Pre- and periconceptional primary cytomegalovirus infection: risk of vertical transmission and congenital disease.

摘要

In both the United States and West Europe, cytomegalovirus (CMV) infection is the most common viral form of congenital infection. Intrauterine transmission of CMV takes place in approximately 40% of infections, and approximately 10% of live-born infants have symptomatic disease at the time of birth and later. Late sequelae such as sensorineural hearing loss and neurodevelopmental disorders occur in 10% to 15% of infants lacking symptoms at birth. Recurrent maternal infection contributes substantially to the rate of congenital infection.This cohort study, covering the years 1990-2003, estimated the risk of congenital CMV infection and disease after primary maternal infection at approximately the time of conception and also in later stages of pregnancy. The study population included 166 pregnant women with serologically confirmed primary CMV infection. The timing of primary infection was studied by measuring CMV-specific immunoglobulin (Ig)M and IgG antibodies, the IgG avidity index, and titers of neutralizing antibodies. Prenatal diagnosis of CMV infection was attempted in 79 of the 166 pregnancies by analyzing amniotic fluid samples for viral DNA by the polymerase chain reaction technique and also for infectious virus.Women with symptomatic primary CMV infection and those with subclinical infection had similar transmission rates (41% and 37%, respectively). Fetal transmission of infection occurred in 45% of pregnancies with periconceptional infection, in 3 of 10 pregnancies before gestational week 6, and in none of 3 pregnancies with preconceptional infection. Eighty-nine women had primary CMV infection at gestational weeks 6-20 and 31 at weeks 20-38. The transmission rate was lowest (30%) when primary infection occurred in weeks 6-20. Rates were 39% for infection gestational at weeks 18-22 and 58% during weeks 20-38. Seven fetuses or newborn infants had congenital disease (defined as ultrasound abnormalities in cases of therapeutic abortion or the presence in newborn infants of neurologic or systemic manifestations of congenital CMV disease), all of them before gestational week 22. None of 18 infected live-born infants infected after 20 weeks gestation had congenital disease. Congenital disease was found in 4 of 25 pregnancies with vertical transmission after maternal infection in gestational weeks 6-20. Four pregnancies were ended at weeks 7-11 when primary infection was diagnosed, and there was 1 missed abortion. Only 1 of 5 live-born infants had mild symptoms at birth. Two of 3 subclinically infected newborn infants were healthy when followed up for 8 months or longer; 1 had late-onset hearing loss.The authors believe that women with periconceptional CMV infection should be managed like those having primary infection in the first 20 weeks of pregnancy. Prenatal diagnosis done at gestational weeks 21-23 can exclude fetal infection with a high degree of accuracy. Congenital infection should be sought in newborn infants of mothers having primary infection late in pregnancy or at approximately thetime of conception.