Congenital cytomegalovirus infection following first trimester maternal infection: Symptoms at birth and outcome

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Abstract

Background

The relationship between gestational age at time of maternal cytomegalovirus (CMV) infection and outcome of fetal infection is not well defined because the timing of maternal infection is usually not known.

Objective

To determine whether congenital cytomegalovirus (CMV) infection following primary maternal infection during the first trimester of pregnancy is more likely to lead to central nervous system (CNS) sequelae than fetal infection due to maternal infection later in pregnancy.

Study design

Using serum collected during pregnancy from mothers of newborns with congenital CMV infection, maternal infection was categorized as first trimester (<13 weeks) or later based on dates and results of IgG and IgM assays for CMV antibody. Outcome of congenital CMV infection was assessed by longitudinal fotlow-up of the infected cohort.

Results

Sensorineural hearing loss was found in 8/34 (24%) of children in the first trimester group, compared with 1/40 (2.5%) in the later infection group (P = 0.01, relative risk, 9.6). Considering any CNS sequela (hearing loss, mental retardation, cerebral palsy, seizures, chorioretinitis) 11/34 (32%) first trimester cases were affected compared with 6/40 (15%) in the later infection group (P = 0.07, relative risk 2.2). None of the later group had more than one sequela, compared with 4 (12%) of the first trimester group (P = 0.04).

Conclusions

Children with congenital CMV infection following first trimester maternal infection are more likely to have CNS sequelae, especially sensorineural hearing loss, than are those whose mothers were infected later in pregnancy. However, some degree of CNS impairment can follow even late gestational infection.

Introduction

Although cytomegalovirus (CMV) is the leading cause of congenital infection in the United States, little is known about the relationship between gestational age at the time of maternal primary infection and clinical expression of fetal infection. Studying the effect of gestational age on the outcome of congenital CMV infection is difficult because it is difficult to define the time of onset of maternal infection. Studies of large cohorts of pregnant women have found that primary CMV infection occurs during pregnancy in around 2% of women, but over 95% of them have no identifiable illness (Ahlfors et al., 1984, Griffiths and Baboonian, 1984, Stagno et al., 1982) information on the effect of gestational age on outcome of congenital CMV infection is of practical prognostic value and is essential for considering strategies for prevention, diagnosis and treatment of infection during pregnancy. In order to determine the effect of gestational age on virulence of fetal infection, we compared the outcome of congenital CMV infection in infants born after a first trimester maternal infection with that of infants born after second or third trimester infection.

Section snippets

Study population

Criteria for inclusion of infants in this report were: (1) Congenital CMV infection proven by isolation of virus prior to 3 weeks of age. (2) Maternal primary CMV infection during pregnancy documented by seroconversion (from serum antibody negative to antibody positive) or detection of serum CMV-IgM antibody on the first prenatal sample. (3) Maternal primary infection could be categorized as occurring during the first trimester (prior to week 14 of gestation) or later (≥14 weeks of gestation).

Detection of primary maternal infection

In order to determine the specificity of the CMV-IgM antibody assay for detection of primary infection, sera from 300 women known to be seropositive for at least 1 year were tested. IgM antibody to CMV was found in 2/300 (1.5%). Among 43 women who seroconverted from CMV-IgG negative to positive, 36 (83.7%) had CMV-IgM in their first positive serum. The mean interval between the last CMV-IgG negative serum and the first positive serum was 30 weeks. When the interval between negative and positive

Discussion

Approximately 20–30% of infants with congenital CMV infection due to a first trimester primary maternal infection will have CNS sequelae. With maternal infection later in pregnancy, the rate of sequelae in infected offspring is lower. However, even third trimester maternal infections are capable of causing hearing loss, a result that is not surprising because progressive deterioration in hearing after birth is a characteristic feature of congenital CMV infection (Dahle et al., 1979, Fowler et

Acknowledgements

This work was supported in part by grants from the National Institute of Child Health and Human Development (P01 HD10699), the National Institute on Deafness and Communication Disorders (K08 DC00079), the National Institutes of Allergy, Immunology and Infectious Diseases (P01 AI-43681) and the UAB General Clinical Research Center (M01 RR00032).

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