Elucidating and modelling complex postnatal steroid hormone changes in preterm infants: insights into the developing immature neonatal adrenal cortex

阐明和模拟早产儿复杂的产后类固醇激素变化：深入了解发育中的未成熟新生儿肾上腺皮质

• 批准号: MR/V037757/1
• 负责人: Harshini Katugampola
• 金额: $ 37.33万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV037757%2F1
• 关键词: Elucidating; modelling; complex; postnatal; steroid

This study will use mathematical models to find out how hormones produced by the adrenal gland in premature babies change after birth. The adrenal glands sit on top of the kidneys. They are part of the endocrine system, which organises the release of hormones within the body. Hormones are chemical messengers that switch on and off processes in the body. The adrenal produces several steroid hormones, which are important for a number of adaptations to life including a stress response, blood sugar regulation, and blood pressure control. Many preterm (born before 37 weeks' gestation) and term babies have problems with blood sugar and blood pressure. Cortisol is an important a steroid hormone that is part of a stress response and helps to maintain blood sugar. We can give a steroid medicine called hydrocortisone if we are concerned that a baby may not be making enough cortisol. Without the right treatment a baby can become very sick. However not all babies need extra steroid medicine but it can be hard to predict which do and which do not. One big problem is that in premature babies, normal reference ranges for many hormones do not exist. A reference range is the range of values that is deemed normal for a physiological measurement in a healthy person. In this study, measurements of blood and urine concentrations of cortisol and other important steroid hormones produced by the adrenal gland will be taken. The main outcome is to find a model that describes the measurements in a way that relates to biological processes. Mathematical models are descriptions of measurements using a system of equations. Investigating which parts of the model differ between babies born at different gestational ages will help to create normal reference ranges for important adrenal hormones and allow correct interpretation of results. With advances in the neonatal care of these preterm babies, and their survival to term, there is a growing need for normative data to support their clinical outcomes. Without such data, these babies may receive inappropriate long-term treatment with steroids. This can lead to serious health-risks such as weight gain, reduced bone strength, slow growth, high blood pressure, high blood sugar and increased susceptibility to infection. This study is a way of gaining knowledge and improving our understanding of the normal adrenal endocrine system of preterm babies in order to improve the standards and quality of care we provide. A secondary objective of this study is the development of a unique bio-resource of anonymised neonatal samples from babies. Any unused material from this study would be deposited in this resource with consent. Full ethical approval would be sought for this bio-resource, and it would be carefully regulated in terms of storage of samples. Every effort will be made to ensure that optimal use is made of donated samples, both in terms of the aims and quality of the research for which it is used and avoidance of duplication/wastage. The bio-resource would also provide opportunity for retrospective studies, and by going back to stored samples and data, the long-term quality of life and clinical outcomes could be improved for generations to come.

这项研究将使用数学模型来发现早产儿肾上腺分泌的激素在出生后是如何变化的。肾上腺位于肾脏的顶部。它们是内分泌系统的一部分，负责组织体内激素的释放。激素是一种化学信使，可以开启和关闭身体的各个过程。肾上腺产生几种类固醇激素，这些激素对许多适应生活的因素都很重要，包括应激反应、血糖调节和血压控制。许多早产儿（怀孕37周前出生）和足月婴儿都有血糖和血压问题。皮质醇是一种重要的类固醇激素，是应激反应的一部分，有助于维持血糖。如果我们担心婴儿的皮质醇分泌不足，我们可以给他们服用一种叫做氢化可的松的类固醇药物。如果没有正确的治疗，婴儿可能会病得很重。然而，并不是所有的婴儿都需要额外的类固醇药物，但很难预测哪些需要，哪些不需要。一个大问题是，在早产儿中，许多激素的正常参考范围不存在。参考范围是在健康人的生理测量中被认为是正常的值范围。在这项研究中，将测量血液和尿液中皮质醇和其他由肾上腺产生的重要类固醇激素的浓度。主要的结果是找到一个模型，以一种与生物过程相关的方式描述测量。数学模型是用方程组来描述测量结果。研究在不同胎龄出生的婴儿之间模型的哪些部分不同，将有助于为重要的肾上腺激素建立正常的参考范围，并允许对结果进行正确的解释。随着这些早产儿的新生儿护理的进步，以及他们的生存到足月，越来越需要规范性数据来支持他们的临床结果。如果没有这些数据，这些婴儿可能会接受不适当的类固醇长期治疗。这可能导致严重的健康风险，如体重增加、骨骼强度降低、生长缓慢、高血压、高血糖和增加感染的易感性。这项研究是获得知识和提高我们对早产儿正常肾上腺内分泌系统的理解，以提高我们提供的护理标准和质量的一种方式。本研究的第二个目的是开发一种独特的生物资源，即匿名新生儿样本。本研究中任何未使用的材料将在征得同意的情况下存放在此资源中。这种生物资源将寻求完全的伦理批准，并将在样本储存方面进行仔细监管。将尽一切努力确保捐赠的样品得到最佳利用，既要考虑到所使用样品的研究目的和质量，又要避免重复/浪费。生物资源还将为回顾性研究提供机会，通过返回存储的样本和数据，可以改善后代的长期生活质量和临床结果。