Review Early life environment, neurodevelopment and the interrelation with atopy J. Sunyer a,b,c,d,n , X. Basagan ˜a a,b,c , J.R. Gonza ´ lez a,b,c , J. Ju ´ lvez a,b,c , S. Guerra a,b,c , M. Bustamante c,e , R. de Cid e , J.M. Anto ´ a,b,c,d , M. Torrent c,f a Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain b Institut Municipal d’Investigacio ´M edica (IMIM)—Hospital del Mar, Barcelona, Spain c CIBER Epidemiologia y Salud Publica (CIBERESP), Barcelona, Spain d Department of Experimental and Health Sciences, University of Pompeu Fabra, Barcelona, Spain e Genes and Disease Program, Centre for Genomic Regulation (CRG), Barcelona, Spain f Menorca Health Area, Ib-Salut, Menorca, Spain article info Article history: Received 17 November 2009 Received in revised form 29 June 2010 Accepted 12 July 2010 Available online 10 August 2010 Keywords: Neurodevelopment Atopy Genes DDT NO 2 abstract Both neurological and immunological systems are vulnerable to early life exposures. Neurological disorders and atopy have been related in animals and humans. Our main objective was to assess whether multiple exposures to early life determinants remain associated with neurodevelopment after considering the potential intermediate role of atopy. A second objective was to assess whether genes associated with atopy may inform about the potential neurotoxical mechanisms. Children were members of the AMICS birth cohort in Menorca (n ¼418, 87% of the recruited). General cognition was measured with the McCarthy Scales at age 4 and atopy through specific IgE at age 4 and prick test at age 6; 85 single nucleotide polymorphisms (SNPs) in 16 atopy and detoxification genes were genotyped. Among the 27 risk factors assessed, lower maternal social class, maternal smoking during pregnancy, being first born, shorter breastfeeding, higher DDT levels in cord blood, and higher indoor levels of NO 2 (among the non-detoxifiers by GSTP1 polymorphism) were independently associated with poorer cognition. These associations were apparently not mediated by the relation between atopy and general cognition. Among the candidate atopic genes, variants in NQ01 (a detoxification gene) and NPRS1 (related with affective disorders like anxiety and stress management) had a significant association with general cognition (p-value o0.001). However, adjustment for the corresponding SNPs did not change the association between the early life determinants and general cognition. Multiple environmental pre-natal exposures were associated with neurodevelopment indepen- dently of their role in the immunological system. Atopic genes related to neurodevelopment suggest some potential mechanisms. & 2010 Elsevier Inc. All rights reserved. Contents 1. Introduction ...................................................................................................... 734 2. Methods ......................................................................................................... 734 2.1. Design and population........................................................................................ 734 2.2. Neurodevelopment .......................................................................................... 734 2.3. Atopy ..................................................................................................... 734 2.4. Candidate gene selection ...................................................................................... 734 2.5. Socio-environmental variables ................................................................................. 735 2.6. Statistical analysis ........................................................................................... 735 3. Results .......................................................................................................... 735 4. Discussion ....................................................................................................... 735 Acknowledgments ................................................................................................. 737 References ....................................................................................................... 737 Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/envres Environmental Research 0013-9351/$ - see front matter & 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.envres.2010.07.005 n Corresponding author at: Centre for Research in Environmental Epidemiology (CREAL), C. Dr. Aiguader, 88, 08003 Barcelona, Spain. Fax: + 34 93 316 05 75. E-mail address: jsunyer@creal.cat (J. Sunyer). Environmental Research 110 (2010) 733–738