Early Life Multiple Exposures and Child Cognitive Function: A Multi-Centric Birth Cohort Study in Six European Countries

Background: Epidemiological studies on environmental risk factors for cognitive outcomes mostly focus on single environmental exposures or exposure families. The present study aims to systematically assess associations between a wide range of prenatal and childhood environmental exposures and cognitive functioning. Methods:The study sample included 1,298 children, aged 6-11 years, from six European birth cohorts. We measured 87 exposures during pregnancy and 122 cross-sectionally during childhood, including air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals and life styles. The measured cognitive domains were fluid intelligence (Raven's Coloured Progressive Matrices test, CPM), attention function (Attention Network Test, ANT) and working memory (N-Back task). We used two statistical approaches to assess associations between exposure and child cognition: the exposome-wide association study (ExWAS) considering each exposure independently, and the deletion-substitution-addition algorithm (DSA) considering all exposures simultaneously to build a final multiexposure model. Findings: Based on multiexposure model, child organic food intake was associated with higher fluid intelligence (CPM) scores (beta=1.18; 95% CI=0.50, 1.87) and higher working memory (N-Back) scores (0.23; 0.05, 0.41), and child fast food intake (-1.25; -2.10, -0.40), house crowding (-0.39; -0.62, -0.16), and child environmental tobacco smoke (ETS) (-0.89; -1.42, -0.35), were all associated with lower CPM scores. Indoor PM 2.5 exposure was associated with lower N-Back scores (-0.09; -0.16, -0.02). Additional associations in the unexpected direction were also found. Namely, higher prenatal mercury levels, maternal alcohol consumption and child higher perfluorooctane sulfonic acid (PFOS) levels were associated with better cognitive performance and higher green exposure during pregnancy with lower cognitive performance. Interpretation:This first comprehensive and systematic study of many prenatal and childhood environmental risk factors suggests that unfavourable child nutrition, family crowdedness and child indoor air pollution and ETS exposures adversely affect cognitive function. Unexpected associations were also observed and maybe due to confounding and reverse causality. Funding:European Community’s Seventh Framework Programme (FP7/2007-206) under grant agreement no 308333 – the HELIX project. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: The ethics committee for each cohort approved the consent form. We obtained written informed consent for all participants, signed by the parent.