Effect of enteral supplementation of DHA with or without ARA in preterm infants - a meta-analysis

Sep 29, 2026

This meta-analysis evaluated whether additional enteral docosahexaenoic acid (DHA) supplementation, with or without arachidonic acid (ARA), alters major neonatal intensive care unit morbidities in preterm infants when not given via formula or parenteral nutrition. Trials of infants born at ≤34 weeks gestational age or birth weight ≤2000 g were searched across major databases up to 9 June 2024. Eleven trials were included; BPD risk increased, while ROP, NEC, sepsis, IVH, PVL, and in-hospital mortality showed no significant benefit.

LanguageEnglish

CategoryResearch & Report

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Pages7

Reading Time18 min

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Abstract

Objective and design

Patients and interventions

Outcomes and results

Conclusions

Original research Effect of enteral supplementation of DHA with or without ARA in preterm infants: a meta-analysis Dan Dang , 1 Zhongyu Gao, 1 Chuan Zhang,2 Xin Mu, 1 Xiaoming Lv, 1 Hui Wu 1 ► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1136/archdischild-2024-](10.1136/archdischild-2024-)[ ](10.1136/archdischild-2024-)[327606](327606)) . 1Department of Neonatology, Children’s Medical Center, The First Hospital of Jilin University, Changchun, Jilin, China 2Department of Pediatric Surgery, Children’s Medical Center, The First Hospital of Jilin University, Changchun, China Correspondence to Dr Hui Wu; [wu](wuhui@jlu.edu.cn)[hui@jlu.edu.cn](wuhui@jlu.edu.cn) Received 29 June 2024 Accepted 21 March 2025 © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. To cite: Dang D, Gao Z, Zhang C, et al. Arch Dis Child Fetal Neonatal Ed Epub ahead of print: [please include Day Month Year] . doi:10 . 1136/archdischild- 2024-327606 ABSTRACT Objective This study aimed to assess whether additional enteral docosahexaenoic acid (DHA) supplementation, with or without arachidonic acid (ARA), influences morbidities diagnosed in the neonatal intensive care unit among preterm infants, excluding administration via formula or parenteral nutrition. Design and setting This meta-analysis involved a comprehensive search of the PubMed, Embase, Web of Science and Cochrane Library databases from their inception to 9 June 2024. Patients and interventions Randomised controlled trials focusing on the effects of enteral DHA with or without ARA in preterm infants born at ≤34 weeks gestational age or a birth weight ≤2000 g were included. Main outcomes and measures The main outcomes included in-hospital mortality, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotising enterocolitis (NEC), sepsis, intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL) . Results Eleven trials evaluating distinct adverse outcomes in preterm infants were incorporated. Of these, nine trials assessing enteral DHA supplementation with or without ARA indicated an increased risk of BPD with a relative risk of 1.11 (95% CI 1.00 to 1. 22) . Additionally, five trials assessing DHA supplementation without ARA showed an increased risk of BPD with a relative risk of 1.15 (95% CI 1.03 to 1. 28) . No significant effects were observed on the incidence of ROP, NEC, sepsis, IVH, PVLor in-hospital mortality. Conclusions and relevance Enteral supplementation of DHA with or without ARA did not demonstrate protective effects against major complications in preterm infants and even increased the risk of BPD. Further research is warranted to evaluate the necessity of DHA and ARA supplementation in this population. PROSPERO registration number CRD42024552578 . INTRODUCTION Preterm birth significantly impacts neonatal health, leading to adverse outcomes and placing a considerable burden on families and society.1 Due to their immaturity, preterm infants frequently encounter complications during hospitalisation, including bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotising enterocolitis (NEC), sepsis, intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL), substantially heightening the risk of adverse outcomes. Among the array of supportive interventions for preterm infants, optimising ex utero nutrition as a scientific substitute for in utero nutrient provision WHAT IS ALREADY KNOWN ON THIS TOPIC | ⇒ Premature birth disrupts the natural maternal supply of essential fatty acids, such as docosahexaenoic acid (DHA) and arachidonic acid (ARA), which are critical for the optimal development of preterm infants.
⇒ Preterm infants usually face a high risk of complications, and e

FAQs

What was the study objective in this meta-analysis?

To assess whether additional enteral DHA supplementation, with or without ARA, influences morbidities diagnosed in the neonatal intensive care unit among preterm infants.

Which studies and preterm infants were included?

Randomised controlled trials were included for preterm infants born at ≤34 weeks gestational age or with birth weight ≤2000 g.

What were the main findings about key outcomes such as BPD and ROP?

Enteral DHA supplementation with or without ARA increased the risk of bronchopulmonary dysplasia (BPD). No significant effects were observed for ROP, NEC, sepsis, IVH, PVL, or in-hospital mortality.

Sep 29, 2026

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