Flu Shots Appear Safe in Successive Pregnancies

Getting flu shots during successive pregnancies did not increase the risk for adverse perinatal outcomes, according to a large U.S. cohort study.

Compared with no vaccination, immunization against influenza in successive pregnancies was not associated with any increased risk for:

• Preeclampsia or eclampsia (adjusted relative risk [aRR] 1.10, 95% CI 0.99-1.21)
• Placental abruption (aRR 1.01, 95% CI 0.84-1.21)
• Preterm birth (aRR 0.83, 95% CI 0.78-0.89)
• Small for gestational age (aRR 0.99, 95% CI 0.93-1.05)
• Maternal fever (aRR 0.87, 95% CI 0.47-1.59)
• Preterm premature rupture of membranes (aRR 1.00, 95% CI 0.94-1.06)
• Chorioamnionitis (aRR 1.03, 95% CI 0.90-1.18)

Of note, interval time length between pregnancies or type of influenza vaccine formulation did not alter the associations, reported Darios Getahun, MD, PhD, MPH, of Kaiser Permanente Southern California in Pasadena, and colleagues in JAMA Network Open.

“Our results have important implications for healthcare practitioners and people having successive pregnancies,” Getahun and investigators posited. “These are reassuring results regarding influenza vaccine safety for pregnant people.”

“The study findings support recommendations to vaccinate people during pregnancy regardless of the interval between any two successive pregnancies and the type of vaccination,” they added.

Pregnant and postpartum women are at higher risk for serious outcomes from the flu than nonpregnant individuals.

Both the CDC and the American College of Obstetricians and Gynecologists recommend that all individuals ages 6 months and older, including women who are pregnant or planning to become pregnant, should be vaccinated against the flu during the respiratory virus season. Vaccination during pregnancy also confers some passive immunity to newborns.

The CDC maintains that flu shots are safe for pregnant women. Even so, although flu vaccine uptake among pregnant people has improved over the years, it still remains suboptimal. During the 2022-2023 respiratory virus season, coverage was 47.2% among pregnant women.

Although adverse maternal and perinatal outcomes have not generally been linked to the flu vaccine, a case-control study analyzing 2010-2012 data from the CDC’s Vaccine Safety Datalink (VSD) found significantly increased odds of spontaneous abortion in mothers who were vaccinated with inactivated influenza A (pH1N1) in the previous influenza season in the first 28 days after vaccination (adjusted OR 7.7, 95% CI 2.2-27.3). However, a larger study of that database during several subsequent flu seasons failed to confirm that association.

For the present study, Getahun and colleagues relied on the VSD’s postmarketing vaccine safety data collected by the CDC and 13 integrated healthcare plans.

The retrospective longitudinal cohort study included VSD data from 82,055 women with two singleton pregnancies from 2004 to 2018. In this population, 54.7% had received a flu shot in successive pregnancies and 45.3% were unvaccinated for both pregnancies. The mean age at the start of the second pregnancy was about 32 years in the vaccinated group and 31 in the unvaccinated group.

Vaccinated women were more likely to be age 30 or older, college graduates, and to have had earlier or more frequent prenatal care and an interval between pregnancies of 1 to 3.49 years. They were also more likely to have one or more comorbidities.

In the initial crude analysis of the study, researchers found that those vaccinated in successive pregnancies had modestly increased risks for preeclampsia or eclampsia (RR 1.15, 95% CI 1.06-1.24), preterm premature rupture of membranes (RR 1.13, 95% CI 1.08-1.18), and chorioamnionitis (RR 1.14, 95% CI 1.03-1.26).

However, after adjusting for a variety of factors known to negatively influence perinatal outcomes, vaccination was no longer an independent risk factor for any adverse perinatal outcome. Factors that were adjusted for included maternal age, smoking and alcohol use during pregnancy, prepregnancy body mass index, gestational weight gain, maternal comorbidities, and a history of adverse perinatal outcomes in a prior pregnancy, among others.

The authors acknowledged several limitations to their study. Women may have received flu vaccines outside healthcare organizations participating in the VSD, such as at work or a retail pharmacy. Only data from pregnancies resulting in live births were included. Also, results may have been biased due to potential unmeasured confounding factors.