(A-295) COVID-19 Vaccination Around the Time of Conception and Risk of Placenta-Mediated Adverse Pregnancy Outcomes

Background: Although numerous studies have documented no association between COVID-19 vaccination during pregnancy and maternal and fetal health outcomes, fewer studies have evaluated fetal health effects following exposure to COVID-19 vaccines around the time of conception and early pregnancy. Exposures during the periconceptional period and first trimester may affect early placentation and the subsequent risk of placenta-mediated adverse pregnancy outcomes.

Objectives: To compare the rate of adverse placenta-mediated outcomes by COVID-19 vaccination status around the time of conception or the first trimester of pregnancy.

Methods: We used province-wide databases in Ontario to conduct a population-based cohort study including all live and stillbirths ≥20 weeks’ gestation between a last menstrual period (LMP) between April 1-December 31, 2021. We deterministically linked birth registry data to vaccine registry for all eligible pregnancies. We identified 80,253 eligible pregnancies, 31,209 (38.9%) of whom received ≥1 dose of COVID-19 vaccine around the time of conception or first trimester. Using Cox regression, we estimated propensity score weighted hazard ratios (aHR) and 95% confidence intervals (CI) for associations between ≥1 dose of mRNA COVID-19 vaccine during the periconceptional/first trimester exposure window (28 days before the LMP to the end of first trimester) and study outcomes: hypertensive disorders (gestational hypertension, preeclampsia, eclampsia), placental abruption, preterm birth [ < 37 weeks], small-for-gestational-age (SGA) birth ( < 10th percentile), and stillbirth.

Results: COVID-19 vaccination around the time of conception or first trimester was associated with a small increased risk of hypertensive disorders in pregnancy in exposed vs. unexposed individuals (7.4% vs. 6.1%; aHR: 1.10, 95% CI: 1.03-1.17), mostly attributed to gestational hypertension (5.0% vs. 4.1%; aHR 1.13, 95% CI: 1.05-1.22). There was no increased risk of preeclampsia (1.8% vs. 1.5%; aHR 1.08, 95% CI: 0.95-1.22), eclampsia (0.1% vs. 0.1%; aHR: 1.12, 95% CI 0.65-1.95), placental abruption (0.8% vs. 1.0%; aHR: 0.77, 95%CI: 0.65-0.91), preterm birth (8.0% vs. 8.9%; aHR: 0.92, 95%CI: 0.87-0.97), SGA birth (8.9% vs. 9.3%; aHR: 1.00, 95%CI: 0.95-1.06), or stillbirth (0.4% vs. 0.6%; aHR: 0.66, 95%CI: 0.52-0.82).

Conclusions: This population-based Canadian study offers unique insights into the health effects of COVID-19 vaccination administered around the start of pregnancy in terms of placenta-mediated outcomes.