Evaluation of Acute Adverse Events after Covid-19 Vaccination during Pregnancy

Abstract

a higher risk of adverse outcomes than do women who are not pregnant. 1,2 In part because of these findings, Covid-19 vaccination has been recommended for pregnant women. However, uptake has been lower in pregnant women than among women who are not pregnant. 3,4 The concern of many women regarding safety remains a barrier to maternal vaccination. We performed a retrospective, observational, matched-cohort study involving pregnant women between the ages of 16 and 49 years at eight Vaccine Safety Datalink sites from December 15, 2020, through July 1, 2021. We matched each dose of a Food and Drug Administration-authorized Covid-19 vaccine received by a pregnant woman to an unvaccinated pregnant woman, according to study site and pregnancy start date. Included in the pregnancy cohort were women who were subsequently found to be pregnant within 28 days after receiving the vaccine. Vaccinations were captured through electronic health records, claims data, and bidirectional linkages with state and local immunization registries. 5 We evaluated the incidences of 25 medically attended acute adverse events (known reactogenic adverse events and clinically serious outcomes) among the vaccinated women as compared with the unvaccinated matched controls. For the primary analyses, we focused on events occurring within 21 days after any vaccination. In secondary analyses, we included events that had occurred within 42 days after the second dose of a messenger RNA (mRNA) vaccine (either the BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna] vaccine) (Table S4 in the Supplementary Appendix, available with the full text of this letter at NEJM .org). We estimated adjusted rate ratios using Poisson regression after applying stabilized inverse probability weighting for propensity to receive a vaccination. Additional details regarding the statistical methods are provided in the Supplementary Appendix. We identified 45,232 pregnant women who had received one or two doses of a Covid-19 vaccine immediately preceding or during pregnancy (78,026 vaccine doses) (Fig. S1). Of these women, 32,794 (72.5%) had received two doses of an mRNA vaccine, 5652 (12.5%) had received only the first dose of an mRNA vaccine, 4912 (10.9%) had received only the second dose of an mRNA vaccine, and 1874 (4.1%) had received a single dose of the Ad26.COV2.S vaccine (Johnson & Johnson-Janssen). (The women who received only a second dose of vaccine had received the first dose >28 days before becoming pregnant.) A higher percentage of vaccinated women were between the ages of 30 and 49 years and were non-Hispanic White or non-Hispanic Asian as compared with unvaccinated women (Table S4). Frequencies of all medically attended acute adverse events were less than 1%. Among vac-cinees, the most common events were fever (ad-justed rate ratio as compared with unvaccinated controls, 2.85; 95% confidence interval [CI], 1.76 to 4.61), malaise or fatigue (adjusted rate ratio, 2.24; 95% CI, 1.71 to 2.93), local reactions (ad-justed rate ratio, 1.89; 95% CI, 1.33 to 2.68), and lymphadenopathy or lymphadenitis (adjusted rate ratio, 2.16; 95% CI, 1.42 to 3.28) (Fig. 1). No serious acute adverse events that were evaluated (e.g., cerebral venous sinus thrombosis, encepha-litis or myelitis, Guillain-Barré syndrome, myo-carditis or pericarditis, or pulmonary embolism) occurred more frequently in vaccinated women after each dose than among matched unvacci-nated controls. Overall associations were similar in subgroup analyses comparing the incidence of outcomes in the two groups, as stratified ac-The New England Journal of Medicine Downloaded from nejm.org by Eline TOMMELEIN on June 23, 2022. For personal use only. No other uses without permission.