Maternal Blood Manganese and Early Neurodevelopment: The Mothers and Children's Environmental Health (MOCEH) Study

Abstract

Background: Manganese is an essential trace element and common component of water, soil, and air. Prenatal manganese exposure may affect fetal and infantile neurodevelopment, but reports on in utero manganese exposure and infant neurodevelopment are rare.

Objective: This study was conducted to investigate a relationship between maternal blood manganese level and neurodevelopment of infants at 6 months of age.

Methods: Data were obtained from the Mothers and Children's Environmental Health (MOCEH) birth cohort study. The study population included 232 pairs of pregnant women and their infants at 6 months of age. Maternal blood manganese was measured at term, just before delivery. Mental and psychomotor development in infancy was assessed at 6 months of age using the Bayley Scales of Infant Development. The relationship between maternal blood manganese level and the mental and psychomotor development indexes (MDI and PDI) was estimated for manganese modeled as a linear and as a categorical variable and using penalized splines for nonlinear modeling.

Results: Mean ± SD maternal blood manganese concentration was 22.5 ± 6.5 μg/L. After adjustment for potential confounders, blood manganese was used as a continuous variable in a linear and nonlinear model. Associations between maternal blood manganese and MDI and PDI scores followed an inverted U-shape dose-response curve after adjustment for potential confounders, with lower scores associated with both low and high blood concentrations [MDI: likelihood-ratio test (LRT) p = 0.075, PDI: LRT p = 0.038]. Associations of both outcomes with increasing blood manganese shifted from positive to negative at concentrations of 24-28 μg/L in this cohort of term, normal birth weight children.

Conclusion: Although no cut-off point has been established to define manganese toxicity, both high and low blood manganese levels may be associated with neurobehavioral function in infants.

Figure 1

Association between maternal blood manganese (Mn) and (A) MDI and (B) PDI at 6 months of age and AIC by inflection point. The GAM plots are penalized spline blood manganese (μg/L) predicting 6-month MDI, after controlling for maternal age, gestation period (days), monthly income, breastfeeding status, maternal total calorie intake (kcal/day), infant birth order, residential area, infant sex, and birth weight (kg) among 232 children. The solid line represents the estimate; dotted lines represent the 95% CIs. Vertical lines on the x-axis represent the distribution of blood manganese observations. Panels on the right represent the AIC values by moving inflection point per 1 blood manganese concentration (μg/L) with the circles, and the solid line represents the maternal blood manganese concentration with the smallest AIC value.

Figure 2

Models of MDI/PDI and maternal blood manganese levels at term, least-square mean after adjusting for maternal age (years), gestation period (days), monthly income, breastfeeding status, maternal total calorie intake (kcal/day), infant birth order, residential area, infant sex, and birth weight (kg). The ranges of blood manganese levels at term were < 20 μg/L (n = 82), 20–24 μg/L (n = 64), 25–29 μg/L (n = 34), and ≥ 30 μg/ L (n = 23), respectively. Error bars represent standard errors.