Clinical Infectious Diseases
CORRESPONDENCE
Maternal Cytomegalovirus
Infection and Fetal Impairment:
Uncertainty Remains
To the Editor—Cytomegalovirus
(CMV) is the most common cause of
congenital infection, with an estimated
birth prevalence of 1 in 200 live births [1].
Up to 30 000 infants per year are expected
to be born with congenital CMV (cCMV)
in the United States. It is therefore cru-
cial that the best evidence-based studies
inform public policy.
Faure-Bardon and colleagues re-
cently described in this journal the re-
lationship between gestational age at
maternal primary infection and clinical
outcome of cCMV. Of 234 congenitally
infected neonates, 126 were determined
to be infected during the first trimester,
72 during the second trimester, and 36
during the third trimester. At 24 months
of age, the reported proportion of senso-
rineural hearing loss and/or neurological
sequelae was 32.4% after maternal pri-
mary infection in the first trimester and,
remarkably, 0% for infections occurring
in the second and third trimesters [2].
There are several aspects to this unex-
pected finding that need to be addressed.
A diagnosis of cCMV was made ret-
rospectively for 14% of the reported
cases. Given the need for serial immuno-
globulin G (IgG) serology to determine
timing of maternal infection, it would be
helpful to have additional information
regarding the methodologies employed
for these women. Considerable variation
exists in the performance and reliability
of different avidity assays, and the utility
of intermediate avidity for the assignment
of primary infection is not clear [3–5].
Acknowledgement and careful consid-
eration of previous work, especially re-
search that drew different conclusions
about the neurodevelopmental and au-
diological impact of non–first trimester
maternal infections, should have been
provided.
Serial IgG serology to detect serocon-
version is not feasible for all pregnant
women. Even in cases of confirmed ma-
ternal primary CMV infection, it is dif-
ficult to determine the timing of fetal
infection, which only occurs in approxi-
mately 30%–40% of such pregnancies [3].
The risk of fetal infection varies by tri-
mester, and the presence of a fetal infec-
tion does not equal fetal damage [4]. It has
repeatedly been shown that fetal infection
caused by maternal infection in the late
second and third trimesters is associated
with a lower, but not absent, risk of fetal
impairment [5–7]. However, the inability
to more precisely define the timing of
virus transmission to the fetus limits de-
finitive interpretation of these studies [8].
The incompletely defined role of
nonprimary maternal CMV infections
must also be considered [8]. There are no
standard tests to define nonprimary infec-
tion in pregnancy. A  large proportion of
children with cCMV are born to women
with nonprimary infection. Therefore, it
is premature to recommend that infants
born to mothers with later gestational
CMV infections do not need to undergo
audiologic and neurologic follow-up [9].
The prevalence of cCMV can be im-
pacted by education, and outcomes can
be improved by early identification and
intervention [8]. Faure-Bardon and
colleagues’ concern regarding increased
parental anxiety in relation to best prac-
tice guidelines for follow-up has not been
a significant factor in our experience, or
in studies of universal newborn hearing
screening [8, 9]. We advise that defini-
tive conclusions regarding timing of ma-
ternal infection must await confirmation
in larger studies, and we strongly counsel
against changes to the current standard of
care for children born with cCMV.
Note
Potential conflicts of interest. S. B. B. has re-
ceived personal fees from Merck and grants
from Meridian Bioscience. K.  B. F.  has received
CORRESPONDENCE • cid 2019:XX (XX XXXX) • 1
personal fees from Merck. All other authors re-
port no potential conflicts of interest. All authors
have submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Conflicts that
the editors consider relevant to the content of the
manuscript have been disclosed.
Kathleen M. Muldoon,1 Suresh B. Boppana,2,3
Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciz400/5489691 by guest on 24 October 2019
Kristen H. Spytek,4 and Karen B. Fowler2,5
1
Department of Anatomy, College of Graduate Studies and
Arizona College of Osteopathic Medicine, Midwestern
University, Glendale; Departments of 2Pediatrics, and
3
Microbiology, University of Alabama at Birmingham;
4
National CMV Foundation, Tampa, Florida; and 5Department
of Epidemiology, University of Alabama at Birmingham
References
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Sequelae of congenital cytomegalovirus (cCMV)
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Correspondence: K. M. Muldoon, Midwestern University, 19555
N. 59th Avenue, Glendale, AZ 85308 (kmuldo@midwestern.edu).
Clinical Infectious Diseases®  2019
© The Author(s) 2019. Published by Oxford University Press for
the Infectious Diseases Society of America. All rights reserved.
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DOI: 10.1093/cid/ciz400