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Two neonates born to COVID-positive mothers in 2020 displayed early-onset seizures, acquired microcephaly, and had significant developmental delay, a case report showed.

In both infants, the neurologic finding at birth mimicked hypoxic-ischemic encephalopathy, reported Shahnaz Duara, MD, of the University of Miami Miller School of Medicine in Florida, and co-authors in .

The cases suggest that maternal SARS-CoV-2 infection with placentitis may have triggered an inflammatory response and oxidative stress injury to the fetoplacental unit that affected the fetal brain, the researchers noted.

The clinical picture of the infants involved "seizures that developed from the first day of life," said co-author Merline Benny, MD, also of the University of Miami, at a media briefing.

"As the babies grew, they had a very small head circumference," Benny noted. Imaging showed significant brain atrophy, she said. "One of these babies died at 13 months of age and the other was in the hospice at the time of our submission of manuscript," she added.

The reports come on the heels of another study of possible transplacental transmission of COVID. Earlier this year, researchers at Kings College London found associated with the presence of SARS-CoV-2 spike protein in 26 samples of fetal brain tissue and placenta collected from the start of the pandemic until April 2022. What caused the hemorrhages was unclear, but researchers speculated it may have been a direct consequence of infection or an indirect consequence of a maternal immune response.

In the University of Miami cases, both placentas showed SARS-CoV-2 protein and significantly increased inflammatory and oxidative stress markers. Human chorionic gonadotropin was markedly decreased.

Neither neonate tested positive for SARS-CoV-2 at birth, but both had detectable SARS-CoV-2 antibodies and increased blood inflammatory markers. MRIs over time showed severe parenchymal atrophy and cystic encephalomalacia.

The first case was an infant born preterm at 32 weeks gestational age to a woman who had been admitted to the ICU in July 2020 with severe COVID-19. The infant was discharged from the hospital after 3 months with a seizure disorder and acquired microcephaly. At 13 months, he had an emergency department visit for an upper respiratory infection. Three days later, his mother found him unresponsive in bed. Paramedics reported he was in asystolic cardiac arrest and could not be revived.

The second infant was born at 39 weeks gestational age to a woman who had asymptomatic COVID in her late second trimester. At 16 hours of age, the infant developed clinical seizures, which were confirmed on electroencephalography. She had cerebrospinal fluid pleocytosis but no detectable virus or bacteria. She was discharged at 5 weeks but subsequently had multiple hospital readmissions for breakthrough seizures and respiratory infections. A follow-up exam at 1 year showed microcephaly, abnormal neurologic examination, and significant neurodevelopmental delay.

SARS-CoV-2 spike glycoprotein 1 (S1) was detected in the placenta of both cases, co-localized with nucleocapsid protein. S1 co-localized with nucleocapsid protein was also found in the brain in the first case. The researchers did not test for viral RNA at autopsy.

There was nothing during labor that heralded an acute hypoxic-ischemic event in either case, Duara and colleagues said. "In retrospect, testing of amniotic fluid and cord blood samples for SARS-CoV-2 as well as uniformity in testing for inflammatory markers would have been helpful," they wrote.

The researchers emphasized that the two cases were extremely rare and occurred early in the pandemic, before SARS-CoV-2 vaccines were available.

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