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High-dose docosahexaenoic acid for bronchopulmonary dysplasia severity in very preterm infants: a collaborative
Isabelle Marc1, Pascal M Lavoie2, Thomas R Sullivan3
1Department of Pediatrics, CHU de Québec-Université Laval, Québec city, Quebec, Canada.
Insights
High-dose docosahexaenoic acid (DHA) supplementation in very preterm infants did not significantly increase the risk of severe bronchopulmonary dysplasia (BPD). This meta-analysis found no significant association between DHA and BPD severity or other neonatal morbidities.
Area of Science:
- Neonatal Medicine
- Pediatric Pulmonology
- Nutritional Science
Background:
- High-dose docosahexaenoic acid (DHA) omega-3 supplementation in very preterm infants may enhance neurodevelopment.
- Concerns exist regarding a potential increased risk and severity of bronchopulmonary dysplasia (BPD) with DHA supplementation.
- Heterogeneity in BPD definitions across trials complicates evidence interpretation.
Purpose of the Study:
- To determine if neonatal enteral high-dose DHA supplementation is associated with severe BPD in very preterm infants.
- Utilized an individual participant data meta-analysis of randomized controlled trials (RCTs).
- Mimicked placental DHA transfer levels.
Main Methods:
- Included RCTs of infants born <29 weeks gestational age (GA) comparing high-dose DHA with placebo.
- Defined severe BPD as requiring high-flow nasal cannula, noninvasive positive airway pressure, or mechanical ventilation at 36 weeks postmenstrual age.
- Employed a one-stage meta-analysis approach for outcome associations.
Main Results:
- Two RCTs (N=1801) were analyzed; severe BPD occurred in 34.4% of the DHA group vs. 31.9% of the placebo group (RR 1.06; P=0.36).
- No significant association was found between DHA and death or severe BPD (RR 1.05; P=0.41).
- Limited evidence of heterogeneity for BPD-related outcomes.
Conclusions:
- Neonatal enteral high-dose DHA supplementation was not significantly associated with an increased risk of severe BPD in very preterm infants.
- No significant associations were observed for other neonatal outcomes.
- Findings suggest DHA supplementation is safe regarding BPD risk in this population.
Background:
Neonatal supplementation with high-dose docosahexaenoic acid (DHA) omega-3 may benefit neurodevelopment in very preterm infants, but concerns remain regarding a potential increased risk and severity of bronchopulmonary dysplasia (BPD). However, the interpretation of evidence on the effect of DHA on severe BPD is challenging because of the heterogeneity in the BPD definitions used across trials.
Objectives:
This study aims to determine whether, compared with placebo, neonatal enteral supplementation with high-dose DHA, mimicking placental transfer, is associated with severe BPD in very preterm infants using an individual participant data meta-analysis of randomized controlled trials (RCTs).
Methods:
RCTs were eligible if recently conducted in infants born with gestational age (GA) <29 wk and compared enteral supplementation with high-dose DHA alone with a placebo. Using a harmonized data set, the primary outcome of severe BPD was defined as the need for "high-flow" nasal cannula >2 L/min, noninvasive positive airway pressure, or invasive mechanical ventilation at 36 wk postmenstrual age. Secondary outcomes (N = 15) included death, "death or severe BPD," ordinal BPD severity grade, and common neonatal morbidities. Associations between high-dose DHA and outcomes were estimated using a one-stage meta-analysis approach.
Results:
Two RCTs were identified in a systematic review (searched up to August 1, 2022; N = 2304) that met inclusion criteria (N = 1801; 904 DHA and 897 placebo; GA 26.7 ± 1.5 wk). Severe BPD in survivors occurred in 290/843 (34.4%) infants in the DHA group and 268/841 (31.9%) infants in the placebo group {relative risk [RR], 1.06 [95% confidence interval (CI): 0.93, 1.21]; P = 0.36}. DHA was not associated with "death or severe BPD" [RR, 1.05 (95% CI: 0.94, 1.17); P = 0.41], the ordinal severity grade [odds ratio for a more severe grade, 1.20 (95% CI: 0.998, 1.45); P = 0.053], or other neonatal outcomes. There was limited evidence of heterogeneity for BPD-related outcomes.
Conclusions:
Neonatal enteral supplementation with high-dose DHA was not significantly associated with severe BPD in very preterm infants.
Trial Registration Number:
This study was registered at clinicaltrials.gov as NCT05915806, https://clinicaltrials.gov/study/NCT05915806.
Meta-Analysis Registry Number And Website:
PROSPERO, CRD42023431063, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=431063.
