# Identifying neonatal hyperglycemia thresholds in preterm infants based on retinopathy of prematurity outcomes: proof-of-concept study

## TL;DR

This study identifies glucose thresholds in preterm infants that may predict severe retinopathy of prematurity, suggesting lower thresholds than current NICU standards.

## Contribution

Preliminary glycemic thresholds for retinopathy of prematurity are identified using mean blood glucose and glycated hemoglobin in preterm infants.

## Key findings

- Severe ROP cases were more common in transfused infants with the lowest gestational ages.
- Glycated hemoglobin (A1C) and mean blood glucose were significantly higher in infants with severe ROP.
- Predictive cutoffs of 5.66% A1C and 93.8 mg/dl mean glucose showed high positive predictive values.

## Abstract

Neonatal hyperglycemia significantly increases risk for retinopathy of prematurity (ROP) in preterm infants, independent of other major ROP risk factors. However, glucose thresholds predictive of ROP remain undefined. This prospective study explored two glycemic metrics—mean blood glucose and glycated hemoglobin [specifically, glycated fetal hemoglobin for non-transfused infants and a neonatal-adapted hemoglobin A1C assay for transfused infants]—to identify thresholds associated with severe ROP.

Infants born at gestational ages <30 weeks and hospitalized at DeVos Children's Hospital (September 2022–August 2024) were eligible. The final cohort included 98 infants. Blood glucose was monitored per clinical care, and glycated hemoglobin was measured on Day 30 using a research prototype assay. Eye exams were conducted per ROP protocol. Predictive thresholds for each biomarker were evaluated using AUC–ROC analysis.

Most cases of severe ROP occurred in the transfused participants, who represent the earliest gestational ages and sickest infants. Both glycated hemoglobin (A1C) and 30-day mean blood glucose were significantly higher in infants with severe ROP compared to counterparts with mild or no ROP. Both biomarkers demonstrated concordant positive predictive values of 94%. Predictive cutoffs were identified as 5.66% for A1C (p = 0.003) and 93.8 mg/dl for 30-day mean glucose (p < 0.001).

Severe ROP may represent a clinical outcome for defining neonatal glycemic thresholds. In this pilot study, preliminary cutoffs for two independent glycemic biomarkers are lower than current NICU intervention criteria; further investigation is needed to potentially refine glucose strategies for ROP mitigation.