Severity of congenital heart disease, maternal environmental factors and neurodevelopmental outcomes: Evidence from a French multicenter cohort

IF 2.9 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Archives of Cardiovascular Diseases Pub Date : 2026-08-01 Epub Date: 2026-08-26 DOI:10.1016/j.acvd.2026.06.015

Betty Bretin, Norbert Winer, Valerie Rouger, Garance Devarenne, Bénédicte Gaillard Le Roux, Marie Demonceaux, Thomas Moyon, Alban-Elouen Baruteau

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Additionally, contribution of CHD severity to NDD remains unclear.</div></div><div>Congenital heart disease (CHD) is the leading cause of fetal malformations and remains a major determinant of morbidity in childhood. Children with CHD are at increased risk of neurodevelopmental disorders (NDD). The severity of CHD strongly influences clinical management and long-term outcomes, including neurodevelopment. Adverse maternal environment may play a major role in CHD and NDD induction. Additionally, contribution of CHD severity to NDD remains unclear.</div><div><h3>Methods</h3><div>We analyzed obstetrical and pediatric data from a French multicenter retrospective cohort including 334 women who delivered infants with CHD between 2012 and 2023. Neurodevelopmental follow-up at 2, 5 or 7 years was available for a third of them. CHD severity was categorized as critical-complex, non-critical complex and non-complex according to the classification used by the French Reference Center for Complex Congenital Cardiac Malformations (M3C) and time to cardiac surgery. NDD were assessed using the Strengths and Difficulties Questionnaire (SDQ), the Ages and Stages Questionnaire (ASQ) and a standardized teacher-completed questionnaire. Multinomial multivariate logistic regression was used to evaluate associations between maternal environmental factors, CHD severity and NDD.</div></div><div>We analyzed obstetrical and pediatric data from a French multicenter retrospective cohort including 334 women who delivered infants with CHD between 2012 and 2023. Neurodevelopmental follow-up at 2, 5 or 7 years was available for a third of them. CHD severity was categorized as critical-complex, non-critical complex and non-complex according to the classification used by the French Reference Center for Complex Congenital Cardiac Malformations (M3C) and time to cardiac surgery. NDD were assessed using the Strengths and Difficulties Questionnaire (SDQ), the Ages and Stages Questionnaire (ASQ) and a standardized teacher-completed questionnaire. Multinomial multivariate logistic regression was used to evaluate associations between maternal environmental factors, CHD severity and NDD.</div><div><h3>Results</h3><div>Maternal psychological distress (OR 0.39, 95% CI [0.18–0.87]) and nulliparity (OR 1.77, 95% CI [1.08–2.90]) were associated with a lower probability of severe CHD. CHD severity was not significantly associated with NDD at 2, 5 or 7 years. Maternal age<25 years or>30 years, second parity and gestational weight gain<12kg were associated with a higher risk of combined CHD and NDD.</div></div><div>Maternal psychological distress (OR 0.39, 95% CI [0.18–0.87]) and nulliparity (OR 1.77, 95% CI [1.08–2.90]) were associated with a lower probability of severe CHD. CHD severity was not significantly associated with NDD at 2, 5 or 7 years. Maternal age<25 years or>30 years, second parity and gestational weight gain<12kg were associated with a higher risk of combined CHD and NDD.</div><div><h3>Conclusion</h3><div>Our study is the first to demonstrate the associations between specific maternal environmental risk factors and NDD in CHD infants when considering CHD severity. We showed no difference in NDD occurrence regarding CHD severity. 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引用次数: 0

Abstract

Introduction

Congenital heart disease (CHD) is the leading cause of fetal malformations and remains a major determinant of morbidity in childhood. Children with CHD are at increased risk of neurodevelopmental disorders (NDD). The severity of CHD strongly influences clinical management and long-term outcomes, including neurodevelopment. Adverse maternal environment may play a major role in CHD and NDD induction. Additionally, contribution of CHD severity to NDD remains unclear.

Methods

We analyzed obstetrical and pediatric data from a French multicenter retrospective cohort including 334 women who delivered infants with CHD between 2012 and 2023. Neurodevelopmental follow-up at 2, 5 or 7 years was available for a third of them. CHD severity was categorized as critical-complex, non-critical complex and non-complex according to the classification used by the French Reference Center for Complex Congenital Cardiac Malformations (M3C) and time to cardiac surgery. NDD were assessed using the Strengths and Difficulties Questionnaire (SDQ), the Ages and Stages Questionnaire (ASQ) and a standardized teacher-completed questionnaire. Multinomial multivariate logistic regression was used to evaluate associations between maternal environmental factors, CHD severity and NDD.

Results

Maternal psychological distress (OR 0.39, 95% CI [0.18–0.87]) and nulliparity (OR 1.77, 95% CI [1.08–2.90]) were associated with a lower probability of severe CHD. CHD severity was not significantly associated with NDD at 2, 5 or 7 years. Maternal age < 25 years or > 30 years, second parity and gestational weight gain < 12 kg were associated with a higher risk of combined CHD and NDD.

