Placenta bacteriology and histology in the etiology of retinopathy of prematurity

描述（由申请人提供）：拟议研究的目的是通过从胎盘细菌学和组织学中获得关于早产儿视网膜病变（ROP）的潜在可预防的产前危险因素的可靠数据支持，帮助减少早产儿视力障碍和失明的发生率。我们建议对胎盘细菌学和组织学作为ROP的危险因素进行全面的二次数据分析，这些数据来自于美国国立卫生研究院资助的一项大规模早产儿队列研究数据库，该研究可获得详细的胎盘、临床和ROP信息（www.elganstudy.org）。我们将用于这里提出的分析的数据库来自ELGAN（极低孕龄新生儿的首字母缩写）研究（NIH 1u01 NS 40069-01A2）。ELGAN研究旨在确定ELGAN中增加结构和功能神经障碍风险的特征和暴露。2002年至2004年期间，在5个州11个城市的14个参与机构之一的妊娠28周前分娩的妇女被要求参加这项研究。所有参与计划的院校，包括现时申请人所属的两所院校，均经个别院校覆核委员会核准注册及同意程序。根据临床情况和机构偏好，在产前入院时或分娩后不久，与母亲取得同意。1506名婴儿的1249名母亲表示同意。在1506名入组婴儿中，1199名至少进行了一次眼科检查后活着出院。其中885例（74%）ROP为任意等级，349例（29%）ROP为高（3-5）级。我们将检验三个零假设：(1)从胎盘组织中培养微生物的婴儿与没有此类证据的同龄人发生ROP的风险相同；（2.） 有胎盘组织学炎症特征的婴儿与无此证据的婴儿发生ROP的风险相同；(3)。产前感染（胎盘微生物学）和炎症（胎盘组织学）的特征不会改变与已知临床危险因素相关的ROP风险。我们将使用多变量回归建模技术来检验这些假设，以调整混淆。相关性：根据美国国家眼科研究所，早产儿视网膜病变（ROP）“是儿童视力丧失的最常见原因之一，并可能导致终身视力障碍和失明。”试图增加已知的可预防的ROP原因是至关重要的。该项目旨在阐明产前暴露于感染和炎症在ROP病因学中的潜在作用，这是可以通过干预有效靶向的过程。

DESCRIPTION (provided by applicant): The objective of the proposed research is to help reduce the incidence of visual disability and blindness in children born preterm by providing solid data support about potentially preventable antenatal risk factors of retinopathy of prematurity (ROP) derived from placenta bacteriology and histology. We propose to perform comprehensive secondary data analyses of placenta bacteriology and histology as risk factors for ROP collected within database from a large-scale NIH-funded cohort study of preterm infants for whom detailed placenta, clinical, and ROP information is available (www.elganstudy.org). The database we will use for the analyses proposed here comes from the ELGAN (the acronym for Extremely Low Gestational Age Newborn) Study (NIH 1 U01 NS 40069-01A2). The ELGAN study was designed to identify characteristics and exposures that increase the risk of structural and functional neurological disorders in ELGANs. During the years 2002-2004, women who were delivered before 28 weeks gestation at one of 14 participating institutions in 11 cities in 5 states were asked to enroll in the study. The enrollment and consent processes were approved by the individual institutional review boards of all participating institutions, including the two institutions of the current applicants. Mothers were approached for consent either upon antenatal admission or shortly after delivery, depending on clinical circumstance and institutional preference. 1,249 mothers of 1,506 infants consented. Of the 1506 enrolled infants, 1199 were discharged alive with at least one eye exam. Of these 885 (74%) had ROP of any grade and 349 (29%) had high (3-5) grade ROP. We will test three null-hypotheses: (1.) Infants with microorganisms cultured from their placenta tissue are at the same risk for ROP as their peers without such evidence; (2.) Infants with placenta histology characteristics of inflammation are at the same risk for ROP as their peers without such evidence; (3.) Characteristics of antenatal infection (placenta microbiology) and inflammation (placenta histology) do NOT modify the ROP risk associated with known clinical risk factors. We will test these hypotheses using multivariable regression modeling techniques in order to adjust for confounding. Relevance: According to the National Eye Institute, retinopathy of prematurity (ROP) "is one of the most common causes of visual loss in childhood and can lead to lifelong vision impairment and blindness." Attempts to add to the known spectrum of preventable causes of ROP are paramount. This project aims at the elucidation of a potential role for antenatal exposure to infection and inflammation in ROP etiology, which are processes that could be effectively targeted by interventions.