Comparative Effectiveness of Prophylactic Methods for the Prevention of Neonatal Ophthalmia: A Systematic Review

Abstract

Aims: This systematic review aims to evaluate the comparative effectiveness, safety profile, and antimicrobial coverage of the main topical prophylactic agents used for the prevention of ophthalmia neonatorum in newborns. The analysis includes povidone-iodine, erythromycin, silver nitrate, and tetracycline, focusing on their clinical performance, local tolerability, and applicability in different public health contexts. Study Design: Systematic literature review. Place and Duration of Study: Databases searched (PubMed, SciELO, LILACS, BVS, MEDLINE) between January 2015 and April 2025. Methodology: The review was conducted following PRISMA guidelines. Eligible studies included randomized clinical trials, observational comparative studies, and systematic reviews published from 2015 to 2025, involving neonates undergoing prophylactic ocular treatment for ophthalmia neonatorum. The main outcomes were incidence of infectious conjunctivitis, chemical conjunctivitis, and spectrum of antimicrobial action. Data extraction and quality assessment were performed independently by two reviewers, using the ROBIS and Jadad tools for methodological evaluation. Results: From 412 initial records, 19 studies met the inclusion criteria, totaling 9,287 neonates. Povidone-iodine 2.5% showed the best overall profile, with a significant reduction in infectious conjunctivitis and lower rates of chemical irritation. It also demonstrated the  broadest antimicrobial activity, including coverage against Neisseria gonorrhoeae, Chlamydia trachomatis, and hospital-associated pathogens. Erythromycin 0.5% remained effective against gonococcal infection but was less effective against chlamydia and associated with increasing bacterial resistance. Silver nitrate 1% showed limited efficacy and higher toxicity, while tetracycline 1% presented intermediate results with less robust supporting evidence. Cost-effectiveness and accessibility favored povidone-iodine in low-resource settings. Conclusion: Povidone-iodine 2.5% is the most effective and safe prophylactic option for   preventing neonatal ophthalmia, outperforming traditional alternatives such as erythromycin and silver nitrate. Its broad spectrum, low cost, and minimal side effects support its adoption as the preferred agent in national health protocols. Further multicenter trials and long-term follow-up studies are recommended to evaluate its impact in vulnerable neonatal subpopulations.