Enteral long-chain polyunsaturated fatty acids and necrotizing enterocolitis: A systematic review and meta-analysis

Belal N Alshaikh; Adriana Reyes Loredo; Kamran Yusuf; Ahmed Maarouf; Tanis R Fenton; Sarfaraz Momin

doi:10.1016/j.ajcnut.2023.01.007

Enteral long-chain polyunsaturated fatty acids and necrotizing enterocolitis: A systematic review and meta-analysis

Am J Clin Nutr. 2023 May;117(5):918-929. doi: 10.1016/j.ajcnut.2023.01.007. Epub 2023 Apr 19.

Authors

Belal N Alshaikh¹, Adriana Reyes Loredo², Kamran Yusuf³, Ahmed Maarouf², Tanis R Fenton⁴, Sarfaraz Momin³

Affiliations

¹ Neonatal 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. Electronic address: balshaik@ucalgary.ca.
² Neonatal 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.
³ Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary AB, Canada.
⁴ Community Health Sciences, Institute of Public Health, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary AB, Canada; Nutrition Services, Alberta Health Services, Calgary AB, Canada.

PMID: 37137615
DOI: 10.1016/j.ajcnut.2023.01.007

Abstract

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.

Keywords: arachidonic acid; docosahexaenoic acid; fish oil; preterm infants.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Dietary Supplements
Enterocolitis, Necrotizing* / prevention & control
Fatty Acids, Unsaturated
Humans
Infant
Infant, Newborn
Infant, Premature
Infant, Premature, Diseases*
Infant, Very Low Birth Weight

Substances

Fatty Acids, Unsaturated