Sequelae of Congenital Cytomegalovirus Following Maternal Primary Infections Are Limited to Those Acquired in the First Trimester of Pregnancy

Clin Infect Dis. 2019 Oct 15;69(9):1526-1532. doi: 10.1093/cid/ciy1128.

Abstract

Background: The known relationship between the gestational age at maternal primary infection an the outcome of congenital CMV is based on small, retrospective studies conducted between 1980 and 2011. They reported that 32% and 15% of cases had sequelae following a maternal primary infection in the first and second or the third trimester, respectively. We aimed to revisit this relationship prospectively between 2011 and 2017, using accurate virological tools.

Methods: We collected data on women with a primary infection and an infected child aged at least 1 year at the time of analysis. An accurate determination of the timing of the primary infection was based upon serial measurements of immunoglobulin (Ig) M and IgG and on IgG avidity in sera collected at each trimester. The case outcome was assessed according to a structured follow-up between birth and 48 months.

Results: We included 255 women and their 260 fetuses/neonates. The dating of the maternal infection was prospective in 86% of cases and retrospective in 14%. At a median follow-up of 24 months, the proportion of sensorineural hearing loss and/or neurologic sequelae were 32.4% (95% confidence interval [CI] 23.72-42.09) after a maternal primary infection in the first trimester, 0 (95% CI 0-6.49) after an infection in the second trimester, and 0 (95% CI 0-11.95) after an infection in the third trimester (P < .0001).

Conclusions: These results suggest that a cytomegalovirus infection can be severe only when the virus hits the fetus in the embryonic or early fetal period. Recent guidelines recommend auditory follow-ups for at least 5 years for all infected children. This raises parental anxiety and generates significant costs. We suggest that auditory and specialized neurologic follow-ups may be recommended only in cases of a maternal infection in the first trimester.

Trial registration: ClinicalTrials.gov NCT01651585 NCT01923636.

Keywords: congenital; cytomegalovirus; first trimester; outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytomegalovirus / pathogenicity*
  • Cytomegalovirus Infections / diagnosis*
  • Female
  • Fetal Diseases / virology
  • Humans
  • Infectious Disease Transmission, Vertical
  • Pregnancy
  • Pregnancy Complications, Infectious / diagnosis*
  • Pregnancy Trimester, First
  • Prospective Studies

Associated data

  • ClinicalTrials.gov/NCT01651585
  • ClinicalTrials.gov/NCT01923636