Valentine Faure-Bardon1,2, Jean-François Magny1,3, Marine Parodi4, Sophie Couderc5, Patricia Garcia6, Anne-Marie Maillotte7, Melinda Benard8, Didier Pinquier9, Dominique Astruc10, Hugues Patural11, Patrick Pladys12, Sophie Parat13, Bernard Guillois14,15, Armelle Garenne16, Laurence Bussières1,17, Tiffany Guilleminot1,18, Julien Stirnemann1,2, Idir Ghout19,20, Yves Ville1,2, Marianne Leruez-Ville1,18. 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
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.
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.
Authors: Raymund R Razonable; Naoki Inoue; Swetha G Pinninti; Suresh B Boppana; Tiziana Lazzarotto; Liliana Gabrielli; Giuliana Simonazzi; Philip E Pellett; D Scott Schmid Journal: J Infect Dis Date: 2020-03-05 Impact factor: 5.226
Authors: Zachary W Berkebile; Dira S Putri; Juan E Abrahante; Davis M Seelig; Mark R Schleiss; Craig J Bierle Journal: Front Immunol Date: 2021-06-15 Impact factor: 7.561