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提供来自胎盘细菌学和组织学的早产儿视网膜病变（ROP）的潜在可预防产前风险因素的可靠数据支持，帮助降低早产儿视力残疾和失明的发生率。我们建议对胎盘细菌学和组织学作为ROP的风险因素进行全面的次要数据分析，这些数据来自NIH资助的一项早产儿大规模队列研究，该研究提供了详细的胎盘、临床和ROP信息（www.elganstudy.org）。我们将用于此处拟定分析的数据库来自ELGAN（极低胎龄新生儿的首字母缩略词）研究（NIH 1 U 01 NS 40069- 01 A2）。ELGAN研究旨在确定增加ELGAN结构和功能性神经系统疾病风险的特征和暴露。在2002-2004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。入组和知情同意过程由所有参与机构的单个机构审查委员会批准，包括当前申请人的两个机构。根据临床情况和机构偏好，在产前入院或分娩后不久，与母亲进行了接触，以征求同意。1,506名婴儿的1,249名母亲同意了。在1506名登记的婴儿中，1199名至少有一次眼部检查后活着出院，其中885名（74%）患有任何级别的ROP，349名（29%）患有高度（3-5）级ROP。我们将测试三个零假设：（1）。从胎盘组织中培养出微生物的婴儿与没有此类证据的同龄人面临相同的ROP风险;（2.）具有炎症胎盘组织学特征的婴儿与没有此类证据的同龄人具有相同的ROP风险;（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风险因素相关的ROP风险。我们将使用多变量回归建模技术来检验这些假设，以调整混杂因素。相关性：据国家眼科研究所称，早产儿视网膜病变（ROP）“是儿童视力丧失的最常见原因之一，可导致终身视力障碍和失明。“试图增加ROP的可预防原因的已知范围是至关重要的。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，这些过程可以通过干预措施有效地针对。

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.