Pregnancy outcomes after first trimester exposure to phentermine/fenfluramine.

BACKGROUND: Fenfluramine was withdrawn from the U.S. market in 1997 because of its association with cardiac-valve abnormalities in adults. The combination of fenfluramine and phentermine had been widely used to promote weight loss, and many women were inadvertently exposed during the first trimester of pregnancy. The possible effect on the developing fetus has not been studied.

METHODS: Controlled prospective cohort study comparing 98 women who had taken phentermine/fenfluramine to 233 women who had not, all of whom contacted the California Teratogen Information Service during pregnancy.

RESULTS: The proportion of liveborn infants with major structural anomalies was similar in the two groups (3.6% vs. 1.0%, relative risk (RR) 3.59; 95% confidence interval (CI) 0.61, 21.10), as was the proportion of infants with >or=3 minor anomalies (11.7% vs. 7.6%, RR 1.53; 95% CI 0.61, 3.82). Furthermore, no pattern of malformation was identified. There were no significant differences between the groups in spontaneous pregnancy loss (6.1% vs. 8.2%, P = 0.65) or premature delivery (8.6% vs. 7.7%, P = 0.95). Birth weight and head circumference were significantly increased in the exposed group; however, these differences were not associated with anorexiant use itself. The rate of gestational diabetes was significantly increased in pregnant women who took phentermine/fenfluramine during the first trimester of pregnancy.

CONCLUSIONS: Although it is not possible from this study to rule out weak to moderate associations, the lack of an increased risk of spontaneous pregnancy loss, and major or minor anomalies in the offspring of women who took phentermine/fenfluramine at the recommended daily dose during the first trimester of pregnancy is reassuring.