Targeted metabolic profiling to predict major morbidity in very preterm newborns

有针对性的代谢分析可预测极早产新生儿的主要发病率

基本信息

批准号：
10825249
负责人：
Laura Lee Jelliffe-Pawlowski
金额：
$ 58.8万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10825249
关键词：
10 year old 37 weeks gestation Benchmarking Biological Biological Markers Birth Brain Death Bronchopulmonary Dysplasia California Caring Cerebral Palsy Cessation of life Characteristics Climacteric Clinical Clinical Management Clinical Trials Counseling Data Decision Making Diagnostic Disease Etiology Family Gestational Age Goals Hospital Mortality Hour Individual Infant Infant Care Infant Mortality Intervention Iowa Lead Life Life Experience Measures Metabolic Modeling Morbidity - disease rate Necrotizing Enterocolitis Neonatal Neonatal Intensive Care Units Neonatal Mortality Neonatal Screening Neurodevelopmental Impairment Newborn Infant Operative Surgical Procedures Outcome Patent Ductus Arteriosus Pattern Pediatric Hospitals Periventricular Leukomalacia Physiology Pregnancy Premature Birth Premature Infant Protocols documentation Research Retinopathy of Prematurity Risk Sampling Sepsis Severity of Illness Index Severity of illness System Therapeutic Agents Time United States Universities Variant Vulnerable Populations Work clinical care clinical practice cost estimate disability extreme prematurity hemodynamics high risk hospital performance improved intraventricular hemorrhage late onset sepsis medical complication metabolic profile mortality mortality risk neonatal morbidity neonate novel patient population patient variability personalized approach predictive modeling preterm newborn prospective research clinical testing risk prediction risk prediction model risk stratification therapeutically effective

项目摘要

Globally, approximately 15 million babies are born preterm each year and 1.1 million deaths are due to preterm birth (PTB), defined as delivery of an infant before 37 post-menstrual weeks. Because mortality and morbidity rates are dependent upon gestational age, the very preterm neonate (<32 weeks gestation) is at the highest risk of developing complications that can result in death or significant life-long disability. Among the most significant and common of the major neonatal morbidities are intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, patent ductus arteriosus (PDA) and retinopathy of prematurity (ROP). While measures of neonatal illness severity have been successful in predicting the risk for mortality in very preterm neonates, our ability to identify newborns likely to develop significant morbidity remains limited. Neonatal illness severity indices have a variety of important clinical and research applications including risk stratification, family counseling, external benchmarking for inter-hospital performance comparisons, and determining individual treatments for infants with a specific risk profile. Scoring systems are needed that not only predict mortality but also morbidity in the very preterm neonate. Our team has shown that metabolic status at the time of routine newborn screening is a novel predictor of neonatal morbidity and mortality in preterm newborns. Further work is needed to optimize these prediction models in very preterm neonates and quantify the ability of metabolites to act as strong, robust and potentially longitudinal biomarkers of neonatal illness severity. We hypothesize that metabolic biomarkers can be used to accurately predict the risk of a composite outcome in very preterm neonates that includes neonatal morbidity and in-hospital mortality. The objectives of our study are: Aim 1: Develop and externally validate metabolic models for predicting neonatal morbidity in very preterm newborns; and Aim 2: Evaluate dynamic metabolic models for predicting neonatal morbidity at multiple time points within the first week of life. The proposed work will examine metabolic predictors of neonatal morbidity and mortality in a retrospective sample of approximately 8,500 very preterm births from California and 1,500 very preterm births from Iowa. Furthermore, we will evaluate the ability of metabolites to predict neonatal morbidity and mortality at four critical time points within the first week of life in a prospective sample of 500 very preterm newborns receiving care in the NICU at UCSF Benioff Children's Hospital (UCSF-BCH) and the University of Iowa Stead Family Children's Hospital (UI-SFCH). Understanding the relationship between specific metabolites and neonatal morbidity will lead to the long-term goal of improved diagnostics, more effective therapeutic agents, and a precision approach to clinical management of the very preterm neonate.

全球每年约有 1500 万婴儿早产，110 万人死于早产 (PTB)，早产定义为婴儿在月经后 37 周之前分娩。由于死亡率和发病率取决于胎龄，因此极早产新生儿（妊娠 <32 周）发生并发症的风险最高，可能导致死亡或严重的终身残疾。最重要和最常见的主要新生儿疾病包括脑室内出血（IVH）、支气管肺发育不良（BPD）、坏死性小肠结肠炎（NEC）、脓毒症、动脉导管未闭（PDA）和早产儿视网膜病变（ROP）。虽然新生儿疾病严重程度的测量已成功预测极早产新生儿的死亡风险，但我们识别可能出现严重发病率的新生儿的能力仍然有限。新生儿疾病严重程度指数具有多种重要的临床和研究应用，包括风险分层、家庭咨询、医院间绩效比较的外部基准以及确定具有特定风险状况的婴儿的个体化治疗。评分系统不仅可以预测早产儿的死亡率，还可以预测其发病率。我们的团队表明，常规新生儿筛查时的代谢状态是早产新生儿发病率和死亡率的新预测因子。需要进一步的工作来优化极早产新生儿的这些预测模型，并量化代谢物作为新生儿疾病严重程度的强、稳健和潜在纵向生物标志物的能力。我们假设代谢生物标志物可用于准确预测极早产新生儿的复合结局风险，包括新生儿发病率和院内死亡率。我们研究的目标是：目标 1：开发并外部验证代谢模型，用于预测极早产新生儿的新生儿发病率；目标 2：评估动态代谢模型，以预测出生后第一周内多个时间点的新生儿发病率。拟议的工作将在加利福尼亚州约 8,500 名极早产儿和爱荷华州约 1,500 名极早产儿的回顾性样本中检查新生儿发病率和死亡率的代谢预测因素。此外，我们将在 UCSF 贝尼奥夫儿童医院 (UCSF-BCH) 新生儿重症监护室接受护理的 500 名极早产新生儿的前瞻性样本中，评估代谢物在生命第一周内四个关键时间点预测新生儿发病率和死亡率的能力。和爱荷华大学斯特德家庭儿童医院 (UI-SFCH)。了解特定代谢物与新生儿发病率之间的关系将有助于实现改进诊断、更有效的治疗药物以及对早产新生儿进行精确临床管理的长期目标。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Developing a resiliency model for survival without major morbidity in preterm infants.

开发早产儿无重大发病率的生存弹性模型。

DOI：
发表时间：
2023-04
期刊：
影响因子：
0
作者：
Steurer, Martina A;Ryckman, Kelli K;Baer, Rebecca J;Costello, Jean;Oltman, Scott P;McCulloch, Charles E;Jelliffe;Rogers, Elizabeth E
通讯作者：
Rogers, Elizabeth E

Evaluation of heparinized syringes for measuring newborn metabolites in neonates with a central arterial line.

肝素注射器用于测量中央动脉导管新生儿代谢物的评估。

DOI：
发表时间：
2022-01
期刊：
影响因子：
2.8
作者：
Ryckman, Kelli K;Ramesh, Abhismitha;Cho, Hyunkeun;Oltman, Scott P;Rogers, Elizabeth E;Dagle, John M;Jelliffe
通讯作者：
Jelliffe