Background: Although maternal infections with coxsackievirus during pregnancy are relatively common, fetal infections are quite rare. Coxsackievirus infection in utero has been associated with myocarditis, but has not been proven a teratogen

Awadallah, Sami

Jaqua, Mary Jo

Watson, William J.

English

PubMed

William J. Watson

Sami Awadallah

Mary Jo Jaqua

Crossref

Infectious Diseases in Obstetrics and Gynecology 3:79-81 (1995)
(C) 1995 Wiley-Liss, Inc.
Intrauterine Infection With Coxsackievirus:
Is It a Cause of Congenital Cardiac Malformations?
William J. Watson, Sami Awadallah, and Mary Jo Jaqua
Department of Perinatal Medicine, Sioux Valley Hospital (W.J.W.), and Division of Pediatric
Cardiology, Department of Pediatrics (S.A.), and Department of Laboratory Medicine (M.J.J.),
University of South Dakota School of Medicine, Sioux Falls, SD
ABSTRACT
Background: Although maternal infections with coxsackievirus during pregnancy are relatively
common, fetal infections are quite rare. Coxsackievirus infection in utero has been associated with
myocarditis, but has not been proven a teratogen.
Case: A patient whose fetus had structural cardiac anomalies and hydrops was found to have an
intrauterine infection with Coxsackie B-1 virus, proven by virus isolation from the amniotic fluid.
This infection led to increasing intrauterine hydrops and subsequent neonatal death.
Conclusion: This interesting association of intrauterine infection with Coxsackie B virus and
structural cardiac anomalies in the fetus warrants further investigation. (C) 1995 Wiley-Liss, Inc.
KEY WORDS
Coxsackie B-1 virus, cardiac diseasemcongenital, pregnancy, viral infection, enterovirus
nterovirus infections during pregnancy are rel-
atively common. The NIH Collaborative Peri-
natal Project found that serologic evidence of infec-
tion with group B coxsackievirus occurred in
approximately 9% of 198 unselected women stud-
ied during pregnancy. There is evidence that sero-
conversion may occur even more frequently in the
peak enterovirus season. 2 Maternal enterovirus in-
fections in pregnancy show a wide variety of symp-
tomatology, ranging from no clinical illness, to an
upper-respiratory-type infection to a febrile disease
characterized by lower abdominal pain.
Most enterovirus infections occurring during
pregnancy result in the delivery of unaffected,
healthy infants. Experimental research has shown
that the transplacental passage of a virus does not
easily occur. 3 In 1986, Modlin4 concluded that no
more than 24 cases of viral infection in utero could
be documented in the medical literature. However,
several reports have indicated that enterovirus in-
fection may occur by a transplacental route. Basso
et al. 5 isolated both echovirus and coxsackievirus
from placental and fetal tissues after maternal infec-
tion.
Rosenberg, 6 in a recent review on the cardiovas-
cular effects of congenital infections, pointed out
that rubella virus infection in utero has been estab-
lished as a cause of fetal cardiovascular malforma-
tions, but that other viruses have not been clearly
established as a cause of these malformations. We
present in this report a case of proven intrauterine
infection with Coxsackie B-1 virus in which the
fetus was noted to have congenital cardiac disease,
resulting in in-utero hydrops fetalis and neonatal
death.
CASE REPORT
The patient, a 27-year-old G2P00 white female,
had an unremarkable pregnancy until 28 weeks
gestation when she was noted to have an elevated
Address correspondence/reprint requests to Dr. William J. Watson, Perinatology, 1201 S. Euclid Avenue, Ste. 204, Sioux
Falls, SD 57105.
Obstetrics Case Report
Received April 10, 1995
Accepted July 5, 1995
INTRAUTERINE INFECTION WITH COXSACKIEVIRUS WATSON ET AL.
blood pressure of 140/90 and 1+ proteinuria. In
her previous pregnancy, she had delivered at term
without complications. There was no history of
birth defects in her family. She was immune to
rubella. Her initial blood pressure during the preg-
nancy had been 120/70. Over the ensuing week,
her blood pressure increased, despite bed rest at
home, to 160/100 and her proteinuria rose to 2 /.
She was admitted for evaluation, at which time an
ultrasound showed a fetus with nonimmune hy-
drops. The fetus had ascites and pleural effusions.
A maternal antibody screen was negative. Cordo-
centesis showed a fetal hemoglobin of 11 mg/dl,
and a fetal karyotype obtained from the fetal blood
was 46, XY. Amniotic fluid was obtained for viral
cultures. The initial ultrasound suggesting a possi-
ble fetal cardiac anomaly was subsequently con-
firmed by echocardiography. Detailed views of the
fetal heart indicated moderate hypoplasia of the left
ventricle and mitral stenosis. A maternal 24-h urine
collection showed 1.4 g of protein in 24 h. Over
the next 3 days of inpatient observation, the mother
developed severe preeclampsia with abnormal liver
function levels. An induction of labor resulted in
the vaginal delivery of a 1,685-g male infant with
Apgars of 1, 2, and 5 at 1, 5, and 10 min, respec-
tively. Immediately after birth, the infant was intu-
bated and ventilated. Despite maximum ventilatory
support with 100% oxygen, the infant had severe
hypercapnia and persistent hypoxemia. The infant
developed disseminated coagulopathy which became
rapidly progressive. After the parents were advised
of the deteriorating situation, the ventilatory sup-
port was withdrawn and the infant died.
A viral culture was not obtained from the new-
born. An autopsy showed severe mitral stenosis
with left atrial hypoplasia, a stenotic foramen ovale,
a markedly enlarged ductus arteriosus, and enlarged
pulmonary veins. Mild aortic stenosis and left ven-
tricular hypoplasia were also noted. A microscopic
examination of the heart showed focal disorganiza-
tion of the nuclei with focal calcification. No viral
studies were done on the myocardial tissue.
The amniotic fluid for the initial viral cultures
was placed into 6 cell-culture tubes: 2 tubes of
A-549 cells, 2 tubes of human foreskin fiberblasts
(at <20 passages), and tube each of rhesus mon-
key kidney and African green monkey kidney cells.
All tubes were observed daily for cytopathic effects.
On day 11, a cytopathic effect was observed in both
the A-549 and African green monkey cell lines
which was consistent with enterovirus. Material
scraped from the tubes was processed for electron
microscopy. Enterovirus/parvovirus-like particles,
27 nm in diameter, were documented. The cell
culture isolate was further characterized by neutral-
ization studies as Coxsackie B-1. The maternal an-
