DHA Modulates Immune Response Associated with Preterm Birth

by | Feb 24, 2022 | 2021, DHA, Pregnancy and Lactation, Women's Health

Written by Chrystal Moulton, Staff Writer. 1000mg DHA supplementation improves gestational age at delivery by supporting IL-6 and sRAGE concentrations during pregnancy.

pregnancyDocosahexanoic acid or DHA is a highly researched fatty acid clinically shown to attenuate inflammatory response 1,2. During pregnancy and childbirth, low DHA serum levels have been associated with preterm birth 3,4. In a previous study, researchers demonstrated that 1000mg supplementation with DHA was associated with a lower risk of preterm birth (less than 37 weeks) and early preterm birth (less than 34 weeks) in women with low serum DHA 5. In the current study, the same researchers wanted to investigate whether specific inflammatory markers were modulated by DHA supplementation using data from the previous trial 6.

This study is a phase 3 clinical trial investigating a secondary hypothesis. Using data from the previous study (focused on the therapeutic dose of DHA which would lower the risk of preterm birth) 5, researchers investigated the effect of DHA supplementation on inflammatory makers associated with preterm birth at enrollment (baseline) and delivery (endpoint).

In the original trial, 1100 pregnant women were randomized to receive 2 capsules of algal oil (800mg DHA) in addition to prenatal vitamins (containing 200mg DHA) or 2 capsules of corn oil (0mg DHA) plus prenatal vitamins (200mg DHA) per day 5. Blood samples were taken at baseline (enrollment) and delivery (at time of birth). These samples were analyzed for fatty acids and immune markers, cytokines, and Receptor for Advanced Glycation End products or sRAGE. In total, 902 women provided samples needed for analysis at enrollment and delivery; however, only 890 of these were included in the final statistics due to missing information from 12 participants.

Researchers used an adaptive form of statistics called the Bayesian statistical modelling. This model was used to assess the effect of DHA supplementation on cytokine and sRAGE levels at enrollment vs. delivery within the high dose vs. low dose DHA groups. It was also used to assess gestational age at birth while accounting for confounders (race, ethnicity, BMI, smoking, DHA at enrollment, history of preeclampsia, and treatment). Data is reported as Bayesian credible intervals with posterior probabilities and posterior means. Therefore, data is interpreted as the likelihood that DHA supplementation is related to the inflammatory makers based on prior knowledge that DHA is associated with preterm birth.

Results showed that 1000mg supplementation with DHA was significantly associated with a longer gestational age at birth compared to 200mg DHA supplementation (posterior probability= 0.99). Higher concentrations of sRAGE at enrollment was associated with longer gestation age at birth as well (posterior probability= 0.99). Data related to preterm birth showed that lower baseline sRAGE increased the probability of experiencing preterm birth (posterior probability= 0.92). Also conversely, low sRAGE concentrations at birth reduced the odds of preterm birth (posterior probability= 0.002). Researchers also found that high concentrations of TNF-alpha and TNF-gamma at delivery were associated with a lower gestational age at birth (posterior probability= 0.07 and 0.06, respectively). When analyzing 1000mg vs. 200mg DHA supplementation effect on sRAGE and cytokines, sRAGE concentration had a significantly lower decrease while IL-6 concentration showed a significantly larger increase from baseline to delivery in women given high dose vs. low dose DHA supplementation (posterior probability= 0.84 and 0.99, respectively).

The study showed that 1000mg DHA supplementation supported IL-6 and sRAGE concentrations at a level that would support healthy delivery (i.e., post 37 weeks). Researchers noted the study limitation that there was more sRAGE (and cytokine) data missing for those born prematurely compared to the term births. They also suggested a prospective trial would be needed to further assess these relationships.

Source: Valentine, Christina J., Aiman Q. Khan, Alexandra R. Brown, Scott A. Sands, Emily A. Defranco, Byron J. Gajewski, Susan E. Carlson, Kristina M. Reber, and Lynette K. Rogers. “Higher-Dose DHA Supplementation Modulates Immune Responses in Pregnancy and Is Associated with Decreased Preterm Birth.” Nutrients 13, no. 12 (2021): 4248.

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

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Posted February 24, 2022.

Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.

References:

  1. Rogers LK, Valentine CJ, Keim SA. DHA supplementation: current implications in pregnancy and childhood. Pharmacol Res. Apr 2013;70(1):13-9. doi:10.1016/j.phrs.2012.12.003
  2. Rogers LK, Graf AE, Bhatia A, Leonhart KL, Oza-Frank R. Associations between maternal and infant morbidities and sRAGE within the first week of life in extremely preterm infants. PLoS One. 2013;8(12):e82537. doi:10.1371/journal.pone.0082537
  3. Kar S, Wong M, Rogozinska E, Thangaratinam S. Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic review and meta-analysis of randomized studies. European journal of obstetrics, gynecology, and reproductive biology. Mar 2016;198:40-46. doi:10.1016/j.ejogrb.2015.11.033
  4. Carlson SE, Colombo J, Gajewski BJ, et al. DHA supplementation and pregnancy outcomes. Am J Clin Nutr. Apr 2013;97(4):808-15. doi:10.3945/ajcn.112.050021
  5. Carlson SE, Gajewski BJ, Valentine CJ, et al. Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial. EClinicalMedicine. Jun 2021;36:100905. doi:10.1016/j.eclinm.2021.100905
  6. Valentine CJ, Khan AQ, Brown AR, et al. Higher-Dose DHA Supplementation Modulates Immune Responses in Pregnancy and Is Associated with Decreased Preterm Birth. Nutrients. Nov 26 2021;13(12)doi:10.3390/nu13124248