Respiratory Syncytial Virus Infection During Pregnancy

By Ahizechukwu C. Eke, MD, PhD, MPH

Associate Professor in Maternal Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore

SYNOPSIS: Although women who developed respiratory syncytial virus (RSV) infection during pregnancy had a higher risk of preterm birth compared to those without RSV infection, the risk of miscarriage, stillbirth, low birth weight, and small for gestational age fetus were similar between the RSV and placebo groups.

SOURCE: Kenmoe S, Chu HY, Dawood FS, et al. Burden of respiratory syncytial virus-associated acute respiratory infections during pregnancy. J Infect Dis 2023; Oct 12:jiad449. doi: 10.1093/infdis/jiad449. [Online ahead of print].

Respiratory syncytial virus (RSV) is a prevalent respiratory infection that affects people of all age groups, although it has a more significant effect on vulnerable populations, such as pregnant women and children. In the United States, approximately 500,000 emergency visits are the result of RSV infection every year in children younger than 5 years of age, making it the leading cause of hospitalization for infants younger than 12 months of age.^1,2 Although RSV infection in children and infants continues to be of significant public health importance, RSV infection during pregnancy has received growing attention because of its possible consequences for the health of both the mother and the fetus.³ Pregnant women, especially those in the second and third trimesters, are more susceptible to severe respiratory infections. In addition, maternal RSV infection has been linked to negative consequences, such as premature birth, low birth weight, neonatal respiratory distress, and maternal and fetal morbidity and mortality.³

The vulnerability of pregnant women to RSV infection is influenced by multiple risk factors. The risk of contracting the RSV virus may be higher in overcrowded environments, during the winter season, and in patients with preexisting lung disease.⁴ Maternal immunization against the virus has become a viable technique to safeguard the mother and the unborn child. Since maternal RSV vaccinations have been approved in the United States and Europe, more information is required to accurately assess the prevalence of acute respiratory infections linked to RSV in pregnancy. Therefore, in this study, Kenmoe and colleagues sought to determine the percentage of acute respiratory infections testing positive for RSV and the incidence rate, hospitalizations, fatalities, and perinatal outcomes linked to RSV among pregnant women.⁵

This study was a systematic review of all available observational studies involving pregnant women infected with RSV (by positive test to RSV culture, RSV antigen, molecular testing, or serology) in all trimesters of pregnancy. Studies were excluded if they were not focused on pregnant women. In addition, studies where clinical specimens were not laboratory tested for RSV, conference abstracts, reviews, and case reports were excluded. Five databases (Embase, Medline, Web of Science, Global Index Medicus, and Global Health) were searched for relevant studies. The primary outcome was the proportion of pregnant women with acute respiratory infections who tested positive for RSV (RSV incident rate among pregnant women). Secondary outcomes included the RSV-associated hospitalization rate among pregnant women, the number of RSV-associated deaths among those with acute respiratory infections, proportion of women delivering preterm (birth before 37 weeks of gestational age), miscarriage rates (pregnancy loss < 20 weeks of gestation), stillbirth rates, and those with low birth weight (birth weight < 2,500 g).

Subgroup analyses were performed based on the case identification settings and whether the study period was seasonal or throughout the year. Random-effects meta-analysis was used to generate overall proportions and rate estimates across studies, and an evaluation of publication bias was conducted using funnel plot asymmetry and a weighted Egger’s regression test with a threshold of 0.05.

In the study period between 2010 and 2022, there were 11 studies (eight cohort and three cross-sectional studies) identified involving pregnant women infected with RSV. Six studies were conducted in high-income countries (Australia, Canada, Israel, Panama, and the United States); four in lower-middle-income countries (El Salvador, Kenya, Mongolia, and Nepal); and two in upper-middle-income countries (South Africa and Thailand). The majority of these studies recruited participants from inpatient, community, and outpatient settings.

