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Enteral long-chain polyunsaturated fatty acids and necrotizing enterocolitis: A systematic review and meta-analysis
Belal N Alshaikh1, Adriana Reyes Loredo1, Kamran Yusuf2
1Neonatal Nutrition and Gastroenterology Program, Cumming School of Medicine, University of Calgary, Calgary AB, Canada; Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary AB, Canada.
Insights
Supplementation with docosahexaenoic acid (DHA) alone may increase necrotizing enterocolitis (NEC) risk in preterm infants. Adding arachidonic acid (ARA) with DHA appears to reduce NEC risk, highlighting the importance of balanced supplementation.
Area of Science:
- Neonatal nutrition
- Pediatric gastroenterology
- Critical care medicine
Background:
- Preterm infants face a risk of long-chain polyunsaturated fatty acid (LCPUFA) deficiency.
- High-dose docosahexaenoic acid (DHA) supplementation in preterm infants shows potential cognitive benefits but raises concerns about neonatal morbidities.
- Controversy exists regarding DHA supplementation due to an imbalanced ratio with arachidonic acid (ARA).
Approach:
- A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted.
- Searched major databases (PubMed, MEDLINE, EMBASE, Cochrane, CINHAL) up to July 2022.
- Evaluated enteral LCPUFA supplementation (DHA alone vs. DHA with ARA) in very preterm infants, assessing necrotizing enterocolitis (NEC) risk.
Key Points:
- Fifteen RCTs involving 3963 infants found DHA-alone supplementation increased NEC risk (RR: 1.56).
- Concurrent ARA supplementation with DHA significantly reduced NEC risk (aRR: 0.42).
- Maternal DHA supplementation also showed an increased NEC risk (RR: 1.92).
Conclusions:
- Enteral DHA supplementation alone may elevate NEC risk in very preterm infants.
- Concurrent ARA supplementation should be considered when administering DHA to preterm infants.
- Balanced LCPUFA supplementation is crucial for optimizing neonatal outcomes and minimizing morbidities.
Background:
Preterm infants are at risk of long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Recent studies on high-dose DHA; n-3 LCPUFA in preterm infants suggested potential positive effects on cognitive outcomes but raised concerns about some increased neonatal morbidities. These studies and recent recommendations for DHA supplementation generated controversy owing to the lack of balance between DHA and arachidonic acid (ARA; n-6 LCPUFA).
Objectives:
To identify the effect of enteral supplementation of DHA, with and without ARA, on necrotizing enterocolitis (NEC) in very preterm infants.
Methods:
A systematic review of randomized and controlled trials compared enteral LCPUFAs with placebo or no supplementation in very preterm infants. We searched PubMed, Ovid-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINHAL databases from inception to July 2022. Data were extracted in duplicate using a structured proforma. A meta-analysis and metaregression with random-effects models were used. The interventions evaluated were DHA alone vs. that combined with ARA, source of DHA, dose, and supplement delivery methods. Methodological qualities and risk of bias were assessed using the Cochrane risk-of-bias tool.
Results:
Fifteen randomized clinical trials (RCTs) included 3963 very preterm infants with 217 cases of NEC. Supplementation with DHA alone increased NEC (2620 infants; RR: 1.56; 95% CI: 1.02, 2.39) with no evidence of heterogeneity (I2 = 0.0%, P = 0.46). Multiple metaregression revealed significant reduction in NEC when ARA was supplemented with DHA (aRR 0.42; 95% CI: 0.21, 0.88). The source of DHA, dose, and feeding type revealed no associations with NEC. Two RCTs supplemented high-dose DHA to lactating mothers. There was a significant increase in risk of NEC with this approach (1148 infants; RR: 1.92; 95% CI: 1.02, 3.61) with no evidence of heterogeneity (I2 = 0.0, P = 0.81).
Conclusions:
Supplementation with DHA alone may increase risk of NEC. Concurrent supplementation with ARA needs to be considered when adding DHA to preterm infants' diet.
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