Safety of haloperidol and penfluridol in pregnancy: a multicenter, prospective, controlled study.

OBJECTIVE: To assess the safety of the butyrophenone neuroleptics haloperidol and penfluridol in pregnancy. METHOD: The rate of major anomalies was compared between a cohort of pregnant women counseled for gestational exposure to haloperidol or penfluridol and a control group counseled for nonteratogen exposure. This multicenter, prospective, controlled study was conducted within the European Network of Teratology Information Services (ENTIS) and included women who contacted 1 of 4 teratology information services for counseling between January 1989 and December 2001. RESULTS: We followed up on the outcomes of 215 pregnancies exposed to haloperidol (N = 188) or penfluridol (N = 27)-78.2% (of 206) were in the first trimester-and compared to outcomes of 631 ENTIS controls. The rate of congenital anomalies did not differ between the haloperidol/penfluridol-exposed group and the control group (6/179 = 3.4% vs. 22/581 = 3.8%, p = .787). No difference was found by limiting the analysis to those exposed to butyrophenones during the first trimester. There were 2 cases of limb defects in the butyrophenone-exposed group (1 after haloperidol and 1 after penfluridol exposure) and none in the controls. A higher rate of elective terminations of pregnancy (8.8% vs. 3.8%, p = .004), a higher rate of preterm birth (13.9% vs. 6.9%, p = .006), a lower median birth weight (3155 g vs. 3370 g, p < .001), and a lower median birth weight of full-term infants (3250 g vs. 3415 g, p = .004) were found in the butyrophenone-exposed group compared to the controls. CONCLUSION: This study suggests that haloperidol and penfluridol do not represent a major teratogenic risk. Since a possible association between butyrophenone exposure and limb defects cannot be ruled out with this sample size, a level II ultrasound with emphasis on the limbs should be considered in pregnancies with first trimester exposure.

Pregnancy outcome after exposure to ranitidine and other H2-blockers. A collaborative study of the European Network of Teratology Information Services.

BACKGROUND: Published data on pregnancy outcome after exposure to H2-blockers is scarce. The aim of the present study was to evaluate the data collected by the memberships of the European Network of Teratology Information Services (ENTIS). METHODS: The patients were pregnant women who or whose doctor or midwife did contact a Teratology Information Service for risk assessment after the use of a H2-blocker in pregnancy. The data were prospectively collected, i.e. before the outcome of pregnancy was known. Standardized procedures for data collection were used by each centre. The data of the exposed women were compared to those of a control group exposed to non-teratogenic substances. RESULTS: Data on the outcome of 553 pregnancies with exposure to an H2-blocker were evaluated (ranitidine n=335; cimetidine n=113, famotidine n=75; nizatidine n=15, roxatidine n=15). Most of them had been exposed at least in the first trimester. The incidence of premature deliveries was higher in the exposed group compared to the control group. There was no increase in the incidence of major malformations. Two pregnancies with maternal use of famotidine in early pregnancy were terminated after the prenatal diagnosis of a neural tube defect. CONCLUSION: There is no indication for an increased risk of major malformations after the use of H2-blockers during pregnancy.