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

Author:

Faure-Bardon Valentine12,Magny Jean-François13,Parodi Marine4,Couderc Sophie5,Garcia Patricia6,Maillotte Anne-Marie7,Benard Melinda8,Pinquier Didier9,Astruc Dominique10,Patural Hugues11,Pladys Patrick12,Parat Sophie13,Guillois Bernard1415,Garenne Armelle16,Bussières Laurence117,Guilleminot Tiffany118,Stirnemann Julien12,Ghout Idir1920,Ville Yves12,Leruez-Ville Marianne118

Affiliation:

1. Equipe d’Accueil, Paris Descartes University, Sorbonne Paris CitéArchet, France

2. Maternity, Hospital Necker-E.M, Paris, France

3. Neonatal Intensive Care Unit, Hospital Necker-E.M, France

4. Otology Department, Assistance Publique de Paris, Hospital Necker-E.M, France

5. Maternity, Hospital Intercommunal Poissy-Saint Germain, Marseille, France

6. Neonatology and Intensive Care Department, Assistance Publique de Marseille, Hospital La Conception, Marseille, France

7. Neonatal Intensive Care Unit, Centre Hospitalier Universitaire Nice, Hospital L’Archet, Marseille, France

8. Department of Neonatalogy, Toulouse University Hospital, Saint-Etienne, France

9. Department of Neonatalogy, Rouen University Hospital, Saint-Etienne, France

10. Department of Neonatalogy, Strasbourg University Hospital, Saint-Etienne, France

11. Neonatal Intensive Care Unit, University Hospital, Saint-Etienne, France

12. Pediatric Department, Neonatology, Centre Hospitalier Universitaire Rennes and Centre d’Investigation Clinique, France

13. Maternity, Assistance Publique Hopitaux de Paris (AP-HP), Hospital Cochin, France

14. Department of Neonatalogy, Centre Hospitalier Universitaire de Caen, France

15. Medical School, Université Caen Normandie, France

16. Brest, Neonatal and Pediatric Intensive Care Unit, Centre Hospitalier Régional Universitaire, France

17. Clinical Research Unit, AP-HP, Hospital Necker-E.M., France

18. Virology Laboratory, Reference Laboratory for Cytomegalovirus Infections, AP-HP, Hospital Necker-E.M., France

19. Unité de Recherche Clinique et Département de Santé Publique, AP-HP, Hôpital Ambroise Paré, Boulogne, France

20. University Versaille-Saint-Quentin, Unité Mixte de recherche S, Université Versailles St-Quentin-en-Yvelines, Montigny, France

Abstract

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.

Funder

Assistance Publique - Hôpitaux de Paris French government

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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