Original Articles
Prenatal indicators of congenital cytomegalovirus infection,☆☆

https://doi.org/10.1067/mpd.2000.107110Get rights and content

Abstract

Objective: To assess the validity of a diagnostic protocol designed to predict the outcome of newborns of mothers suspected to have primary cytomegalovirus (CMV) infection during the first 4 months of pregnancy. Study design: Anti-CMV immunoglobulin (Ig) M detection by enzyme immunoassay and immunoblot together with the determination of anti-CMV IgG avidity allowed us to classify 456 women as (1) uninfected, (2) undergoing either a primary or a recurrent infection, or (3) having an undefined serologic condition. Prenatal diagnosis was carried out at 21 to 23 weeks’ gestation for women. The presence of the virus in the amniotic fluid was determined by culture, polymerase chain reaction, and quantitative polymerase chain reaction. Macroscopic and histologic examinations were undertaken on tissue from aborted fetuses, whereas for newborns culture was performed on urine sampled during the first week of life. Results: Congenital infections were found exclusively among women undergoing a primary infection. The quantitative determination of CMV DNA in the amniotic fluid of at least 103 genome equivalents gave a 100% certainty of detecting an infected fetus. Higher viral loads were associated with fetuses or newborns with symptoms. Conclusions: IgM tests and the IgG avidity determination can identify all women at risk of transmitting CMV. Furthermore, a high CMV DNA load in amniotic fluid could be an indicator of symptomatic congenital infection at a relatively early stage of pregnancy. (J Pediatr 2000;137:90-5)

Section snippets

Methods

As a CMV referral center, we have adopted a 3-step diagnostic protocol. The first step, based on serologic tests, was aimed at identifying the presence of primary and recurrent infection. This step included the following serologic tests carried out on at least 1 pair of serum samples from each woman: redetermination of CMV-specific IgG and IgM by enzyme immunoassay,19 determination of the avidity of anti-CMV IgG (cytomegalovirus IgG avidity EIA WELL; RADIM, Rome, Italy),10 and confirmation of

Results

Between March 1994 and July 1998, we tested the sera of 456 pregnant women that were identified by screening laboratories of several Italian regions. No active infection was observed in 220 cases, a diagnosis of recurrent infection was made in 106 cases, a diagnosis of primary infection was made in 110 women, whereas no indication of the type of infection was obtained in 20 cases (“undefined”).

We offered amniocentesis to all women with primary or undefined infection, and 44% accepted. The main

Discussion

The diagnostic protocol adopted in this study accurately predicted both infection and clinical presentation of maternal CMV infection on the fetus or newborn. The 3-step protocol sequentially filters mothers and fetuses at high risk. Primary CMV infections that were difficult to detect until recently can now be diagnosed by disclosing presence of the low avidity anti-CMV antibody that persists for ”20 weeks after primary infection.10

We and others carried out invasive prenatal diagnosis, mainly

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      If the fetus is infected and ultrasound does not show an abnormality, determination of viral load in amniotic fluid may help to distinguish those who will be asymptomatic at birth from those who are likely to be symptomatic and at high risk of developing serious sequelae [3,69,70]. A study of 456 women at weeks 21–23 of pregnancy for example, found that higher viral loads in amniotic fluid (>100,000 copies/mL) were associated with symptomatic new-borns [3,70]. In another small study of 21 fetuses, the median DNA level in amniotic fluid was higher in symptomatic newborns, but the difference was not statistically significant [71].

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    Supported in part by grants from the ministry of public health (ISS, AIDS projects), the Ministry of University, Scientific and Technological Research and the University of Bologna.

    ☆☆

    Reprint requests: Maria Paola Landini, MD, PhD, Laboratorio Di Microbiologia E Virologia, Policlinico S. Orsola-Malpighi, via Massarenti N. 9, 40138 Bologna, Italy.

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