title: Familial confounding of the association between maternal smoking during pregnancy and ADHD in offspring.
abstract: BACKGROUND
  Maternal Smoking During Pregnancy (SDP) has consistently been associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring, but recent studies indicate that this association might be due to unmeasured familial confounding.
  
  
  METHODS
  A total of 813,030 individuals born in Sweden between 1992 and 2000 were included in this nationwide population-based cohort study. Data on maternal SDP and ADHD diagnosis were obtained from national registers and patients were followed up from the age of 3 to the end of 2009. Hazard Ratios (HRs) were estimated using stratified Cox regression models. Cousin and sibling data were used to control for unmeasured familial confounding.
  
  
  RESULTS
  At the population level maternal SDP predicted ADHD in offspring (HR(ModerateSDP) = 1.89; HR(HighSDP)= 2.50). This estimate gradually attenuated toward the null when adjusting for measured confounders (HR(ModerateSDP)= 1.62; HR(HighSDP)= 2.04), unmeasured confounders shared within the extended family (i.e., cousin comparison) (HR(ModerateSDP)= 1.45; HR(HighSDP)= 1.69), and unmeasured confounders within the nuclear family (i.e., sibling comparison) (HR(ModerateSDP)= 0.88; HR(HighSDP)= 0.84).
  
  
  CONCLUSIONS
  Our results suggest that the association between maternal SDP and offspring ADHD are due to unmeasured familial confounding.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Skoglund
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Brian M
authors.initials: BM
authors.lastname: D'Onofrio
authors.forename: Paul
authors.initials: P
authors.lastname: Lichtenstein
authors.forename: Henrik
authors.initials: H
authors.lastname: Larsson
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D008297:Male; D009035:Mothers / Q000706:statistics & numerical data*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology* / Q000235:genetics; D016016:Proportional Hazards Models; D012307:Risk Factors; D035781:Siblings; D012907:Smoking / Q000453:epidemiology*; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
keywords: Maternal smoking during pregnancy; attention-deficit/hyperactivity disorder; confounding; sibling comparisons