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.

在全球范围内，每年大约有1500万婴儿出生于早产，而110万人死亡是由于早产（PTB），定义为月经后37周之前的婴儿。由于死亡率和发病率取决于胎龄，因此早产（<32周的妊娠）是发展并发症的最高风险，可能导致死亡或重大的终身残疾。在主要新生儿病原体中，最重要和常见的是室内出血（IVH），支气管肺发育异常（BPD），坏死性小肠结肠炎（NEC），败血症，专利性动脉导管（PDA）（PDA）和过早（ROP）。尽管新生儿疾病严重程度的措施已经成功地预测了非常早产的新生儿死亡率，但我们鉴定出可能发展出明显发病率的新生儿的能力仍然有限。新生儿疾病的严重性指数具有各种重要的临床和研究应用，包括风险分层，家庭咨询，外部基准测试，用于院间绩效比较，并确定具有特定风险概况的婴儿的个人治疗。需要评分系统，不仅可以预测早产新生儿的死亡率，而且还需要发病。我们的团队表明，常规新生儿筛查时的代谢状况是对早产新生儿新生儿发病率和死亡率的新预测指标。需要进一步的工作来在非常早产的新生儿中优化这些预测模型，并量化代谢物的作用能力，是新生儿疾病严重程度的强，坚固且潜在的纵向生物标志物。我们假设代谢生物标志物可用于准确预测包括新生儿发病率和院内死亡率的非常早产新生儿中复合结果的风险。我们研究的目标是：目标1：开发和外部验证代谢模型，以预测非常早产的新生儿新生儿发病率；和目标2：评估动态代谢模型，用于在生命的第一周内在多个时间点预测新生儿发病率。拟议的工作将在回顾性样本中检查新生儿发病率和死亡率的代谢预测因子，该样本的大约8500个来自加利福尼亚州的早产和来自爱荷华州的1,500个非常早产的早产。此外，我们将评估代谢产物在生命第一周内在四个关键时间点预测新生儿发病率和死亡率的能力，该样本的前瞻性样本是在UCSF Benioff Benioff儿童医院（UCSF-BCH）接受NICU接受护理的500名非常早产的新生儿。以及爱荷华大学Stead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导致改进诊断，更有效的治疗剂以及对早产新生儿的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.

DOI：
10.1038/s41372-022-01521-3
发表时间：
2023-04
期刊：
JOURNAL OF PERINATOLOGY
影响因子：
2.9
作者：
Steurer, Martina A.;Ryckman, Kelli K.;Baer, Rebecca J.;Costello, Jean;Oltman, Scott P.;McCulloch, Charles E.;Jelliffe-Pawlowski, Laura L.;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.

DOI：
10.1016/j.clinbiochem.2021.10.007
发表时间：
2022-01
期刊：
Clinical biochemistry
影响因子：
2.8
作者：
Ryckman KK;Ramesh A;Cho H;Oltman SP;Rogers EE;Dagle JM;Jelliffe-Pawlowski LL
通讯作者：
Jelliffe-Pawlowski LL