Practice Point: Consider the newly FDA-approved maternal RSV vaccine at 24-36 weeks’ gestation to prevent severe RSV infection in infants.

EBM Pearl: Lack of transparency about whether an intention-to-treat or per-protocol analysis was done often suggests the latter and demands a thorough review of appendices.

The Pfizer respiratory syncytial virus (RSV) vaccine was recently approved for pregnant women in an effort to protect infants. The vaccine targets RSV surface glycoproteins from both RSV A and RSV B (therefore bivalent) and triggers the body to produce antibodies which prevent RSV fusion and infection in human cells. Vaccination during late pregnancy gives newborns passive immunity through the transfer of maternal antibodies, similar to Tdap and influenza vaccination. The FDA’s decision was supported by an interim analysis of a phase 3 randomized control trial published in the New England Journal of Medicine (NEJM).

From June 2020 through October 2022, investigators randomized 7,392 healthy pregnant adults with uncomplicated singleton pregnancies at 24-36 weeks’ gestation to one dose of RSV vaccine vs. placebo. RSV infection was monitored via weekly contact with parents of infants ≤ six months old and with RT-PCR swabs for RSV collected during all visits for respiratory infections. The trial was conducted over four RSV seasons and infants were followed for up to two years. The primary efficacy outcomes were (1) severe RSV that was both laboratory-confirmed and medically attended (i.e., seen by a healthcare provider) and (2) RSV of any severity occurring within 90, 120, 150, and 180 days after birth.

At the time of the interim analysis, 77 percent of pregnant adults had given birth and 79 percent of infants had completed a six-month follow-up.

Infants in the vaccinated group were significantly less likely to develop severe RSV infection at six months, with only 19 cases in the vaccinated group compared to 62 cases in the placebo group (0.5% vs. 1.85%, vaccine efficacy 69.4% [97.58% CI 44.3%-84.1%]). RSV infection of any severity was also significantly lower in the vaccinated group at six months (1.6% vs. 3.4%). Additionally, fewer hospitalizations for RSV occurred in infants born to mothers in the vaccinated group.

In terms of safety, maternal recipients of the RSV vaccine experienced more local reactions, muscle pain, and headaches than in the placebo group. Otherwise, there were similar rates of serious adverse events in maternal and infant participants in both groups, such as preeclampsia, fetal distress syndrome, and neonatal jaundice. Premature delivery rates were also similar, while a higher number of deaths occurred in infants born to mothers in the placebo group.

We think the overall results are promising. One challenge, however, is that the authors did not specify whether they did an intention-to-treat or per-protocol analysis. After some digging into the supplementary data, we found language that evaluable participants had “no major protocol violations,” strongly suggesting that a per-protocol analysis was done instead of the more conservative and preferred intention-to-treat analysis. The confidence intervals were also wide, and the generalizability is somewhat limited given the exclusion of adults with high-risk pregnancies.

Despite these considerations, it appears that the benefits of maternal vaccination outweigh the risks. We estimate that the number needed to treat (NNT) is about 70 to prevent one case of severe RSV, though we will need the final analysis to confirm. For a potentially severe illness with no treatment other than supportive care, we are generally on board with vaccinating pregnant women.

For more information, see the topic Respiratory Syncytial Virus (RSV) Infection in Infants and Children in DynaMedex.

Reference: N Engl J Med. 2023 Apr 20;388(16):1451-1464