Prenatal alcohol exposure and offspring cognition and school performance. A 'Mendelian randomization' natural experiment.
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.
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK, Section of Developmental Psychiatry, University of Nottingham, Nottingham, UK, Department of Health Sciences, University of Leicester, Leicester, UK, School of Medicine, University of Sheffield, Sheffield, UK, Clinical Genetics, University Hospitals of Leicester, Leicester, UK, School of Population Health, University of Queensland, Brisbane, Queensland, Australia and National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK.
Luisa
L
Zuccolo
Sarah J
SJ
Lewis
George Davey
GD
Smith
Kapil
K
Sayal
Elizabeth S
ES
Draper
Robert
R
Fraser
Margaret
M
Barrow
Rosa
R
Alati
Sue
S
Ring
John
J
Macleod
Jean
J
Golding
Jon
J
Heron
Ron
R
Gray
D000124:Achievement; D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology* / Q000235:genetics; D015984:Causality; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D002648:Child; D003071:Cognition / Q000187:drug effects*; D015331:Cohort Studies; D004521:Educational Measurement / Q000706:statistics & numerical data; D004739:England / Q000453:epidemiology; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006801:Humans; D007361:Intelligence Tests / Q000706:statistics & numerical data; D016014:Linear Models; D008137:Longitudinal Studies; D008425:Maternal Behavior; D057182:Mendelian Randomization Analysis; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D055815:Young Adult
D002492:Central Nervous System Depressants; D000431:Ethanol; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase
Alcohol dehydrogenase; Mendelian randomization analysis; causality; cognition; confounding factors; educational measurement; ethanol; pregnancy