Pregnancy outcome after in utero exposure to itraconazole: A prospective cohort study

OBJECTIVE: This study was undertaken to determine whether itraconazole use during the first trimester of pregnancy was associated with increased risks of major malformations, spontaneous abortions, premature deliveries, and n eonatal complications. STUDY DESIGN: In a prospective cohort study pregnant women exposed to oral itraconazole were matched with control subjects not exposed to any known te ratogens. Primary outcome was the rate of major malformations. Secondary ou tcomes were live birth rate, rates of spontaneous abortion and therapeutic abortion, gestational age at delivery, birth weight, and neonatal complicat ions. RESULTS: A total of 229 women exposed to itraconazole were reported to the manufacturer, 198 of whom used the drug during the first trimester of pregn ancy. The rate of major malformations in the study group (156 live births) was 3.2%, compared with 4.8% in the control group (187 live births; relativ e risk, 0.67; 95% confidence interval, 0.23-1.95). The rate of any pregnanc y loss was higher in the exposed group (relative risk, 1.75; 95% confidence interval, 1.47-2.09). Birth weight was lower in the itraconazole group, al though that difference may not be clinically significant. Gestational age a t birth, rate of preterm delivery, Apgar scores at 1 and 5 minutes, and neo natal complications were comparable between the groups. CONCLUSION: Our study supports the hypothesis that the use of itraconazole during pregnancy is safe. Further surveillance and reporting of pregnancy o utcomes will help to support this conclusion.