Maternal Respiratory Syncytial Virus (RSV) vaccination
RSV is a major cause of respiratory infections among young infants. It can spread through respiratory droplets from infected individuals or contaminated surfaces. It is frequently acquired by infants during first few weeks of life. 2/3 of all infants become infected with RSV in the first year of life, 1/3 develop lower respiratory tract symptoms, 3% become hospitalized, and 0.02% die from RSV infection in high income countries. After infection, a proportion may go on to develop chronic wheezing.
Vaccinating the mother during the pregnancy has been shown to reduce severe RSV infection to the infant by 80% at 3 months and 70% at 6 months of age. The antibodies produced by the mother would be passively passed to the fetus, being effective as early as 14 days after administration, and protection may last up to 6 months after birth. If the baby is born <14 days after the mother has been vaccinated, that protection would be expected to be less.
Minor side effects that may be expected include:
· Pain and redness
· Swelling
· Headache
· Tiredness
· Nausea and vomiting
· Diarrhea
· Fever
· Sore joints
· Body aches
Major side effects:
Preterm birth. There were reports of a possible increased risk of preterm birth when it was given in low-income countries between 24 - 36 weeks. In real life data, this increased risk was not seen when given at 32-36 weeks in high-income countries. A more detailed analysis of this is discussed below.
Generalized weakness or tingling sensations over the limbs and upper body (or Guillain Barre syndrome) was noted in 1 per 100,000 elderly people vaccinated. In about 1,000,000 pregnant women vaccinated so far, this has not been reported yet.
So, does maternal RSV vaccination cause preterm birth?
Recently, Pfizer has come out with a maternal RSV vaccine that has been licensed for use in pregnancy by Health Science Authority (HSA).
Let me summarize the 2 studies that form my views about this RSV vaccine.
GSK had initially planned for a trial involving 10,000 pregnant women with its RSV vaccine given at 24 to 34 weeks but prematurely terminated their study when the number of participants reach 5,328 because of some adverse safety signals (see https://pubmed.ncbi.nlm.nih.gov/38477988/). Whilst the vaccine reduced the risk of severe RSV lung infection in infants < 6 months by 69%, the rates of preterm births and neonatal deaths were higher in the vaccinated group compared to the non-vaccinated group (preterm births 6.8% vs 4.9%, and neonatal deaths 0.4% vs 0.2%). For this reason, GSK has not sought to license their vaccine during pregnancy.
Pfizer's study, on the other hand, involved 7,358 pregnant women with its RSV vaccine given 24-36 weeks. It reported that the vaccine reduced severe lung infections in infants < 3 months by 81.8% and in infants < 6 months by 69.4%. It reported no safety signals (see https://pubmed.ncbi.nlm.nih.gov/37018474/). However, if you look at the rate of premature delivery in the table attached below), it was higher for the vaccinated group (like the GSK maternal RSV vaccine) by about 1% (5.7% vs 4.7%) though it was not statistically significant.
Figure 1 from the NEJM paper in 2023 - Rates of premature delivery amongst those vaccinated with the Pfizer vaccine between 24-36 weeks gestation and those not.
When the Pfizer study was reanalyzed according to the income level of country where the vaccination was given, it was found that there was no difference in preterm birth rates between those vaccinated and those not in patients from high income countries, and a higher rate of preterm birth rates in those vaccinated from low income countries.
Figure 2 figure from the paper by Madhi in February 2025 which showed that the increased preterm delivery rates were only noticed in those vaccinated in South Africa, and not others in higher income countries.
An observational study of the vaccine use between 32-36 weeks in 1,026 pregnant women showed did not show an increased risk of preterm birth (5.9% vs 6.7% amongst those who did not take the vaccine' see https://pubmed.ncbi.nlm.nih.gov/38976271/).
The Pfizer RSV vaccine called Abrysvo(R) is now approved for use in US and Singapore for pregnant women at 32-36 weeks gestation. This was modified from the initial study's protocol of 24-36 weeks, probably in response to its possible associated risk of preterm birth. This is also consistent with the recommendations from American College of Obstetricians and Gynaecologists. Other Colleges from UK, Europe and Australia recommend its use starting from 28-36 weeks.
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