The eXtraordinarY Babies Study: Natural History of Health and Neurodevelopmentin Infants and Young Children with Sex Chromosome Trisomy

非凡婴儿研究：性染色体三体性婴幼儿健康和神经发育的自然史

• 批准号: 10670580
• 负责人: Nicole Renee Tartaglia
• 金额: $ 20.23万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-13 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10670580
• 关键词: 4 year old; Achievement; Administrative Supplement; Age-Months; Attention deficit hyperactivity disorder; Behavior; Biological Specimen Banks; Birth; Child; Childhood; Chromosome abnormality; Cognitive; Collection; Congenital Abnormality; Coupled; Data Collection; Data Set; Development; Developmental Delay Disorders; Diagnosis; Disease; Dyslexia; Emotional disorder; Enrollment; Failure; Family; Funding; Genetic Counseling; Goals; Guidelines; Health; Hormonal; Infant; Insulin Resistance; Intervention; Intervention Trial; Klinefelter' s Syndrome; Language Disorders; Learning Disabilities; Linear Models; Logistic Regressions; Measures; Medical; Medical Genetics; Morbidity - disease rate; Motor; Natural History; Neonatal Screening; Neurodevelopmental Problem; Outcome; Participant; Persons; Phase; Phenotype; Population; Prenatal Diagnosis; Quality of life; Recording of previous events; Research; Resources; Risk; Risk Factors; Seizures; Sex Chromosomes; Speech; Statistical Models; Testing; Trisomy; Trisomy 2; Trisomy X syndrome; Uncertainty; Visit; XYY Karyotype; autism spectrum disorder; biobank; clinical care; cohort; comorbidity; coronavirus disease; data repository; demographics; high risk; mortality; neurodevelopment; novel; ovarian failure; prenatal; prenatal testing; primary endpoint; prospective; psychologic; success; telehealth

PROJECT SUMMARY Background: Sex Chromosome Trisomies (SCT) including Klinefelter (XXY), XYY syndrome, and Trisomy X (XXX), occur in 1 out of every 500 births. In childhood there are increased risks for language and learning disabilities, ADHD, autism, and emotional disorders. Medically, SCTs are associated with testicular failure in XXY, ovarian failure in XXX, and all have increased morbidity and mortality due to high risks for insulin resistance, seizures, and other health conditions. Prenatal SCT diagnosis has drastically increased over the past decade in the US with more widespread noninvasive prenatal screening (NIPS). The eXtraordinarY Babies Study was launched in 2017, and has enrolled the largest and most diverse prenatally diagnosed SCT cohort to date, including 271 infants followed prospectively from 2 months to 3-4 years of age with detailed medical, hormonal, and developmental phenotyping coupled with a longitudinal biobank including over 1300 biospecimens. Results have identified medical features not previously described in SCT, detailed acquisition of developmental milestones, and identified differences in early speech and behavior profiles known to be `red flags' of later diagnoses such as autism, dyslexia, and ADHD. Despite successes described above, we have gaps in our dataset due to COVID research restrictions during a significant portion of our data collection period, and uncertainty about renewal funding for the continuation of this project. The focus of this administrative supplement year will be to complete comprehensive data collection for the 36-month in-person visits (including direct neurodevelopmental assessment and biospecimen collection that was not possible due to COVID). This will allow for achievement of a complete dataset through 36-months of age which was the primary endpoint for the 1st phase of the study (2017-2022). We aim to: (1) Describe and compare the natural history of neurodevelopment, medical and hormonal profiles of SCT, and (2) To identify predictors of phenotypic variability in developmental and health outcomes in SCT. We will maintain the current Biobank. Approach: Current study participants (n=271) ranging from 12 to 60 months of age will complete an annual assessment, with goals of completing 50 36-month in-person visits, and the remainder conducted by telehealth. Demographics, health, family history, and interventions will be collected, along with assessments of: (1) cognitive, psychological and motor functioning; (2) physical and gonadal measures and (3) quality of life. Statistical models will contrast longitudinal profiles for each SCT group and compare to population norms. Linear models and logistic regression will test the association between potential early risk factors and selected outcomes at 36 months. The biorepository will be expanded and maintained. Impact: The largest cohort of prenatally identified children with SCT provides a novel resource that will inform the natural history of developmental and medical profiles in SCTs, guide genetic counseling, identify targets for intervention trials, inform newborn screening, and provide an invaluable data and biospecimen repository for future research.

项目摘要 背景：性别染色体trisomies（SCT），包括Klinefelter（XXY），XYY综合征和三体X （xxx），每500个出生中有1个发生。在童年时期，语言和学习的风险增加 残疾，多动症，自闭症和情绪障碍。在医学上，SCT与XXY中的睾丸衰竭有关， XXX中的卵巢衰竭，并且由于胰岛素抵抗的高风险，所有卵巢衰竭都有增加的发病率和死亡率， 癫痫发作和其他健康状况。在过去的十年中，产前SCT诊断已大大增加 美国具有更广泛的非侵入性产前筛查（NIP）。非凡的婴儿研究是 于2017年启动，并招收了迄今为止最大，最多样化的产前诊断的SCT队列，包括 有271名婴儿从2个月到3-4岁，均具有详细的医疗，荷尔蒙和 发育表型，再加上纵向生物库，其中包括1300多个生物测量。结果有 确定了以前在SCT中未描述的医学功能，对发展里程碑的详细获取以及 确定了已知的早期语音和行为概况的差异 自闭症，阅读障碍和多动症。 尽管上面描述了成功，但由于在一个过程中的研究限制，我们在数据集中仍然存在差距 我们的数据收集期的很大一部分，以及有关此次续签资金的不确定性 项目。此行政补充年的重点将是完成全面的数据收集 36个月的面对面访问（包括直接的神经发育评估和生物传播收集 由于共同导致）。这将允许通过36个月的年龄实现一个完整的数据集 是研究第一阶段（2017-2022）的主要终点。我们的目标是：（1）描述和比较 SCT的神经发育，医学和激素谱的自然历史，以及（2）确定的预测指标 SCT的发育和健康结果的表型变异性。我们将维护当前的生物库。 方法：当前的研究参与者（n = 271）年龄在12到60个月之间 评估，其目标是完成50个36个月的面对面访问，其余的远程医疗进行。 将收集人口统计，健康，家族史和干预措施，并评估：（1）认知， 心理和运动功能； （2）身体和性腺措施以及（3）生活质量。统计模型 将为每个SCT组对比纵向概况，并与人口规范进行比较。线性模型和逻辑 回归将测试潜在的早期危险因素和36个月的选定结果之间的关联。这 生物座位将被扩展和维护。影响：最大的产前确定儿童 SCT提供了一种新颖的资源，该资源将为SCT中的发展和医疗概况的自然历史提供信息， 指导遗传咨询，确定干预试验的目标，为新生儿筛查提供信息，并提供 可用于未来研究的宝贵数据和生物测量存储库。