Prenatal smoking, alcohol and caffeine exposure and ADHD risk in childhood: parental comparisons and polygenic risk score (PRS) analyses

摘要: Background and aimsSeveral studies have indicated that maternal prenatal substance use may be associated with offspring ADHD via intrauterine effects. We investigated associations between smoking, alcohol caffeine consumption childhood risk accounting for shared familial factors. DesignFirst, we used a negative control design comparing paternal use. Three models were analyses: unadjusted (without confounders); adjusted (including confounders) mutually confounders partners use). The results meta-analysed across the cohorts. Second, polygenic scores (PRS) as proxies exposures. Maternal PRS genetic variants of coffee regressed against risk. triangulated two approaches to infer causality. SettingWe data from three longitudinal pregnancy cohorts: Avon Longitudinal Study Parents Children (ALSPAC) in UK, Generation R study (GenR) Netherlands Norwegian Mother, Father Child Cohort (MoBa) Norway. ParticipantsPhenotype available children was: NALSPAC=7,850; NGENR=3,849; NMOBA=43,512. Genotype mothers NALSPAC=7,074 NMOBA=14,583. MeasurementsOffspring around age 7-8 was derived by dichotomising symptom multiple questionnaires parental self-reported measured at 2nd trimester. FindingsThe pooled estimate showed an association (ORSMOKING=1.11, 95%CI 1.00-1.23; ORALCOHOL=1.27, 1.08-1.49; ORCAFFEINE=1.05, 1.00-1.11), while not fathers (ORSMOKING=1.03, 0.95-1.13; ORALCOHOL=0.83, 0.47-1.48; ORCAFFEINE=1.02, 0.97-1.07). However, did persist sensitivity analyses (substance before pregnancy, adjustment MoBa). show evidence ALSPAC or MoBa. ConclusionsOur do provide support causal effect on attention-deficit hyperactivity disorder