Pregnancy Outcomes After Human Papillomavirus Vaccination in Periconceptional Period or During Pregnancy: A Systematic Review and Meta-analysis

Background: National immunization schedules in many countries recommend HPV vaccination for females until the age of 26?years, and thus substantial numbers with reproductive age may be exposed to HPV vaccines. Objective: To assess whether inadvertent HPV vaccine exposures in the periconceptional period or during pregnancy were associated with increased risks for adverse pregnancy outcomes. Search strategy: A search of PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang databases (until March 31, 2019) was performed. Selection criteria: Studies that assess the risk of adverse pregnancy outcomes in HPV vaccine exposed/unexposed pregnancies were included. The adverse pregnancy outcomes included spontaneous abortion, stillbirth, small for sestational age, preterm birth, and birth defects. Data collection and analysis: The pooled relative risk (RR) was applied for the effect measure of the study. RRs and 95% confidence interval (CI) were measured when the paper did not report the effect. Heterogeneity between studies was assessed using the Cochrane?s Q and I-2 statistics. Main results: Of 374 identified citations, 8?met inclusion criteria. Compared with the unexposed pregnancies, HPV vaccine exposed pregnancies were associated with no higher risk for spontaneous abortion (RR, 0.99 [95% CI, 0.90 to 1.08]); stillbirth (RR, 1.16 [95% CI, 0.71 to 1.90]); small for gestational age (RR, 0.96 [95% CI, 0.86 to 1.07]); preterm birth (RR, 1.04 [95% CI, 0.91 to 1.18]); or birth defects (RR, 1.18 [95% CI, 0.97 to 1.43]). Conclusions: Inadvertent bivalent/quadrivalent HPV vaccination during pregnancy was not associated with significantly greater risks of adverse pregnancy outcomes.