A 21-year-old woman was admitted to the neonatal intensive care unit (NICU) at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center in Florida hospital at 27 weeks of gestation, diagnosed with pneumonia and SARS-CoV-2. Her infant son was delivered via Cesarean section at 32 weeks of gestation. At the time of birth, the mother was negative for COVID-19. The male infant, born with Apgar scores of 4 and 7 at 1 and 5 minutes, displayed seizures and respiratory difficulty, requiring intubation and ventilation. The infant remained in the hospital for 3 months, then discharged, diagnosed with a seizure disorder and microcephaly. Although the seizures resolved, the infant was readmitted several times because of failure to thrive. At 13 months, the child was admitted to the emergency department (ED) for an upper respiratory infection, treated, and discharged. Three days later, the mother found her son unresponsive in bed; paramedics were called and found the child in cardiac arrest. He died shortly thereafter. The autopsy findings included reduction in brain weight and cerebral white matter volume, along with virus throughout the brain.

The second mother gave birth at 39 weeks to a Hispanic female. The 20-year-old mother had been diagnosed with asymptomatic COVID-19 in the second trimester. At the time of delivery, she again tested for (asymptomatic) COVID-19, as well as clinical chorioamnionitis. The infant had Apgar scores of 4 and 6 at 1 and 5 minutes and required nasal continuous positive airway pressure for apnea. She was given antibiotics for presumptive sepsis. At 16 hours of age, the baby developed clinical seizures but no virus or bacteria. At 4 days of age, MRIs revealed diffuse restricted diffusion. The child was discharged at 5 weeks, but there were multiple readmissions for seizures and respiratory disorders. Her exam at 1 year showed microcephaly, an abnormal neurologic examination, and significant neurodevelopmental delay.

Both infants had placentas that revealed thrombosis, recanalization of stem villous vessels, and stromal fibrosis, and increased stromal karyorrhexis of terminal villi, all pointing to high-grade fetal vascular malperfusion. COVID-19 spike proteins were detected in both placentas.

“To our knowledge, this is the first time that neonates born of mothers who tested positive for COVID-19 presented with a neonatal clinical course mimicking hypoxic ischemic encephalopathy of the newborn,” noted the study. Both placentas and brains showed evidence of COVID-19 infections, with the placentas displaying alterations in inflammatory and oxidative stress markets.

Investigators concluded that midtrimester maternal COVID-19 infection can infect the infant’s placenta and fetal or infant brain, triggering inflammatory events in both placenta and fetus, which can be associated with critical brain injury and progressive neurological sequelae. Researchers urge for future studies to assess the impact of timing of in uteroSARS-CoV-2 on placental inflammation and long-term consequences of the infant brain.


Benny M, Bandstra ES, Saad AG, et al. Maternal SARS-CoV-2, placental changes and brain injury in 2 neonates. Pediatrics. 2023;151(5):e2022058271

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