The Darbepoetin Kindergarten Development Study

达贝泊汀幼儿园发展研究

• 批准号: 10734625
• 负责人: CARLA M BANN
• 金额: $ 225.48万
• 依托单位: RESEARCH TRIANGLE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734625
• 关键词: 2 year old; 4 year old; Academic achievement; Academic skills; Adopted; Affect; Aftercare; Age; Animal Model; Behavior; Behavior assessment; Birth; Brain; Caregivers; Child; Child Behavior Checklist; Childhood; Clinical Data; Cognition; Cognitive; Collaborations; Data; Development; Dimensions; Enrollment; Erythropoiesis; Evaluation; Exposure to; Family; Funding; Goals; Human; Impaired cognition; Infant; Infrastructure; Masks; Mediating; Mediator; Motor; Motor Skills; Movement; Multicenter Neonatal Research Network; National Heart, Lung, and Blood Institute; Nature; Neonatal Intensive Care Units; Neuroprotective Agents; Nursery Schools; Outcome; Outcome Assessment; Parents; Participant; Placebos; Premature Infant; Preschool Child; Randomized; Recording of previous events; Red Cell Mass result; Reporting; Research; Research Personnel; Role; School-Age Population; Schools; Site; Socioeconomic Status; Testing; Time; Toddler; United States; United States National Institutes of Health; Very Low Birth Weight Infant; Vulnerable Populations; behavioral outcome; biological sex; clinical research site; cognitive function; cognitive testing; cohort; early childhood; emotional functioning; executive function; experience; extreme prematurity; follow-up; high risk; high risk infant; improved; improved outcome; insight; interest; kindergarten; middle childhood; motor impairment; multidisciplinary; neonatal exposure; neurodevelopment; neuroprotection; neurorestoration; novel; participant enrollment; peer; phonology; pre-clinical; randomized trial; routine therapy; social skills; teacher

PROJECT SUMMARY/ABSTRACT Improved survival of very preterm infants has not translated into improved neurodevelopment at school age. One promising neuroprotective therapy is the use of erythropoiesis stimulating agents (ESAs) such as darbepoetin. Preclinical and preliminary clinical data suggest that darbepoetin treatment will lead to improved neurodevelopmental outcomes in high-risk preterm infants. The NHLBI-funded “Darbepoetin Trial to Improve Red Cell Mass and Neurodevelopment in Preterms” (Darbe Trial) is a multicenter masked, randomized trial to test the hypothesis that darbepoetin leads to improved neurodevelopment at 2 years in very preterm infants. In the current application, we propose the Darbepoetin Kindergarten Development Study (Darbe-KIDS) in which we will evaluate neurodevelopment in the same children at preschool and school age. The specific aims of Darbe-KIDS are to (1) test the impact of neonatal exposure to darbepoetin on neurodevelopment and behavior at 4.0-5.0 and 6.0-7.0 years corrected age; (2) test the impact of neonatal exposure to darbepoetin on longitudinal neurodevelopment and behavior from 2.0 to 7.0 years corrected age; and (3) evaluate mediating and moderating factors on the effects of darbepoetin on school functioning at 6.0-7.0 years corrected age. We hypothesize that preschool children treated with darbepoetin will have better cognitive, motor, and behavior outcomes at each time point and over time, as compared to those treated with placebo. Further, we hypothesize that executive function and cognition will be significant mediators and biological sex and family socioeconomic status will be significant moderators of the effects of darbepoetin on pre-academic skills and teacher-reported behavior and social skills. Darbe-KIDS builds on the collective expertise in follow-up of preterm infants among our core group of investigators and at the 16 clinical sites that enrolled children in the Darbe Trial and capitalizes on the existing infrastructure that supports both the Darbe Trial and other ongoing school-age studies funded by NHLBI. The study is led by a highly collaborative, interdisciplinary multi-PI team with extensive relevant experience studying the impacts of ESAs in preterm infants and a long history of successful collaborations in conducting high-quality developmental follow-up through school-age in large cohorts of high-risk infants. Darbe-KIDS will be the first comprehensive evaluation of developmental impacts over time and school functioning at school age in a large, multicenter cohort of school-age children treated with darbepoetin. In addition to providing critical data about the multidimensional effects of darbepoetin on outcomes through school age, Darbe-KIDS will yield novel and important data on school functioning in a large contemporary cohort of preterm infants treated in U.S. neonatal intensive care units. Results of this study will directly impact interpretation of the Darbe Trial and influence whether darbepoetin should be adopted as a neuroprotective therapy to improve outcomes for preterm infants.

项目概要/摘要 极早产儿存活率的提高并未转化为学龄期神经发育的改善。 一种有前途的神经保护疗法是使用红细胞生成刺激剂（ESA），例如 达贝泊汀。临床前和初步临床数据表明达贝泊汀治疗将导致改善 高危早产儿的神经发育结果。 NHLBI 资助的“达贝泊汀改善试验” 早产儿的红细胞质量和神经发育”（Darbe 试验）是一项多中心、随机试验 检验达贝泊汀可改善极早产儿 2 岁时神经发育的假设 婴儿。在当前的申请中，我们提出了达贝泊汀幼儿园发展研究 （Darbe-KIDS），我们将评估同一儿童在学前班和 学龄。 Darbe-KIDS 的具体目标是 (1) 测试新生儿接触达贝泊汀的影响 4.0-5.0 岁和 6.0-7.0 岁校正年龄时的神经发育和行为； (2) 测试影响 新生儿接触达贝泊汀对 2.0 至 7.0 岁纵向神经发育和行为的影响 修正年龄； (3)评估达贝泊汀对学校影响的中介和调节因素 校正年龄为 6.0-7.0 岁。我们假设学龄前儿童接受达贝泊汀治疗 与其他人相比，在每个时间点和一段时间内都会有更好的认知、运动和行为结果 那些用安慰剂治疗的人。此外，我们假设执行功能和认知将很重要 生物性别和家庭社会经济地位将是影响的重要调节因素 达贝泊汀关于学前技能和教师报告的行为和社交技能。 Darbe-KIDS 建立在 我们的核心研究小组和 16 名研究人员在早产儿随访方面的集体专业知识 招募儿童参加 Darbe 试验并利用现有基础设施的临床中心 支持 Darbe 试验和 NHLBI 资助的其他正在进行的学龄研究。该研究由一位 高度协作、跨学科的多 PI 团队，具有研究影响的丰富相关经验 早产儿 ESA 的使用以及在开展高质量的 ESA 方面的成功合作的悠久历史 对大量高危婴儿进行学龄期发育跟踪。 Darbe-KIDS 将是第一个 对一段时间内的发展影​​响和学龄期学校运作的综合评估 使用达贝泊汀治疗的大型多中心学龄儿童队列。除了提供关键数据外 关于达贝泊汀对整个学龄期成绩的多维影响，Darbe-KIDS 将得出 关于在接受治疗的当代一大群早产儿中学校运作的新颖而重要的数据 美国新生儿重症监护病房。这项研究的结果将直接影响对达布试验的解释 并影响是否应采用达贝泊汀作为神经保护疗法以改善预后 早产儿。