RSV Vaccine in Pregnancy: The 2023 U.S. Recommendation

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. On September 22, 2023, CDC's Advisory Committee on Immunization Practices (ACIP) and CDC recommended a vaccine given during pregnancy to protect babies through their first six months. The committee voted 11 to 1.

The recommendation

Every infant should be protected by one of the two. Most infants do not need both.

The recommendation was to be updated as new evidence arrived.

Why infants

• Most U.S. infants catch RSV in their first year, and every infant is at risk of severe disease.
• 2% to 3% of young infants are hospitalized for it.
• Each year, among U.S. children under 5, RSV causes an estimated 58,000–80,000 hospitalizations and 100–300 deaths.
• About 79% of children under 2 hospitalized with RSV had no underlying medical condition.
• Hospitalization rates are highest under 6 months and peak at 1 month of age.

Before COVID-19, RSV reliably peaked in winter, with timing varying by region. The pandemic scrambled that — very little RSV in 2020–21, an early, drawn-out season in 2021–22, and a 2022–23 season that started later than 2021–22 but earlier than before the pandemic. Activity in August and September 2023 suggested the old pattern was returning.

The evidence

Since October 2021, an ACIP work group had met at least monthly to review RSV and the products to prevent it in infants. It weighed two multicountry Pfizer trials in which pregnant people were randomly given vaccine or placebo at 24–36 weeks:

• a phase 2b trial of 581 (115 given the final vaccine dose and formulation, 117 placebo), in Argentina, Chile, New Zealand, South Africa and the United States;
• a phase 3 trial of 7,392, randomized one to one to vaccine or placebo, in Argentina, Australia, Brazil, Canada, Chile, Denmark, Finland, The Gambia, Japan, Mexico, the Netherlands, New Zealand, the Philippines, South Africa, South Korea, Spain, Taiwan and the United States.

Protection for the baby, first 180 days

ICU admission and mechanical ventilation were rare: in the approved window, one ICU admission in the vaccine group against two with placebo, and no ventilated infants against two.

Safety

The most common reactions were injection-site pain, headache, muscle pain and nausea. In the phase 3 trial:

Overall, the work group rated the certainty of the evidence very low, mainly because of one question: preterm birth.

The preterm-birth question

In the trials, more preterm births (before 37 weeks) occurred after vaccine than after placebo. The difference was not statistically significant, and the data could neither establish nor rule out that the vaccine caused it. FDA put the potential risk on the label as a warning and approved the vaccine only from 32 weeks, to avoid the chance of a birth before 32 weeks, which carries more risk of illness and death.

• In the full trial, most preterm births came more than 30 days after the shot (60% in the vaccine group, 58% with placebo), and nearly all at 33 weeks or later (97% and 95%).
• Among people vaccinated at 32–36 weeks, most preterm births came at 36 weeks (72% and 59%).
• People at higher risk of preterm delivery were excluded from the trials.

Pregnancy blood pressure disorders were also somewhat more common after vaccine, again not significantly:

More babies of vaccinated mothers had neonatal jaundice too, again not significantly; both jaundice and low birthweight are more common in babies born early.

In trials of the same vaccine in adults 60 and older, three inflammatory neurologic events — two cases of Guillain-Barré syndrome (one the Miller-Fisher variant) and one undifferentiated motor-sensory polyneuropathy — occurred within 42 days among 20,255 vaccine recipients, and none with placebo. None occurred in the pregnancy trials.

ACIP judged that, given at 32–36 weeks, the benefits outweigh the potential risks of preterm birth and blood pressure disorders — the same conclusion FDA reached.

Cost

At $295 a dose, vaccinating year-round would cost about $400,304 per quality-adjusted life year (QALY) saved. Limited to September–January, assuming a typical pre-pandemic RSV season, the figure falls to $167,280 per QALY.

Clinical guidance

• Why September–January: it targets pregnancies whose babies will be in their first months — when the mother's antibodies protect best — during RSV season, starting 1–2 months before the season and ending 2–3 months before it ends. The window should not shift with year-to-year swings in RSV.
• Different seasons: in Alaska, southern Florida, Guam, Hawaii, Puerto Rico, the U.S.-affiliated Pacific Islands and the U.S. Virgin Islands, follow state, local or territorial guidance.
• Other vaccines: it can be given with Tdap, influenza and COVID-19 vaccines, on the same day at different sites.
• Later pregnancies: there were no data yet on whether a first dose protects babies of later pregnancies, or on the safety of further doses.
• Do not give to anyone with a history of severe allergic reaction, such as anaphylaxis, to any vaccine component; delay during moderate or severe acute illness.

Vaccine or nirsevimab?

Providers should discuss the pros and cons of each and weigh the patient's preference. No study had compared them directly. Protection from the mother's vaccine will likely wane after 3 months, as with influenza and COVID-19 vaccines in pregnancy — but because the shot is given only September–January, most babies of vaccinated mothers are born during RSV season.

Nirsevimab is recommended for infants under 8 months, born during or entering their first RSV season, when:

• the mother was not vaccinated, or it is not known whether she was;
• the baby was born less than 14 days after the mother's vaccination — antibodies need at least that long to form and cross the placenta;
• the baby was born before 34 weeks — the earliest a baby could be protected by a vaccine given at 32 weeks;
• the baby was born April–September, outside RSV season, when most mothers will not have been vaccinated.

Most babies whose mothers were vaccinated 14 days or more before birth do not need nirsevimab. It may still be considered, on the clinician's judgment, where the baby may lack protection or face much higher risk: a mother with a weakened immune system or a condition that reduces antibody transfer (such as HIV infection); a baby who may have lost maternal antibodies, for example after cardiopulmonary bypass or ECMO; or a baby at substantially increased risk — such as significant congenital heart disease, or intensive care requiring oxygen at discharge.

Children 8–19 months at increased risk and entering their second RSV season should get nirsevimab whatever the mother received.

Watching for problems

Adverse events should be reported to the Vaccine Adverse Event Reporting System (vaers.hhs.gov, 1-800-822-7967) — any clinically significant event, even when it is unclear whether the vaccine caused it. CDC would watch for preterm birth, blood pressure disorders of pregnancy and inflammatory neurologic events through VAERS, the Vaccine Safety Datalink and v-safe, and FDA required Pfizer to run post-marketing studies of preterm birth and hypertensive disorders, including preeclampsia.

Sources

Based on Fleming-Dutra KE, Jones JM, Roper LE, et al., "Use of the Pfizer Respiratory Syncytial Virus Vaccine During Pregnancy for the Prevention of Respiratory Syncytial Virus–Associated Lower Respiratory Tract Disease in Infants: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023," MMWR Morbidity and Mortality Weekly Report volume 72, number 41, Centers for Disease Control and Prevention, first posted as an Early Release on October 6, 2023; a work of the United States government in the public domain. The report is inconsistent in places, and this page leaves those details out: it counts the vaccine group's preterm births as 201 in the text and 202 in its table; it gives two different follow-up periods for serious adverse events in infants; and it spells nirsevimab's brand name two ways.