Seronegative pregnant women at high risk for CMV infection

Pregnant women who were seronegative for cytomegalovirus infection in the first trimester had an approximately 14% chance of acquiring the virus during their pregnancy, according to research published in The Journal of Infectious Diseases.

The researchers also found that cytomegalovirus (CMV)-infected infants were most often born to women with pre-existing seroimmunity.

“The prevalence of congenital CMV (cCMV) infection has been reported to vary according to the epidemiological characteristics of women of childbearing age,” Marisa M. Mussi-Pinhata, MD, of the pediatrics department at Ribeirão Preto Medical School, University of São Paulo, and colleagues wrote.

“Both primary and nonprimary maternal CMV infections have been associated with intrauterine transmission of this virus that can result in birth defects and long-term developmental disabilities. Most congenital infections in populations with high CMV seroprevalence are a consequence of nonprimary maternal infection among seropositive women. However, opportunities for exposure to CMV in these settings could also pose a significant risk to pregnant seronegative women.”

For their study, Mussi-Pinhata and colleagues recruited pregnant women who presented in the first trimester at six public health care centers. Almost all of the women — 99.2% — came for prenatal care were in a low-income group. Women were enrolled at the first antenatal visit and followed up in the second and third trimesters and at 1 month after delivery.

The analysis included 1,952 women who had at least one additional serum sample collected 14 weeks or more after an initial specimen was gathered in the first trimester. Most women — 1,915 (98.1%; 95% CI, 85.3%-96.7%) — tested positive for CMV-IgG in the first trimester. The 36 women (1.8%; 95% CI, 1.3%-2.6%) who tested seronegative during the same period had more education, were slightly older at sexual debut and were less frequently exposed to children before and during gestation compared with CMV-positive women, Mussi-Pinhata and colleagues reported.

Of the women who tested seronegative, five women experienced seroconversion (cumulative rate, 13.9%; 95% CI, 4.8%-30.6%) between 10 and 28 weeks of gestation.

Newborns were screened for CMV. One in 36 infants (2.8%; 95% CI, 0.5%-14.2%) born to initially seronegative mothers and eight in 1,685 infants (0.5%; 95% CI, 0.2%-1%) born to seropositive mothers were diagnosed with cCMV infection.

“In this study, only a small proportion (1.9%) of low-income urban Brazilian women were seronegative for CMV during the first trimester of pregnancy, a result that was consistent with our previous findings that most women in this maternal population have acquired CMV at a young age” the researchers wrote. “The finding that seronegative women in this population have a high risk of becoming infected during gestation with a cumulative incidence rate of 13.9% and an annualized seroconversion rate of 19.5% indicates that CMV exposure in this maternal population is significant. ... The rate of annual seroconversion among seronegative pregnant women observed in our study is higher than most reports from several countries and populations.”

Mussi-Pinhata and colleagues noted that because there were few seronegative women in the study, they could not examine risk factors for seroconversion or why the women remained seronegative before becoming pregnant while facing significant CMV exposures.

“This report adds to the natural history of CMV infection in this highly seropositive maternal population and highlights the relevance of developing intervention strategies for the prevention of maternal and congenital CMV infections that are culturally appropriate,” they concluded.

In a related editorial, Stanley A. Plotkin, MD, emeritus professor of pediatrics at the University of Pennsylvania, said the study provides important data on congenital CMV infection.

“If we extrapolate from the 14% of seronegative women who were infected during pregnancy, it would suggest that 259 of the seropositive women were also exposed to CMV, of whom eight, or 3%, were shown to transmit the virus to their fetuses. If these numbers are correct, the conclusion must be drawn that maternal immunity is largely protective against CMV fetal transmission.”

He said the implication is that duplicating maternal immunity after natural infection in a vaccine would confer a high degree of protection against transmission of CMV to the fetus. – by Bruce Thiel

Disclosures: The authors report no relevant financial disclosures. Plotkin reports acting as a consultant to many entities developing a CMV vaccine but holding no royalty position on any particular candidate vaccine.