Selective fetal malnutrition: the effect of nicotine, ethanol, and acetaldehyde upon in vitro uptake of alpha-aminoisobutyric acid by human term placental villous slices.

Intrauterine growth retardation (IUGR) is often associated with either tobacco smoking or ethanol abuse during pregnancy, and the two habits usually coexist. We tested the hypothesis that nicotine is placentotoxic, thereby contributing to tobacco-associated IUGR. In vitro uptake of alpha-aminoisobutyric acid (AIB) by normal human placental slices was examined in the presence of nicotine, 0.2-20 microM. Significant (p less than 0.05) reductions in AIB uptake were observed for nicotine, 2.5-20 microM, with a linear dose-response. Since ethanol, and its major metabolite, acetaldehyde, have previously been shown to impair human placental uptake of AIB, these two substances were tested for synergism with nicotine. No interaction was observed between nicotine (0.2 microM) and ethanol (1,000 mg/dl). An increased inhibition was observed for the combination of nicotine (0.2 microM) and acetaldehyde (500 microM), but two-way analysis of variance indicated that the effects are additive, rather than synergistic. It is concluded that nicotine inhibits term human placental transport of the actively transported, nonmetabolized amino acid, AIB. Such placentotoxicity may be a contributing factor in tobacco-associated IUGR. Abuse of ethanol concurrent with tobacco smoking by a pregnant woman may be more detrimental to placental amino acid transport than either substance alone.