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

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 ≤2000g 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, PVL or 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.