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Title: Prenatal alcohol exposure and offspring cognition and school performance. A 'Mendelian randomization' natural experiment
Authors: Zuccolo, L.
Lewis, S. J.
Smith, G. D.
Sayal, K.
Draper, Elizabeth S.
Fraser, R.
Barrow, Margaret
Alati, R.
Ring, S.
Macleod, J.
Golding, J.
Heron, J.
Gray, R.
First Published: 24-Sep-2013
Publisher: Oxford University Press for International Epidemiological Association
Citation: International Journal of Epidemiology, 2013, 42 (5), pp. 1358-1370
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.
DOI Link: 10.1093/ije/dyt172
ISSN: 0300-5771
eISSN: 1464-3685
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © The Author 2013. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Appears in Collections:Published Articles, Dept. of Health Sciences

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