tibodies to Coxsackie B-1 virus were not measured.
DISCUSSION
Coxsackievirus infection during pregnancy may
cause transplacental infection in the fetus unrelated
to the clinical severity of the disease in the mother.
The spectrum of neonatal disease ranges from no
sequela whatsoever to fatal encephalomyocarditis. 7
Hydrops due to myocarditis in a fetus with pre-
sumed coxsackievirus infection in utero has been
reported. Hydrops fetalis has been known to be
associated with maternal preeclampsia, as observed
in our patient.
Brown and Evans, 9 in a prospective study, dem-
onstrated an association between the serologic evi-
dence of Coxsackie B virus infection during the
first trimester of pregnancy and the subsequent
birth of infants with congenital heart disease. How-
ever, the documentation of cardiovascular malfor-
mations in their study was poor. In a careful review
of the cardiovascular effects of congenital infec-
tions, Rosenberg6 concluded that coxsackievirus in-
fection is a known cause of fetal myocarditis, but
not a proven cause of fetal anomalies.
It is interesting to speculate as to when the infec-
tion may have occurred in our patient. Because she
had no clinical evidence of infection, definitively
determining when the in utero infection occurred
was not possible. However, if the virus caused the
congenital malformation of the fetal heart, the in-
fection must have occurred quite early in the gesta-
tion. The virus was isolated from this patient by
amniocentesis at 28 weeks gestation. Since so few
cases of coxsackievirus infection in utero have been
reported, there is little information on how long the
virus can be cultured after a primary infection.
Magnius et al. 10 pointed out that enteroviruses may
be excreted for several weeks after an acute illness.
The finding of focal calcification on microscopic
evaluation of the fetal heart and the lack of an
inflammatory response suggest that infection in this
fetus was not recent.
In following Coxsackie B virus infections dur-
80 INFECTIOUS DISEASES 1N OBSTETRICS AND GYNECOLOGY
INTRAUTERINE INFECTION WITH COXSACKIEVIRUS WATSON ET AL.
ing the first trimester, Rosenberg6 noted that the
incidence of congenital cardiac disease increases
from approximately 5-7/1,000 live births to
9/1,000 live births. However, such observations
do not prove teratogenesis, since other factors, such
as maternal fever or medications taken for viral
illness, may increase the incidence of malforma-
tions.
Other investigators have demonstrated the pre-
dilection of coxsackievirus B infections for myocar-
dial tissue. The association of coxsackievirus anti-
gen with myocarditis has been demonstrated by
immunofluorescent studies. 5 Whether this type of
myocarditis can result in teratogenesis is unproven.
It is reasonable to hypothesize, however, that myo-
carditis occurring in the fetus during the early first
trimester may interfere with the complex embryo-
logical development occurring at this time.
Most studies on coxsackievirus infection during
pregnancy have relied on the maternal serologic
evidence of infection. The isolation of virus from
the amniotic fluid presents a stronger case for trans-
placental infection. The association of group B cox-
sackievirus infection with fetal congenital cardiac
disease in this case report, although not conclusive,
suggests that transplacental coxsackievirus infection
may result in fetal congenital cardiovascular mal-
formations.
In the evaluation of a mother whose infant is
noted to have congenital cardiac disease by fetal
echocardiography performed during pregnancy, an
amniocentesis for fetal karyotype is often obtained
to search for aneuploidy as a cause of such malfor-
mations. In such a case, it is reasonable to consider
sending an aliquot of the fluid obtained during
amniocentesis for viral culture, since such an infec-
tion may occur in an asymptomatic mother.
REFERENCES
1. Sever JL, Huebner RJ, Castellano GA, et al. Serologic
diagnosis "en masse" with multiple antigens. Am Rev
Respir Dis 88(2):342-349, 1963.
2. Cherry JD, Soriano F, Jahn CL: Search for perinatal
viral infection. Am J Dis Child 116:245-250, 1968.
3. Amstey MS, Miller RK, Menegus MA, di Sant’Agnese
PA: Enterovirus in pregnant women and the perfused
placenta. Am J Obstet Gynecol 158(4):775-782, 1988.
4. Modlin J: Perinatal echovirus infection: Insights from a
literature review of 61 cases of" serious infection and 16
outbreaks in nurseries. Rev Infect Dis 8:918-926, 1986.
5. Basso NGS, Fonseca MEF, Garsia AGP, Zuardi JAT,
Silva MR, Outani H: Enterovirus isolation from foetal
and placental tissues. Acta Virol 34:49-57, 1990.
6. Rosenberg HS: Cardiovascular effects of congenital in-
fections. Am J Cardiovasc Pathol 1(2):147-156, 1987.
7. Modlin JF: Perinatal echovirus and group B coxsackievi-
rus infections. Clin Perinatol 15(2):233-246, 1988.
8. Benirschke K, Swartz WH, Leopold G: Hydrops due to
myocarditis in a fetus. Am J Cardiovasc Pathol 1:131-
133, 1986.
9. Brown GC, Evans EN: Serologic evidence of coxsackie-
virus etiology of congenital heart disease. JAMA 199:
183-187, 1967.
10. Magnius L, Sterner G, Enocksson E: Infections with
echoviruses and coxsackieviruses in late pregnancy. Scand
J Infect Dis 7 l(Suppl):53-57, 1990.
INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY 81
Submit your manuscripts at
http://www.hindawi.com
Stem Cells
International
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
MEDIATORS
INFLAMMATION
of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Behavioural 
Neurology
Endocrinology
International Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Disease Markers
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
BioMed 
Research International
Oncology
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Oxidative Medicine and 
Cellular Longevity
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
PPAR Research
The Scientific 
World Journal
Hindawi Publishing Corporation 
http://www.hindawi.com Volume 2014
Immunology Research
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Journal of
Obesity
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
 Computational and  
Mathematical Methods 
in Medicine
Ophthalmology
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Diabetes Research
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Research and Treatment
AIDS
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Gastroenterology 
Research and Practice
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Parkinson’s 
Disease
Evidence-Based 
Complementary and 
Alternative Medicine
Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com


