Related Experiment Video
Updated: May 8, 2026
MicroRNA Expression Profiles of Human iPS Cells, Retinal Pigment Epithelium Derived From iPS, and Fetal Retinal Pigment Epithelium
Published on: June 24, 2014
Proteomic Profile in Retinopathy of Prematurity: A Secondary Analysis of the Mega Donna Mega Randomized Clinical
Pia Lundgren1,2, Hanna Danielsson3,4,5, Mohit B Panwar1
1The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Insights
A rapid increase in fibroblast growth factor 21 (FGF-21) in preterm infants is linked to severe retinopathy of prematurity (ROP). Early interventions targeting metabolic status may prevent ROP development.
Area of Science:
- Neonatal Medicine
- Ophthalmology
- Proteomics
Background:
- Severe retinopathy of prematurity (ROP) is a leading cause of vision loss in preterm infants.
- Early identification of biomarkers may enable preventive strategies against ROP.
- Proteomic profiling offers insights into complex disease development.
Purpose of the Study:
- To investigate longitudinal blood protein profiles in preterm infants.
- To identify early proteomic signatures associated with severe ROP.
- To assess the impact of arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation on these profiles.
Main Methods:
- Exploratory, post hoc analysis of the Mega Donna Mega (MDM) randomized clinical trial data.
- Targeted proteomics using Olink Proximity Extension Assay (538 analytes) on serum samples.
- Longitudinal analysis of protein profiles during the first postnatal month in extremely preterm infants (born <28 weeks GA).
Main Results:
- 109 of 538 proteins were associated with severe ROP in the first month of life.
- A rapid rise in fibroblast growth factor 21 (FGF-21) and tissue plasminogen activator (tPA) was strongly linked to severe ROP.
- Elevated FGF-21 in the first week correlated with lower GA, birth weight, enteral intake, and increased mechanical ventilation.
Conclusions:
- A fast increase in FGF-21 during early postnatal days is a significant predictor of severe ROP in extremely preterm infants.
- These findings suggest that interventions aimed at improving bioenergetic status could be crucial for ROP prevention.
- No association was found between AA/DHA supplementation and the observed proteomic profiles.
Importance:
Identifying early proteomic profiles in infants who develop severe retinopathy of prematurity (ROP) may reveal targets for preventive interventions to reduce retinal vessel loss and the subsequent risk of severe ROP.
Objective:
To assess early longitudinal profiles of blood protein levels in preterm infants with or without severe ROP and the effect of arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation.
Design, Setting, And Participants:
This was an exploratory, post hoc analysis of serum proteome profiles in preterm infants in the double-masked Mega Donna Mega (MDM) randomized clinical trial using targeted Olink Proximity Extension Assay proteomics covering 538 analytes. The setting was 3 university hospitals in Sweden and included extremely preterm infants born before 28 weeks of gestational age (GA), from 2016 to 2019. Data were analyzed from January to March 2025.
Exposures:
All infants received standard nutrition; additionally, half received enteral lipid supplementation with AA/DHA (100/50 mg/kg per day) from birth to term equivalent age.
Main Outcomes And Measures:
Longitudinal protein profiles during the first month of life were examined using mixed models for repeated measures, adjusted for GA, study center, and AA/DHA supplementation, and tested for the interaction between severe ROP (stage ≥3 and/or treated) and postnatal age.
Results:
A total of 177 extremely preterm infants (mean [SD] GA, 25.6 [1.4] weeks; 100 male [56.5%]) were included, of whom 50 (28.2%) developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life associated with severe ROP, proteins related to immune response, apoptotic processes, blood coagulation, and lipid metabolism. The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; β = 0.68; 95% CI, 0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; β = 0.21; 95% CI, 0.13-0.29; Q <.001) during the first postnatal days. The increase in serum FGF-21 level in the first week of life was associated with lower GA, lower birth weight, low enteral energy intake, and more days receiving mechanical ventilation. No association was observed between AA/DHA supplementation and the proteome.
Conclusions And Relevance:
In this post hoc exploratory analysis of data from the MDM randomized clinical trial, a fast rise in FGF-21 levels, a metabolic stress-induced hormone, during the first postnatal days was strongly associated with the development of severe ROP in extremely preterm infants. These findings suggest that early interventions improving bioenergetic status may help prevent severe ROP.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03201588.
