Physiologic and Genetic Contributions of Impaired Fetal Brain Development in Congenital Heart Disease

先天性心脏病胎儿大脑发育受损的生理和遗传贡献

• 批准号: 10399424
• 负责人: Cynthia Marie Ortinau
• 金额: $ 18.17万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10399424
• 关键词: Address; Adult; Area; Area Under Curve; Award; Brain; Cardiac; Cardiac Output; Cardiac Surgery procedures; Caring; Cerebrum; Child; Congenital Abnormality; Copy Number Polymorphism; Counseling; Data; Development; Development Plans; Diagnosis; Diagnostic; Echocardiography; Education; Environment; Ethnic Origin; Fetus; Future; Genetic; Genetic Markers; Genetic Risk; Genetic Variation; Genomics; Goals; Image; Impairment; Infant; Infrastructure; Intervention; K-Series Research Career Programs; Knowledge; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medical; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; National Heart, Lung, and Blood Institute; Neurodevelopmental Deficit; Neurodevelopmental Disability; Neurodevelopmental Impairment; Newborn Infant; Operative Surgical Procedures; Outcome; Pathogenicity; Pathway interactions; Patients; Pattern; Physiological; Physiology; Play; Population; Pregnancy; Pregnant Women; Preventive; Probability; Prospective Studies; Quality of life; ROC Curve; Race; Reporting; Research; Research Activity; Research Design; Resistance; Resources; Risk; Role; Scientist; Sensitivity and Specificity; Socioeconomic Factors; Surface; Syndrome; Techniques; Testing; Therapeutic; Third Pregnancy Trimester; Time; Training; Training and Education; Universities; Vulnerable Populations; Washington; adverse outcome; aortic arch; brain magnetic resonance imaging; brain volume; care outcomes; career development; cerebral hemodynamics; cerebral oxygenation; cerebrovascular; clinically significant; congenital anomaly; congenital heart disorder; design; experience; fetal; fetal diagnosis; genetic variant; gray matter; hemodynamics; imaging study; impaired brain development; improved; indexing; infant outcome; medical schools; middle cerebral artery; mortality; patient oriented; postnatal; prenatal; primary outcome; recruit; risk prediction; risk stratification; secondary analysis; sex; skills; white matter

PROJECT SUMMARY Congenital heart disease (CHD) is the most common birth defect and, as survival has improved for patients with moderate-severe CHD, adults now outnumber children with this diagnosis. This reduction in mortality has shifted research focus to improving long-term outcomes and quality of life. The most common adverse outcome is neurodevelopmental impairment and occurs in 50% of patients with moderate-severe CHD. While postnatally measured medical and surgical factors play a crucial role in the care and outcomes of these infants, brain magnetic resonance imaging (MRI) studies have identified impaired brain development even before cardiac surgery and have emphasized the fetal period as a time when these abnormalities are evolving. These data suggest fetal interventions may be an important aspect of improving the high rates of neurodevelopmental impairments in CHD. The National Heart, Lung, and Blood Institute has highlighted a need for research focused on preventive and therapeutic strategies for reducing neurodevelopmental deficits in CHD. This Mentored Patient-Oriented Career Development Award aligns well with this need by aiming to characterize the trajectory of disrupted cortical brain development in fetuses with moderate-severe CHD and to understand mechanistic interactions between physiologic and genetic variation that underlie brain disruption in this population. These data will assist in identifying the timing and population of CHD fetuses that may benefit from fetal neuroprotective interventions and will inform risk prediction for patient counseling. This Award will provide the candidate the education, training, and mentoring necessary to successfully undertake this proposal and to develop the skills required to become an independent clinician scientist focused on improving neurodevelopmental outcomes in patients with CHD. Dr. Ortinau has already developed expertise in MR analysis techniques. Thus, the training and mentorship for this award will focus on: 1) enhancing knowledge of fetal cardiac physiology and developing expertise in the association of cardiac physiology with cerebral hemodynamics and fetal brain development; and 2) gaining knowledge and experience in genetic and genomic research to understand the contribution of genetic variation to cerebral cortical development. The unique environment at Washington University School of Medicine provides the opportunity to train in these key areas using the infrastructure, resources, and mentorship outlined in the candidate’s Career Development Plan. These research activities will provide the preliminary data necessary for development of an hypothesis-driven R01 application in Year 2 of this Award, aimed at understanding mechanistic interactions between physiologic and genetic pathways that may underlie disruption of brain development in moderate-severe CHD.

项目总结

项目成果

Management of comfort and sedation in neonates with neonatal encephalopathy treated with therapeutic hypothermia.

用治疗性体温过低治疗的新生儿脑病的新生儿的舒适和镇静处理。

• DOI: 10.1016/j.siny.2021.101264
• 发表时间: 2021-08
• 期刊: Seminars in fetal & neonatal medicine
• 影响因子: 3
• 作者: McPherson C;Frymoyer A;Ortinau CM;Miller SP;Groenendaal F;Newborn Brain Society Guidelines and Publications Committee
• 通讯作者: Newborn Brain Society Guidelines and Publications Committee

Placental delayed villous maturation is associated with fetal congenital heart disease.

• DOI: 10.1016/j.ajog.2022.08.013
• 发表时间: 2023-02
• 期刊: American journal of obstetrics and gynecology
• 影响因子: 9.8