Coxsackie virus infection of the placenta associated with neurodevelopmental delays in the newborn

doi:10.1016/S0029-7844(01)01625-8

Obstetrics & Gynecology

Volume 98, Issue 6, December 2001, Pages 1019-1026

https://doi.org/10.1016/S0029-7844(01)01625-8 Get rights and content

Abstract

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.

Section snippets

Tissue analysis

Tissue sections were fixed in 10% of buffered formalin for 1–7 days, then embedded in paraffin. Multiple 4-μ sections were placed on silane-coated glass slides as previously described.15, 16, 17 This allowed direct comparison of the hematoxylin and eosin stain with the viral findings. Eight placental tissues from six cases were analyzed. We also analyzed ten normal placentas. Additionally, hematoxylin and eosin stained sections from five placentas known to be infected with cytomegalovirus

Results

Six of the seven children ranged in age from 4 to 15-years-old, and included five boys. One child died 1 day after birth. Each of the six living children experienced marked, global cognitive defects evident soon after birth, which required intensive physical therapy, occupational therapy, and, occasionally, antiseizure therapy, and institutional therapy. All children (except for case 4 below) have not shown evidence of cerebral palsy because there have been minimal motor-related symptoms. The

Discussion

Coxsackie virus is an enterovirus that usually produces relatively mild symptoms in adults, although myocarditis and encephalitis are well-recognized complications. Coxsackie virus has been associated with both early and late trimester fetal losses.4, 5, 6, 7, 8, 9, 10, 11, 12 Early losses associated with coxsackie virus have been diagnosed when mothers have been symptomatic and had titers drawn.6, 7, 8 Two studies have found a significant increase of coxsackie B viral titers in pregnant women

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^☆: Supported by a grant from the Lewis Foundation (GJN).

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Coxsackie virus infection of the placenta associated with neurodevelopmental delays in the newborn☆

Abstract

Section snippets

Tissue analysis

Results

Discussion

Placenta

J Infect

J Infect

Lancet

Placenta

J Reprod Immunol

Is there an association between fetal viral infection and fetal malformation? Detection of specific IgM antibodies in the serum of malformed fetuses

J Perinat Med

Detection of CMV in chronic placentitis by in situ hybridization

Pediatr Pathol

Enterovirus in pregnant women and the perfused placenta

Am J Obstet Gynecol

Intrauterine coxsackie virus, group B type I, infectionViral cultivation from amniotic fluid in the third trimester

Am J Perinatol