Intrauterine Infection With Coxsackievirus: Is it a Cause of Congenital Cardiac Malformations?

Sami  Awadallah

Directory of Open Access Journals

Infectious Diseases in Obstetrics and Gynecology

Cardiovascular effects of congenital infections.

CL: Search for perinatal viral infection.

di Sant’Agnese PA: Enterovirus in pregnant women and the perfused placenta.

Enocksson E: Infections with echoviruses and coxsackieviruses in late pregnancy.

Evans EN: Serologic evidence of coxsackievirus etiology of congenital heart disease.

Hydrops due to myocarditis in a fetus.

Outani H: Enterovirus isolation from foetal and placental tissues. Acta Virol 34:49-57,

Perinatal echovirus and group B coxsackievirus infections. Clin Perinatol

Perinatal echovirus infection: Insights from a literature review of 61 cases of&quot; serious infection and 16 outbreaks in nurseries. Rev Infect Dis 8:918-926,

Serologic diagnosis &quot;en masse&quot; with multiple antigens. Am Rev Respir Dis 88(2):342-349,

http://downloads.hindawi.com/journals/idog/1995/532479.pdf

Intrauterine Infection With Coxsackievirus: Is it a Cause of Congenital Cardiac Malformations?

Abstract

Similar works

Full text

Available Versions

Crossref

Directory of Open Access Journals