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：性染色体三体（SCT），包括Klinefelter（XXY）、XYY综合征和X三体 (XXX)每500个新生儿中就有1个发生。在儿童时期，语言和学习的风险增加 残疾、多动症、自闭症和情绪障碍。医学上，SCT与XXY的睾丸衰竭有关， XXX的卵巢功能衰竭，并且由于胰岛素抵抗的高风险，所有患者的发病率和死亡率均增加， 癫痫和其他健康问题。产前SCT诊断在过去十年中急剧增加， 在美国进行更广泛的无创产前筛查（NIPS）。非凡婴儿研究是 2017年推出，迄今为止招募了最大和最多样化的产前诊断SCT队列，包括 271名婴儿从2个月到3-4岁进行了前瞻性随访， 发育表型分析与包括1300多个生物样本的纵向生物库相结合。结果 已识别的SCT中未描述的医学特征，发育里程碑的详细采集，以及 发现早期言语和行为特征的差异，这些差异被认为是后来诊断的“危险信号”， 自闭症，阅读障碍，多动症 尽管取得了上述成功，但由于COVID研究的限制，我们的数据集存在差距， 我们的数据收集期的很大一部分，以及关于继续这一更新资金的不确定性 项目本行政补充年的重点将是完成 36-个月的亲自访视（包括直接神经发育评估和生物标本采集， 由于COVID的原因无法实现）。这将允许在36个月龄内获得完整的数据集， 是研究第1阶段（2017-2022）的主要终点。我们的目标是：（1）描述和比较 神经发育的自然史，SCT的医学和激素概况，以及（2）确定 SCT中发育和健康结果的表型变异性。我们将保留现有的生物库。 方法：目前的研究参与者（n=271），年龄从12个月到60个月不等，将每年完成一次 评估，目标是完成50次36个月的面对面访问，其余的通过远程保健进行。 将收集人口统计学、健康、家族史和干预措施，沿着评估：（1）认知， 心理和运动功能;（2）身体和性腺测量;（3）生活质量。统计模型 将对比每个SCT组的纵向特征，并与人群标准进行比较。线性模型和logistic 回归将测试潜在的早期风险因素与36个月时选定结果之间的关联。的 将扩大和维持生物储存库。影响：最大的产前确定的儿童队列 SCT提供了一种新的资源，将告知SCT的发育和医学概况的自然史， 指导遗传咨询，确定干预试验的目标，告知新生儿筛查，并提供 为今后的研究提供了宝贵的数据和生物标本储存库。