Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0–5.0 years), mid (5.0–10.0 years) and late childhood (10.0–18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.

Numerous ubiquitous environmental chemicals are established or suspected neurotoxicants, and infants are exposed to a mixture of these during the critical period of brain maturation. However, evidence for associations with the risk of attention-deficit/hyperactivity disorder (ADHD) is sparse. We investigated early-life chemical exposures in relation to ADHD. We used a birth cohort of 2606 Norwegian mother-child pairs enrolled 2002-2009 (HUMIS), and studied a subset of 1199 pairs oversampled for child neurodevelopmental outcomes. Concentrations of 27 persistent organic pollutants (14 polychlorinated biphenyls, 5 organochlorine pesticides, 6 brominated flame retardants, and 2 perfluoroalkyl substances) were measured in breast milk, reflecting the child's early-life exposures. We estimated postnatal exposures in the first 2 years of life using a pharmacokinetic model. Fifty-five children had a clinical diagnosis of ADHD (hyperkinetic disorder) by 2016, at a median age of 13 years. We used elastic net penalized logistic regression models to identify associations while adjusting for co-exposure confounding, and subsequently used multivariable logistic regression models to obtain effect estimates for the selected exposures. Breast milk concentrations of perfluorooctane sulfonate (PFOS) and β‑hexachlorocyclohexane (β-HCH) were associated with increased odds of ADHD: odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.16, 2.72 and OR = 1.75, 95% CI: 1.22, 2.53, per interquartile range increase in ln-transformed concentrations, respectively. Stronger associations were observed among girls than boys for PFOS (pinteraction = 0.025). p,p'‑Dichlorodiphenyltrichloroethane (p,p'-DDT) levels were associated with lower odds of ADHD (OR = 0.64, 95% CI: 0.42, 0.97). Hexachlorobenzene (HCB) had a non-linear association with ADHD, with increasing risk in the low-level exposure range that switched to a decreasing risk at concentrations above 8 ng/g lipid. Postnatal exposures showed similar results, whereas effect estimates for other chemicals were weaker and imprecise. In a multi-pollutant analysis of four classes of chemicals, early-life exposure to β-HCH and PFOS was associated with increased risk of ADHD, with suggestion of sex-specific effects for PFOS. The unexpected inverse associations between p,p'-DDT and higher HCB levels and ADHD could be due to live birth bias; alternatively, results may be due to chance findings.

Early disruption of the microbial community may influence life-long health. Environmental toxicants can contaminate breast milk and the developing infant gut microbiome is directly exposed. We investigated whether environmental toxicants in breastmilk affect the composition and function of the infant gut microbiome at 1 month. We measured environmental toxicants in breastmilk, fecal short-chain fatty acids (SCFAs), and gut microbial composition from 16S rRNA gene amplicon sequencing using samples from 267 mother-child pairs in the Norwegian Microbiota Cohort (NoMIC). We tested 28 chemical exposures: polychlorinated biphenyls (PCBs), polybrominated flame retardants (PBDEs), per- and polyfluoroalkyl substances (PFASs), and organochlorine pesticides. We assessed chemical exposure and alpha diversity/SCFAs using elastic net regression modeling and generalized linear models, adjusting for confounders, and variation in beta diversity (UniFrac), taxa abundance (ANCOM), and predicted metagenomes (PiCRUSt) in low, medium, and high exposed groups. PBDE-28 and the surfactant perfluorooctanesulfonic acid (PFOS) were associated with less microbiome diversity. Some sub-OTUs of Lactobacillus, an important genus in early life, were lower in abundance in samples from infants with relative “high” (> 80th percentile) vs. “low” (< 20th percentile) toxicant exposure in this cohort. Moreover, breast milk toxicants were associated with microbiome functionality, explaining up to 34% of variance in acetic and propionic SCFAs, essential signaling molecules. Per one standard deviation of exposure, PBDE-28 was associated with less propionic acid (− 24% [95% CI − 35% to − 14%] relative to the mean), and PCB-209 with less acetic acid (− 15% [95% CI − 29% to − 0.4%]). Conversely, PFOA and dioxin-like PCB-167 were associated with 61% (95% CI 35% to 87%) and 22% (95% CI 8% to 35%) more propionic and acetic acid, respectively. Environmental toxicant exposure may influence infant gut microbial function during a critical developmental window. Future studies are needed to replicate these novel findings and investigate whether this has any impact on child health.

