Numerous cross-sectional studies of school-age children have observed that exposure to manganese (Mn) adversely affects neurodevelopment. However, few prospective studies have looked at the effects of both prenatal and postnatal Mn exposure on child neurodevelopment. We measured Mn levels in prenatal and early postnatal dentine of shed teeth and examined their association with behavior, cognition, memory, and motor functioning in 248 children aged 7, 9, and/or 10.5 years living near agricultural fields treated with Mn-containing fungicides in California. We used generalized linear models and generalized additive models to test for linear and nonlinear associations, and generalized estimating equation models to assess longitudinal effects. We observed that higher prenatal and early postnatal Mn levels in dentine of deciduous teeth were adversely associated with behavioral outcomes, namely internalizing, externalizing, and hyperactivity problems, in boys and girls at 7 and 10.5 years. In contrast, higher Mn levels in prenatal and postnatal dentine were associated with better memory abilities at ages 9 and 10.5, and better cognitive and motor outcomes at ages 7 and 10.5 years, among boys only. Higher prenatal dentine Mn levels were also associated with poorer visuospatial memory outcomes at 9 years and worse cognitive scores at 7 and 10.5 years in children with higher prenatal lead levels (≥0.8 μg/dL). All these associations were linear and were consistent with findings from longitudinal analyses. We observed that higher prenatal and early postnatal Mn levels measured in dentine of deciduous teeth, a novel biomarker that provides reliable information on the developmental timing of exposures to Mn, were associated with poorer behavioral outcomes in school-age boys and girls and better motor function, memory, and/or cognitive abilities in school-age boys. Additional research is needed to understand the inconsistencies in the neurodevelopmental findings across studies and the degree to which differences may be associated with different Mn exposure pathways and biomarkers.

Lead (Pb), mercury (Hg), and manganese (Mn) are neurotoxic, but little is known about the neurodevelopmental effects associated with simultaneous prenatal exposure to these metals. We aimed to study the associations of Pb, Hg, and Mn prenatal levels (jointly and separately) with neurodevelopment in the first year of life. Methods: Pb, Hg, and Mn blood lead levels were measured in 253 pregnant women. Their offspring’s neurodevelopment was assessed through the Bayley Scale of Infant Development III^® at one, three, six, and twelve months. The metals’ mean blood levels (µg/L) were Pb = 11.2, Hg = 2.1, and Mn = 10.2. Mean language, cognitive, and motor development scores of the infants at each age were between low-average and average. Multilevel models’ results showed that language development coefficients of the offspring decreased by 1.5 points per 1 µg/dL increase in maternal blood lead levels (p = 0.002); the magnitude of the aforementioned association increased in children with maternal blood Mn < 9.6 µg/L (ß = −1.9, p = 0.003) or Hg > 1.9 µg/L (ß = −1.6, p = 0.013). Cognitive and motor development had negative associations with maternal blood Pb levels; the latter was statistically significant when the interaction term between Pb, Mn, and Hg was included (ß = −0.037, p = 0.03). Prenatal exposure to low Pb levels may impair infants’ neurodevelopment in the first year of life, even more so if they are exposed to Hg or deficient in Mn.

Pesticide exposure may affect young children's neurodevelopment, but only few cohort studies have addressed possible effects of non-organophosphate pesticides. We evaluated associations between prenatal current-use pesticide exposure and neurodevelopmental outcomes among 1-year-old children from the Infants' Environmental Health (ISA) birth cohort. To determine prenatal pesticide exposure, we measured biomarkers of pyrimethanil, chlorpyrifos, synthetic pyrethroids, and 2,4-D in urine samples among 355 women, 1-3 times during pregnancy. One-year post-partum, we evaluated children's neurodevelopment with the Bayley Scales of Infant and Toddler Development 3rd edition (BSID-III). We assessed associations between exposures and neurodevelopmental outcomes (composite and z-scores) using single-chemical linear regression models adjusted for possible confounders (maternal education, parity, sex, gestational age at birth, child age, HOME-score, location of assessment, biomarkers of mancozeb), and studied effect-modification by sex. We evaluated non-linear associations of multiple pesticide exposures with Bayesian kernel machine regression (BKMR). We found higher prenatal urinary 2,4-D concentrations were associated with lower language (β_{per ten-fold increase} = -2.0, 95 % confidence interval (CI) = -3.5, -0.5) and motor (β_{per ten-fold increase} = -2.2, 95 %CI = -4.2, -0.1) composite scores among all children. Also, higher chlorpyrifos exposure [measured as urinary 3,5,6-trichloro-2-pyridinol (TCPy)] was associated with lower cognitive composite scores (β_{per ten-fold increase} = -1.9, 95 %CI = -4.7, 0.8), and lower motor composite scores among boys (β_{per ten-fold increase} = -3.8, 95 % CI = -7.7, 0.1) but not girls (β_{per ten-fold increase} = 2.3, 95 %CI = -1.6, 6.3, pINT = 0.11). Finally, higher pyrimethanil was associated with lower language abilities among girls, but not boys. Pyrethroid metabolite concentrations did not explain variability in BSID-III composite scores. Associations were similar for BSID-III z-scores, and we found no evidence for non-linear associations or mixture effects. Prenatal exposure to common-use pesticides may affect children's neurodevelopment at 1-year of age, some effects may be sex-specific.