In vitro Fertilisation and Prolonged Continuous Positive Airway Pressure are Associated with Treatment-Requiring Retinopathy of Prematurity in a Tertiary Referral Cohort: An Exploratory Clinical Epidemiology Study.

PURPOSE: To investigate the associations of in vitro fertilisation (IVF) conception and prolonged continuous positive airway pressure (CPAP) with treatment-requiring retinopathy of prematurity (ROP) among infants with established ROP referred to a tertiary vitreoretinal center.

METHODS

This retrospective exploratory referral-cohort study included 60 consecutive infants with established ROP evaluated at a tertiary retina center in Erbil, Iraq, between April 2023 and April 2025. The primary outcome was treatment-requiring ROP, defined as disease requiring laser photocoagulation, intravitreal anti-vascular endothelial growth factor therapy, or vitreoretinal surgery because of Type 1, aggressive, or Stage 4-5 ROP. The primary exposures were IVF conception and CPAP duration (>10 vs ≤10 days, including no CPAP). Associations were summarized using crude odds ratios (ORs), absolute risk differences with 95% confidence intervals (CIs), and two-sided Fisher's exact tests. Because of sparse data, complete outcome separation, overlap between IVF and prolonged CPAP, non-independence among twin observations, and incomplete neonatal covariate documentation, adjusted regression analyses were not presented.

RESULTS

Treatment-requiring ROP occurred in 17 of 20 IVF-conceived infants (85.0%) compared with 18 of 40 spontaneously conceived infants (45.0%), corresponding to a crude OR of 6.93 (95% CI, 1.75-27.43) and an absolute risk difference of 40.0% points (95% CI, 14.1-57.3; Fisher's exact P=0.0048). Treatment-requiring ROP occurred in 35 of 52 infants (67.3%) requiring CPAP for >10 days and in none of eight infants receiving no CPAP or CPAP for ≤10 days. The continuity-corrected descriptive OR was 34.49 (95% CI, 1.88-632.45), reflecting complete outcome separation and substantial statistical uncertainty. Three term infants with prolonged neonatal respiratory morbidity also developed treatment-requiring ROP. All findings were interpreted as exploratory associations within a selected referral population.

CONCLUSION

Among infants with established ROP referred to a tertiary vitreoretinal center, treatment-requiring disease occurred more frequently in IVF-conceived infants and in those requiring prolonged CPAP. However, these associations were strongly influenced by exposure overlap, sparse data, referral selection, and incomplete neonatal information, precluding reliable causal inference. The findings should therefore be regarded as hypothesis-generating and require confirmation in adequately powered prospective multicenter studies before informing screening strategies or clinical practice.