Is Jaundice in Premature Infants a Risk Factor for Autism?

早产儿黄疸是自闭症的危险因素吗？

• 批准号: 8770719
• 负责人: SANJIV B AMIN
• 金额: $ 19.19万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8770719
• 关键词: 10 year old; Acidosis; Age; Albumins; Asphyxia; Auditory; Autistic Disorder; Basal Ganglia; Bilirubin; Binding; Biochemical; Biochemical Markers; Biological; Birth; Brain Stem; Child; Clinic; Clinical; Clinical Data; Consent; Coupled; Data; Databases; Detection; Development; Developmental Disabilities; Diagnosis; Diagnostic; Early Intervention; Early identification; Effectiveness; Enrollment; Etiology; Evaluation; Foundations; Funding; Gestational Age; Gold; Guidelines; Health Benefit; Hemolysis; Hippocampus (Brain); Hyperbilirubinemia; Hypercapnia; Hypoxia; Icterus; ImProv; Impaired cognition; Incidence; Infant; Injury; Intervention; Knowledge; Language; Link; Literature; Live Birth; Measurement; Measures; Medical center; Minocycline; Morbidity - disease rate; Neonatal; Neonatal Jaundice; Neurodevelopmental Disorder; Neuropathy; Observational Study; Outcome; Pattern; Population; Pregnancy; Premature Infant; Prevalence; Preventive; Process; Prospective Studies; Proteins; Public Health; Publishing; Questionnaires; Receiver Operating Characteristics; Regression Analysis; Reporting; Risk; Risk Factors; Schedule; Sensory; Sensory Process; Sepsis; Serum; Site; Societies; Symptoms; Temperature; Testing; Therapeutic Intervention; United States National Institutes of Health; Universities; Vulnerable Populations; autism spectrum disorder; base; clinical risk; cognitive function; cohort; cost; developmental disease; disorder control; disorder subtype; follow-up; high risk; improved; neurotoxicity; programs; prospective; public health relevance; research clinical testing; screening; social communication

DESCRIPTION (provided by applicant): The reported prevalence of autism spectrum disorder (ASD) has been rising, at least partly due to increased detection and broadened diagnostic criteria, and is now estimated at 1 in 88. ASD appears to be even more prevalent among premature infants with a reported prevalence of ~8%. Neonatal clinical factors that increase the risk among premature infants are not well studied. Neonatal unconjugated hyperbilirubinemia (jaundice) may be one such factor. Jaundice is ubiquitous among premature infants and may be associated with cerebellar, hippocampal, brainstem, and basal ganglia injury, which in turn has recently been linked to autism. Recently, neonatal jaundice, assessed using total serum bilirubin levels, was found to be associated with ASD in late preterm and term infants, but its association with ASD in premature infants remains unknown. Moreover, recent studies suggest that unbound bilirubin (bilirubin not bound to protein, UB) may be a better predictor of neurodevelopmental disorder than total serum bilirubin, but no studies have evaluated whether UB is linked to ASD. This proposal is for a two year study of premature infants d 33 weeks gestational age to evaluate association between neonatal jaundice and ASD among premature infants using UB, a better bilirubin biochemical marker of neurotoxicity. The University of Rochester Medical Center has a unique opportunity to conduct the proposed prospective observational study for the following reasons: 1) A large cohort of infants d 33 weeks gestational age and enrolled in NIH-funded bilirubin study soon after birth has consented to be prospectively followed for neurodevelopmental outcomes at a later age; 2) These premature infants are actively followed for neurodevelopmental outcomes by the Neonatal Developmental Program up to 10 years of age with 90% retention; 3) A database has been created with requisite maternal, pregnancy, and neonatal clinical data prospectively collected on all enrolled premature infants; 4) All enrolled premature infants had prospective evaluation for jaundice using measurement of UB levels, total serum bilirubin levels, and albumin levels during the first 2 weeks after birth; 5) Clinical risk factors for jaundice associated neurotoxicity has been prospectively evaluated and requisite data on risk factors has been prospectively collected on all these premature infants; and 6) The site has expertise in both neonatal jaundice and ASD diagnosis. The project will involve 470 premature infants enrolled in the bilirubin-induced neurotoxicity study and who have consented for follow-up neurodevelopmental evaluation. These infants will be screened for ASD with the SCQ and those with positive screens will complete the Autism Diagnostic Observation Schedule. Establishing the association between jaundice and ASD in high-risk premature infants will suggest one preventable etiology of ASD and will lay the foundation for preventive trials to confirm the causal association between jaundice and ASD in a larger population. Ultimately, the findings of such trial will help to improv management of jaundice with secondary reduction in ASD. Not studying this established cohort with unique information on UB will be a lost opportunity.

描述（由申请人提供）：据报道，自闭症谱系障碍（ASD）的患病率一直在上升，至少部分原因是检测的增加和诊断标准的扩大，目前估计为1 / 88。ASD在早产儿中更为普遍，据报道患病率约为8%。增加早产儿风险的新生儿临床因素尚未得到很好的研究。新生儿非结合性高胆红素血症（黄疸）可能是其中一个因素。黄疸在早产儿中普遍存在，可能与小脑、海马、脑干和基底神经节损伤有关，而这些损伤最近又与自闭症有关。最近，使用血清总胆红素水平评估的新生儿黄疸被发现与晚期早产儿和足月儿的ASD有关，但其与早产儿ASD的关系尚不清楚。此外，最近的研究表明，未结合胆红素（未与蛋白质结合的胆红素，UB）可能比血清总胆红素更好地预测神经发育障碍，但没有研究评估UB是否与ASD有关。本研究计划对胎龄为33周的早产儿进行为期两年的研究，利用UB（一种更好的胆红素神经毒性生化标志物）评估早产儿新生儿黄疸与ASD之间的关系。罗彻斯特大学医学中心有一个独特的机会来进行拟议的前瞻性观察性研究，原因如下：1)一大批出生后不久就加入美国国立卫生研究院资助的胆红素研究的33周孕龄婴儿同意在以后的年龄进行前瞻性随访，以观察神经发育结果；2)这些早产儿通过新生儿发育计划积极跟踪神经发育结果，直到10岁，保留率为90%；3)建立了一个数据库，前瞻性地收集了所有入组早产儿的必要的孕产妇、妊娠和新生儿临床数据；4)所有入组的早产儿在出生后2周内通过测量UB水平、血清总胆红素水平和白蛋白水平对黄疸进行前瞻性评估；5)前瞻性评估了所有早产儿黄疸相关神经毒性的临床危险因素，前瞻性收集了必要的危险因素数据；6)该站在新生儿黄疸和ASD诊断方面都有专长。该项目将涉及470名早产儿，这些早产儿参加了胆红素诱导的神经毒性研究，并同意进行后续的神经发育评估。这些婴儿将通过SCQ进行ASD筛查，筛查呈阳性的婴儿将完成自闭症诊断观察计划。在高危早产儿中建立黄疸与ASD之间的关联，将提示一种可预防的ASD病因学，并为在更大的人群中进行黄疸与ASD之间因果关系的预防性试验奠定基础。最终，该试验的发现将有助于改善黄疸的管理，并减少ASD的继发性发病。不研究这个具有独特信息的已建立的队列将失去机会。