The Male to Female Ratio in Treatment-Warranted Retinopathy of Prematurity

Abstract

Literature and anecdotal evidence suggest a relationship between male sex and retinopathy of prematurity (ROP). It is not known whether a difference, if present, is sex-related pathophysiologic predisposition or sex difference in meeting ROP screening criteria. To evaluate the association of sex with the development of treatment-warranted ROP. PubMed, Embase, and Web of Science databases were searched from 2000 to 2022. The search strategy used keywords including retinopathy of prematurity or ROP or retrolental fibroplasia and treatment or anti-VEGF or bevacizumab or ranibizumab or aflibercept or conbercept or laser or cryotherapy and gender or sex or male or female and medical subject headings terms. All studies reporting on treatment with anti-vascular endothelial growth factor, laser photocoagulation, and/or cryotherapy for ROP were identified. Studies reporting sex distribution in the treatment group were included in the meta-analysis. Exclusion criteria included case reports, case series of fewer than 10 treated patients, systematic reviews, conference abstracts, letters to the editor, animal studies, and non-English records. Two reviewers independently screened and extracted the data following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The proportions of treated male and female infants were combined using random-effects meta-analysis. Numbers and percentages of male and female infants treated for ROP. Of 11 368 identified studies, 316 met inclusion criteria, yielding a total of 31 026 treated patients. A higher percentage of male infants were treated for ROP (55% [95% CI, 0.54%-0.55%]), with low heterogeneity between studies (I2 = 34%; P < .001). Thirty-eight studies reported sex distribution in the screened population (170 053 patients; 92 612 [53%] male vs 77 441 [47%] female). There was no significant difference in the odds of receiving treatment between screened male and female infants (pooled odds ratio, 1.04 [95% CI, 0.91-1.18]; P = .67). More male infants are treated for ROP than female infants. This could be due to a known relative pathophysiological fragility of preterm male infants in addition to a difference in ROP screening rates, with more male infants meeting the criteria than female infants. These findings have implications for future studies and may prompt more careful clinical monitoring of male neonates.