Sex differences in sensitivity to prenatal and early childhood manganese exposure on neuromotor function in adolescents.

INTRODUCTION: While studies have suggested that exposure to manganese (Mn) may be associated with neurodevelopment in school-age children, there is limited information on prenatal and postnatal Mn exposures and tremor or motor function in children. METHODS: We measured Mn levels in dentine of shed teeth, representing prenatal, early postnatal, and cumulative childhood exposure windows, from 195 children (predominantly right-handed, 92%) in Italy. Pursuit Aiming, Luria Nebraska Motor Battery, as well as Tremor and Sway system from Computerized Adaptive Testing System (CATSYS) were administered at 11-14 years old. We examined the relationships of tooth Mn (ln-transformed) with motor function using multivariable linear regressions and generalized additive models, adjusting for age, sex, and socioeconomic status index. Effect modification by sex was also examined. RESULTS: We found that higher prenatal Mn was associated with better body stability in boys in a number of sway tests (including mean sway, transversal sway, sagittal sway, sway area, and sway intensity), while Mn was associated with poorer performance in girls on all of these metrics (all p for Mn × sex interaction < 0.05). Higher prenatal Mn was also modestly associated with better hand/finger and eye-hand coordination in boys compared to girls in sex-stratified analyses, although interaction models did not reach statistical significance. For tremor, on the other hand, higher early postnatal Mn was associated with increased right-hand center frequency in girls (p for interaction < 0.01), but increased Mn level at the later postnatal period was associated with increased center frequency in boys (p for interaction = 0.01). CONCLUSIONS: This study, which used a direct measure of prenatal and childhood Mn exposure, suggested sex-specific critical windows of early life Mn exposure in relation to neuromotor function in adolescents. The sex-specific associations might be strongest with measures of whole body stability, for which the critical exposure window was during the prenatal period.

Prenatal particulate air pollution exposure and body composition in urban preschool children: Examining sensitive windows and sex-specific associations.

BACKGROUND: Evolving animal studies and limited epidemiological data show that prenatal air pollution exposure is associated with childhood obesity. Timing of exposure and child sex may play an important role in these associations. We applied an innovative method to examine sex-specific sensitive prenatal windows of exposure to PM2.5 on anthropometric measures in preschool-aged children. METHODS: Analyses included 239 children born ≥ 37 weeks gestation in an ethnically-mixed lower-income urban birth cohort. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatio-temporal model. Body mass index z-score (BMI-z), fat mass, % body fat, subscapular and triceps skinfold thickness, waist and hip circumferences and waist-to-hip ratio (WHR) were assessed at age 4.0 ± 0.7 years. Using Bayesian distributed lag interaction models (BDLIMs), we examined sex differences in sensitive windows of weekly averaged PM2.5 levels on these measures, adjusting for child age, maternal age, education, race/ethnicity, and pre-pregnancy BMI. RESULTS: Mothers were primarily Hispanic (55%) or Black (26%), had ≤ 12 years of education (66%) and never smoked (80%). Increased PM2.5 exposure 8-17 and 15-22 weeks gestation was significantly associated with increased BMI z-scores and fat mass in boys, but not in girls. Higher PM2.5 exposure 10-29 weeks gestation was significantly associated with increased WHR in girls, but not in boys. Prenatal PM2.5 was not significantly associated with other measures of body composition. Estimated cumulative effects across pregnancy, accounting for sensitive windows and within-window effects, were 0.21 (95%CI = 0.01-0.37) for BMI-z and 0.36 (95%CI = 0.12-0.68) for fat mass (kg) in boys, and 0.02 (95%CI = 0.01-0.03) for WHR in girls, all per µg/m3 increase in PM2.5. CONCLUSIONS: Increased prenatal PM2.5 exposure was more strongly associated with indices of increased whole body size in boys and with an indicator of body shape in girls. Methods to better characterize vulnerable windows may provide insight into underlying mechanisms contributing to sex-specific associations.