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.

Findings: 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 21.80 (95% CI =22.63 to 20.97) p = 0.00002, with no effect among children whose mothers abstained during pregnancy (0.16 (95%CI =21.05 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.

Sarah J. Lewis1*, Luisa Zuccolo1,2, George Davey Smith2, John Macleod1, Santiago Rodriguez1,2,
Elizabeth S. Draper4, Margaret Barrow5, Rosa Alati6, Kapil Sayal7, Susan Ring1, Jean Golding1, Ron Gray3