Remmele Julia, Helm Paul Christian, Oberhoffer-Fritz Renate, Bauer Ulrike Mm, Pickardt Thomas, Ewert Peter, Tutarel Oktay
Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center of Munich, Munich, Germany.
Institute of Preventive Pediatrics, Technical University Munich, Munich, Germany.
JMIR Res Protoc. 2021 May 13;10(5):e26404. doi: 10.2196/26404.
Due to the increased survival rates of patients with congenital heart defects (CHD), associated disorders are an increasing focus of research. Existing studies figured out an association between CHD and its treatment, and neurodevelopmental outcomes including motor competence impairments. All these studies, however, compared their test results with reference values or results of healthy control groups. This comparison is influenced by socioeconomic and genetic aspects, which do have a known impact on neurodevelopmental outcomes.
This study protocol describes a setting that aims to find out the role of CHD and its treatments on neurodevelopmental outcomes, excluding socioeconomic and genetic aspects. Only a twin comparison provides the possibility to exclude these confounding factors.
In a German-wide prospective cohort study, 129 twin siblings registered in the National Register for Congenital Heart Defects will undergo testing on cognitive function (Wechsler Intelligence Tests age-dependent: Wechsler Adult Intelligence Scale, fourth edition; Wechsler Intelligence Scale for Children, fifth edition; and Wechsler Preschool and Primary Scale of Intelligence, fourth edition) and motor competence (Movement Assessment Battery for Children, second edition). Additionally, the self-reported health-related quality of life (KINDL-R for children, Short Form 36 for adults) and the parent-reported strength and difficulties of the children (Strength and Difficulties Questionnaire, German version) will be assessed by standardized questionnaires. CHD data on the specific diagnosis, surgeries, transcatheter procedures, and additional medical information will be received from patient records.
The approval of the Medical Ethics Committee Charité Mitte was obtained in June 2018. After getting funded in April 2019, the first enrollment was in August 2019. The study is still ongoing until June 2022. Final results are expected in 2022.
This study protocol provides an overview of the study design's technical details, offering an option to exclude confounding factors on neurodevelopmental outcomes in patients with CHD. This will enable a specific analysis focusing on CHD and clinical treatments to differentiate in terms of neurodevelopmental outcomes of patients with CHD compared to twin siblings with healthy hearts. Finally, we aim to clearly define what is important to prevent patients with CHD in terms of neurodevelopmental impairments to be able to develop targeted prevention strategies for patients with CHD.
German Clinical Trials Register DRKS00021087; https://tinyurl.com/2rdw8w67.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26404.
由于先天性心脏病（CHD）患者生存率的提高，相关疾病日益成为研究的重点。现有研究发现CHD及其治疗与包括运动能力受损在内的神经发育结局之间存在关联。然而，所有这些研究都将其测试结果与参考值或健康对照组的结果进行了比较。这种比较受到社会经济和遗传因素的影响，而这些因素确实对神经发育结局有已知影响。
本研究方案描述了一种旨在找出CHD及其治疗对神经发育结局的作用的研究设置，排除社会经济和遗传因素。只有双胞胎比较才有排除这些混杂因素的可能性。
在一项全德范围的前瞻性队列研究中，129对登记在国家先天性心脏病登记册中的双胞胎兄弟姐妹将接受认知功能测试（韦氏智力量表，根据年龄而定：韦氏成人智力量表第四版；韦氏儿童智力量表第五版；韦氏学前和小学智力量表第四版）和运动能力测试（儿童运动评估量表第二版）。此外，将通过标准化问卷评估自我报告的与健康相关的生活质量（儿童用KINDL-R，成人用简明健康调查问卷36项简短版本）以及父母报告的儿童的优势和困难（优势与困难问卷，德文版）。关于具体诊断、手术、经导管操作和其他医疗信息的CHD数据将从患者记录中获取。
2018年6月获得了柏林夏里特医科大学中心医学伦理委员会的批准。2019年4月获得资金后，首次招募于2019年8月进行。该研究一直持续到2022年6月。预计2022年得出最终结果。
本研究方案概述了研究设计的技术细节，提供了一种排除CHD患者神经发育结局混杂因素的方法。这将能够进行一项侧重于CHD和临床治疗的具体分析，以便在CHD患者与心脏健康的双胞胎兄弟姐妹的神经发育结局方面进行区分。最后，我们旨在明确界定在预防CHD患者神经发育障碍方面什么是重要的，以便能够为CHD患者制定有针对性的预防策略。
德国临床试验注册中心DRKS00021087；https://tinyurl.com/2rdw8w67。
国际注册报告识别码（IRRID）：DERR1-10.2196/26404。
