ObjectiveTo assess the influence of active maternal smoking on fetal amino acid and enzyme levels in early pregnancy.MethodsThe concentrations of 23 free amino acids and total protein, and the activity levels of four enzymes were measured in samples of maternal and fetal plasma from nine nonsmokers who were not exposed to tobacco smoke and nine long-term, heavy smokers matched for gestational age. To determine fetal exposure to smoking, cotinine levels were measured in maternal and fetal plasma and fetal liver samples from both groups. The pregnancies were between 12 and 17 weeks' gestation.ResultsIn women who smoke, the median cotinine concentrations were 156 mg/mL in maternal plasma and 89 ng/mL in fetal plasma, but only one fetal liver sample contained detectable cotinine. Significantly lower concentrations of serine, proline, &agr;-aminobutyric acid, leucine, and arginine were found in smokers compared with nonsmokers, with the lowest in arginine. Fetal plasma amylase activity was significantly higher in smokers than controls. There were no differences in concentrations of other amino acids or activity levels of other enzymes in the two groups.ConclusionMaternal smoking affected placental and fetal protein metabolism and enzyme activity from at least 12 weeks' gestation. That finding indicates that high levels of tobacco exposure in the first trimester might cause irreversible changes in the cellular functions of the villous trophoblastic barrier.