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Z Geburtshilfe Neonatol 2020; 224(02): 71-78
DOI: 10.1055/a-0966-9915
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Therapeutische Optionen bei konnataler Zytomegalievirus (CMV)-Infektion – Implikationen für die Einführung eines Screeningprogramms

Therapy Options for Infants with Congenital Cytomegalovirus Infection – Implications for Setting Up Neonatal Screening Programs
Christoph Bührer
1   Klinik für Neonatologie, Charité – Universitätsmedizin Berlin, Berlin
,
Oliver Blankenstein   *
2   Neugeborenen-Screeninglabor Berlin-Brandenburg, Charité – Universitätsmedizin, Berlin
,
Rainer Rossi   *
3   Kinder- und Jugendmedizin – Perinatalzentrum, Vivantes Klinikum Neukölln, Berlin
,
für die Screeningkommission der Deutschen Gesellschaft für Kinder- und Jugendmedizin (Mitglieder am Ende des Artikels) › Institutsangaben
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Publikationsverlauf

eingereicht 23. April 2019

angenommen nach Überarbeitung 24. Juni 2019

Publikationsdatum:
19. August 2019 (online)

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Zusammenfassung

Einleitung Seit der bundesweiten Einführung des Neugeborenen-Screenings auf Phenylketonurie (1968) ist die Liste der Zielkrankheiten in Deutschland stetig auf mittlerweile 17 (mit Hörminderung und Hüftgelenksdysplasie) angewachsen (2018). Das Beispiel des fehlgeschlagenen Neuroblastom-Screenings hat gezeigt, wie durch Therapie von Erkrankungen, die nur durch ein Screening entdeckt werden, Kinder zu Schaden kommen können. Für das versuchsweise in verschiedenen Regionen eingeführte Screening auf konnatale Zytomegalievirus (CMV)-Infektionen ist derzeit ungeklärt, ob und wie ein auf diese Weise identifiziertes Kind behandelt werden soll.

Methodik Selektive Suche nach Therapiestudien in PubMed und der Internationalen Plattform Klinischer Studienregister (ICTRP) der Weltgesundheitsorganisation (WHO).

Ergebnisse Bisher liegen lediglich Ergebnisse einer einzigen randomisierten Studie mit einer nicht behandelten Kontrollgruppe vor (Intervention: Ganciclovir über 6 Wochen intravenös). In diese waren nur Kinder mit symptomatischer CMV-Infektion eingeschlossen. Die Intervention war mit einer signifikanten Reduktion neu auftretender Hörminderungen assoziiert. Leichte Vorteile einer 6-monatigen gegenüber einer 6-wöchigen Therapie mit der oral applizierbaren Ganciclovir-Vorstufe Valganciclovir zeigten sich bezüglich der neurologischen Entwicklung in einer zweiten, ebenfalls auf Kinder mit symptomatischer CMV-Infektion beschränkten randomisierten Studie. In einer Beobachtungsstudie von Kindern mit konnataler CMV-Infektion und isolierter Hörstörung, die über 12 Monate mit Valganciclovir behandelt wurden, wiesen 2/3 eine Verbesserung des Hörens auf (mediane Nachbeobachtungszeit 4½ Jahre).

Schlussfolgerung Aufgrund des fehlenden Wirksamkeitsnachweis wird die Behandlung von Neugeborenen mit oligosymptomatischer konnataler CMV-Infektion einschließlich einer isolierten Hörstörung kontrovers diskutiert. Eine generell akzeptierte Therapieempfehlung ist jedoch eine notwendige Voraussetzung für ein Screening auf konnatale CMV-Infektionen.

Abstract

Introduction The number of diseases covered by universal neonatal screening in Germany has risen steadily from 1 (phenylketonuria) in 1968 to 17 (with hearing impairment and congenital hip dysplasia) in 2018. Treatment, however, of disorders diagnosed by screening may harm children, as failed neuroblastoma screening has shown. There are several pilot studies to detect congenital cytomegalovirus (CMV) infection but no consensus as to the treatment of the infants identified.

Methodology Systematic search for studies investigating therapy of congenital CMV infection, using PubMed and the WHO International Clinical Trials Registry Platform (ICTRP).

Results We found only one controlled trial that randomized infants with symptomatic congenital CMV infection (involving the central nervous system) to treatment (intravenous ganciclovir for 6 weeks) or no treatment. Treatment was associated with significantly less hearing deterioration. A second trial comparing 6 weeks vs. 6 months of treatment with valganciclovir, an oral prodrug of ganciclovir, found no benefit for hearing but modestly improved developmental outcomes associated with 6 months of treatment. In contrast, an open-label registry reported benefits for infants with congenital CMV infection and isolated hearing who received valganciclovir for 12 months, with hearing improvement in 2/3 of cases after a median follow-up of 4½ years.

Conclusions Antiviral treatment of neonates with congenital CMV infection and few symptoms including isolated hearing loss remains controversial. A generally accepted therapy, however, is pivotal before introducing universal or targeted screening for congenital CMV infection.

Schlüsselwörter

cytomegalovirus - valganciclovir - screening - CMV - congenital Cytomegalovirus

Key words

Zytomegalievirus - konnatale Infektion - Valganciclovir - Screening

* für die Screening-Kommission der Deutschen Gesellschaft für Kinder- und Jugendmedizin. Weitere Mitglieder der Screening- Kommission der Deutschen Gesellschaft für Kinder- und Jugendmedizin: Jutta Gärtner (Göttingen), Orsolya Genzel Boroviczeny (München), Uta Nennstiel (Oberschleißheim), Georg F. Hoffmann (Heidelberg), Burkhard Lawrenz (Arnsberg), Olaf Sommerburg (Heidelberg), Carsten Speckmann (Freiburg).


 

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