Cytomegalovirus Screening Strategies

Abstract & Commentary

By John C. Hobbins, MD, Professor and Chief of Obstetrics, University of Colorado Health Sciences Center, Denver, is Associate Editor for OB/GYN Clinical Alert.

Dr. Hobbins reports no financial relationship to this field of study.

Synopsis: Universal screening for primary maternal cytomegalovirus (CMV) is cost-effective. More study is needed to evaluate the efficacy of CMV-intravenous immune globulin for prevention.

Source: Cahill AG, et al. Screening and treating primary cytomegalovirus infection in pregnancy: Where do we stand? A decision-analytic and economic analysis. Am J Obstet Gynecol 2009;201:466.e1-7.

Currently, there is no consensus on how to screen for CMV, a problem that affects about 1% of pregnancies in the United States. Since one study has emerged showing that treatment of CMV is about 90% effective in avoiding sequelae in neonates,1 Cahill et al from St. Louis used various assumptions while constructing a mathematical model to assess the theoretical efficacy and cost-effectiveness of three methods of screening: 1) universal screening; 2) screening of those at historical risk (those with children < 5 years of age, or who are employed in a childcare setting); or 3) screening only those with ultrasound signs suspicious for fetal CMV infection.

The screening method involved maternal blood testing for CMV IgG and IgM antibodies. If IgM was positive without the presence of IgG antibodies, the patient was considered to be screen-positive. If both IgM and IgG were present, but with the latter having < 25% avidity, these patients were also considered screen-positive. The method also assumed that every screen-positive patient's amniotic fluid would be tested for the presence of CMV/DNA by PCR. Those with the diagnosis of CMV would then be treated with 200 U/kg of CMV immunoglobulin (CMV/IVIG).

Based on a yearly birth rate of about 4 million in the United States, the authors calculated that universal screening after 20 weeks would result in 66,368 false-positive tests. In this category (category 1), there would be 1979 neonatal deaths and 615 cases of severe disability. In category 2, 2.1 million women would be screened, resulting in 26,348 patients having false-positive results, and with this strategy there would be 2058 neonatal deaths and 8253 severely disabled infants. Using ultrasound findings for screening (category 3), 1.6 million patients would be screened, resulting in 2078 neonatal deaths and 8327 cases of severe disability.

The authors concluded that the most effective strategy was universal screening, but only if there was a 47% reduction in disease with the above treatment. Specifically, when comparing universal screening (category 1) with screening only for risk factors (category 2), treatment of diagnosed cases would save 7638 more children from severe CMV morbidity, and when comparing universal screening (category 1) with ultrasound findings alone (category 3), severe disability would be averted in 7712 infants.

Commentary

Unfortunately, as the authors point out, the efficacy of universal screening after 20 weeks is based on the assumption that treatment with CMV/IVIG will be effective in at least 1 of 2 fetuses/neonates, and, although the study cited showed a 90% effectiveness,1 it is the only study in the literature and the numbers of patients in the study are not overly impressive. Also, at present the therapy has limited availability and is costly.

Obviously, we are not there yet, and I am simply including this paper in this month's OB/GYN Clinical Alert to apprise the reader of a possibly effective screening strategy that still needs major fine-tuning through rigorous prospective investigation. In the meantime, we will certainly continue testing those with suspicious ultrasound findings such as ventriculomegaly, periventricular calcifications, large cisterna magna (with or without cerebellar hypoplasia), ascites, or intra-abdominal calcifications. Whether to screen those in category 2 is not so clear. Interestingly, the above results are essentially the same between those screened for risk factors and those with ultrasound findings. However, once the ultrasound signs appear, is it already too late?

Reference

  1. Nigro G, et al; Congenital Cytomegalovirus Collaborating Group. Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 2005;353:1350-1362.