title: Fetal alcohol exposure and IQ at age 8: evidence from a population-based birth-cohort study.
abstract: BACKGROUND
  Observational studies have generated conflicting evidence on the effects of moderate maternal alcohol consumption during pregnancy on offspring cognition mainly reflecting problems of confounding. Among mothers who drink during pregnancy fetal alcohol exposure is influenced not only by mother's intake but also by genetic variants carried by both the mother and the fetus. Associations between children's cognitive function and both maternal and child genotype at these loci can shed light on the effects of maternal alcohol consumption on offspring cognitive development.
  
  
  METHODS
  We used a large population based study of women recruited during pregnancy to determine whether genetic variants in alcohol metabolising genes in this cohort of women and their children were related to the child's cognitive score (measured by the Weschler Intelligence Scale) at age 8.
  
  
  RESULTS
  We found that four genetic variants in alcohol metabolising genes in 4167 children were strongly related to lower IQ at age 8, as was a risk allele score based on these 4 variants. This effect was only seen amongst the offspring of mothers who were moderate drinkers (1-6 units alcohol per week during pregnancy (per allele effect estimates were -1.80 (95% CI= -2.63 to -0.97) p=0.00002, with no effect among children whose mothers abstained during pregnancy (0.16 (95%CI= -1.05 to 1.36) p=0.80), p-value for interaction  =0.009). A further genetic variant associated with alcohol metabolism in mothers was associated with their child's IQ, but again only among mothers who drank during pregnancy.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. s.j.lewis@bristol.ac.uk
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lewis
authors.forename: Luisa
authors.initials: L
authors.lastname: Zuccolo
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.forename: John
authors.initials: J
authors.lastname: Macleod
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Draper
authors.forename: Margaret
authors.initials: M
authors.lastname: Barrow
authors.forename: Rosa
authors.initials: R
authors.lastname: Alati
authors.forename: Kapil
authors.initials: K
authors.lastname: Sayal
authors.forename: Susan
authors.initials: S
authors.lastname: Ring
authors.forename: Jean
authors.initials: J
authors.lastname: Golding
authors.forename: Ron
authors.initials: R
authors.lastname: Gray
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics*; D002648:Child; D003071:Cognition / Q000187:drug effects*; D015331:Cohort Studies; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D007361:Intelligence Tests; D015810:Linkage Disequilibrium; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors; D012680:Sensitivity and Specificity; D011795:Surveys and Questionnaires; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000431:Ethanol; D000426:Alcohol Dehydrogenase