Length of Day during Early Gestation as a Predictor of Risk for Severe Retinopathy of Prematurity

Abstract

Purpose Fetal mice require light exposure in utero during early gestation for normal vascular development in the eye. Because angiogenic abnormalities in retinopathy of prematurity (ROP) are manifested in preterm infants, we investigated whether day length during early gestation was associated with severe ROP (SROP). Design Single-center, retrospective cohort study. Participants We included a total of 343 premature infants (401–1250 g birth weight [BW], from 1998–2002): 684 eyes (1 eye each of 2 patients excluded) with 76 eyes developing SROP, defined as (1) classic threshold ROP in zone I or II, (2) type 1 ROP in zone I, or (3) in a few eyes, type 1 ROP in posterior zone II that was treated. Methods For each infant, average day length (ADL) was calculated during different cumulative time periods and time windows after the estimated date of conception (EDC). Multiple logistic regression analysis (with generalized estimating equations to account for inter-eye correlation) was performed. Main Outcome Measures Association of ADL during early gestation with SROP. Results In a model evaluating all 684 eyes with 76 eyes developing SROP, BW, gestational age, multiple births, race, per capita income in the mother's residence ZIP code, and ADL during the first 90 days after the EDC were factors associated with the development of SROP. Each additional hour of ADL (90 days) decreased the likelihood of SROP by 28% (P = 0.015; odds ratio [OR], 0.72; 95% confidence interval [CI], 0.55–0.94). In a model evaluating the subset of 146 prethreshold ROP eyes with 76 eyes developing SROP, each additional hour of ADL during the first 105 days after the EDC decreased the likelihood of SROP by 46% (P = 0.001; OR, 0.54; 95% CI, 0.37–0.78). Time windows when ADL was most closely associated with SROP were 31 to 60 days and 61 to 90 days after the EDC for the all eyes and the prethreshold ROP eyes models, respectively. Conclusions Higher ADL during early gestation was associated with a lower risk for SROP and may imply a role for prophylactic light treatment during early gestation to decrease the risk of SROP. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Predictors for the Development of Referral-Warranted Retinopathy of Prematurity in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study

“…17,18,24,27 However, this study did not find multiple birth to be associated with the risk for RW-ROP. This lack of association was also found in a very large cohort of infants (N = 2105) in New Zealand.…”

“…This result is consistent with findings from large natural history cohort studies of infants in the Cryotherapy for Retinopathy of Prematurity Study, 17,18 the Early Treatment for Retinopathy of Prematurity Study, 24 and a few other large observational clinical studies. 27,28 …”

Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina

“…In humans, patients affected by total congenital cataract before 6 months of age show a 30%–35% decrease in cone-driven retinal function versus healthy controls up to 9 years following surgical removal of cataracts (Esposito Veneruso et al, 2017). Low light exposure during human gestation, as observed in northern climates, has also been shown to strongly correlate with the incidence of retinopathy of prematurity (Yang et al, 2013). Understanding the impacts of early light exposure may lead to novel treatments for multiple light-related disorders.…”

Genetic Variants Associated With Severe Retinopathy of Prematurity in Extremely Low Birth Weight Infants

“…36 Recently, it was found that mice in utero reared in the dark or lacking the gene encoding melanopsin, which is involved in certain ganglion cell responses to light, 37 developed vascular anomalies that could predispose to conditions like ROP. 38 Additional clinical evidence that higher average day length during early gestation was associated with lower risk of ROP 42 provides an additional link among light, ganglion cell maturation, retinal vascular development, and reduced risk of later ROP. There is strong clinical evidence of reduced circulating BDNF levels in severe ROP.…”