Prenatal cadmium exposure and behavioural and emotional problems across childhood: findings from the INMA birth cohort.

Prenatal cadmium (Cd) exposure may impair placental function and disrupt biological processes relevant to foetal neurodevelopment, including oxidative stress and metal homeostasis, but epidemiological evidence linking Cd to childhood behavioural and emotional problems remains inconsistent. We examined whether prenatal Cd exposure was associated with behavioural and emotional symptoms from early childhood to pre-adolescence in the Spanish INMA birth cohort. We included 1270 mother-child pairs from Valencia, Sabadell, and Gipuzkoa. Cd and creatinine were measured in maternal urine collected in the first and third trimesters of pregnancy, and average prenatal Cd exposure was analysed. Behavioural and emotional outcomes were assessed at ages 4-5, 7-8, 9, and 11 years using the ADHD-DSM-IV, Strengths and Difficulties Questionnaire, and Conners' Parent Rating Scales-Revised. Associations were estimated using multivariable negative binomial and mixed-effects models, with additional analyses for trimester-specific exposure, non-linearity, and effect modification by selected single nucleotide polymorphisms. Prenatal Cd exposure was not associated with any behavioural or emotional outcome across childhood. Results were also null when exposure was analysed separately for the first and third trimesters. In contrast, male sex and maternal smoking during pregnancy were consistently associated with poorer behavioural scores, whereas higher parental education and parity were generally associated with lower symptom levels. Interaction analyses indicated greater susceptibility among children whose mothers carried the MT1DP rs8044719 GT + TT genotype. In this population-based cohort, prenatal Cd exposure was not associated with behavioural or emotional problems across childhood. The findings nevertheless suggest that genetic susceptibility may contribute to interindividual differences in Cd-related neurodevelopmental vulnerability.