Per- and polyfluoroalkyl substances (PFAS) are shown to have neurotoxic effects on animals, but epidemiological evidence for associations between childhood PFAS exposure and neurodevelopment is inconclusive. We examined if childhood PFAS concentrations are associated with a diagnosis of autism spectrum disorder (ASD), developmental delay (DD), and other early concerns (OEC) in development. We included 551 children 2 to 5 years old from the CHildhood Autism Risks from Genetics and Environment (CHARGE) case-control study. Children were clinically diagnosed and classified as having ASD, DD, OEC, and typical development (TD). Fourteen PFAS were quantified in child serum samples collected when diagnostic assessments were performed. We used multinomial logistic regression models to investigate the cross-sectional associations of individual PFAS concentrations with neurodevelopmental outcomes and weighted quantile sum (WQS) regression models with repeated holdout validation to investigate the associations with PFAS mixtures. Childhood perfluorooctanoic acid (PFOA) was associated with increased odds of ASD (odds ratio [OR] per ln ng/mL increase: 1.99, 95% confidence interval [CI]: 1.20, 3.29) and DD (OR: 2.16, 95% CI: 1.21, 3.84) versus TD. Perfluoroheptanoic acid (PFHpA) was associated with increased odds of ASD (OR: 1.61, 95% CI: 1.21, 2.13). However, perfluroundecanoic acid (PFUnDA) was associated with decreased odds of ASD (OR: 0.43, 95% CI: 0.26, 0.69). From mixture analyses, the WQS index was associated with increased odds of ASD (average OR: 1.57, 5^th and 95^th percentile: 1.16, 2.13). Child’s sex and homeownership modified associations of perfluorodecanoic acid (PFDA) with DD and ASD, respectively. In this case-control study, childhood PFOA, PFHpA, and a PFAS mixture was associated with increased odds of ASD, while PFUnDA was associated with decreased odds of ASD. Because we used concurrent measurements of PFAS, our results do not imply causal relationships and thus need to be interpreted with caution.

Adequate nutrition is important for neurodevelopment. Although nutrients are ingested in combination, the impact of specific nutrients within the context of a nutrient mixture has not been studied with respect to health, such as neurodevelopment. Therefore, we examined the impact of prenatal and childhood nutrient mixtures on neurodevelopmental outcomes. Participants included mother–child pairs in the Programming Research in Obesity, Growth, Environment, and Social Stress (PROGRESS) prospective birth cohort in Mexico City. We assessed prenatal and child micro- and macronutrient profiles among 65 and 329 children, respectively, via food frequency questionnaires. Neurodevelopmental outcomes of 4–6 year-old children were measured using the McCarthy Scales of Children’s Abilities (MSCA). We conducted weighted quantile sum (WQS) regression analyses to calculate indices reflecting “good” and “poor” prenatal and childhood nutrition. After adjusting for maternal education, socioeconomic status, the Home Observation for Measurement of the Environment (HOME) score, and total caloric intake, the good prenatal and childhood nutrition indices predicted more favorable neurodevelopment, while both poor nutrition indices predicted poorer neurodevelopment. These associations were stronger in prenatal than childhood models. Monounsaturated fats predicted various neurodevelopmental abilities relatively strongly in both models. Prenatal and childhood consumption of combinations of beneficial nutrients may contribute to more favorable neurodevelopment.

Maternal and cord plasma metabolomics were used to elucidate biological pathways associated with increased diagnosis risk for autism spectrum disorders (ASD). Metabolome-wide associations were assessed in both maternal and umbilical cord plasma in relation to diagnoses of ASD and other non-typical development (Non-TD) compared to typical development (TD) in the Markers of Autism risk in Babies: Learning Early Signs (MARBLES) cohort study of children born to mothers who already have at least one child with ASD. Analyses were stratified by sample matrix type, machine mode, and annotation confidence level. Dimensionality reduction techniques were used [i.e, principal component analysis (PCA) and random subset weighted quantile sum regression (WQS_RS)] to minimize the high multiple comparison burden. With WQS_RS, a metabolite mixture obtained from the negative mode of maternal plasma decreased the odds of Non-TD compared to TD. These metabolites, all related to the prostaglandin pathway, underscored the relevance of neuroinflammation status. No other significant findings were observed. Dimensionality reduction strategies provided confirming evidence that a set of maternal plasma metabolites are important in distinguishing Non-TD compared to TD diagnosis. A lower risk for Non-TD was linked to anti-inflammatory elements, thereby linking neuroinflammation to detrimental brain function consistent with studies ranging from neurodevelopment to neurodegeneration.

