The aim of this study was to evaluate the association between maternal smoking  during pregnancy (MSP) and lifetime risk for alcohol use disorder (AUD) and to  explore possible mechanisms through which MSP may be related to neurobehavioral  conditions during infancy and childhood, which could, in turn, lead to increased  risk for AUD. 
A sample of 1,625 individuals was followed from pregnancy  for more than 40 years. Capitalizing on the long follow-up time, we used  survival analysis to examine lifetime risks of AUD (diagnosed according to the  Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) in  relation to levels of MSP (none, <20 cigarettes/day, and ≥20 cigarettes/day).  We then used structural equation modeling to test hypotheses regarding potential  mechanisms, including lower birth weight, neurological abnormalities, poorer  academic functioning, and behavioral dysregulation.
Relative to  unexposed offspring, offspring of mothers who smoked 20 cigarettes per day or  more exhibited greater risks for AUD (hazard ratio = 1.31, 95% CI [1.08, 1.59]).  However, no differences were observed among offspring exposed to fewer than 20  cigarettes per day. In structural equation models, MSP was associated with  neurobehavioral problems during infancy and childhood, which, in turn, were  associated with an increased risk for adult AUD. 
MSP was associated  with an increased lifetime risk for AUD. Adverse consequences were evident from  birth to adulthood. A two-pronged remedial intervention targeted at both the  mother (to reduce smoking during pregnancy) and child (to improve academic  functioning) may reduce the risk for subsequent AUD. 
Request Reprint E-Mail:  yoko.nomura@mssm.edu    
