Timing of primary maternal cytomegalovirus infection and rates of vertical transmission and fetal consequences

Abstract Objective Cytomegalovirus (CMV) infection is the most frequent congenital infection and a major cause of long-term neurological morbidity. The aim of this meta-analysis was to calculate the pooled rates of vertical transmission and fetal consequences according to the timing of primary maternal infection. Data sources MEDLINE, Scopus, Cochrane Library and grey literature sources were searched from inception until January 2020. Study eligibility criteria Cohort and observational studies reporting timing of maternal CMV infection and rate of vertical transmission or fetal consequences were included. The primary outcomes were (i) vertical transmission and ii) fetal insult, defined either as prenatal findings from the central nervous system (CNS) leading to termination of pregnancy, or the presence of neurological symptoms at birth. The secondary outcomes included (i) sensorineural hearing loss (SNHL) and/or neurodevelopmental delay at follow-up, and (ii) prenatal CNS ultrasound findings Study appraisal and synthesis methods The pooled rates of the outcomes of interest with their 95% confidence intervals [CI], were calculated for primary maternal infection at the (i) preconceptional period, (ii) periconceptional period, (iii) first trimester, (iv) second trimester and (v) third trimester. Results Seventeen studies were included. The pooled rates of vertical transmission (10 studies, 2942 fetuses) at the preconceptional period, periconceptional period, first, second and third trimester were 5.5% (95%CI: 0.1% to 10.8%), 21.0% (95%CI: 8.4% to 33.6%), 36.8% (95%CI: 31.9% to 41.6%), 40.3% (95%CI: 35.5% to 45.1%) and 66.2% (95%CI: 58.2% to 74.1%), respectively. The pooled rates of fetal insult in case of transmission (10 studies, 796 fetuses) were 28.8% (95%CI: 2.4% to 55.1%), 19.3% (95%CI: 12.2% to 26.4%), 0.9% (95%CI: 0% to 2.4%), and 0.4% (95%CI: 0% to 1.5%), for maternal infection at the periconceptional period , first, second and third trimester, respectively. The pooled rates of SNHL for maternal infection at the first, second and third trimester were 22.8% (95%CI: 15.4% to 30.2%), 0.1% (95%CI: 0% to 0.8%), and 0% (95%CI: 0% to 0.1%), respectively. Conclusions Vertical transmission after maternal primary CMV infection increases with advancing pregnancy, starting from the preconceptional period. However, severe fetal consequences are rare after first-trimester infection.