PORTLAND, ORE—Impaired lung development and function in children whose mothers smoked cigarettes during pregnancy is well documented, but the component of tobacco that causes these deficits is unknown. New research in monkeys comes closer to identifying a “smoking gun”: nicotine.[1] The finding may have strong implications for pregnant women who are considering nicotine replacement.

Eliot R. Spindel, MD, PhD, and colleagues assessed lung development and function in newborn monkeys exposed to nicotine in utero. A number of nicotine’s effects on the monkeys strikingly resembled deficits in human children exposed in utero to maternal smoking, said Dr. Spindel, a senior scientist at Oregon Regional Primate Research Center in Beaverton: “First, the size and weight of the lung was slightly reduced. Second, expiratory flows were decreased, and mean mid-expiratory flow was lower. Third, airway resistance increased.” Thus, the research implicates nicotine in causing lung abnormalities associated with maternal smoking during pregnancy.

Previous discovery of nicotinic acetylcholine receptors in fetal lung tissue by Dr. Spindel’s team raised the possibility that nicotine itself might impair growth and development. The researchers tested this idea by subjecting seven pregnant monkeys to nicotine delivered continuously at 1.5 mg/kg/d, a dosage equivalent to that experienced by heavy smokers. The monkeys’ amniotic fluid nicotine titers were comparable to amniotic levels in pregnant human smokers. Seven monkeys receiving saline served as controls.

While nicotine exposure did not significantly affect overall somatic growth in the small sample of newborn monkeys, respiratory development was markedly impaired: Lungs were significantly lower in weight and volume than those of control monkeys. Vital capacity, expiratory reserve volume, and tidal volume were also reduced in the nicotine-exposed monkeys, although the decrement did not reach significance.

Prenatal maternal smoking is linked with sudden infant death syndrome (SIDS), as well as with pulmonary function deficits and increased risk for lower respiratory illness in older children and adolescents. Compared with children of nonsmokers, infants exposed in utero to maternal smoking show reduced peak expiratory flow, mean mid- expiratory flow, forced expiratory flow, and static compliance, and they have elevated airway resistance. Further, airway walls of SIDS victims whose mothers smoked during their gestation are thickened, a structural abnormality that may reduce both airway caliber and elasticity to impair function.

REDUCED PROLIFERATION, MORE CONNECTIVE TISSUE

“What we postulate is that interaction of nicotine with fibroblasts expressing the acetylcholine receptors leads to increased connective tissue and decreased cell proliferation,” Dr. Spindel told RESPIRATORY REVIEWS. In monkeys, “we’ve seen decreases in epithelial cells and fibroblasts. What we think is that the thickening is coming from the increase in connective tissue.”

—Mimi Zucker, PhD