Quadrivalent human papillomavirus vaccination before pregnancy and pregnancy outcomes: nationwide, population based case-control study.
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OBJECTIVE: To evaluate the association between quadrivalent human papillomavirus vaccination before pregnancy and subsequent risk of adverse pregnancy outcomes. DESIGN: Nationwide, population based matched case-control study. SETTING: Population of Sweden, from 1 January 2006 to 31 December 2023. PARTICIPANTS: 624 713 singleton births among nulliparous women aged 16-35 years in Sweden between 2006 and 2023; 92 620 (14.8%) women had received quadrivalent human papillomavirus vaccination before pregnancy. MAIN OUTCOME MEASURES: Risk of adverse pregnancy outcomes associated with quadrivalent human papillomavirus vaccination, with preterm birth (<37 weeks), including its subtypes, and spontaneous preterm birth as primary outcomes and preterm prelabour rupture of membranes, prelabour rupture of membranes, small for gestational age infant (<10th centile), severe small for gestational age infant (<3rd centile), stillbirth, and neonatal mortality as secondary outcomes. Effect modification by age at human papillomavirus vaccination was assessed. Conditional logistic regression was used to estimate odds ratios and adjusted odds ratios with 95% confidence intervals (CIs). RESULTS: After adjustment for confounders, quadrivalent human papillomavirus vaccination was associated with lower odds of all included adverse pregnancy outcomes. Statistically significant associations were observed for preterm birth (<37 weeks) (adjusted odds ratio 0.95, 95% CI 0.91 to 0.99), very preterm birth (28 weeks to 31 weeks) (0.85, 0.75 to 0.97), spontaneous preterm birth (0.95, 0.91 to 0.99), preterm prelabour rupture of membranes (0.93, 0.87 to 1.00), and severe small for gestational age infant (0.92, 0.87 to 0.97). Risk reduction was generally more pronounced among women vaccinated at younger ages. CONCLUSIONS: Quadrivalent human papillomavirus vaccination before pregnancy was associated with a lower risk of adverse pregnancy outcomes, particularly among women vaccinated at earlier ages, extending benefits of human papillomavirus vaccination beyond cancer prevention.