Conclusion

Our study is the first to demonstrate the associations between specific maternal environmental risk factors and NDD in CHD infants when considering CHD severity. We showed no difference in NDD occurrence regarding CHD severity. These results support systematic neurodevelopmental screening in all CHD patients during childhood regardless the severity of the cardiac pathology.

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先天性心脏病的严重程度、母体环境因素和神经发育结局：来自法国多中心队列的证据

先天性心脏病（CHD）是导致胎儿畸形的主要原因，也是儿童发病的主要决定因素。患有冠心病的儿童患神经发育障碍（NDD）的风险增加。冠心病的严重程度强烈影响临床管理和长期预后，包括神经发育。不良的母体环境可能在CHD和NDD的诱发中起重要作用。此外，冠心病严重程度对NDD的影响尚不清楚。先天性心脏病（CHD）是胎儿畸形的主要原因，仍然是儿童发病率的主要决定因素。患有冠心病的儿童患神经发育障碍（NDD）的风险增加。冠心病的严重程度强烈影响临床管理和长期预后，包括神经发育。不良的母体环境可能在CHD和NDD的诱发中起重要作用。此外，冠心病严重程度对NDD的影响尚不清楚。方法：我们分析了来自法国多中心回顾性队列的产科和儿科数据，其中包括2012年至2023年间分娩冠心病婴儿的334名妇女。其中三分之一的人在2年、5年或7年的时候进行了神经发育随访。根据法国复杂先天性心脏畸形参考中心（French Reference Center for complex Congenital Cardiac formations, M3C）的分类和心脏手术时间，将冠心病的严重程度分为危重复杂、非危重复杂和非复杂。采用优势与困难问卷（SDQ）、年龄与阶段问卷（ASQ）和标准化教师填写问卷对NDD进行评估。采用多项多因素logistic回归评估母体环境因素、冠心病严重程度与NDD之间的关系。我们分析了来自法国多中心回顾性队列的产科和儿科数据，其中包括2012年至2023年间分娩冠心病婴儿的334名妇女。其中三分之一的人在2年、5年或7年的时候进行了神经发育随访。根据法国复杂先天性心脏畸形参考中心（French Reference Center for complex Congenital Cardiac formations, M3C）的分类和心脏手术时间，将冠心病的严重程度分为危重复杂、非危重复杂和非复杂。采用优势与困难问卷（SDQ）、年龄与阶段问卷（ASQ）和标准化教师填写问卷对NDD进行评估。采用多项多因素logistic回归评估母体环境因素、冠心病严重程度与NDD之间的关系。结果产妇心理困扰（OR 0.39, 95% CI[0.18-0.87]）和未生育（OR 1.77, 95% CI[1.08-2.90]）与发生严重冠心病的可能性较低相关。在2、5或7年时，冠心病严重程度与NDD无显著相关性。产妇年龄25岁或30岁、第二次分娩和妊娠体重增加12公斤与合并CHD和NDD的高风险相关。母亲心理困扰（OR 0.39, 95% CI[0.18-0.87]）和未生育（OR 1.77, 95% CI[1.08-2.90]）与较低的严重冠心病发生概率相关。在2、5或7年时，冠心病严重程度与NDD无显著相关性。产妇年龄25岁或30岁、第二次分娩和妊娠体重增加12公斤与合并CHD和NDD的高风险相关。结论我们的研究首次证明了特定的母亲环境危险因素与CHD婴儿NDD的相关性，并考虑了CHD的严重程度。我们发现NDD的发生与冠心病的严重程度没有差异。这些结果支持在儿童时期对所有冠心病患者进行系统的神经发育筛查，无论心脏病理的严重程度如何。在考虑冠心病严重程度时，我们的研究首次证明了特定的母亲环境危险因素与冠心病婴儿NDD之间的关联。我们发现NDD的发生与冠心病的严重程度没有差异。这些结果支持在儿童时期对所有冠心病患者进行系统的神经发育筛查，无论心脏病理的严重程度如何。

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来源期刊

Archives of Cardiovascular Diseases 医学-心血管系统

CiteScore

4.40

自引率

6.70%

发文量

审稿时长

34 days

期刊介绍： The Journal publishes original peer-reviewed clinical and research articles, epidemiological studies, new methodological clinical approaches, review articles and editorials. Topics covered include coronary artery and valve diseases, interventional and pediatric cardiology, cardiovascular surgery, cardiomyopathy and heart failure, arrhythmias and stimulation, cardiovascular imaging, vascular medicine and hypertension, epidemiology and risk factors, and large multicenter studies. Archives of Cardiovascular Diseases also publishes abstracts of papers presented at the annual sessions of the Journées Européennes de la Société Française de Cardiologie and the guidelines edited by the French Society of Cardiology.