Development of a clinical marker of the fetal autonomic maturation

子宫内成熟障碍永久性地改变了胎儿期的发育。这对晚年的严重健康问题有影响。产后治疗不能完全弥补这些“胎儿程序”失调。产前发育过程的高度可塑性使得在妊娠期就可能采取新的一级预防性治疗策略。由于形态学成像反映了最严重的宫内成熟障碍，产前诊断的新方法是必要的功能水平上的失调的早期识别。在这种情况下，申请人开发了成熟评分（功能性自主脑年龄评分，fABAS）。考虑到自主神经系统的活动，可以通过无创心率记录进行评估，研究胎儿功能成熟的关键功能。本项目的目标是在研究和临床应用中精确和稳健地使用fABAS。将使用高质量的胎儿心磁图（fMCG）记录来研究评分在多大程度上可以根据母体自主神经张力、胎动和胎儿行为状态进行调整。将使用外部fMCG数据集验证所得评分。此外，还将研究这些结果在何种程度上可以转移到广泛建立的，但技术上受到限制的记录技术（胎儿心电图CTG，胎儿心电图fECG）。由此产生的fABAS系统将提供给国际科学界。最后，fABAS系统将在评估成熟障碍的初步研究中进行测试，以设计和启动多中心前瞻性研究。

Disturbances of the intrauterine maturation permanently alter the development already in the prenatal period. This has implications for serious health problems in later age. Postnatal therapies cannot completely compensate those 'fetal programmed' maladjustments. The high plasticity of the prenatal developmental process causes the possibility of new primary preventive therapy strategies already during the gestation. Since morphological imaging reflects most serious intrauterine maturation disturbances only, novel approaches of prenatal diagnosis are necessary for an early identification of maladjustments on the functional level. In that context the applicants developed a maturation score (functional Autonomic Brain Age Score, fABAS). Considering the activity of the autonomic nervous system, that can be assessed by means of noninvasive heart rate recordings, a key function of the fetal functional maturation is investigated. The objective of the present project is an advancement of fABAS with respect to precise and robust use in research and clinical application. Using high quality fetal magnetocardiographic (fMCG) recordings it will be investigated, to which extent the score can be adjusted to maternal autonomic tone, fetal movements and fetal behavioural states. The resulting score will be validated using an external fMCG data set. Furthermore, it will be investigated to which extent those results can be transferred to widespread established, but technically restricted recording technologies (Cardiotocography CTG, fetal electrocardiograph fECG). The resulting fABAS system will be made available for the international scientific community. Finally, fABAS system will be tested in pilot studies of the assessment of maturation disturbances in order to design and initiate multicenter prospective studies.