Prenatal alcohol exposure and offspring cognition and school performance. A ‘Mendelian randomization’ natural experiment

Luisa Zuccolo,George Davey Smith,Ron Gray,Sarah J Lewis,Jon Heron,Rosa Alati,Robert Fraser,John Macleod,Elizabeth S Draper,Margaret Barrow,Jean Golding,Kapil Sayal,Sue Ring

doi:10.1093/ije/dyt172

Abstract

Background There is substantial debate as to whether moderate alcohol use during pregnancy could have subtle but important effects on offspring, by impairing later cognitive function and thus school performance. The authors aimed to investigate the unconfounded effect of moderately increased prenatal alcohol exposure on cognitive/educational performance.Methods We used mother-offspring pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) and performed both conventional observational analyses and Mendelian randomization using an ADH1B variant (rs1229984) associated with reduced alcohol consumption. Women of White European origin with genotype and self-reported prenatal alcohol consumption, whose offspring’s IQ score had been assessed in clinic (N = 4061 pairs) or Key Stage 2 (KS2) academic achievement score was available through linkage to the National Pupil Database (N = 6268), contributed to the analyses.Results Women reporting moderate drinking before and during early pregnancy were relatively affluent compared with women reporting lighter drinking, and their children had higher KS2 and IQ scores. In contrast, children whose mothers’ genotype predisposes to lower consumption or abstinence during early pregnancy had higher KS2 scores (mean difference +1.7, 95% confidence interval +0.4, +3.0) than children of mothers whose genotype predisposed to heavier drinking, after adjustment for population stratification.Conclusions Better offspring cognitive/educational outcomes observed in association with prenatal alcohol exposure presumably reflected residual confounding by factors associated with social position and maternal education. The unconfounded Mendelian randomization estimates suggest a small but potentially important detrimental effect of small increases in prenatal alcohol exposure, at least on educational outcomes.

Highlights

Women reporting moderate drinking before and during early pregnancy were relatively affluent compared with women reporting lighter drinking, and their children had higher Key Stage 2 (KS2) and intelligence quotient (IQ) scores
Better offspring cognitive/educational outcomes observed in association with prenatal alcohol exposure presumably reflected residual
We investigated the association of early prenatal alcohol exposure based on mothers’ self-reported alcohol use before and in the early stages of pregnancy with child intelligence quotient (IQ) at age 8 years and school performance at age 11 years among the offspring of women participating in Avon Longitudinal Study of Parents and Children (ALSPAC)

Summary

Introduction

Heavy alcohol drinking during pregnancy is known to have detrimental effects on the foetus.[1,2,3,4] Whereas the majority of expectant mothers do not drink heavily, there is concern that the more prevalent light-to-moderate alcohol use could have subtle but important effects on offspring, by influencing cognitive function and school performance.[5,6,7,8] Such an effect could be of substantial public health importance, as educational success is a key influence on subsequent life trajectories.Epidemiological research on the effects of alcohol use during pregnancy has generated contrasting and occasionally paradoxical findings—reminding us that identifying true causal effects in observational research is often difficult.[9]. Heavy alcohol drinking during pregnancy is known to have detrimental effects on the foetus.[1,2,3,4] Whereas the majority of expectant mothers do not drink heavily, there is concern that the more prevalent light-to-moderate alcohol use could have subtle but important effects on offspring, by influencing cognitive function and school performance.[5,6,7,8] Such an effect could be of substantial public health importance, as educational success is a key influence on subsequent life trajectories. There is substantial debate as to whether moderate alcohol use during pregnancy could have subtle but important effects on offspring, by impairing later cognitive function and school performance. The authors aimed to investigate the unconfounded effect of moderately increased prenatal alcohol exposure on cognitive/educational performance

Methods

Discussion

Conclusion