What are the risks and recommended timing for administering the Respiratory Syncytial Virus (RSV) vaccine to pregnant women?

RSV Vaccination in Pregnancy: Risks and Timing

The RSV vaccine (RSVpreF/Abrysvo) is recommended for pregnant women at 32-36 weeks' gestation during September-January, with potential but not statistically significant risks of preterm birth and hypertensive disorders that are outweighed by infant protection benefits. 1

Key Safety Considerations

Potential Risks Identified

The FDA labeled a warning for potential preterm birth risk based on clinical trial data, though differences were not statistically significant: 1

• Trial dosing interval (24-36 weeks): 5.7% preterm births in vaccine group vs. 4.7% in placebo group 1
• Approved dosing interval (32-36 weeks): 4.2% preterm births in vaccine group vs. 3.7% in placebo group 1
• Most preterm births in the approved interval occurred at 36 weeks' gestation (72% of vaccine group preterm births) 1

Hypertensive disorders of pregnancy were observed more frequently in vaccine recipients compared to placebo, though again not statistically significant 1

Other Safety Outcomes

No statistically significant differences were found for: 1

• Low birthweight: 4.1% (vaccine) vs. 3.4% (placebo) at 32-36 weeks
• Neonatal jaundice: 6.3% (vaccine) vs. 6.7% (placebo) at 32-36 weeks

No cases of Guillain-Barré syndrome or inflammatory neurologic events were reported in pregnancy trials, though such events occurred in elderly vaccine recipients 1

Recommended Timing Algorithm

Gestational Age Window

Administer between 32 weeks 0 days and 36 weeks 6 days' gestation 1, 2

This narrower window (compared to the 24-36 week trial interval) was specifically chosen to avoid potential preterm birth risk at <32 weeks, which carries significantly higher morbidity and mortality 1

Seasonal Timing

September through January in most of the continental United States 1, 3

• Start 1-2 months before anticipated RSV season onset 1, 3
• Continue through 2-3 months before anticipated season end 1
• Regional exceptions: Alaska, southern Florida, Guam, Hawaii, Puerto Rico, U.S.-affiliated Pacific Islands, and U.S. Virgin Islands should follow local guidance due to different RSV seasonality 1, 3

Minimum Protection Window

At least 14 days needed after maternal vaccination for antibody development and transplacental transfer to protect the infant 3, 2

Risk-Benefit Assessment

The FDA determined that benefits outweigh risks when administered at 32-36 weeks' gestation, including the potential risks of preterm birth and hypertensive disorders 1

Benefits Supporting Recommendation:

• Protection during infants' most vulnerable period (first 6 months of life) 1
• RSV is the leading cause of infant hospitalization with 58,000-80,000 annual hospitalizations in children <5 years 1
• Peak hospitalization rates occur at 1 month of age 1

Important Caveats:

• Protection wanes after approximately 3 months, similar to maternal influenza and COVID-19 vaccines 1, 2
• No data available on safety or efficacy of repeat doses in subsequent pregnancies 1
• Current recommendation is for single lifetime dose 3, 2

Practical Implementation

Co-administration

Can be given simultaneously with other pregnancy vaccines (Tdap, influenza, COVID-19) at different anatomic sites on the same day 1

Alternative Strategy

Either maternal vaccination OR infant nirsevimab is recommended, but both are not needed for most infants 1, 2

Exception: Nirsevimab is recommended for all infants born <34 weeks' gestation regardless of maternal vaccination status 3, 2

When Infant Needs Nirsevimab Despite Maternal Vaccination:

• Mother did not receive RSV vaccine 2
• Maternal vaccination status unknown 2
• Infant born <14 days after maternal vaccination 2

Common Pitfalls to Avoid

• Do not vaccinate before 32 weeks to minimize potential preterm birth risk at very early gestational ages 1
• Do not vaccinate after 36 weeks 6 days as this is outside the approved indication 1
• Do not vaccinate year-round outside September-January in most U.S. regions, as this reduces cost-effectiveness and may not provide protection during RSV season 1
• Do not assume protection lasts beyond 3 months when counseling patients 1, 2