Adverse pregnancy and infant outcomes by COVID-19 infection status before and during pregnancy.

Introduction: To examine the association between pre-pregnancy and gestational COVID-19 infection by trimester with adverse pregnancy and infant outcomes. Methods: A retrospective cohort study was conducted to evaluate singleton live births and fetal deaths among pregnant women in South Carolina (SC) from January 2020 through December 2022. Birth certificate and COVID-19 diagnosis data obtained from the SC Department of Health and Environmental Control were linked to inpatient hospital discharge and emergency department records and Medicaid eligibility files from the SC Revenue and Fiscal Affairs Office. Log-binomial and modified Poisson models were used in matched and unmatched analyses to estimate risk ratios (RRs) for maternal and infant outcomes associated with COVID-19 infection pre-pregnancy, during the first/second trimester, and during the third trimester. Results: Of 145,028 pregnancies, first infection with COVID-19 occurred for 7.5% before pregnancy, 5.5% during the first/second trimester, and 3.4% during the third trimester. In matched analyses following adjustment for sociodemographic, clinical, and behavioral factors, COVID-19 infection pre-pregnancy increased the risk for hypertensive disorders of pregnancy (HDP) (RR = 1.07, 95% CI: 1.03-1.14), preeclampsia/eclampsia (RR = 1.09, 95% CI: 1.01-1.17), and cesarean delivery (RR = 1.06, 95% CI: 1.00-1.11). COVID-19 infection during the first/second trimester increased the risk for preeclampsia/eclampsia (RR = 1.10, 95% CI: 1.00-1.20) as well as placental abruption (RR = 1.15, 95% CI: 1.01-1.30) and severe maternal morbidity (SMM) with (RR = 1.60, 95% CI: 1.32-1.93) and without transfusion (RR = 1.91, 95% CI: 1.52-2.40) after full adjustment. COVID-19 during the third trimester increased the risk for preeclampsia/eclampsia (RR = 1.15, 95% CI: 1.02-1.29), placenta abruption (RR = 1.38, 95% CI: 1.15-1.66), postpartum hemorrhage (RR = 1.24, 95% CI: 1.02-1.51), and SMM with (RR = 2.07, 95% CI: 1.65-2.59) and without transfusion (RR = 2.56, 95% CI: 1.98-3.35) after full adjustment. Conclusion: This study demonstrated that COVID-19 infection during pregnancy and more notably before pregnancy was significantly associated with multiple adverse pregnancy events, after controlling for pertinent sociodemographic, clinical, and behavioral factors. Keypoints: While prior studies have examined potential risks associated with COVID-19 infection during pregnancy, our study is one of the first to investigate potential risks associated with COVID-19 prior to pregnancy. We report significantly increased risk of hypertensive disorders of pregnancy (HDP), specifically preeclampsia/eclampsia, among pregnant women who had COVID-19 infection prior to pregnancy compared to those without COVID-19 in a statewide matched analyses after adjustment for covariates.COVID-19 infection during the first or second trimester was associated with increased risk for preeclampsia/eclampsia, placental abruption, and severe maternal morbidity (SMM) relative to those with no history of COVID-19.COVID-19 infection during the third trimester was associated with increased risk of preeclampsia/eclampsia, placental abruption, postpartum hemorrhage, and SMM (both including and excluding transfusion).