(SLC-051) A Pregnancy Registry to Evaluate the Safety of CYD Tetravalent Dengue Vaccine among Inadvertently Exposed Pregnant Women and their Offspring

Background: CYD tetravalent dengue vaccine (CYD-TDV) is a live attenuated vaccine and contraindicated in pregnancy due to a theoretical risk to the fetus. Large-scale CYD-TDV vaccination programs in Paraná (Brazil) included women of childbearing age. As many pregnancies are unplanned, inadvertent exposure to CYD-TDV in pregnancy occurred.

Objectives: To assess the safety of CYD-TDV in inadvertently exposed pregnant women and their offspring.

Methods: This pregnancy registry study used Brazil's national database of spontaneous adverse events to identify and enroll pregnant women and their offspring who were inadvertently exposed to CYD-TDV in pregnancy or 30 days preceding their last menstrual period. The exposed pregnant women lived in the municipalities of Paraná during public vaccination campaigns (2016-2018). Data collection involved structured interviews, medical records, and government databases. Descriptive analyses (frequencies and 95% confidence interval [CI]) summarized pregnancy, birth, neonatal and infant outcomes, and were qualitatively compared with those expected from age- and municipality-matched unvaccinated pregnant women identified using government databases (when data was available) and with Brazilian studies in unvaccinated pregnant women.

Results: A total of 97 CYD-TDV exposed women and 97 fetuses were included in the analysis along with 964 unvaccinated pregnancies and 981 unexposed infants. A total of 55 (56.7%, 95% CI: 46.8, 66.1) and 20 exposed women (20.6%, 95% CI 13.8, 29.7) reported at least one complication of pregnancy and at least one complication of labor, delivery, and puerperium, respectively. The frequencies of each complication in exposed pregnant women were similar to either those obtained for unvaccinated pregnant women or from studies. Four exposed pregnancies (4.2%, 95% CI: 1.6, 10.2) ended in miscarriage and one (1.0%, 95% CI: 0.2, 5.7) in stillbirth, which are frequencies comparable with those in studies. Most exposed infants born alive were born at term (93.5%, 95% CI: 86.5, 97.0) and had a normal 5-min APGAR score (98.8%, 95% CI: 93.4, 99.8), similar to unexposed infants. Frequencies of the most common neonatal and infant adverse outcomes in exposed infants were comparable with those in studies, with intensive care unit admission, jaundice, and hypoglycemia each reported in 6 neonates (6.5%, 95% CI 3.0, 13.5), and seizures, asthma, and bronchiolitis/bronchitis each reported in 2 infants (2.2%, 95% CI: 0.6, 7.6). No adverse event was assessed as related to CYD-TDV.

Conclusions: No safety concerns were identified from inadvertent CYD-TDV pregnancy exposure. Given that such exposures are rare, and the study’s sample size was small, further safety assessment would require more pregnancy exposure data.