Maternal and Infant Outcomes After Human Papillomavirus Vaccination in the Periconceptional Period or During Pregnancy

Abstract

Objective: To evaluate whether quadrivalent human papillomavirus vaccine (4vHPV) administered during the periconceptional period or during pregnancy was associated with increased risks for adverse obstetric events, adverse birth outcomes, or selected major structural birth defects.

Methods: We conducted a retrospective, observational cohort study using administrative and health care data from the Vaccine Safety Datalink. Insured women 13-27 years old with singleton pregnancies and a live birth from January 1, 2007, through September 1, 2013, who received 4vHPV during the periconceptional period (2 weeks before to 2 weeks after their last menstrual period), during pregnancy, or during both periods combined were compared with women who had a live birth during the same time period and received 4vHPV 4-18 months before their last menstrual period. We examined risks of gestational diabetes, hypertensive disorders of pregnancy, chorioamnionitis, preterm birth, small-for-gestational-age birth, and selected major structural birth defects in offspring. We estimated relative risks associated with receipt of 4vHPV during the periconceptional period, during pregnancy, and both exposure periods combined using a generalized linear model with Poisson distribution including a propensity score that included relevant maternal demographic and pregnancy characteristics.

Results: Of 92,579 potentially eligible pregnant women, 720 received 4vHPV during the periconceptional period, 638 received 4vHPV during pregnancy, and 8,196 received 4vHPV during the comparison period. Administration of 4vHPV during pregnancy was not associated with increased risk of adverse obstetric events, birth outcomes. Preterm birth occurred in 7.9% of pregnancies with vaccine exposures during pregnancy compared with 7.6% of pregnancies with vaccination in the comparison period (adjusted relative risk 0.97, 95% CI 0.72-1.3). Major structural birth defects were diagnosed in 2.0% of pregnancies with vaccine exposure during pregnancy compared with 1.8% of pregnancies with vaccine exposure during the comparison period (adjusted prevalence ratio 1.0, 95% CI 0.52-1.9). Results were similar for 4vHPV exposure during the periconceptional period.

Conclusion: Quadrivalent HPV vaccine inadvertently administered in pregnancy or during the periconceptional period was not associated with adverse pregnancy or birth outcomes.

Fig. 1.

Flowchart. 4vHPV, quadrivalent human papillomavirus (HPV) vaccine. *Except for one site, January 20, 2009–September 30, 2013. ^†Continuous insurance enrollment from 6 months before their last menstrual period through 6 weeks postpartum. ^‡Eighteen to 4 months before pregnancy. ^§Two weeks before to 2 weeks after last menstrual period. ^‖Two to 28 weeks of gestation. ^¶Isotretinoin, bexarotene, acitretin, misoprostol, methotrexate, mycophenolate mofetil, azathioprine, thalidomide, warfarin, lithium, amiodarone, dronedarone, carbamazepine, fosphenytoin, phenytoin, mephobarbital, phenobarbital, primidone, topiramate, valproate, leflunamide. ^#Toxoplasmosis, syphilis, varicella, rubella, and cytomegalovirus in mother’s chart. **Infants surviving to age 1 year; enrollment consists of 4 non-consecutive months during the first year of life, at least 1 month of insurance in the first 3 months of life, and at least one care encounter. Infants who died during the first year of life and those hospitalized for more than 30 days after birth were not required to meet criteria. Twelve percent of infants did not meet enrollment criteria: 10.7% of during-pregnancy exposures, 12.1% of exposures during the periconceptional period, and 12.9% of the comparison group for these birth defect analyses. ^††Toxoplasmosis, syphilis, varicella, rubella, and cytomegalovirus in infant chart.

Fig. 2.

Exposure periods of interest for quadrivalent human papillomavirus vaccination: control period*, periconceptional period^†, and during pregnancy^‡. *Eighteen months to 4 months before last menstrual period. ^†Two weeks before to 2 weeks after last menstrual period. ^‡Two weeks to 28 weeks of gestation.