title: Moderate alcohol drinking in pregnancy increases risk for children's persistent conduct problems: causal effects in a Mendelian randomisation study.
abstract: BACKGROUND
  Heavy alcohol use during pregnancy can cause considerable developmental problems for children, but effects of light-moderate drinking are uncertain. This study examined possible effects of moderate drinking in pregnancy on children's conduct problems using a Mendelian randomisation design to improve causal inference.
  
  
  METHODS
  A prospective cohort study (ALSPAC) followed children from their mother's pregnancy to age 13 years. Analyses were based on 3,544 children whose mothers self-reported either not drinking alcohol during pregnancy or drinking up to six units per week without binge drinking. Children's conduct problem trajectories were classified as low risk, childhood-limited, adolescence-onset or early-onset-persistent, using six repeated measures of the Strengths and Difficulties Questionnaire between ages 4-13 years. Variants of alcohol-metabolising genes in children were used to create an instrumental variable for Mendelian randomisation analysis.
  
  
  RESULTS
  Children's genotype scores were associated with early-onset-persistent conduct problems (OR = 1.29, 95% CI = 1.04-1.60, p = .020) if mothers drank moderately in pregnancy, but not if mothers abstained from drinking (OR = 0.94, CI = 0.72-1.25, p = .688). Children's genotype scores did not predict childhood-limited or adolescence-onset conduct problems.
  
  
  CONCLUSIONS
  This quasi-experimental study suggests that moderate alcohol drinking in pregnancy contributes to increased risk for children's early-onset-persistent conduct problems, but not childhood-limited or adolescence-onset conduct problems.
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Murray
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Burgess
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.|MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: Luisa
authors.initials: L
authors.lastname: Zuccolo
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hickman
authors.affiliation: National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Ron
authors.initials: R
authors.lastname: Gray
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lewis
mesh_terms: D000293:Adolescent; D000428:Alcohol Drinking / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D019955:Conduct Disorder / Q000139:chemically induced* / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics*; D011897:Random Allocation
keywords: ALSPAC; Foetal alcohol effects; conduct disorder; longitudinal study; mendelian randomization analysis