Behavioral and neural consequences of prenatal exposure to nicotine.
OBJECTIVE
To review evidence for the neurodevelopmental effects of in utero exposure to nicotine. Concerns about long-term cognitive and behavioral effects of prenatal exposure to nicotine arise from reports of increased rates of disruptive behavioral disorders in children whose mothers smoked during pregnancy. The relatively high rate of tobacco smoking among pregnant women (25% of all pregnancies in the U.S.) underlines the seriousness of these concerns.


METHODS
This review examines the largest and most recent epidemiological and clinical studies that investigated the association of prenatal nicotine exposure with health, behavioral, and cognitive problems. Because of the numerous potential confounding variables in human research, findings from animal studies, in which environmental factors are strictly controlled, are also discussed. Finally, neural and molecular mechanisms that are likely to underlie neurodevelopmental disruptions produced by prenatal nicotine exposure are outlined.


RESULTS
A dose-response relationship between maternal smoking rates and low birth weight (potentially associated with lower cognitive ability) and spontaneous abortion is consistently found, whereas long-term developmental and behavioral effects in the offspring are still controversial, perhaps because of the difficulty of separating them from other genetic and environmental factors. Despite the wide variability of experimental paradigms used in animal studies, common physical and behavioral effects of prenatal exposure to nicotine have been observed, including low birth weight, enhanced locomotor activity, and cognitive impairment. Finally, disturbances in neuronal pathfinding, abnormalities in cell proliferation and differentiation, and disruptions in the development of the cholinergic and catecholaminergic systems all have been reported in molecular animal studies of in utero exposure to nicotine.


CONCLUSIONS
Prenatal exposure to nicotine may lead to dysregulation in neurodevelopment and can indicate higher risk for psychiatric problems, including substance abuse. Knowledge of prenatal exposure to nicotine should prompt child psychiatrists to closely monitor at-risk patients.
Ernst
M
M
Brain Imaging Center in the Neuroimaging Branch of the Intramural Research Program of the National Institute on Drug Abuse, Bethesda, MD 20892-0135, USA. ernstm@intra.nimh.nih.gov
Moolchan
E T
ET
Robinson
M L
ML
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000209:etiology*; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000453:epidemiology / Q000209:etiology*; D001921:Brain / Q000187:drug effects*; D002675:Child, Preschool; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005315:Fetal Diseases / Q000209:etiology*; D006801:Humans; D007223:Infant; D008425:Maternal Behavior; D009538:Nicotine / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects*; D013995:Time
D011978:Receptors, Nicotinic; D009538:Nicotine