Purpose/Background: Trazodone is indicated for the treatment of major depressive disorder, but more frequently prescribed off-label at lower doses for insomnia in women of childbearing age. The aim of this study was to assess the risks linked to trazodone exposure during pregnancy for which limited safety data are available. Methods/Procedures: This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to trazodone in early pregnancy against those in a reference group of women exposed to a selective serotonin reuptake inhibitors (SSRIs) between 1996 and 2021. Findings/Results: The sample included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the first trimester was not associated with a significant difference in the risk of major congenital anomalies (trazodone [1/169, 0.6%]; SSRI [19/730, 2.6%]; adjusted odds ratio, 0.2; 95% confidence interval, 0.03–1.77). The cumulative incidences of live birth were 61% and 73% in the trazodone and reference group, respectively (25% vs 18% for pregnancy loss and 14% vs 10% for pregnancy termination). Trazodone exposure was not associated with a significantly increased risk of pregnancy termination and pregnancy loss. The rate of small for gestational age infants did not differ between the groups. Implications/Conclusions: This study did not reveal a significant difference in the risk of major congenital anomalies after first trimester exposure to trazodone, compared with SSRI exposure. Although this study is the largest so far, these results call for confirmation through further studies.

Background: Bilastine is a long-acting, nonsedating antihistamine used to treat allergic conditions. Human pregnancy experience with bilastine remains limited. Objectives: The primary aim was to evaluate the risk of major anomalies following first-trimester bilastine exposure. Secondary endpoints included additional pregnancy outcomes. Methods: This observational, prospective cohort study included women counseled by the Israeli Teratology Information Service regarding first-trimester bilastine exposure between July 2019 and June 2023. Participants were contacted by telephone for follow-up using a structured questionnaire. Pregnancy outcomes were compared with fexofenadine-exposed pregnancies. The data analysis, comparison, and presentation followed the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guide. Results: Follow-up was obtained for 36 pregnancies with at least first-trimester bilastine exposure. The median daily bilastine dose was 20 mg, with treatment discontinued at a median gestational age of 5 + 6 weeks. First-trimester bilastine exposure was not associated with an increased risk of major anomalies [bilastine: 2/33, 6.1% vs. fexofenadine: 2/27, 7.4%; crude OR 0.81, 95% CI 0.11–6.14]. No pattern of malformations was observed. Rates of live-birth, miscarriage, and pregnancy termination were 91.7%, 5.6%, and 2.8% in the bilastine group, and 72.2%, 19.4%, and 8.3% in the fexofenadine group, respectively. Conclusions: This cohort study, although small, provides preliminary reassurance for counseling regarding inadvertent early pregnancy exposure to bilastine. Larger studies are needed to validate these findings.