There were 203 cases of RSV infection among 8,126 pregnant women tested (3.4%; 95% confidence interval [CI], 1.9; 54). Pregnant women had a pooled incidence rate of 26.0 (95% CI, 15.8; 36.2) RSV infection episodes per 1,000 person-years. The RSV hospitalization rates varied between 2.4-3.0 per 1,000 person-years. There were no RSV-associated deaths among 4,708 pregnant individuals (five studies). Women with RSV infection had a higher odds of preterm birth compared to those without RSV infection (odds ratio, 3.6; 95% CI, 1.3; 10.3). The odds of miscarriage, stillbirth, low birth weight, and small for gestational age fetus were not statistically significant (based on data from three studies comparing pregnant women who tested positive or negative for RSV).

COMMENTARY

Preventing RSV infection during pregnancy and in newborns is a major public concern. In randomized trials that compared the administration of a single intramuscular dose of 120 mcg of a bivalent prefusion RSV vaccine (RSV preF) compared to placebo, RSV preF prevented medically attended lower respiratory tract infections by 81.8% (99.5% CI, 40.6-96.3) within 90 days postpartum and 69.4% within 180 days postpartum compared to placebo.⁶

Despite RSV vaccine efficacy, there was a nonsignificant increase in the rate of preterm birth that was observed between the RSV vaccine vs. the control group (5.7% vs. 4.7%), of which 60% of preterm births occurred more than 30 days following RSV vaccination, and 90% occurred between 34-37 weeks. The most common adverse effects following RSV vaccination were pain at the injection site, nausea, headache, and muscle pain, but these were not statistically significant between groups.

Despite the efficacy and safety of the RSV vaccine, healthcare practitioners also should offer pregnant women the choice of nirsevimab for their infants. In several Phase III randomized trials assessing the efficacy of nirsevimab, a monoclonal antibody active against RSV, in infants born at a gestational age of at least 35 weeks compared to placebo, a single parenteral dose of nirsevimab administered at the time of birth provided a constant immunity against RSV-related lower respiratory tract infections in healthy late-preterm and term newborns, neonates who required medical attention, and very severe cases of RSV-related lower respiratory tract infections in neonates and infants that required hospitalization.^7,8 Through the RSV season, nirsevimab may be able to protect a large portion of neonates and infants, including those who are born preterm or full term but have certain medical issues that put them at risk for RSV disease.

Based on the results of these randomized trials of RSV preF and nirsevimab, the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recommend a single dose of RSV preF to all pregnant women between 32 and 36 weeks of gestation as a safe and effective way to prevent against RSV infection in neonates and infants.^9,10 In pregnant women who decline the RSV vaccine but opt for nirsevimab, the infants of such women should receive nirsevimab at the time of birth to prevent RSV infection and other related lower respiratory tract infections. Patients should be counseled about the nonsignificant risk of preterm birth and lack of breastfeeding data for RSV preF.

While RSV preF and nirsevimab are nationally available at most hospitals and pharmacies, shortages have been reported in some states. The American Academy of Pediatrics recommends the use of palivizumab while the supply of nirsevimab is limited.⁹

REFERENCES

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5. Kenmoe S, Chu HY, Dawood FS, et al. Burden of respiratory syncytial virus-associated acute respiratory infections during pregnancy. J Infect Dis 2023; Oct 12. doi:10.1093/infdis/jiad449. [Online ahead of print].
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7. Hammitt LL, Dagan R, Yuan Y, et al. Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med 2022;386:837-846.
8. Griffin MP, Yuan Y, Takas T, et al. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med 2020;383:415-425.
9. The American College of Obstetricians and Gynecologists. ACOG, SMFM, and AAP statement on nirsevimab shortage. Published Oct. 25, 2023. https://www.acog.org/news/news-releases/2023/10/acog-smfm-aap-statement-on-nirsevimab-shortage
10. Society for Maternal-Fetal Medicine. RSV vaccination in pregnancy. Published Sept. 25, 2023. https://s3.amazonaws.com/cdn.smfm.org/media/4196/SMFM_Statement_RSV_September_2023.pdf