Sex Differences in the Risk of Retinopathy of Prematurity: a Systematic Review, Frequentist and Bayesian Meta-analysis, and Meta-regression

Background: Retinopathy of prematurity (ROP) is generally considered to be more frequent in males than in females. However, it is not known whether sex differences in ROP affect all degrees of the condition, are global and have changed as neonatology has developed. We aimed to conduct a systematic review and meta-analysis of studies addressing sex differences in the risk of developing ROP.

Methods: PubMed/MEDLINE and Embase databases were searched. The frequentist, random-effects risk ratio (RR) and 95% confidence interval (CI) were calculated. Bayesian model averaged (BMA) meta-analysis was used to calculate the Bayes factors (BFs). The BF is the ratio of the probability of the data under the alternative hypothesis (H) over the probability of the data under the null hypothesis (H).

Results: We included 205 studies (867,252 infants). Frequentist meta-analysis showed a positive association between male sex and severe ROP (113 studies, RR = 1.14, 95% CI = 1.07-1.22) but no association with any ROP (144 studies, RR = 1.00, 95% CI = 0.96-1.03). BMA showed extreme evidence in favor of H for severe ROP (BF = 71,174) and strong evidence in favor of H for any ROP (BF = 0.05). The association between male sex and severe ROP remained stable over time and was present only in cohorts from countries with a high or high-middle sociodemographic index.

Conclusions: Our study confirms the presence of a male disadvantage in severe ROP but not in less severe forms of the disease. There are variations in the sex differences in ROP, depending on geographical location and sociodemographic level of the countries.