Childhood obesity is a growing problem worldwide. Recent research suggests that the gut microbiota may play an important and potentially causal role in the development of obesity and may be one mechanism that explains the transgenerational transmission of obesity risk. Here we examine the early-life gut microbiota at days 4, 10, 30, 120, 365, and 730 and the association with body mass index (BMI) z-scores at age 12 in a Norwegian prospective cohort (n = 165), and evaluate how these BMI-associated taxa relate to maternal overweight/obesity (Ow/Ob) and excessive gestational weight gain (GWG). We performed 16S rRNA gene sequencing on the gut microbiota samples. Taxonomic phylogeny at days 10 and 730 was significantly associated with childhood BMI, and the gut microbiota taxa at two years of age explained over 50% of the variation in childhood BMI in this cohort. The subset of the early-life taxa within the gut microbiota that best predicted later childhood BMI showed substantial overlap with the maternal taxa most strongly associated with maternal Ow/Ob and excessive GWG. Our results show an association between the infant gut microbiota and later BMI, and they offer preliminary evidence that the infant gut microbiota, particularly at 2 years of age, may have potential to help identify children at risk for obesity. IMPORTANCE Understanding the role of the early-life gut microbiota in obesity is important because there may be opportunities for preventive strategies. We examined the relationships between infant gut microbiota at six times during the first two years of life and BMI at age 12 in a birth cohort of 165 children and their mothers. We found that the gut microbiota from early life to two years shows an increasingly strong association with childhood BMI. This study provides preliminary evidence that the gut microbiome at 2 years of age may offer useful information to help to identify youth who are at risk for obesity, which could facilitate more-targeted early prevention efforts.

ObjectivesThe aim of this study was to review epidemiologic evidence, provide summary risk estimates of the association between exposure to chlorination disinfection by-products (DBPs) and congenital anomalies, and provide recommendations for future studies.Data sources and extractionWe included all published epidemiologic studies that evaluated a relationship between an index of DBP exposure (treatment, water source, DBP measurements, and both DBP measurements and personal characteristics) and risk of congenital anomalies. When three or more studies examined the same exposure index and congenital anomaly, we conducted a meta-analysis to obtain a summary risk estimate comparing the highest exposure group with the lowest exposure group. When five or more studies examined total trihalomethane (TTHM) exposure and a specific congenital anomaly, we conducted a meta-analysis to obtain exposure–response risk estimates per 10 μg/L TTHM.Data synthesisFor all congenital anomalies combined, the meta-analysis gave a ...

BackgroundHypospadias is one of the most common urogenital congenital anomalies affecting baby boys. Prevalence estimates in Europe range from 4 to 24 per 10,000 births, depending on definition, with higher rates reported from the United States. Relatively little is known about potential risk factors, but a role for endocrine-disrupting chemicals (EDCs) has been proposed.ObjectiveOur goal was to elucidate the risk of hypospadias associated with occupational exposure of the mother to endocrine-disruptor chemicals, use of folate supplementation during pregnancy, and vegetarianism.DesignWe designed a case–control study of 471 hypospadias cases referred to surgeons and 490 randomly selected birth controls, born 1 January 1997–30 September 1998 in southeast England. Telephone interviews of mothers elicited information on folate supplementation during pregnancy and vegetarianism. We used a job exposure matrix to classify occupational exposure.ResultsIn multiple logistic regression analysis, there were increased...