Higher-Dose DHA Supplementation Modulates Immune Responses in Pregnancy and Is Associated with Decreased Preterm Birth

Nutrients. 2021 Nov 26;13(12):4248. doi: 10.3390/nu13124248.


Pregnancy and parturition involve extensive changes in the maternal immune system. In our randomized, multi-site, double-blind superiority trial using a Bayesian adaptive design, we demonstrated that 1000 mg/day of docosahexaenoic acid (DHA) was superior to 200 mg/day in preventing both early preterm birth (less than 34 weeks' gestation) and preterm birth (less than 37 weeks' gestation). The goal of this secondary study is to compare the effects of 1000 mg/day versus 200 mg/day on maternal inflammation, a possible mechanism by which DHA may prevent preterm birth. Maternal blood samples were collected at enrollment (12-20 weeks' gestation) and at delivery. Red blood cell DHA levels were measured by gas chromatography, and plasma concentrations of sRAGE, IL-6, IL-1β, TNFα, and INFγ were measured by ELISA. Data were analyzed for associations with the DHA dose, gestational age at birth, and preterm birth (<37 weeks). Higher baseline and lower delivery levels of maternal sRAGE were associated with a greater probability of longer gestation and delivery at term gestation. Higher-dose DHA supplementation increased the probability of a smaller decrease in delivery sRAGE levels. Higher IL-6 concentrations at delivery were associated with the probability of delivering after 37 weeks, and higher-dose DHA supplementation increased the probability of greater increases in IL-6 concentrations between enrollment and delivery. These data provide a proposed mechanistic explanation of how a higher dose of DHA during pregnancy provides immunomodulatory regulation in the initiation of parturition by influencing sRAGE and IL-6 levels, which may explain its ability to reduce the risk of preterm birth.

Keywords: Bayesian adaptive design; DHA; IL-6; pregnancy; preterm birth; sRAGE.

Publication types

  • Equivalence Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antigens, Neoplasm / blood
  • Bayes Theorem
  • Dietary Supplements*
  • Docosahexaenoic Acids / administration & dosage*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Erythrocytes / chemistry
  • Female
  • Gestational Age
  • Humans
  • Immunity / drug effects*
  • Interferon-gamma / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Maternal Nutritional Physiological Phenomena / immunology*
  • Mitogen-Activated Protein Kinases / blood
  • Pregnancy
  • Premature Birth / prevention & control*
  • Prenatal Care / methods
  • Tumor Necrosis Factor-alpha / blood


  • Antigens, Neoplasm
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Docosahexaenoic Acids
  • Interferon-gamma
  • MOK protein, human
  • Mitogen-Activated Protein Kinases