Elsevier

Environment International

Volume 84, November 2015, Pages 39-54
Environment International

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

https://doi.org/10.1016/j.envint.2015.07.009Get rights and content

Highlights

  • Measured prenatal and postnatal Mn in dentine of deciduous teeth

  • Assessed neurodevelopment in children at ages 7, 9, and 10.5 years

  • Higher Mn associated with poorer behavioral outcomes

  • Higher Mn associated with better memory, cognitive, and motor abilities in boys

  • Not statistically significant but notable interaction between prenatal Mn and lead

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.

Introduction

Manganese (Mn) is an essential element involved in important enzymatic reactions (Aschner, 2000, Gwiazda et al., 2002), but in excess, it is a potent neurotoxicant (Menezes-Filho et al., 2009a, Mergler and Baldwin, 1997, Roels et al., 2012). Food is the main source of Mn for the general population (ATDSR, 2012), but environmental exposure to Mn can occur from water naturally high in Mn or contaminated by industrial waste (Bouchard et al., 2007, Bouchard et al., 2011b, He et al., 1994, Kondakis et al., 1989), combustion of anti-knock additives in gasoline (Zayed et al., 1999), Mn mining operations (Riojas-Rodriguez et al., 2010), ferromanganese production facilities (Haynes et al., 2010, Menezes-Filho et al., 2009b), and spraying of Mn-containing fungicides (Gunier et al., 2013, Mora et al., 2014). Absorption and distribution of ingested Mn are closely regulated through homeostatic mechanisms (Papavasiliou et al., 1966, Roth, 2006). However, inhaled Mn can directly enter the systemic circulation through the lungs (Vitarella et al., 2000) and access the brain directly through the olfactory bulb (Dorman et al., 2002, Elder et al., 2006, Leavens et al., 2007), bypassing biliary excretion mechanisms.

Children and infants may be particularly susceptible to the neurotoxic effects of Mn exposure as their Mn homeostatic mechanisms are poorly developed (Aschner, 2000, Ljung and Vahter, 2007, Yoon et al., 2009) and Mn can enter their developing brains by crossing the blood–brain barrier (Aschner, 2000, Aschner and Dorman, 2006). Multiple studies have reported associations between exposure to Mn and neurodevelopmental problems in children. Higher in utero Mn levels measured in blood and teeth have been associated with attention problems (Ericson et al., 2007, Takser et al., 2003), behavioral disinhibition (Ericson et al., 2007), impaired non-verbal memory (Takser et al., 2003), and poor cognitive and language development (Lin et al., 2013) in toddlers and preschoolers, and with externalizing behavior and attention problems (Ericson et al., 2007) in school-aged children. Postnatal Mn exposure has been associated with poor language development in toddler boys (Rink et al., 2014), and behavioral problems in school-aged boys and girls (Ericson et al., 2007). Studies of school-aged children and adolescents (6–14 year olds) have linked elevated Mn levels in drinking water, blood, and hair samples with oppositional behavior and hyperactivity (Bouchard et al., 2007), impaired cognitive abilities (Bouchard et al., 2011b, Kim et al., 2009, Menezes-Filho et al., 2011, Riojas-Rodriguez et al., 2010, Wasserman et al., 2006), and poor memory (He et al., 1994, Torres-Agustin et al., 2013), motor coordination (He et al., 1994, Hernandez-Bonilla et al., 2011, Lucchini et al., 2012), and visuoperceptive speed (He et al., 1994, Zhang et al., 1995). To date, only one epidemiologic study has assessed exposure to Mn both prenatally and postnatally (Ericson et al., 2007).

Blood Mn has typically been used as a biomarker of exposure to Mn in occupational and population-based studies of adults and children (Mergler et al., 1999, Takser et al., 2003), while studies in environmentally-exposed children have also measured Mn levels in hair (Bouchard et al., 2007, Bouchard et al., 2011b, Eastman et al., 2013, Menezes-Filho et al., 2011, Riojas-Rodriguez et al., 2010, Wright et al., 2006), in the exposure medium (e.g., water) (Bouchard et al., 2011b, Khan et al., 2012, Wasserman et al., 2006), or in teeth (Arora et al., 2012, Ericson et al., 2007). Studies on Mn toxicokinetics suggest that blood may best reflect recent exposures (i.e., days), while teeth may integrate longer-term exposures (e.g., months or longer) (Arora et al., 2011, Arora et al., 2012, Ericson et al., 2007, Smith et al., 2007). Deciduous teeth incorporate Mn in an incremental pattern and dentine, unlike enamel, can provide reliable information on the developmental timing of exposures to Mn that occur between the second trimester of pregnancy (starting at 13–16 weeks gestation, when incisors begin forming) and 10–11 months after birth (when molars stop developing) (Arora et al., 2012).

In this study, we measured prenatal and early postnatal dentine Mn levels in children's deciduous teeth, and examined the association of Mn levels with behavior, cognition, memory, and motor development in 7-, 9-, and 10.5-year-old children living in an agricultural community in California where large amounts of Mn-containing fungicides are applied.

Section snippets

Study population

The Center for the Health Assessment of Mother and Children of Salinas (CHAMACOS) is a birth cohort study examining the health effects of pesticide and other environmental exposures in Mexican-American children living in the Salinas Valley, California. Common crops in this agricultural region include lettuce, strawberries, grapes, and broccoli. About 110,000 kg of Mn-containing fungicides, mancozeb and maneb (20% Mn by weight) (FAO, 1980), were used in Monterey County in 2012 (CDPR, 2014), but

Results

Most women in the present study were young (mean age = 26.8 ± 5.1 years at delivery of their CHAMACOS child), born in Mexico (88%), multiparous (67%), did not complete high school (76%), did not work in agriculture during pregnancy (63%), and had a family income below the U.S. poverty threshold (60%, Table 1). Many women reported sufficient symptoms at the 7- and 9-year follow-up visits to qualify as “at-risk” of depression on the CES-D scale (21% and 27%, respectively; data not shown). Geometric

Discussion

We found that prenatal and early postnatal Mn levels in dentine of deciduous teeth were adversely associated with behavioral outcomes, namely maternal-reported internalizing, externalizing, and hyperactivity problems, in school-age boys and girls. In contrast, we observed that prenatal and postnatal Mn dentine levels were favorably associated with several measures of cognition, visuospatial and verbal memory, and motor function in boys. We also found that higher prenatal Mn levels were

Funding sources

This work was funded by research grant numbers P01 ES009605 and R01 ES015572 from the National Institute for Environmental Health Sciences (NIEHS) and R 82670901, RD 83171001, and RD 83451301 from the U.S. Environmental Protection Agency (EPA). Mora is a scholar of the Ministry of Science, Technology and Telecommunications of Costa Rica (MICITT) and the Universidad Nacional, Costa Rica. Its contents are solely the responsibility of the authors and do not necessarily represent the official views

Conflict of interest statement

One of the authors (AB) has served as a consultant on cases unrelated to the issues covered in this paper and has participated as a member of the board for The Organic Center, a non-profit organization that provides information for scientific research about organic food and farming. The other authors declare that they have no actual or potential competing financial interests.

Acknowledgments

We thank the CHAMACOS staff, students, community partners, and participants and families, as well as N. Holland and biorepository staff for their assistance in specimen management. We would also like to thank L. Pardo for her assistance with the literature review.

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