Association between sepsis and retinopathy of prematurity: a systematic review and meta-analysis

OBJECTIVE: To explore the association between sepsis and retinopathy of prematurity (ROP) in premature infants. DESIGN: A systematic review and meta-analysis. DATA SOURCES: We performed a systematic search of PubMed, the Cochrane Library and Embase from 1 January, 2000, to 1 January, 2018, with no language restrictions and reported the relationship between sepsis and ROP. ELIGIBILITY CRITERIA: Original observational studies, including cohort studies and case-control studies. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently completed the study selection and data extraction. The OR and corresponding 95% CI were used to measure the risk of sepsis in patients with ROP. The heterogeneity between studies was evaluated using Cochran’s Q test and the I(2) statistic. The Newcastle-Ottawa Scale was adopted to evaluate the quality of each of the included studies, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the quality of the evidence. RESULTS: Sixteen studies with a total sample size of 12 466 premature infants and 2494 cases of ROP were included in this meta-analysis. Adjusted analysis showed that sepsis was closely related to any stage of ROP (OR = 1.57, 95% CI 1.31 to 1.89) and severe stage of ROP (OR = 2.33, 95% CI 1.21 to 4.51) in premature infants, with 56.3% and 81.8% heterogeneity, respectively. Subgroup analyses showed that heterogeneity was obvious in prospective cohort studies (I(2) = 62.1%, p<0.001). In a sensitivity analysis, we found that removing any single study did not significantly change the overall effect value. The quality of the evidence was rated as low for both any stage of ROP and severe stage of ROP. CONCLUSIONS: Sepsis increases the risk of ROP in preterm infants. However, considering that all included studies are observational and causality can rarely be established, additional evidence is needed to substantiate this finding and provide advice for practice.