Influenza-Related Morbidity in Pregnancy: A Call for Maternal Immunization

During the 2009 influenza A H1N1 pandemic, pregnant women experienced disproportionately high rates of severe morbidity and mortality. Several reports highlighted that young, healthy pregnant women, particularly those in the third trimester, were at higher risk for severe maternal illness, with more intensive care unit (ICU) admissions, extracorporeal membrane oxygenation use, mechanical ventilation, and death than nonpregnant women (1, 2). Furthermore, it was noted that delays in antiviral therapy were associated with greater morbidity and mortality (3, 4). Hence, in 2009, the recommendations that had been in place since 1997 were strengthened to recommend vaccinating all pregnant women against influenza, regardless of trimester; avoiding delays in antiviral treatment; and treating women exposed to influenza during pregnancy with antivirals. In their article, Holstein and colleagues report on the characteristics and outcomes of hospitalized pregnant women over 9 influenza seasons after the 2009 H1N1 pandemic (5). The authors analyzed data for the 2010–2011 through 2018–2019 influenza seasons from the U.S. Influenza Hospitalization Surveillance Network (FluSurvNET), which represents approximately 9% of the U.S. population. A total of 9652 women were hospitalized during these seasons; almost a third were pregnant (n= 2690), and most were young (median age, 28 years) and otherwise healthy (42% had ≥1 underlying condition). Most were in the third trimester of pregnancy. Five percent were admitted to the ICU, 2% requiredmechanical ventilation, and 8 died. Other notable findings were that outcomes seemed to be worse for pregnant women exposed to H1N1 versus H3N2 and only 32% of pregnant women were vaccinated overall. Although over the course of 9 seasons there was a small incremental increase in vaccinations, disparities in vaccination persisted, with the lowest vaccination rates among non-Hispanic Black women and younger women (aged 15 to 34 years). Although most women left the hospital still pregnant, it is not known how many went on to have term versus preterm deliveries because postdischarge maternal and neonatal outcomes were not available. The findings of this study confirm those of other smaller studies highlighting why pregnant women remain a critical population to focus on for vaccine-preventable diseases, such as influenza and COVID-19. The physiologic changes that evolve over 9 months and extend into the postpartum period, such as decreased lung capacity and perturbations of the immune system required to maintain the pregnancy, contribute to the increased morbidity shown in pregnant women with influenza and are similarly seen with SARS-CoV-2 infection. In fact, these unique physiologic changes in pregnancy and the needs of the developing fetus underscore the importance of testing vaccines and therapeutics specifically in pregnant women to ensure safety and efficacy when there is a clear need based on disease severity. Influenza vaccination has an excellent safety profile in pregnancy, with more than 15 years of data showing no increased risk for miscarriage, preterm labor, small size for gestational age, or birth defects when inactivated vaccine is given in any trimester (6). Given the morbidity from influenza, which has been shown over multiple seasons, every scientific body responsible for women's health strongly encourages annual influenza vaccination to prevent maternal morbidity and protect the newborn until age 6 months. Pregnant women are known to be more likely to accept influenza vaccination when it is recommended by their provider and are even more likely to accept it if it is given in the office after a discussion of the risks of influenza for the mother and the safety of the vaccine for the baby (7). The Advisory Committee on Immunization Practices and the American College of Obstetricians and Gynecologists both recommend antiviral medication for pregnant women when they have symptoms consistent with influenza (8). In fact, viral testing for influenza is not recommended in pregnant women with symptoms even if they are vaccinated because of concerns that testing will delay antiviral treatment and lead to greater maternal morbidity and mortality. This recommendation was made during the 2009 H1N1 pandemic, when increased mortality was noted for those who had a treatment delay longer than 2 days. As seen in Holstein and colleagues' study, overall, 88.1% of pregnant women received antiviral therapy, with increasing use noted over time. This study was not designed to evaluate whether pregnant women had received antiviral medications for exposure to influenza, but that is a clear and strong recommendation as well. In summary, pregnant women are encouraged to be vaccinated, regardless of trimester; are reminded to contact their provider if they have influenza-like symptoms to allow prompt treatment, even if they are vaccinated; and are asked to contact their provider after exposure to influenza to obtain prophylactic antiviral medication. As the authors note, the FluSurv-NET data showed that most pregnant women were admitted with influenza symptoms. This contrasts with data from the COVID-19– Associated Hospitalization Surveillance Network (COVIDNET), which showed that only 45.5% of pregnant women were symptomatic. This largely reflects the obstetric practice of universal screening for SARS-CoV-2 infection at delivery and does not suggest that COVID-19 is less serious in pregnancy. In fact, maternal outcomes related to SARS-CoV-2 infection also seem to be more severe than those seen with influenza, with ICU admission, mechanical ventilation, and in-hospital mortality more frequently reported (9). Hence, there is a strong recommendation for SARS-CoV-2 vaccination, particularly as more safety data are amassed. If we apply the lessons learned from