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

Abstract

BackgroundManganese 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.ObjectiveThis study was conducted to investigate a relationship between maternal blood manganese level and neurodevelopment of infants at 6 months of age.MethodsData 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.ResultsMean ± 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.ConclusionAlthough 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.CitationChung SE, Cheong HK, Ha EH, Kim BN, Ha M, Kim Y, Hong YC, Park H, Oh SY. 2015. Maternal blood manganese and early neurodevelopment: the Mothers and Children’s Environmental Health (MOCEH) study. Environ Health Perspect 123:717–722; http://dx.doi.org/10.1289/ehp.1307865

Perinatal and Childhood Exposure to Cadmium, Manganese, and Metal Mixtures and Effects on Cognition and Behavior: A Review of Recent Literature

“…We identified 14 studies that examined the association between Mn and neurodevelopmental or cognitive outcomes in neonates or children (Supplement 2) [55–68]. Most studies were cross-sectional (n=10), and four were prospective cohorts.…”

“…All four of the prospective studies reviewed support the notion that the prenatal and early postnatal period may be a sensitive developmental window for Mn exposure with regards to neurodevelopment [58, 61, 67, 68]. In a large prospective cohort study of neonates from China, a cord serum Mn threshold of 5 μg/L was identified, above which three-day-olds showed cognitive deficits as measured by the Neonatal Behavioral Neurological Assessment (NBNA) [67].…”

“…However, there are well known limitations to assessing neonates, given the limited neurologic repertoire inherent in newborns. Two studies reported an inverted U-shaped association between blood Mn levels measured at delivery or at 12 months of age and mental development scores on the BSID at ages 6 to 12 months [58, 68], indicating the potential for Mn to act as both an essential element and a toxic metal. Chung et al .…”

“…Chung et al . reported a transition from beneficial to adverse effects on six month mental development scores when maternal blood Mn levels were 24–28 μg/L [68]. Finally, a prospective cohort study of 2-year-old children in Taiwan reported that cord blood Mn was associated with decrements in cognitive and language subscales of the Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) [61].…”

“…[56–61, 63–68]. These studies were conducted in various geographic locations and populations, had moderate sample sizes (many with n>200), and adjusted for important covariates (e.g.…”