Sepsis and Necrotizing Enterocolitis are Associated with Thinner Retinal Nerve Fiber Layer in Preterm Infants at 36 Weeks Postmenstrual Age

Abstract

Purpose : Neonatal insults from systemic diseases have been implicated in the pathway of impaired neurodevelopment in preterm infants. Thinner retinal nerve fiber layer (RNFL) assessed by optical coherence tomography (OCT) has been associated with poorer neurodevelopment in preterm infants, suggesting RNFL thickness may reflect the brain as a whole in preterm infants. However, it remains unknown if RNFL thickness can serve as a noninvasive biomarker for the impact of systemic diseases on the central nervous system in preterm infants. We aimed to investigate associations between systemic health factors and RNFL thickness in preterm infants.

Methods : The STudy of Eye imaging in Preterm infantS (BabySTEPS) prospectively enrolled infants eligible for retinopathy of prematurity screening based on standard guidelines. We imaged both eyes of these infants at 36 ± 1 weeks postmenstrual age (PMA) using a handheld OCT system at the bedside in the Duke intensive care nurseries. RNFL thickness of the right and left eyes was averaged for each infant. We evaluated associations between RNFL thickness and 27 systemic health factors using multivariable regression models.

Results : We included 83 infants with RNFL thickness measures in this study. Of the 83, 16 infants had sepsis or necrotizing enterocolitis (NEC).These events occurred before the OCT imaging (time interval = 50 ± 22 days). Among 27 systemic factors, infant weight at imaging and sepsis/NEC were independently associated with RNFL thickness. RNFL was 10.4 μm thinner in infants with sepsis/NEC than without sepsis/NEC (52.7±9.0 vs. 63.1±10.2 μm; P < 0.001). This difference remained statistically significant after adjustment for confounding variables (birth weight, birth weight percentile, gestational age, infant weight at OCT imaging, and growth velocity). A 250-g increase in infant weight at OCT imaging was associated with a 3.1 μm (95%CI = 2.1 to 4.2) increase in RNFL thickness (P < 0.001).

Conclusions : Low infant weight and sepsis/NEC were independently associated with thinner RNFL in preterm infants at 36 weeks PMA. To our knowledge, this study is the first to suggest that sepsis/NEC may affect retinal neurodevelopment. OCT-measured RNFL may offer a noninvasive biomarker to assess the negative impact of sepsis/NEC on the central nervous system in preterm infants.

This is a 2021 ARVO Annual Meeting abstract.