We appreciate the excellent analysis by Cahill et al. The approach they modeled assumed a one time serologic screening for cytomegalovirus (CMV) at approximately 20 weeks’ gestation.

It would be very helpful for the design of future studies and/or practice options if they had modeled other approaches which are likely to be more effective, although perhaps not quite as simple. A problem with the one time screening approach is that it relies too heavily on IgM testing. This test lacks specificity and thus this type of testing will have to rely on frequent avidity testing. Furthermore, negative IgM detection at 20 weeks does not exclude a primary infection that occurred early in pregnancy. Including a model that used monthly IgG testing for seroconversion should be the gold standard against which other approaches are compared. Monthly screening for seroconversion has other possible advantages. It would allow CMV-intravenous immune globulin (IVIG) to be given as early as possible during pregnancy and as soon as possible after maternal infection, thus optimizing the chances for the prevention of fetal and/or placental infection. Prevention is always preferred to treatment and in the one time testing approach at 20 weeks’ gestation, CMV-IVIG would nearly always be given for treatment of infected placentas and fetuses. CMV crosses the placenta and infects the fetus by binding to low avidity IgG molecules. IgG is internalized by the placenta in the first trimester and begins to reach the fetal bloodstream at midgestation accelerating during the third trimester. Administering high avidity CMV-IgG early in pregnancy should reduce virus replication in the placenta, inflammation and fetal infection. In the Nigro study, CMV-IVIG was given monthly to women without confirmed fetal infection (the prevention group) and this group had a significantly reduced rate of fetal infection and the few infected infants were normal at birth and at 2 years of age. Hence, another approach that should be modeled in the cost-benefit analysis would be monthly serologic screening and for those that seroconvert, the prompt monthly infusion of low-dose CMV-IVIG until the mother develops her own high avidity antibodies.

Finally, in the future intramuscularly administered monoclonal antibodies may replace CMV-IVIG, making passive immunization during the first half of pregnancy of all CMV seronegative women a practical possibility. This option should also be tested in a cost-benefit analysis.