Pregnancy outcomes following unintentional exposure to TAK-003, a live-attenuated tetravalent dengue vaccine.

Background: The tetravalent dengue vaccine TAK-003 is contraindicated during pregnancy. Pregnant women were excluded from TAK-003 clinical studies; however, some pregnancies occurred unintentionally.

Research design and methods: This post-hoc analysis of phase 2 and 3 studies, evaluated pregnancy outcomes and neonatal adverse events (AEs) following unintentional vaccination during the time period ('exposure window') when women could be pregnant (within 44 days before last menstrual period until the outcome of pregnancy).

Results: Of the 557 reported pregnancies, 38 (TAK-003, n = 28/375; placebo, n = 10/182) occurred inside the exposure window. Of these, 28 (TAK-003, n = 23; placebo, n = 5) resulted in live births, four resulted in elective terminations (TAK-003, n = 2; placebo, n = 2), five in spontaneous abortions (TAK-003, n = 3; placebo, n = 2) and one unknown outcome (placebo).Of the spontaneous abortions, there was no significant difference between TAK-003 and placebo recipients, or between those occurring within or outside the exposure window. Six participants who received TAK-003 in the exposure window and two neonates experienced serious AEs; none were considered TAK-003 related.

Conclusions: This post-hoc analysis found no evidence of increased adverse pregnancy outcomes following unintentional TAK-003 vaccination occurring inside the exposure window compared with placebo.

Clinical trial registration: The clinical trials from which data were extracted are registered at www.clinicaltrials.gov (identifiers are NCT02193087, NCT01511250, NCT02302066, NCT02425098, NCT03746015, NCT02747927, NCT03999996, NCT03423173, NCT03342898, NCT03771963, NCT04313244, NCT02948829, NCT035252119, NCT03341637).