Severe Acute Respiratory Syndrome Coronavirus 2, the Human Placenta, and Adverse Perinatal Outcomes

Rebecca L Linn; Markolline Forkpa; Rita Leite; Jessenia C Guerrero; Maria C Reyes; Lauren E Schwartz; Rebecca A Simmons; Samuel Parry; Thea N Golden

doi:10.1016/j.ajpath.2025.04.009

Severe Acute Respiratory Syndrome Coronavirus 2, the Human Placenta, and Adverse Perinatal Outcomes

Am J Pathol. 2025 Apr 30:S0002-9440(25)00150-6. doi: 10.1016/j.ajpath.2025.04.009. Online ahead of print.

Authors

Rebecca L Linn¹, Markolline Forkpa², Rita Leite², Jessenia C Guerrero¹, Maria C Reyes³, Lauren E Schwartz³, Rebecca A Simmons⁴, Samuel Parry⁵, Thea N Golden²

Affiliations

¹ Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
² Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
³ Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
⁴ Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
⁵ Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: parry@pennmedicine.upenn.edu.

PMID: 40316213
DOI: 10.1016/j.ajpath.2025.04.009

Abstract

The relationship among timing and severity of coronavirus disease 2019 (COVID-19) during pregnancy, placental pathology, and adverse pregnancy outcomes is not well understood. A prospective cohort study of 497 pregnant patients with COVID-19 whose placentas underwent systematic pathologic examination was conducted. The main exposure was timing of COVID-19 during pregnancy (first/second versus third trimester). The primary outcome was composite placental pathology that included high-grade maternal vascular malperfusion or >25% perivillous fibrin deposition. There were 63 patients who had the composite placental pathology outcome. In adjusted analyses that controlled for maternal age, parity, active infection at delivery, interval from time of diagnosis to delivery, and COVID-19 variant, timing of COVID-19 during pregnancy was not associated with risk of the composite placental pathology outcome. Among secondary COVID-19-related exposures that were investigated, severity of disease and treatment for COVID-19 were associated with risk of the composite placental pathology outcome. In addition, patients with COVID-19 in the first 9 months of the pandemic had the highest rate of the composite placental pathology outcome. In this large cohort, placental vascular pathology was common among COVID-19 cases but was unrelated to timing of COVID-19 during pregnancy or adverse pregnancy outcomes. These findings suggest that uncomplicated COVID-19 during pregnancy does not require intensive fetal surveillance or detailed pathologic examination of the placenta after delivery.