Accuracy of prenatal ultrasound screening to identify fetuses infected by cytomegalovirus which will develop severe long-term sequelae

M Leruez-Ville, S Ren, J-F Magny, F Jacquemard, S Couderc, P Garcia, A-M Maillotte, M Benard, D Pinquier, P Minodier, D Astruc, H Patural, M Ugolin, S Parat, B Guillois, A Garenne, M Parodi, L Bussières, J Stirnemann, P Sonigo, A E Millischer, Y Ville, M Leruez-Ville, S Ren, J-F Magny, F Jacquemard, S Couderc, P Garcia, A-M Maillotte, M Benard, D Pinquier, P Minodier, D Astruc, H Patural, M Ugolin, S Parat, B Guillois, A Garenne, M Parodi, L Bussières, J Stirnemann, P Sonigo, A E Millischer, Y Ville

Abstract

Objectives: To compare the ability of detailed routine ultrasound examination, performed without knowledge of maternal serology and fetal status, with that of targeted prenatal imaging performed in prenatal diagnostic units in cases of known fetal infection to identify cytomegalovirus (CMV)-infected fetuses that will develop long-term sequelae.

Methods: All prenatal imaging reports were collected for 255 children with congenital CMV in a registered cohort between 2013 and 2017 (NCT01923636). All women had undergone detailed routine fetal ultrasound examination at 20-24 and 30-34 weeks as part of routine antenatal care. All cases of known fetal CMV infection had also undergone targeted prenatal ultrasound examination. Postnatal structured follow-up for up to 48 months of age involved clinical, audiological and neurological assessment, including Brunet-Lezine scoring. Long-term sequelae (> 12 months) were considered to be mild in cases with isolated unilateral hearing loss and/or vestibular disorders, and severe in cases with bilateral hearing loss and/or neurological sequelae. All imaging reports were analyzed retrospectively with the knowledge of congenital CMV infection, searching for reference to findings that were, or could have been, related to fetal infection. Findings were analyzed in relation to whether the cases were diagnosed with CMV in utero or only postnatally.

Results: There were 237 children with complete follow-up data (> 12 months), for a median of 24 (range, 12-48) months. Of these, 30% (71/237) were diagnosed with CMV prenatally and 70% (166/237) were diagnosed within 3 weeks after birth. 72.5% (29/40) of children with long-term sequelae, including 74% (14/19) with severe long-term sequelae, were not identified in the prenatal period. Among those diagnosed prenatally, the sensitivity of prenatal imaging for predicting long-term sequelae and severe long-term sequelae was 91% and 100%, respectively, while, in the group diagnosed only postnatally, non-specific infection-related ultrasound findings had been reported without raising suspicion in 48% of cases with long-term sequelae and 64% of those with severe long-term sequelae.

Conclusions: Routine detailed ultrasound examination in pregnancy is not an appropriate screening tool for congenital CMV infection that leads to long-term sequelae, in contrast with the high performance of targeted prenatal imaging in known cases of fetal infection. The non-specific nature of ultrasound features of CMV and their evolution, and a lack of awareness of caregivers about congenital CMV, are likely explanations. Awareness of the sonologist regarding congenital CMV and knowledge of the maternal serological status in the first trimester seem key to the performance of prenatal ultrasound. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Keywords: CMV; congenital infection; cytomegalovirus; outcome; ultrasound.

Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

References

    1. Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 2007; 17: 253-276.
    1. Dollard SC, Grosse SD, Ross, DS. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol 2007; 17: 355-363.
    1. Leruez-Ville M, Magny J-F, Couderc S, Pichon C, Parodi M, Bussières L, Guilleminot T, Ghout I, Ville Y. Risk Factors for Congenital Cytomegalovirus Infection Following Primary and Nonprimary Maternal Infection: A Prospective Neonatal Screening Study Using Polymerase Chain Reaction in Saliva. Clin Infect Dis 2017; 65: 398-404.
    1. Puhakka L, Renko M, Helminen M, Peltola V, Heiskanen-Kosma T, Lappalainen M, Surcel H-M, Lönnqvist T, Saxen H. Primary versus non-primary maternal cytomegalovirus infection as a cause of symptomatic congenital infection - register-based study from Finland. Infect Dis 2017; 49: 445-453.
    1. Foulon I, De Brucker Y, Buyl R, Lichtert E, Verbruggen K, Piérard D, Camfferman FA, Gucciardo L, Gordts F. Hearing Loss With Congenital Cytomegalovirus Infection. Pediatrics 2019; 144: e20183095.
    1. Faure-Bardon V, Magny J-F, Parodi M, Couderc S, Garcia P, Maillotte A-M, Benard M, Pinquier D, Astruc D, Patural H, Pladys P, Parat S, Guillois B, Garenne A, Buissières L, Guilleminot T, Stirnemann J, Ghout E, Ville Y, Leruez-Ville M. Sequelae of Congenital Cytomegalovirus Following Maternal Primary Infections Are Limited to Those Acquired in the First Trimester of Pregnancy. Clin Infect Dis 2019; 69: 1526-1532.
    1. Pass RF, Fowler KB, Boppana SB, Britt WJ, Stagno S. Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome. J Clin Virol 2006; 35: 216-220.
    1. Faure-Bardon V, Millischer A-E, Deloison B, Sonigo P, Grévent D, Salomon L, Stirnemann J, Nicloux M, Magny J-F, Leruez-Ville M, Ville Y. Refining the prognosis of fetuses infected with cytomegalovirus in the first trimester of pregnancy by serial prenatal assessment: A single center retrospective study. BJOG 2019; 127: 355-362.
    1. Leruez-Ville M, Stirnemann J, Sellier Y, Guilleminot T, Dejean A, Magny J-F, Couderc S, Jacquemard F, Ville Y. Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis. Am J Obstet Gynecol 2016; 215: 342.e1-9.
    1. Leyder M, Vorsselmans A, Done E, Van Berkel K, Faron G, Foulon I, Naessens A, Jansen A, Foulon W, Gucciardo L. Primary maternal cytomegalovirus infections: accuracy of fetal ultrasound for predicting sequelae in offspring. Am J Obstet Gynecol 2016; 215: 638.e1-638.e8.
    1. Lipitz S, Yinon Y, Malinger G, Yagel S, Levit L, Hoffman C, Rantzer R, Weisz B. Risk of cytomegalovirus-associated sequelae in relation to time of infection and findings on prenatal imaging. Ultrasound Obstet Gynecol 2013; 41: 508-514.
    1. Picone O, Vauloup-Fellous C, Cordier AG, Guitton S, Senat MV, Fuchs F, Ayoubi JM, Grangeot Keros L, Benachi A. A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome. Prenat Diagn 2013; 33: 751-758.
    1. Society for Maternal-Fetal Medicine (SMFM), Hughes BL, Gyamfi-Bannerman C. Diagnosis and antenatal management of congenital cytomegalovirus infection. Am J Obstet Gynecol 2016; 214: B5-B11.
    1. Guerra B, Simonazzi G, Puccetti C, Lanari M, Farina A, Lazzarotto T, Rizzo N. Ultrasound prediction of symptomatic congenital cytomegalovirus infection. Am J Obstet Gynecol 2008; 198: 380.e1-7.
    1. Fowler KB, Boppana SB. Congenital cytomegalovirus infection. Semin Perinatol 2018; 42: 149-154.
    1. Leruez-Ville M, Sellier Y, Salomon LJ, Stirnemann JJ, Jacquemard F, Ville Y. Prediction of fetal infection in cases with cytomegalovirus immunoglobulin M in the first trimester of pregnancy: a retrospective cohort. Clin Infect Dis 2013; 56: 1428-1435.
    1. Fily A, Pierrat V, Delporte V, Breart G, Truffert P, EPIPAGE Nord-Pas-de-Calais Study Group. Factors associated with neurodevelopmental outcome at 2 years after very preterm birth: the population-based Nord-Pas-de-Calais EPIPAGE cohort. Pediatrics 2006; 117: 357-366.
    1. . 20 april 2018. French Lax ‘Recommendations for ultrasound assessment in antenatal care in pregnant women’ 2018.
    1. Lipitz S, Elkan Miller T, Yinon Y, Weissbach T, De-Castro H, Hoffman C, Katorza E, Weisz B. Revisiting short- and long-term outcome after fetal first-trimester primary cytomegalovirus infection in relation to prenatal imaging findings. Ultrasound Obstet Gynecol 2020; 56: 572-578.
    1. Picone O, Grangeot-Keros L, Senat M, Fuchs F, Bouthry E, Ayoubi J, Benachi A, Vauloup-Fellous C. Cytomegalovirus non-primary infection during pregnancy. Can serology help with diagnosis? J Matern-Fetal Neonatal Med 2017; 30: 224-227.
    1. Zalel Y, Gilboa Y, Berkenshtat M, Yoeli R, Auslander R, Achiron R, Goldberg Y. Secondary cytomegalovirus infection can cause severe fetal sequelae despite maternal preconceptional immunity. Ultrasound Obstet Gynecol 2008; 31: 417-420.
    1. Medical and scientific report from the French BioMedecine Agency on medically assisted reproduction and prenatal diagnosis in 2017. https://www.agence-biomedecine/annexes/bilan.
    1. Lanzieri TM, Chung W, Flores M, Blum P, Caviness AC, Bialek SR, Grosse SD, Miller JA, Demmler-Harrison G, Congenital Cytomegalovirus Longitudinal Study Group. Hearing Loss in Children With Asymptomatic Congenital Cytomegalovirus Infection. Pediatrics 2017; 139: e20162610.
    1. Townsend CL, Forsgren M, Ahlfors K, Ivarsson S-A, Tookey PA, Peckham CS. Long-term outcomes of congenital cytomegalovirus infection in Sweden and the United Kingdom. Clin Infect Dis 2013; 56: 1232-1239.

Source: PubMed

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