Pfizer vaccine significantly lowers risk of Covid infection in pregnancy: JAMA

A phase 3 trial of the Pfizer-BioNTech BNT162b2 messenger RNA (mRNA) vaccine demonstrated 95% efficacy in preventing SARS-CoV-2 infection 7 days from the second dose; however, pregnant women were excluded from the trial. Association with SARS-CoV-2 infection also has been examined by several observational studies, but like the clinical trials, none included pregnant women.

On December 19, 2020, Israel launched its BNT162b2 vaccination campaign. Although pregnant women were not excluded from receiving the vaccine, they were initially advised to discuss the possibility of vaccination with their treating physician.

A month into the campaign, the Israel Ministry of Health released updated recommendations encouraging pregnant women to receive the vaccine. Goldshtein et al carried out a study in this regard. The purpose of this study was to assess the association between receipt of a BNT162b2 mRNA vaccine and incidence of SARS-CoV-2 infection among pregnant women.

This was a retrospective cohort study within the pregnancy registry of a large state-mandated health care organization in Israel. Pregnant women vaccinated with a first dose from December 19, 2020, through February 28, 2021, were 1:1 matched to unvaccinated women by age, gestational age, residential area, population subgroup, parity, and influenza immunization status. Follow-up ended on April 11, 2021. Exposure was defined by receipt of the BNT162b2 mRNA vaccine. To maintain comparability, nonexposed women who were subsequently vaccinated were censored 10 days after their exposure, along with their matched pair.

The primary outcome was documented SARS-CoV-2 infection 28 days or more after the first vaccine dose. This period was chosen because previous analyses have suggested that immunity develops gradually, reaching full immunity approximately 7 days after the second dose. The number of events between day 28 and the end of follow-up included those occurring on day 28.

RESULTS:

• A total of 29,911 eligible pregnant women were identified. By February 28, 2021, 12,066 women had received the first vaccination dose during pregnancy. Among women with a follow-up of 21 days or longer, 5626 (99%) received the second dose by the end of follow-up, with a mean and median of 21 days between the first and second dose.

• The cohort included 7530 vaccinated and 7530 matched unvaccinated women, 46% and 33% in the second and third trimester, respectively, with a mean age of 31.1 years.

• The median follow-up for the primary outcome was 37 days Overall, SARS-CoV-2 infections occurred in 118 vaccinated women and 202 unvaccinated ones during a median follow-up of 37 days.

• At 28 days, when 4788 women (63.6%) remained at follow-up in each group, the absolute cumulative number of events was 109 in the vaccinated group and 158 in the unvaccinated group, and the difference in cumulative incidence rates was 0.80%, with cumulative incidence rates of 1.55% among vaccinated women and 2.34% among unvaccinated women.

• At 10 weeks, when 955 women (12.7%) remained, the cumulative number of events was 118 in the vaccinated group and 202 in the unvaccinated group, and the difference in cumulative incidence rates was higher.

• Among infected women, 88 of 105 (83.8%) were symptomatic in the vaccinated group vs 149 of 179 (83.2%) in the unvaccinated group (P .99). During 28 to 70 days of follow-up, there were 10 infections in the vaccinated group and 46 in the unvaccinated group.

• The hazards of infection were 0.33% vs 1.64% in the vaccinated and unvaccinated groups, respectively, representing an absolute difference of 1.31% (95% CI, 0.89%-1.74%), with an adjusted hazard ratio of 0.22 (95% CI, 0.11-0.43).

• Vaccine-related adverse events were reported by 68 patients; none was severe. The most commonly reported symptoms were headache (n = 10, 0.1%), general weakness (n = 8, 0.1%), nonspecified pain (n = 6, <0.1%), and stomachache (n = 5, ><0.1%).

• During 28 days or more post vaccination, a statistically significant hazard reduction was observed among the vaccinated group compared with the unvaccinated group (aHR = 0.22; 95% CI, 0.11-0.43; robustP < .001).

• A higher risk of outcome was observed in the second and third trimesters but with no evidence of an interaction (P = .39) between vaccination and trimester at index.

• During the study follow-up period, 1387 (18.4%) of the vaccinated women and 1427 (18.9%) of the unvaccinated reached the end of pregnancy. There were no notable differences between the vaccinated and unvaccinated groups regarding preeclampsia, intrauterine growth restriction, infant birth weight, abortions, stillbirth, maternal death, or pulmonary embolism.

In this large population-based cohort of pregnant women, BNT162b2 vaccination compared with no vaccination was associated with a significantly lower risk of SARS-CoV-2 infection, although the absolute risk differencewas small.

The aHR of 0.22 (95% CI, 0.11-0.43) at 28 days or more after vaccination corresponded to an estimate of vaccine effectiveness (1 − HR) of 78%. Although this finding suggests that the vaccine was associated with a substantially lower risk among pregnant patients, the magnitude of the risk reduction was slightly lower than reported previously among the general population. The benefit from the vaccine may be somewhat attenuated among this population compared with the general public because pregnant women were generally advised to take extra precautions during the pandemic and to maintain particular adherence to social distancing guidelines, regardless of vaccination status.

"In this retrospective cohort study of pregnant women, BNT162b2 mRNA vaccination compared with no vaccination was associated with a significantly lower risk of SARS-CoV-2 infection. Interpretation of study findings was limited by the observational design."

Source: Goldshtein et al; JAMA Research

doi:10.1001/jama.2021.11035