COVID-19 vaccination during or just prior to pregnancy and hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy (HDP) are leading causes of maternal and fetal morbidity/mortality. To identify potential safety concerns, we evaluated whether COVID-19 vaccination during pregnancy or within 30 days of last menstrual period was associated with self-reported HDP. We also evaluated HDP risk associated with COVID-19 illness during pregnancy. We conducted a matched cohort study using data from the Centers for Disease Control and Prevention's COVID-19 Vaccine Pregnancy Registry (C19VPR; vaccinated) and Pregnancy Risk Assessment Monitoring System (PRAMS; unvaccinated). Participants included nulliparous women with singleton pregnancies ending in livebirth (C19VPR, December 2020-March 2022; PRAMS, 2019-2021). Participants were matched by age group, race/ethnicity, and gestational age at delivery. We estimated relative risk (RR) for self-reported HDP by vaccination status using Poisson regression, adjusting for confounders. We tested for effect modification by vaccine manufacturer and vaccination timing (<20 or ≥ 20 weeks' gestation). Among matched pairs with data on self-reported COVID-19 illness in pregnancy, we estimated risk of HDP by illness status. Of 8030 eligible C19VPR participants, 8024 (99.9%) were matched to a PRAMS participant. Most C19VPR participants delivered in 2021 (98.9%); PRAMS participants delivered predominantly in 2020 (54.5%) and 2019 (17.4%). Adjusted RR for HDP was 1.24 (95% confidence interval [CI]: 1.08, 1.43) among C19VPR versus PRAMS participants. We observed no effect modification. Results of an analysis restricted to matched pairs who delivered in 2021 (n = 2231) were similar. Among matched pairs (n = 4039) with data on COVID-19 illness in pregnancy, adjusted RR for HDP was 1.28 (95%CI: 1.02, 1.60) for those reporting illness compared with no illness. Risk of HDP was higher among COVID-19 vaccinated compared to unvaccinated women; however, the two groups were sampled from different cohorts. Risk was similar to those who reported COVID-19 illness. Given cohort differences, the associations observed cannot be considered causal; updated assessments of HDP risks after illness and vaccination would be useful.