Clinical Infectious Diseases Advance Access published April 1, 2015
1
In utero exposure to zidovudine and heart anomalies in the ANRS-EPF French Perinatal Cohort and the nested PRIMEVA randomized trial Jeanne Sibiude1, Jérôme Le Chenadec2, Damien Bonnet3, Roland Tubiana4, Albert
ipt
Faye5, Catherine Dollfus6, Laurent Mandelbrot7, Sandrine Delmas8, Nathalie
Lelong9, Babak Khoshnood10, Josiane Warszawski11, Stéphane Blanche12, the
an us cr
ANRS-French Perinatal Cohort/Primeva trial 1
Department of Obstetrics and Gynecology, Hôpital Louis Mourier, Colombes, 92700 France; Department of Epidemiology, CESP, INSERM U1018, Le Kremlin-Bicêtre 94270, France 2
ce
pt e
d
M
Statistician, Department of Epidemiology, CESP, INSERM U1018, Le Kremlin-Bicêtre 94270, France 3 Professor, M3C-Necker Enfants malades, Pediatric Cardiology, AP-HP, Université Paris Descartes, Paris 75015, France 4 Department of infectiology, GH Pitié Salpétrière, Paris 75013, France Sorbonne Universités, UPMC Univ Paris 06 F-75005; INSERM- UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health, Paris France 5 Professor, Department of Pediatrics, AP-HP Hôpital Robert Debré, Paris 75019, France; Univ Diderot Paris 7, Paris, France 6 Department of Pediatrics AP-HP Hôpital Trousseau, Paris 75014, France 7 Professor, Department of Obstetrics and Gynecology, Hôpital Louis Mourier, Colombes, 92700 France, Department of Epidemiology. CESP, INSERM U1018, Le Kremlin-Bicêtre 94270, France. Univ Diderot Paris 7, Paris, France 8 Department of Epidemiology, CESP, INSERM U1018, Le Kremlin-Bicêtre 94270, France 9 Epidemiologist, Inserm, UMR S953, Université Paris-6 75006, Paris, France 10 Professor in epidemiology, Inserm, UMR S953, Université Paris-6 75006, Paris, France 11 Epidemiologist, CESP, INSERM U1018, Le Kremlin-Bicêtre 94270, France, INED, Paris, France, Univ Paris Sud, Le Kremlin-Bicêtre 94270, France 12 Professor, Department of Pediatrics, Hôpital Necker, Paris, 75015 France; EA 7223: Évaluation Thérapeutique et Pharmacologie Périnatale et Pédiatrique, Univ Paris Descartes 5, Paris 75006, France Corresponding author: Jeanne Sibiude Address : Equipe VIH/IST CESP 1018 Inserm, 82 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France, Telephone: +33 1 49 59 53 05,
Ac
Fax: +33 1 49 59 53 00, e-mail: [email protected]
Alternate corresponding author: Stephane Blanche, Address: Hôpital Necker, 149 rue de Sèvres, 75015 Paris, France, Telephone: +33 1 44 49 48 24, Fax: +33 1 44 49 48 18, e-mail : [email protected]
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
2 40-word summary In utero exposure to zidovudine in the first trimester was associated to congenital heart defects, mostly ventricular septal defects. Girls exposed to zidovudine had a higher left
ipt
ventricular shortening fraction and posterior wall thickness at one month and one year.
an us cr
Abstract
Background – Antiretroviral (ARV) regimens during pregnancy are highly effective to prevent mother-to-child transmission of HIV. Congenital heart defects (CHD) and anomalies in cardiac function have been reported in zidovudine exposed uninfected children. We
explored these associations in a large observational cohort and a randomized clinical trial. Methods – Since 1986, EPF prospectively enrolled all HIV-infected women in 90 centers and collected follow-up on their children through 2 years of age. All CHD were reviewed by a CHD specialist, blinded to exposures. Additionally, in a randomized trial (Primeva ANRS
M
135) of two ARV regimens during pregnancy, one of which without nucleoside reverse transcriptase inhibitors, infants had a specific follow-up including echocardiograms at 1 and 12 months.
