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Coxsackie Virus Infection of the Placenta Associated With Neurodevelopmental Delays in the Newborn

From the Department of Pathology, Ohio State University Medical Center, Columbus, Ohio; Department of Pediatrics (Neonatology), Winthrop University Hospital, SUNY Stony Brook School of Medicine, Mineola, New York; and Mt. Sinai School of Medicine, New York, New York.

Address reprint requests to: Gerard J. Nuovo, MD, Department of Pathology, Ohio State University Medical Center, 450 West 10th Avenue, S 305E Rhodes Hall, Columbus, OH 43210; E-mail: gnuovomd{at}pol.net.

OBJECTIVE: To determine if viral infection of the placenta was associated with long-term neurodevelopmental delays in the newborn.

METHODS: Placental tissue from seven newborn infants with severe respiratory failure and subsequent neurodevelopmental abnormalities as well as ten normal controls and five cases of known placental infection (cytomegalovirus, herpes simplex virus, and parvovirus) were tested by in situ hybridization or reverse transcriptase in situ polymerase chain reaction (PCR) for adenovirus, coxsackie virus, cytomegalovirus, Epstein Barr virus, herpes simplex virus, influenza A virus, picornavirus, polyoma virus, parvovirus, respiratory syncytial virus, rotavirus, and varicella zoster virus.

RESULTS: Coxsackie virus RNA was detected in six of the seven cases, and in none of the ten normal controls or five cases with known viral infection. Viral RNA localized primarily to the Hofbauer cells and trophoblasts of the terminal villi. Immunohistochemical analysis for the coxsackie virus antigen VP1 yielded equivalent results.

CONCLUSIONS: In utero coxsackie virus of the placenta is associated with the development of severe respiratory failure and central nervous system sequelae in the newborn. This underscores the importance of detailed pathologic and viral examination of the placenta in cases of systemic illness in the newborn.

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