title: Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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/mm(3), 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 were 95% and 100%, respectively. In fetuses presenting with nonsevere ultrasound features, the positive predictive values of ultrasound alone and in combination with amniotic fluid viral load or with fetal blood parameters were 60%, 78%, and 79%, respectively.
  
  
  
  Risk assessment of infected fetuses for being symptomatic at birth is possible as early as the time of diagnosis by using a combination of targeted ultrasound examination along with viral load in amniotic fluid and in fetal blood together with platelet count. The advantage of using amniotic fluid is that it is available at prenatal diagnosis. One may wonder if increasing the negative predictive value of the overall assessment of an infected fetus from 95-100% is worth the additional risk of cordocentesis for fetal blood sampling. This can only be an individual decision made by well-informed women and it seems therefore appropriate to use the figures presented here and their confidence intervals for counseling.
authors.affiliation: Equioe d'accueil 73-28, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire de Microbiologie Clinique, Assistance publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France; Centre National de Réfèrence Cytomegalovirus-Laboratoire Associé, Paris, France. Electronic address: marianne.leruez@nck.aphp.fr.
authors.forename: Marianne
authors.initials: M
authors.lastname: Leruez-Ville
authors.affiliation: Equioe d'accueil 73-28, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Maternité, Unité de Médecine Fœtale, Assistance publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Stirnemann
authors.affiliation: Equioe d'accueil 73-28, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Maternité, Unité de Médecine Fœtale, Assistance publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Sellier
authors.affiliation: Equioe d'accueil 73-28, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Laboratoire de Microbiologie Clinique, Assistance publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France; Centre National de Réfèrence Cytomegalovirus-Laboratoire Associé, Paris, France.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Guilleminot
authors.affiliation: Equioe d'accueil 73-28, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Maternité, Unité de Médecine Fœtale, Assistance publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dejean
authors.affiliation: Equioe d'accueil 73-28, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Réanimation Néonatale, Assistance publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Magny
authors.affiliation: Department of Obstetrics and Fetal Medicine, Poissy Hospital, Poissy, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Couderc
authors.affiliation: Hôpital Intercommunal de Poissy-Saint Germain, Maternité, Poissy; Hôpital Américain de Paris, Unité de Médecine prénatale, Neuilly Sur Seine, France.
authors.forename: François
authors.initials: F
authors.lastname: Jacquemard
authors.affiliation: Equioe d'accueil 73-28, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Maternité, Unité de Médecine Fœtale, Assistance publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Ville
mesh_terms: D000649:Amniocentesis; D000653:Amniotic Fluid / Q000821:virology*; D001921:Brain / Q000002:abnormalities / Q000000981:diagnostic imaging*; D003587:Cytomegalovirus / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000150:complications / Q000175:diagnosis*; D004279:DNA, Viral / Q000032:analysis; D002658:Developmental Disabilities / Q000821:virology; D005260:Female; D005312:Fetal Blood / Q000821:virology*; D005315:Fetal Diseases / Q000175:diagnosis; D034381:Hearing Loss / Q000821:virology; D006801:Humans; D007231:Infant, Newborn; D010976:Platelet Count; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis; D011296:Prenatal Diagnosis; D011379:Prognosis; D018570:Risk Assessment; D016216:Ultrasonography, Prenatal; D019562:Viral Load
chemical_list: D004279:DNA, Viral
keywords: cytomegalovirus; fetal DNA; fetal platelet count; prenatal diagnosis; ultrasound