d
Results – Among 12,888 children included, Zidovudine exposure in the first trimester was significantly associated with CHD, 1.5% vs 0.7%, p
1
In utero exposure to zidovudine and heart anomalies in the ANRS-EPF French Perinatal Cohort and the nested PRIMEVA randomized trial Jeanne Sibiude1, Jérôme Le Chenadec2, Damien Bonnet3, Roland Tubiana4, Albert
ipt
Faye5, Catherine Dollfus6, Laurent Mandelbrot7, Sandrine Delmas8, Nathalie
Lelong9, Babak Khoshnood10, Josiane Warszawski11, Stéphane Blanche12, the
an us cr
ANRS-French Perinatal Cohort/Primeva trial 1
Department of Obstetrics and Gynecology, Hôpital Louis Mourier, Colombes, 92700 France; Department of Epidemiology, CESP, INSERM U1018, Le Kremlin-Bicêtre 94270, France 2
ce
pt e
d
M
Statistician, Department of Epidemiology, CESP, INSERM U1018, Le Kremlin-Bicêtre 94270, France 3 Professor, M3C-Necker Enfants malades, Pediatric Cardiology, AP-HP, Université Paris Descartes, Paris 75015, France 4 Department of infectiology, GH Pitié Salpétrière, Paris 75013, France Sorbonne Universités, UPMC Univ Paris 06 F-75005; INSERM- UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health, Paris France 5 Professor, Department of Pediatrics, AP-HP Hôpital Robert Debré, Paris 75019, France; Univ Diderot Paris 7, Paris, France 6 Department of Pediatrics AP-HP Hôpital Trousseau, Paris 75014, France 7 Professor, Department of Obstetrics and Gynecology, Hôpital Louis Mourier, Colombes, 92700 France, Department of Epidemiology. CESP, INSERM U1018, Le Kremlin-Bicêtre 94270, France. Univ Diderot Paris 7, Paris, France 8 Department of Epidemiology, CESP, INSERM U1018, Le Kremlin-Bicêtre 94270, France 9 Epidemiologist, Inserm, UMR S953, Université Paris-6 75006, Paris, France 10 Professor in epidemiology, Inserm, UMR S953, Université Paris-6 75006, Paris, France 11 Epidemiologist, CESP, INSERM U1018, Le Kremlin-Bicêtre 94270, France, INED, Paris, France, Univ Paris Sud, Le Kremlin-Bicêtre 94270, France 12 Professor, Department of Pediatrics, Hôpital Necker, Paris, 75015 France; EA 7223: Évaluation Thérapeutique et Pharmacologie Périnatale et Pédiatrique, Univ Paris Descartes 5, Paris 75006, France Corresponding author: Jeanne Sibiude Address : Equipe VIH/IST CESP 1018 Inserm, 82 rue du Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France, Telephone: +33 1 49 59 53 05,
Ac
Fax: +33 1 49 59 53 00, e-mail: [email protected]
Alternate corresponding author: Stephane Blanche, Address: Hôpital Necker, 149 rue de Sèvres, 75015 Paris, France, Telephone: +33 1 44 49 48 24, Fax: +33 1 44 49 48 18, e-mail : [email protected]
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
2 40-word summary In utero exposure to zidovudine in the first trimester was associated to congenital heart defects, mostly ventricular septal defects. Girls exposed to zidovudine had a higher left
ipt
ventricular shortening fraction and posterior wall thickness at one month and one year.
an us cr
Abstract
Background – Antiretroviral (ARV) regimens during pregnancy are highly effective to prevent mother-to-child transmission of HIV. Congenital heart defects (CHD) and anomalies in cardiac function have been reported in zidovudine exposed uninfected children. We
explored these associations in a large observational cohort and a randomized clinical trial. Methods – Since 1986, EPF prospectively enrolled all HIV-infected women in 90 centers and collected follow-up on their children through 2 years of age. All CHD were reviewed by a CHD specialist, blinded to exposures. Additionally, in a randomized trial (Primeva ANRS
M
135) of two ARV regimens during pregnancy, one of which without nucleoside reverse transcriptase inhibitors, infants had a specific follow-up including echocardiograms at 1 and 12 months.
d
Results – Among 12,888 children included, Zidovudine exposure in the first trimester was significantly associated with CHD, 1.5% vs 0.7%, p
