Behavioral and Neural Consequences of Prenatal Exposure to Nicotine

doi:10.1097/00004583-200106000-00007

Journal of the American Academy of Child & Adolescent Psychiatry

Volume 40, Issue 6, June 2001, Pages 630-641

https://doi.org/10.1097/00004583-200106000-00007 Get rights and content

ABSTRACT

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.

Method

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.

Section snippets

NEUROBEHAVIORAL EFFECTS IN HUMANS

Epidemiological evidence from prospective and case-control studies displays a high degree of consistency for the association of adverse pregnancy outcomes with maternal smoking. Overall, the magnitude of the long-term effects of maternal smoking on the physical and mental development of offspring is small but measurable (Weitzman et al., 1992). There is strong support for a dose-response relationship of maternal smoking rates to low birth weight (potentially associated with lower cognitive

NEUROBEHAVIORAL EFFECTS OF IN UTERO EXPOSURE TO NICOTINE IN ANIMALS

Major outcome variables measured in animals prenatally exposed to nicotine have included birth weight, locomotor activity, and cognitive performance. These outcome measures can vary significantly as a function of nicotine dose, schedule of administration (continuous versus intermittent), route of administration, time of exposure (e.g., early versus late in gestation), and species. For example, a dose of 1.5 mg/kg per day produces a plasma nicotine concentration in rats similar to that of humans

NEURAL MECHANISMS OF BEHAVIORAL EFFECTS OF IN UTERO EXPOSURE TO NICOTINE

Because nicotine is readily transferred to the fetal compartment throughout pregnancy, the fetuses of mothers who smoke are exposed to relatively higher nicotine concentrations than their mothers (Luck et al., 1985). Nicotine acts primarily through its action on nAChRs. Although the premature activation of nAChRs by exogenous nicotine in the fetus has consequences that extend beyond the central nervous system CNS (e.g., autonomic ganglia and adrenal medulla), only CNS events will be considered.

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View all citing articles on Scopus

: The authors thank Dr. Bruce Vaupel for his help in preparing the manuscript.

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ArticlesBehavioral and Neural Consequences of Prenatal Exposure to Nicotine

ABSTRACT

Objective

Method

Results

Conclusions

Section snippets

NEUROBEHAVIORAL EFFECTS IN HUMANS

NEUROBEHAVIORAL EFFECTS OF IN UTERO EXPOSURE TO NICOTINE IN ANIMALS

NEURAL MECHANISMS OF BEHAVIORAL EFFECTS OF IN UTERO EXPOSURE TO NICOTINE

Pharmacol Biochem Behav

Biol Psychiatry

J Biol Chem

Lancet

Neurotoxicol Teratol

Nucl Med Biol

Brain Res Dev Brain Res

Neurotoxicol Teratol

Neurotoxicol Teratol

Eur J Pharmacol

Lancet

Am J Obstet Gynecol

Int J Dev Neurosci

Brain Res Dev Brain Res

Brain Res

Life Sci

Int J Dev Neurosci

Prog Brain Res

Neurotoxicol Teratol

Pharmacol Biochem Behav

Brain Res Dev Brain Res

J Am Acad Child Adolesc Psychiatry

Life Sci

Brain Res Bull

Brain Res Bull

Brain Res Dev Brain Res

Neurotoxicol Teratol

Appetite

Pharmacol Biochem Behav

Neurotoxicol Teratol

Early Hum Dev

Pharmacol Biochem Behav

Brain Res Dev Brain Res

Brain Res

Brain Res Bull

Brain Res Bull

Smoking during pregnancy: a review of effects on growth and development of offspring

Hum Biol

Smoking and reproductive health

Objectively measured tobacco exposure during pregnancy: neonatal effects and relation to maternal smoking

Br J Obstet Gynaecol

Fetal growth retardation due to maternal tobacco smoke exposure in the rat

Pediatr Res

Parental cigarette smoking and cognitive performance of children

Health Psychol

Cranial ultrasound abnormalities identified at birth: their relationship to perinatal risk and neurobehavioral outcome

Pediatrics

Effects of prenatal exposure to cigarette smoke and nicotine on pregnancy, offspring development and avoidance behavior in rats

Neurobehav Toxicol Teratol

Maternal smoking during pregnancy and adult male criminal outcomes

Arch Gen Psychiatry

A gradient relationship between low birth weight and IQ at age 6 years

Arch Pediatr Adolesc Med

High incidence of sudden infant death syndrome among northern Indians and Alaska natives compared with southwestern Indians: possible role of smoking

J Community Health

Smoking in pregnancy and subsequent child development

Br Med J

Cigarette smoking in pregnancy: its influence on birth weight and perinatal mortality

Br Med J

Postnatal development in the rat following pre or post natal exposure to nicotine

Res Commun Subst Abuse

Articles
Behavioral and Neural Consequences of Prenatal Exposure to Nicotine