Safety of the Seasonal Influenza Vaccine in 2 Successive Pregnancies

Abstract

Importance: Although influenza vaccination has been found to be safe in pregnancy, few studies have assessed repeated influenza vaccination over successive pregnancies, including 2 vaccinations in a year, in terms of adverse perinatal outcomes.

Objective: To examine the association of seasonal influenza vaccination across successive pregnancies with adverse perinatal outcomes and whether the association varies by interpregnancy interval (IPI) and vaccine type (quadrivalent or trivalent).

Design, setting, and participants: This retrospective cohort study included individuals with at least 2 successive singleton live-birth pregnancies between January 1, 2004, and December 31, 2018. Data were collected from the Vaccine Safety Datalink, a collaboration between the Centers for Disease Control and Prevention and integrated health care organizations. Data analysis was performed between January 8, 2021, and July 17, 2024.

Exposures: Influenza vaccination was identified using vaccine administration codes. The vaccinated cohort consisted of people who received influenza vaccines during the influenza season (August 1 through April 30) in 2 successive pregnancies. The comparator cohort consisted of people identified as unvaccinated during both pregnancies.

Main outcomes and measures: Main outcomes were risk of preeclampsia or eclampsia, placental abruption, fever, preterm birth, preterm premature rupture of membranes, chorioamnionitis, and small for gestational age among individuals with and without vaccination in both pregnancies. Adjusted relative risks (RRs) from Poisson regression were used to assess the magnitude of associations. The associations with adverse outcomes by IPI and vaccine type were evaluated.

Results: Of 82 055 people with 2 singleton pregnancies between 2004 and 2018, 44 879 (54.7%) had influenza vaccination in successive pregnancies. Mean (SD) age at the start of the second pregnancy was 32.2 (4.6) years for vaccinated individuals and 31.2 (5.0) years for unvaccinated individuals. Compared with individuals not vaccinated in both pregnancies, vaccination in successive pregnancies was not associated with increased risk of preeclampsia or eclampsia (adjusted RR, 1.10; 95% CI, 0.99-1.21), placental abruption (adjusted RR, 1.01; 95% CI, 0.84-1.21), fever (adjusted RR, 0.87; 95% CI, 0.47-1.59), preterm birth (adjusted RR, 0.83; 95% CI, 0.78-0.89), preterm premature rupture of membranes (RR, 1.00; 95% CI, 0.94-1.06), chorioamnionitis (adjusted RR, 1.03; 95% CI, 0.90-1.18), or small for gestational age birth (adjusted RR, 0.99; 95% CI, 0.93-1.05). IPI and vaccine type did not modify the observed associations.

Conclusions and relevance: In this large cohort study of successive pregnancies, influenza vaccination was not associated with increased risk of adverse perinatal outcomes, irrespective of IPI and vaccine type. Findings support recommendations to vaccinate pregnant people or those who might be pregnant during the influenza season.

Figure.. Outcome Incidence Based on Maternal Vaccination Status in Successive Pregnancies and Adjusted Relative Risk (RR) of Adverse Perinatal Outcomes in Second Pregnancy

The vaccinated group included individuals who were vaccinated with a seasonal influenza vaccine in 2 successive pregnancies, and the unvaccinated group was individuals who were not vaccinated with influenza vaccine in 2 successive pregnancies. Analyses were adjusted for maternal age, race and ethnicity, maternal education, smoking and alcohol use during pregnancy, prepregnancy body mass index, gestational weight gain, timing of prenatal care initiation and number of prenatal care visits, maternal comorbidities (chronic hypertension, diabetes, kidney disease, and autoimmune disease), history of adverse perinatal outcomes in a prior pregnancy, month of conception, year of pregnancy, interpregnancy interval, receipt of influenza vaccine during the interpregnancy period, receipt of other vaccines during pregnancy, and Vaccine Safety Datalink site. PPROM indicates preterm premature rupture of membranes.