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

Abstract

ImportanceLiterature 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.ObjectiveTo evaluate the association of sex with the development of treatment-warranted ROP.Data SourcesPubMed, 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.Study SelectionAll 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.Data Extraction and SynthesisTwo 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.Main Outcomes and MeasuresNumbers and percentages of male and female infants treated for ROP.ResultsOf 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).Conclusions and RelevanceMore 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.

Sex differences in the risk of retinopathy of prematurity: a systematic review, frequentist and Bayesian meta-analysis, and meta-regression

“…To our knowledge, this is the most comprehensive meta-analysis to date on sex differences in the development of ROP. Our data confirm the previous observations that the more severe forms of ROP are more common in preterm boys than in preterm girls [ 9 ]. However, when the study focused on any ROP, we did not observe sex differences.…”

“…Very recently, Bahmani et al conducted a meta-analysis of risk factors for any ROP and found no sex differences when they pooled the 121 studies that reported these data [ 8 ]. In addition, Hoyek et al performed a meta-analysis of the male-to-female ratio in preterm infants requiring treatment for ROP [ 9 ]. They included 316 studies and found that a higher percentage of boys than girls were screened and treated for ROP [ 9 ].…”

“…In addition, Hoyek et al performed a meta-analysis of the male-to-female ratio in preterm infants requiring treatment for ROP [ 9 ]. They included 316 studies and found that a higher percentage of boys than girls were screened and treated for ROP [ 9 ]. These findings confirm the existence of a male disadvantage in the incidence of severe ROP.…”

Impact of premature rupture of membranes on clinical outcomes of extremely premature infants: A propensity score matching study

“…Preterm birth and postpartum oxygen therapy have been reported to be closely related to the occurrence of ROP, but many studies have proposed that the pathogenesis of ROP may exist in utero , and the prenatal intrauterine environment may be related to the occurrence of severe ROP ( 30 , 31 ), including maternal preeclampsia ( 32 ), chorioamnionitis ( 33 ), and smoking ( 34 ). In addition, gender has also been shown to be associated with the occurrence of severe ROP ( 35 ). At present, there are conflicting reports about the relationship between PROM and ROP.…”

Impact of sex, race, and social determinants of health on neonatal outcomes

“…The incidence of retinopathy of prematurity among infants born between 22 and 28 weeks gestational age remains 12.8% ( 69 ). Males are more likely to be screened for Retinopathy of Prematurity (ROP), and a higher percentage of male infants are treated for ROP as compared to female infants (55%, 95% CI: 52–58%) ( 43 ). Males are also at higher risk of having severe ROP (RR: 1.14, 95% CI: 1.07–1.22) ( 36 , 44 ), suggesting that males are at higher risk of progression of ROP.…”