Essential Fatty Acid Supplementation and Early Inflammation in Preterm Infants: Secondary Analysis of a Randomized Clinical Trial

Neonatology. 2023;120(4):465-472. doi: 10.1159/000530129. Epub 2023 Apr 28.

Abstract

Introduction: Postnatal inflammation is associated with increased mortality and adverse outcomes in preterm infants. The essential fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) are precursors of lipid mediators with a key role in resolving inflammation. Our aim was to investigate the effect of ARA and DHA supplementation on systemic inflammation in very preterm infants and to identify clinical factors associated with early inflammation.

Methods: Secondary analysis of data from a randomized clinical trial (ImNuT study). Infants with gestational age (GA) less than 29 weeks were randomized to receive a daily enteral supplement with ARA 100 mg/kg and DHA 50 mg/kg (ARA:DHA group) or MCT oil (control group) from the second day of life to 36 weeks postmenstrual age. ARA, DHA, and four proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were analyzed in repeated dried blood samples from birth to day 28 and the area under the curve (AUC) for each variable was calculated.

Results: The intention to treat population included 120 infants with mean (SD) GA 26.4 (1.7). The ARA:DHA group had significantly lower IL-6 levels from day 3 to day 28 compared to the control group, mean difference AUC log10 (95% CI): 0.16 (0.03-0.30) pg/mL, p = 0.018. There was no correlation between ARA or DHA blood concentrations and cytokine levels. Having a low gestational age was independently associated with increased levels of all cytokines during the first 4 weeks of life.

Conclusions: Enhanced supplementation with ARA and DHA may modulate inflammation in very preterm infants.

Keywords: Inflammation; LCPUFA; Nutrition; Premature infant.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acid
  • Cytokines
  • Dietary Supplements
  • Docosahexaenoic Acids
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature*
  • Interleukin-6*

Substances

  • Interleukin-6
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • Cytokines

Grants and funding

The study was sponsored by funding from the Research Council of Norway, with additional contribution from public foundations the South-East Norway Regional Health Authority (Helse Sør-Øst RHF) and Barnestiftelsen, Oslo University Hospital. DSM Nutritional Products Inc. sponsored the investigational nutrition product, Formulaid™. This was an investigator-initiated study. The DSM Nutritional Products Inc. had no role in the design or conduct of the study.