Prenatal metals exposure and pre-adolescents’ emotional and behavioral problems

BACKGROUND AND AIM Humans are regularly exposed to metals and most of them can cross the placental barrier which can lead to adverse effects on the developing foetus. Our aim was to study the association between maternal metals and trace elements exposure during gestation and preadolescent’s emotional and behavioural problems at 9 years of age. Socio-demographic, environmental and dietary variables, as well as single nucleotide polymorphisms (SNPs) in brain- and metabolism-related genes, were considered. METHODS The study sample comprised Spanish mother-child pairs in the INMA (Environment and Childhood) cohort study recruited in the regions Valencia, Sabadell and Gipuzkoa (n=1027). Metals (Cd, Co, Cu, Mo, Ni, Pb, Sb, Se, Tl and Zn) were measured in urine samples collected during first and third trimesters of pregnancy. Arsenic (As) metabolites (monomethylarsenic acid, [MMA], dimethylarsenic acid, and inorganic As) were determined in a subsample (n=729). Behaviour was assessed at 9 years of age using the Child Behaviour Checklist (CBCL) composed of three scales: internalizing, externalizing and total problems. Sociodemographic, dietary and environmental variables were obtained through questionnaires. SNPs in APOE, BDNF, GSTP1, and PON1 were genotyped in cord blood DNA. Multivariate negative binomial models were built. The interaction with sex and genotypes was evaluated including interaction terms. RESULTS Increasing maternal urinary concentrations of Cu, MMA and Pb were associated with an increased incidence ratio risk (IRR 4.6-7.5%) in pre-adolescents for all three CBCL scales. Increasing Mo, Ni and Co concentrations were associated with higher IRR for internalizing problems (up to 8%), and Cd for the externalizing scale (6.7%). Modifications of sex and genotypes were found for several associations. CONCLUSIONS In our population, prenatal exposure to several metals was associated with worse scores on behavioral tests in pre-adolescents. Sex and genetic background may play a role in metals toxicity. KEYWORDS Metals, behavioral problems, prenatal exposure