Tooth Matrix Biomarkers of Pre- and Postnatal Manganese Exposure and Motor Function in Adolescents

Abstract

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 192 children in Italy. Pursuit Aiming, Luria Nebraska Motor Battery, as well as Tremor and Sway system from Computerized Adaptive Testing System (CATSYS) were measured at 11-14 years old. We examined the relationships of tooth Mn (log-transformed) with motor function using generalized linear models 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 increased number of correct aiming dots (β=10.8, p=0.02) on the Pursuit Aiming test, particularly in boys (p for Mn × sex interaction=0.04). In contrast, higher cumulative childhood Mn was associated with poorer accuracy as indicated by the ratio of correct-to-total number of aiming dots (β=−0.04, p=0.04), particularly in girls (p for interaction=0.05). Higher prenatal Mn was also associated with lower tremor intensity of non-dominant hand (β=−1.16, p=0.048). We did not observe significant effect estimates of prenatal or postnatal Mn on Luria battery or Sway test. Conclusions: Our findings suggest that higher prenatal Mn levels measured in tooth dentine, a novel biomarker that provides reliable information on the timing of exposures to Mn, may be associated with better eye-hand coordination, particularly in boys. On the other hand, higher postnatal Mn was inversely associated with eye-hand coordination in girls. These data potentially support the existence of two distinct critical windows (prenatal vs. postnatal) of Mn exposure in relation to motor function.