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

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Abstract
Objective To estimate the risk of congenital cytomegalovirus infection and disease following primary maternal infection around the time of conception compared with the risk during later stages of pregnancy. Design Cohort study between 1990 and 2003. Setting Germany. Participants One hundred and sixty‐six pregnant women with serologically confirmed primary cytomegalovirus infection and known outcome. Methods Timing of primary cytomegalovirus infection by analysing the kinetics of cytomegalovirus‐specific IgG and IgM antibodies, the IgG avidity index and neutralising antibodies. Main outcome measure Onset of maternal primary infection in relation to congenital infection and disease. Results Preconceptional (between eight and two weeks before onset of the last menstrual period) was determined in three women and did not lead to congenital infection. Periconceptional infection (between one week before and five weeks after last menstrual period) occurred in 20 women with congenital infection in nine cases (45%). Timing was less precise (between eight weeks before and five weeks after last menstrual period) in an additional 10 women, three cases of which resulted in congenital infection. Of the 12 pregnancies in which congenital infection occurred, seven were terminated, six before the 12th week of gestation (WG 12) and one at WG 19 due to fetal hyperechogenic bowel. One of the five infected live‐born infants delivered to a mother with periconceptional infection showed dystrophy and mild microcephaly at birth, but had a rather normal development at two years of age. Primary infections occurring between WG 6–20 and WG 20–38 resulted in transmission rates of 30% (27/89) and 58% (18/31), respectively. Conclusions Counselling of women with periconceptional primary cytomegalovirus infection should be adjusted to offer prenatal diagnosis and high‐level ultrasound controls due to the considerable risk for fetal infection and uncertainty of clinical outcome and disease.