Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial.

Autor:	Gaynor JW; Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Moldenhauer JS; Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Zullo EE; Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Burnham NB; Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Gerdes M; Department of Psychology, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Bernbaum JC; Department of Pediatrics, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., D'Agostino JA; Department of Pediatrics, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Linn RL; Division of Anatomic Pathology, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Klepczynski B; Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Randazzo I; Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Gionet G; Department of Biostatistics, Epidemiology, and Informatics, the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Choi GH; Department of Biostatistics, Epidemiology, and Informatics, the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Karaj A; Department of Biostatistics, Epidemiology, and Informatics, the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Russell WW; Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Zackai EH; Division of Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Johnson MP; Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Gebb JS; Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Soni S; Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., DeBari SE; Center for Fetal Diagnosis and Treatment, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Szwast AL; Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Ahrens-Nicklas RC; Division of Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Drivas TG; Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia., Jacobwitz M; Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Licht DJ; Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Vossough A; Division of Radiology, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Nicolson SC; Division of Cardiac Anesthesia, Department of Anesthesia and Critical Medicine, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Spray TL; Division of Cardiothoracic Surgery, Department of Surgery, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania, Philadelphia., Rychik J; Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., Putt ME; Department of Biostatistics, Epidemiology, and Informatics, the Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2024 May 01; Vol. 7 (5), pp. e2412291. Date of Electronic Publication: 2024 May 01.
DOI:	10.1001/jamanetworkopen.2024.12291
Abstrakt:	Importance: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. Objectives: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. Design, Setting, and Participants: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Intervention: Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. Main Outcomes and Measures: The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. Results: The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). Conclusions and Relevance: In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. Trial Registration: ClinicalTrials.gov Identifier: NCT02133573.
Databáze:	MEDLINE
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