PDF(Pubmed)
Abstract：
UNASSIGNED: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years.
UNASSIGNED: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT02133573.
UNASSIGNED: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT02133573.
摘要：
在过去的20年中，先天性心脏病（CHD）儿童的神经发育结果有了最小的改善。
■评估母体孕酮治疗的可行性和耐受性以及对CHD胎儿神经发育的影响程度。
■这项双盲的独立随机平行组临床试验是在2014年7月至2021年11月期间，在患有冠心病的胎儿的参与者中进行的。参与者包括母胎二位，其中胎儿在胎龄28周前被确定为CHD，并且在新生儿期可能需要体外循环手术。排除标准包括除22q11缺失综合征以外的主要遗传或心外异常以及已知的孕酮禁忌症。统计分析于2022年6月至2024年4月进行。
■参与者被诊断为1：1分组随机接受阴道孕酮或安慰剂：左心发育不良综合征（HLHS），大动脉转位（TGA），和其他冠心病诊断。在28至39周胎龄之间，每天两次治疗。
主要结果是Bayley婴儿和幼儿发育量表-III的运动评分；次要结果包括语言和认知量表。探索性预设亚组包括心脏诊断，胎儿性别,遗传概况,和母体胎儿环境。
■102名注册胎儿主要患有HLHS（n=52[50.9%]）和TGA（n=38[37.3%]），更常见的是男性（n=67[65.7%]），无遗传异常(n=61[59.8%])。与安慰剂相比，孕酮的平均运动评分相差2.5个单位（90％CI，-1.9至6.9个单位；P=0.34），与0没有统计学差异的值。探索性亚组分析显示，心脏诊断的运动评分（P为交互作用=.03）和胎儿性别（P为交互作用=.04）的治疗异质性。但不是遗传特征（相互作用的P=0.16）或母胎环境（相互作用的P=0.70）。
■在这项母体孕酮治疗的随机临床试验中，总体效果与0无统计学差异。亚组分析表明，CHD诊断和胎儿性别对孕酮反应的异质性。
■ClinicalTrials.gov标识符：NCT02133573。
■评估母体孕酮治疗的可行性和耐受性以及对CHD胎儿神经发育的影响程度。
■这项双盲的独立随机平行组临床试验是在2014年7月至2021年11月期间，在患有冠心病的胎儿的参与者中进行的。参与者包括母胎二位，其中胎儿在胎龄28周前被确定为CHD，并且在新生儿期可能需要体外循环手术。排除标准包括除22q11缺失综合征以外的主要遗传或心外异常以及已知的孕酮禁忌症。统计分析于2022年6月至2024年4月进行。
■参与者被诊断为1：1分组随机接受阴道孕酮或安慰剂：左心发育不良综合征（HLHS），大动脉转位（TGA），和其他冠心病诊断。在28至39周胎龄之间，每天两次治疗。
主要结果是Bayley婴儿和幼儿发育量表-III的运动评分；次要结果包括语言和认知量表。探索性预设亚组包括心脏诊断，胎儿性别,遗传概况,和母体胎儿环境。
■102名注册胎儿主要患有HLHS（n=52[50.9%]）和TGA（n=38[37.3%]），更常见的是男性（n=67[65.7%]），无遗传异常(n=61[59.8%])。与安慰剂相比，孕酮的平均运动评分相差2.5个单位（90％CI，-1.9至6.9个单位；P=0.34），与0没有统计学差异的值。探索性亚组分析显示，心脏诊断的运动评分（P为交互作用=.03）和胎儿性别（P为交互作用=.04）的治疗异质性。但不是遗传特征（相互作用的P=0.16）或母胎环境（相互作用的P=0.70）。
■在这项母体孕酮治疗的随机临床试验中，总体效果与0无统计学差异。亚组分析表明，CHD诊断和胎儿性别对孕酮反应的异质性。
■ClinicalTrials.gov标识符：NCT02133573。
