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.

项目概要 背景：性染色体三体 (SCT)，包括 Klinefelter (XXY)、XYY 综合征和 X 三体 (XXX)，每 500 名新生儿中就有 1 人发生。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。从医学上来说，SCT 与 XXY、 XXX 的卵巢功能衰竭，由于胰岛素抵抗的高风险，所有疾病的发病率和死亡率均增加， 癫痫发作和其他健康状况。过去十年中，产前 SCT 诊断急剧增加 美国有更广泛的无创产前筛查（NIPS）。非凡婴儿研究是 于 2017 年启动，已招募了迄今为止规模最大、最多样化的产前诊断 SCT 队列，包括 对 271 名 2 个月至 3-4 岁的婴儿进行了前瞻性随访，详细了解了医疗、激素和 发育表型分析与包含 1300 多个生物样本的纵向生物库相结合。结果有 识别出先前在 SCT 中未描述的医学特征，详细获取发育里程碑，以及 确定了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”，例如 自闭症、阅读障碍和多动症。 尽管取得了上述成功，但由于新冠肺炎研究期间的限制，我们的数据集仍存在空白。 我们的数据收集期的很大一部分，以及续订资金的不确定性 项目。今年行政补充的重点是完成全面的数据收集工作。 36 个月的亲自访问（包括直接神经发育评估和生物样本采集） 由于新冠肺炎 (COVID-19) 原因无法实现）。这将允许获得 36 个月龄的完整数据集， 是该研究第一阶段（2017-2022）的主要终点。我们的目标是： (1) 描述和比较 神经发育的自然史、SCT 的医学和激素特征，以及 (2) 确定以下因素的预测因素： SCT 中发育和健康结果的表型变异。我们将维持现有的生物样本库。 方法：当前研究参与者 (n=271) 年龄在 12 至 60 个月之间，将完成年度 评估，目标是完成 50 次为期 36 个月的亲自就诊，其余部分通过远程医疗进行。 将收集人口统计、健康、家族史和干预措施，以及以下方面的评估：(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 组的纵向概况并与人口标准进行比较。线性模型和逻辑 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。这 将扩大和维持生物样本库。影响：最大的产前诊断儿童群体 SCT 提供了一种新颖的资源，可以为 SCT 中的发育和医学概况的自然史提供信息， 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 为未来研究提供宝贵的数据和生物样本库。