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.
| VanderVeen, Deborah K; Allred, Elizabeth N; Wallace, David K et al. (2016) Strabismus at Age 2 Years in Children Born Before 28 Weeks' Gestation: Antecedents and Correlates. J Child Neurol 31:451-60 |
| Holm, Mari; Msall, Michael E; Skranes, Jon et al. (2015) Antecedents and correlates of visual field deficits in children born extremely preterm. Eur J Paediatr Neurol 19:56-63 |
| Logan, J Wells; Allred, Elizabeth N; Fichorova, Raina N et al. (2014) Endogenous erythropoietin varies significantly with inflammation-related proteins in extremely premature newborns. Cytokine 69:22-8 |
| Lee, Jennifer W; McElrath, Thomas; Chen, Minghua et al. (2013) Pregnancy disorders appear to modify the risk for retinopathy of prematurity associated with neonatal hyperoxemia and bacteremia. J Matern Fetal Neonatal Med 26:811-8 |
| VanderVeen, Deborah K; Martin, Camilia R; Mehendale, Reshma et al. (2013) Early nutrition and weight gain in preterm newborns and the risk of retinopathy of prematurity. PLoS One 8:e64325 |
| Lee, Jennifer; Dammann, Olaf (2012) Perinatal infection, inflammation, and retinopathy of prematurity. Semin Fetal Neonatal Med 17:26-9 |
| Chen, Minghua L; Allred, Elizabeth N; Hecht, Jonathan L et al. (2011) Placenta microbiology and histology and the risk for severe retinopathy of prematurity. Invest Ophthalmol Vis Sci 52:7052-8 |
| Chen, Minghua; Citil, Ayse; McCabe, Frank et al. (2011) Infection, oxygen, and immaturity: interacting risk factors for retinopathy of prematurity. Neonatology 99:125-32 |
| Tolsma, Kristi Washburn; Allred, Elizabeth N; Chen, Minghua L et al. (2011) Neonatal bacteremia and retinopathy of prematurity: the ELGAN study. Arch Ophthalmol 129:1555-63 |
| Hauspurg, Alisse K; Allred, Elizabeth N; Vanderveen, Deborah K et al. (2011) Blood gases and retinopathy of prematurity: the ELGAN Study. Neonatology 99:104-11 |
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