Background: Adequate nutrition is essential for individual and population level health. However, determining adequacy of daily nutrient intake in research studies is often challenging given the unique nutritional needs of individuals. Herein, we examine construct, predictive, criterion, content, and concurrent validity of a dietary analytic tool – My Nutrition Index (MNI) for measuring nutrient intake in relation to personalized daily nutrient intake guidelines. MNI gauges adequacy of an individual’s daily nutrient intake based on his or her unique demographic and lifestyle characteristics. MNI accounts for potential adverse effects of inadequate and excess nutrient consumption. Methods: MNI, calculated based on 34 nutrients, provides an overall index score ranging from 0 to 100, with higher scores reflecting a more nutritious diet. We calculated MNI scores for 7154 participants ages 18-65 in the National Health and Nutrition Examination Surveys (2007-2014) by using average nutrient intakes from two 24-h dietary recalls. Survey-weighted binary logistic regression models were used to assess associations between MNI scores and obesity, depression, health perceptions, and past or present cardiovascular disease. Results: Higher MNI scores were associated with lower prevalence of self-reported cardiovascular disease (OR = 0.69, CI: 0.52, 0.92, p = 0.012), depression (OR = 0.76, CI: 0.65, 0.90, p < 0.001), and obesity (OR = 0.92, CI: 0.87, 0.99, p = 0.016), as well as more favorable health perceptions (OR = 1.24, CI: 1.13, 1.37, p < 0.001). Conclusions: MNI provides an individualized approach for measuring adequacy/sufficiency of daily nutrient intake that can validly be employed to assess relationships between nutrition and health outcomes in research studies.

Objective: Cotinine is the preferred biomarker to validate levels of tobacco smoke exposure (TSE) in children. Compared to enzyme-linked immunosorbent assay methods (ELISA) for quantifying cotinine in saliva, the use of liquid chromatography tandem mass spectrometry (LC-MS/MS) has higher sensitivity and specificity to measure very low levels of TSE. We sought to compare LC-MS/MS and ELISA measures of cotinine in saliva samples from children overall and the associations of these measures with demographics and TSE patterns. Method: Participants were nonsmoking children (N = 218; age mean (SD) = 6.1 (5.1) years) presenting to a pediatric emergency department. Saliva samples were analyzed for cotinine using both LC-MS/MS and ELISA. Limit of quantitation (LOQ) for LC-MS/MS and ELISA was 0.1 ng/mL and 0.15 ng/mL, respectively. Results: Intraclass correlations (ICC) across methods = 0.884 and was consistent in sex and age subgroups. The geometric mean (GeoM) of LC-MS/MS = 4.1 (range: < LOQ to 382 ng/mL; 3% < LOQ) which was lower (p < 0.0001) than the ELISA GeoM = 5.7 (range: < LOQ to 364 ng/mL; 5% < LOQ). Similar associations of cotinine concentrations with age ( $\widehat{\beta }$ < −0.10, p < 0.0001), demographic characteristics (e.g., income), and number of cigarettes smoked by caregiver ( $\widehat{\beta }$ > 0.07, p < 0.0001) were found regardless of cotinine detection method; however, cotinine associations with sex and race/ethnicity were only found to be significant in models using LC-MS/MS-derived cotinine. Conclusions: Utilizing LC-MS/MS-based cotinine, associations of cotinine with sex and race/ethnicity of child were revealed that were not detectable using ELISA-based cotinine, demonstrating the benefits of utilizing the more sensitive LC-MS/MS assay for cotinine measurement when detecting low levels of TSE in children.

Fluoride exposure is associated with later pubertal development and decreased testosterone production in adolescent and adult males. However, its effects on female reproductive health and pubertal development are unclear. Therefore, we examined associations of fluoride exposure with reproductive health outcomes among adolescent girls and women in the United States. Participants were from The National Health and Nutrition Examination Surveys (2013 to 2016), aged 16–19 and identified as female. There were 524 and 460 participants with measures of plasma fluoride and household tap water fluoride respectively, who had at least one reproductive health outcome examined, and complete covariate data. We applied covariate adjusted survey-weighted linear or logistic regression to examine associations of fluoride exposure with age of menarche, menstrual cycle regularity, or serum sex steroid hormone levels. Median interquartile range (IQR) water and plasma fluoride concentrations were 0.48 (0.53) mg/L and 0.34 (0.30) µmol/L respectively. An IQR increase in water fluoride was associated with a 3.3 month earlier first menstrual period (B = − 0.28, 95%CI − 0.54, − 0.02, p = 0.05). Additionally, we observed a significant interaction between plasma fluoride and race/ethnicity in association with age of menarche (p = 0.01). Among Non-Hispanic Black adolescents, each IQR increase in plasma fluoride was associated with a 5-month earlier age of menarche (B = − 0.42, 95%CI − 0.61, − 0.23, p < 0.001). Potential impacts of chronic low-level fluoride exposure on reproductive health outcomes are an important area of study. Current study findings, as well as potential health disparities due to disproportionate fluoride exposure should be examined in prospective studies.