Prenatal and postnatal manganese teeth levels and neurodevelopment at 7, 9, and 10.5years in the CHAMACOS cohort

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Polymorphisms in manganese transporters show developmental stage and sex specific associations with manganese concentrations in primary teeth

“…Generally women in menstruating ages are known to absorb more Mn concentrations than men due to lower iron stores (Finley et al, 1994), which allows increased uptake of Mn via shared transporters such as DMT1 (Au et al, 2008). However, several other studies have shown differences between sexes in Mn related neurotoxic also in early life (Gunier et al, 2015; Mora et al, 2015; Riojas-Rodriguez et al, 2010). Using the same tooth matrix Mn biomarker as the current study, Mora et al and Gunier et al showed that girls were generally more sensitive to early life Mn exposure than boys.…”

“…Several studies have also shown sex differences in the health effects of Mn exposure (Gunier et al, 2015; Menezes-Filho et al, 2011; Riojas-Rodriguez et al, 2010), suggesting that there may be important differences in Mn homeostasis and toxicity between girls and boys. Furthermore, studies in animals and humans have indicated differences in the effects of exposure related to the developmental stage at which the exposure was experienced (Betharia and Maher, 2012; Gunier et al, 2015; Mora et al, 2015). …”

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

“…The use of tooth biomarkers in this PHIME study and the CHAMACOS study conducted by Mora et al (Mora et al, 2015) and Gunier et al (Gunier et al, 2015) has enabled the estimation of effects in different exposure windows in prenatal and early childhood periods, in order to ascertain a more complete perspective of the impact of Mn during early life. It has been suggested that Mn levels in pregnant women are significantly higher than that in non-pregnant women, likely due to the essentiality of Mn for neurodevelopment (Oulhote et al, 2014b).…”

“…Mora et al (2015) measured Mn levels in prenatal and early postnatal dentine of shed teeth in children living near agricultural fields treated with Mn-containing fungicides in the Center for the Health Assessment of Mother and Children of Salinas (CHAMACOS) cohort in California and found that higher concentrations of prenatal Mn was associated with improved motor outcomes assessed by Finger tapping test at age 7 years and Luria-Nebraska Motor Scale at age 9 and 10.5 years, but only in boys (Mora et al, 2015). They also found sex differences in the associations between early postnatal Mn and these motor function tests, where in general beneficial associations were found in boys but adverse associations were found in girls.…”

“…The most widely studied neurological health outcome related to Mn exposure is termed manganism, a Parkinson’s-like condition observed in adults with high occupational exposure to Mn (Lucchini et al, 2009; O'Neal and Zheng 2015). The negative neurological health outcomes correlated with Mn overexposure in children include behavioral disinhibition (Ericson et al, 2007), olfactory and motor function (Lucchini et al, 2012), and hyperactivity (Mora et al, 2015). However, investigation of the pediatric health outcomes of Mn effects has also led to inconsistent findings.…”