing from low to high” (10.5%, n = 283), “stable mild” (30.1%, n = 808), and “stable low” (15.1%, n = 405) groups. Compared with children delivered by VD, those who delivered by CD (both elective and non-elective combined), elective CD, and non-elective CD were associated with the “increasing from moderate to high” trajectory [odds ratio (OR) = 1.61, 95% confidence interval (CI): 1.13–2.29; OR = 1.64, 95%CI: 1.06–2.54; and OR = 1.59, 95%CI: 1.05–2.39, respectively] and were also associated with the “increasing from low to high” trajectory (OR = 1.60, 95%CI: 1.17–2.19, OR = 1.75, 95%CI: 1.16–2.63; and OR = 1.53, 95%CI: 1.00–2.34, respectively).Conclusion: Both elective and non-elective CD were associated with the risk of accelerated weight gain in early childhood.

Abstract 16135: Higher Body Mass Index in Early Childhood is Associated With Adult Obesity in Patients With a Fontan Circulation

Introduction: Obesity is associated with comorbidities that may be detrimental to single-ventricle patients who have had a Fontan procedure. We assessed the prevalence of obesity in adults with a Fontan circulation and evaluated the hypothesis that higher body mass index (BMI) in early childhood is associated with obesity in adulthood. Methods: Retrospective cohort study of patients with a Fontan circulation aged 18-32 years, seen 2011-2019. Those with an atriopulmonary Fontan or chromosomal abnormality known to affect growth were excluded. Historical height and weight measurements, results of recent cardiac testing, and body mass index (BMI) over time were recorded. Obesity was defined as BMI ≥30 kg/m 2 . The associations between childhood anthropometrics, adult BMI, and most recent cardiac testing were assessed. Results: The cohort included 113 adults with a Fontan circulation (median age 22.7 [IQR 20.2-26.4] years; 44% female). There were no significant differences in age, age at Fontan, Fontan type, or ventricular morphology between obese (n=21, 19%; 52% female) and non-obese (n=92, 81%; 41% female) patients. Compared to non-obese adults, obese patients had higher BMI percentiles at age 2 years (80 th [33-95] vs 43 rd [13-82] percentile, p=0.02), at age 4 years (90 th [73-93] vs 57 th [22-81] percentile, p=0.002), and at the time of the Fontan procedure (85 th [51-98] vs 20 th [5-57] percentile, p=0.002). Being overweight at time of Fontan (BMI percentile &gt;85%) strongly predicted later obesity (OR=18.3, 95% CI 3.7-90.3, p&lt;0.001). Obese adults had lower peak VO 2 (19.1±5.2 vs 25.5±6.6 mL/kg/min, p&lt;0.001,) a trend to a lower % predicted VO 2 (59±13 vs 65±14% predicted, p=0.06), higher systolic blood pressure (121±17 vs 112±12 mmHg, p=0.007) and higher ventricular end-diastolic pressure (11±4 vs 9±3 mmHg, p= 0.03). Adult BMI weakly correlated with ventricular end-diastolic pressure (r=0.24, p=0.048). Conclusions: Higher BMI in early childhood is associated with obesity in adults with a Fontan circulation. Adult obesity is associated with worse exercise capacity, higher blood pressure, and higher ventricular end-diastolic pressure. Weight interventions in children with a Fontan circulation may help prevent later obesity and its adverse consequences.