Chorioamnionitis as a Risk Factor for Retinopathy of Prematurity: A Systematic Review and Meta-Analysis

Abstract

Background: The role of chorioamnionitis (CA) in the development of retinopathy of prematurity (ROP) has not been well established. Objective: To conduct a systematic review and meta-analysis of the association between CA and ROP in preterm infants. Data Sources: The authors searched MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials and PubMed, reviewed reference lists of relevant articles, abstracts and conference proceedings (Society for Pediatric Research, European Society for Paediatric Research 1990-2012), sought results of unpublished trials, and contacted the primary authors of relevant studies. Study Selection: Studies were included if they had a comparison group, examined preterm infants, and reported primary data that could be used to measure the association between exposure to CA and the development of ROP. Data Extraction: Two reviewers independently screened the search results, applied inclusion criteria and assessed methodological quality using the Newcastle-Ottawa Scale. One reviewer extracted data and a second reviewer checked data extraction. Summary relative risks (RRs) were calculated using a random effects model. Data Synthesis: We identified 1,249 potentially relevant studies from the electronic databases. Twenty-seven studies involving 10,590 preterm neonates with 2,562 cases of ROP were included. Taking into account all included studies without adjusting for gestational age (GA), CA was significantly associated with ROP (any stage) [summary RR 1.33 (95% CI 1.14-1.55, I² = 77%, p_{heterogeneity} < 0.0001)], and a borderline significant association was observed for severe ROP (stage ≥3) [summary RR 1.27 (95% CI 0.99-1.63, I² = 74%, p_{heterogeneity} < 0.0001)]. There was no publication bias with Begg's test. However, subgroup analysis of studies adjusting for GA showed no significant association on CA with ROP [summary RR 0.98 (95% CI 0.77-1.26, I² = 0%, p_{heterogeneity} = 0.89)]. Conclusion: Unadjusted analyses showed that CA was significantly associated with ROP (any stage) as well as with severe ROP (stage ≥ 3). However, the association disappeared on analysis of studies adjusting for GA. Hence, CA cannot be definitively considered as a risk factor for ROP, and further studies should adjust for potential confounding factors and report results by stage to clarify the association with severe ROP.

Chorioamnionitis appears not to be a Risk Factor for Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis

“…Previous meta-analyses on the relationship between CA and BPD10, cerebral palsy6, or ROP13 showed that the positive association observed with unadjusted data was significantly reduced, or became non-significant, when adjusted data were pooled. The differences that we observed herein are even more marked since the significant positive association between CA and PDA became a significant negative association when only adjusted data were taken into consideration.…”

“…Moreover, CA may induce a fetal inflammatory response which is thought to play an important role in short- and long-term morbidity after very preterm birth12345678910111213. In recent years, numerous observational studies have been summarized in several meta-analyses attempting to clarify the association between CA and neonatal brain injury11, cerebral palsy6, bronchopulmonary dysplasia (BPD)710, necrotizing enterocolitis (NEC)12, and retinopathy of prematurity (ROP)13, among other adverse outcomes of prematurity. Nevertheless, since CA is a major risk factor for spontaneous preterm birth, the GA-independent contribution of CA to mortality and morbidity of preterm infants is very difficult to assess3.…”

Role of macular xanthophylls in prevention of common neovascular retinopathies: Retinopathy of prematurity and diabetic retinopathy

“…Higher rates of ROP have been demonstrated in infants born to mothers with histological and clinical chorioamnionitis relative to mothers without chorioamnionitis [54,55]. Chorioamnionitis and the accompanying fetal inflammatory response syndrome may increase the risk of ROP by directly sensitizing the developing retina to oxygen-induced changes in VEGF availability and subsequent vascular development and/or by causing systemic hypotension resulting in retinal hypoperfusion/ischemia [37,56]. These clinical data indicate a need for experimental studies to elucidate the pathophysiological mechanisms underlying the increased risk of ROP in infants exposed to chorioamnionitis [56].…”

“…Chorioamnionitis and the accompanying fetal inflammatory response syndrome may increase the risk of ROP by directly sensitizing the developing retina to oxygen-induced changes in VEGF availability and subsequent vascular development and/or by causing systemic hypotension resulting in retinal hypoperfusion/ischemia [37,56]. These clinical data indicate a need for experimental studies to elucidate the pathophysiological mechanisms underlying the increased risk of ROP in infants exposed to chorioamnionitis [56]. Although the role of inflammation in ROP has been poorly investigated, some evidence in humans points to its contribution in ROP.…”

Current Management and Long-term Outcomes Following Chorioamnionitis

“…Retrospective studies must consider this relationship when evaluating the association with morbidity, as preterm delivery itself is an independent risk factor for many of the morbidities that are associated with chorioamnionitis, and without careful analysis can overestimate the association of chorioamnionitis with various morbidities 33,34 . A result of this relationship between chorioamnionitis and preterm delivery is a synergistic exacerbation of neonatal morbidity, further incentivizing the importance of diagnosis and treatment of chorioamnionitis 55 .…”