Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis

• Published in: American journal of obstetrics and gynecology 2016-09, Vol.215 (3), p.342.e1-342.e9
• Main Authors: Leruez-Ville, Marianne, MD, Stirnemann, Julien, MD, Sellier, Yann, MSc, Guilleminot, Tiffany, BA, Dejean, Anne, MSc, Magny, Jean-François, MD, Couderc, Sophie, MD, Jacquemard, François, MD, Ville, Yves, MD
• Format: Article
• Language: English
• Subjects: Amniocentesis; Amniotic Fluid - virology; Brain - abnormalities; Brain - diagnostic imaging; cytomegalovirus; Cytomegalovirus - genetics; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - diagnosis; Developmental Disabilities - virology; DNA, Viral - analysis; Female; Fetal Blood - virology; Fetal Diseases - diagnosis; fetal DNA; fetal platelet count; Hearing Loss - virology; Humans; Infant, Newborn; Obstetrics and Gynecology; Platelet Count; Polymerase Chain Reaction; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Infectious - diagnosis; Prenatal Diagnosis; Prognosis; Risk Assessment; Ultrasonography, Prenatal; ultrasound; Viral Load
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2016.03.052

Background Congenital cytomegalovirus infection occurs in 0.7% of live births with 15-20% of infected children developing long-term disability including hearing loss and cognitive deficit. Fetal cytomegalovirus infection is established by viral DNA amplification by polymerase chain reaction in amniotic fluid obtained by amniocentesis following maternal seroconversion or after the diagnosis of ultrasound features suggestive of fetal infection. Severe brain ultrasound anomalies are associated with a poor prognosis. The prognosis of an infected fetus showing either no ultrasound features or nonsevere ultrasound anomalies is difficult to establish up until late in the second or third trimester of pregnancy. Objective We sought to evaluate the prognostic value of fetal ultrasound, amniotic fluid, and fetal blood analysis at the time of prenatal diagnosis of fetal infection. Study Design We reviewed all cases of fetal cytomegalovirus infection with a sample of amniotic fluid positive for viral DNA and/or fetal blood analyzed in our laboratory from 2008 through 2013. Prenatal ultrasound features along with cytomegalovirus DNA loads in amniotic fluid and in fetal blood and fetal platelet counts were reviewed in relation to gestational age at maternal infection, neonatal examination, and postnatal follow-up or postmortem examination. Results In all, 82 fetuses were infected following maternal infection mainly in the first trimester. At the time of prenatal diagnosis at a median of 23 weeks, 19, 22, and 41 fetuses showed severe brain ultrasound abnormalities, nonsevere ultrasound features, and normal ultrasound examination, respectively. Nonsevere ultrasound features, higher DNA load in amniotic fluid, fetal platelet count ≤114,000/mm3 , and DNA load ≥4.93 log10 IU/mL in fetal blood were associated with a symptomatic status at birth in univariate analysis ( P < .001, P  = .001, and P  = .018, respectively). Bivariate analysis combining ultrasound results and either adjusted viral load in amniotic fluid or fetal blood profile showed that these were independent prognostic factors of a symptomatic status at birth. Both fetal blood parameters were better predictors than amniotic fluid viral load. At the time of prenatal diagnosis, the ultrasound negative predictive value for symptoms at birth or at termination of pregnancy was 93%. The combined negative predictive values of ultrasound and viral load in amniotic fluid and that of ultrasound and fetal blood parameters wer