Sequelae of Congenital Cytomegalovirus Risk Limited to First Trimester

Congenital cytomegalovirus (CMV) infection may be severe only when the virus affects the fetus in the embryonic period during the first trimester, according to a study recently published in Clinical Infectious Diseases.

Human CMV is the most prevalent cause of congenital infection and a major cause of neurological disabilities. Worldwide, the prevalence is approximately 7 cases per 1000 live births; 20% of neonates infected with CMV endure long-term sequelae. The relationship between gestational age at maternal primary infection and the risk for long-term sequelae in congenital CMV suggests an increased risk in the first trimester, but with a similar sequelae in 6% to 15% of neonates infected in the second or third trimester. Because maternal CMV primary infection is commonly asymptomatic, its timing relies on serological investigation. 

The relationship between gestational age at maternal primary infection and outcome in congenital CMV infection was based on small studies that occurred between 1980 and 2011, which reported a sequelae in 32% of infants exposed during the first trimester and 15% exposed during the second or third trimester. However, accurate serological timing of primary CMV infection was difficult at that time, as IgG avidity assays either were conducted in the early stage of development or were not available. Therefore, this study assessed the association between gestational age at maternal primary infection and outcome in a large cohort of congenital CMV cases that occurred between 2011 and 2017.

A total of 255 women with primary infection and their 260 fetuses were included. To determine the accurate timing of primary infection, serial measurements of IgM, IgG, and IgG avidity in sera were collected at each trimester, using recently developed serological tools and a standardized algorithm. The study outcome was assessed according to a follow-up between birth and 48 months, which included standardized clinical assessment of motor, cognitive, speech, and psychological development according to age. Audiological and Sensorineural Hearing Loss scores were also recorded at each visit.

Results suggested that CMV infection can be severe only when the virus affects the fetus during the embryonic or early fetal period. Of the 234 infected neonates, 126 were infected after maternal in the first trimester, 72 in the second trimester, and 36 in the third trimester. A main finding is that audiological and sensorineural scores, as well as neurological sequelae, were only seen in children who were infected after primary infection in the first trimester. At the 24‑month follow-up, the percentage of these 2 parameters were 32.4% after maternal primary infection in the first trimester and 0 for both the second and third trimesters (P <.0001).

Overall, the study authors concluded that, “Our results may have major implications for counselling pregnant women with primary infection and for parents dealing with an infected newborn.”

Reference

Faure-Bardon V, Magny JF, Parodi M, et al. Sequelae of congenital cytomegalovirus (cCMV) following maternal primary infection are limited to those acquired in the first trimester of pregnancy [published online December 31, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy1128/5267872