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Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial
Ann Hellström1, Anders K Nilsson1, Dirk Wackernagel2
1Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Insights
Enteral supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) significantly reduced severe retinopathy of prematurity (ROP) in extremely preterm infants. This fatty acid intervention offers a novel preventive strategy for ROP.
Area of Science:
- Neonatalogy
- Ophthalmology
- Nutritional Science
Background:
- Extremely preterm infants often experience deficiencies in arachidonic acid (AA) and docosahexaenoic acid (DHA).
- These deficiencies may contribute to preterm infant morbidities, including retinopathy of prematurity (ROP).
Purpose of the Study:
- To evaluate the efficacy of enteral fatty acid supplementation (AA and DHA) in reducing severe ROP in extremely preterm infants.
- To determine if supplementation from birth to 40 weeks' postmenstrual age impacts ROP incidence.
Main Methods:
- A multicenter randomized clinical trial (Mega Donna Mega trial) involving 206 extremely preterm infants (born <28 weeks' gestation).
- Infants received either enteral AA (100 mg/kg/d) and DHA (50 mg/kg/d) or standard care from birth to 40 weeks' postmenstrual age.
- Primary outcome was severe ROP (stage 3 and/or type 1); secondary outcomes included serum fatty acid levels and other preterm complications.
Main Results:
- Enteral AA:DHA supplementation reduced severe ROP by 50% compared to standard care (15.8% vs 33.3%, P=.02).
- Infants receiving AA:DHA supplementation showed significantly higher serum levels of both fatty acids.
- No significant differences were observed in rates of bronchopulmonary dysplasia, intraventricular hemorrhage, or sepsis between groups.
Conclusions:
- Enteral supplementation with AA and DHA is an effective strategy to decrease the incidence of severe ROP in extremely preterm infants.
- This supplementation leads to improved serum levels of essential fatty acids, suggesting enhanced nutritional status.
- AA:DHA supplementation represents a promising novel preventive approach for ROP in this vulnerable population.
Importance:
Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP).
Objective:
To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants.
Design, Setting, And Participants:
The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 28 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020.
Interventions:
Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age.
Main Outcomes And Measures:
The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth.
Results:
A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P < .001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died.
Conclusions And Relevance:
This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03201588.
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