Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study

Abstract

Background: Neonates undergoing surgery are at risk for uncontrolled inflammatory response and adverse clinical outcomes. Docosahexaenoic acid (DHA) ameliorates inflammation, improving clinical outcomes. However, its effect has not been evaluated in neonates undergoing surgery. We evaluated the effect of DHA on markers of inflammation and clinical outcomes in neonates undergoing surgery. Methods: A double-blind clinical trial evaluated the effect of enteral DHA (DHA group) versus sunflower oil (SO group) perioperatively administered in neonates scheduled for cardiovascular surgery. Inflammation was evaluated by percentage of cells⁺ for cytokines and CD69 in mononuclear cells at baseline, 24 h and 7 days post surgery. Clinical outcomes measured were sepsis, organ dysfunctions (ODs), length of stay in intensive care and bleeding. Repeated measures analysis of variance and logistic regression were applied. Results: Sixteen neonates received DHA and 18 received SO. Cells⁺ from neonates in the DHA group showed an early increase in receptor antagonist of interleukin (IL)-1⁺ (IL-1ra⁺) and IL-10⁺ and a late decrease in IL-6⁺. IL-1β⁺ and IL-10⁺ changes were different between groups. After adjusting for confounders, less cells from DHA group were IL-1β⁺, IL-6⁺, IL-1ra⁺ and IL-10⁺. DHA group presented less sepsis, ODs and shorter stay, but no difference in CD69⁺CD4⁺ cells or bleeding between groups. Conclusions: Administration of enteral DHA ameliorates markers of inflammation and improves clinical outcomes in surgical neonates.

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery

“…DHA may reach 1% of total fatty acids in human milk at the high normal levels; considering that it contains a lipid concentration of 41.3 g/l, breastfed infants with an average intake of 180 ml/kg/day would then receive ∼ 75 mg of DHA/kg/day physiologically [39] . Lien [39] and Makrides and Uauy [40] , and our group [17,27] reported that DHA at this dose does not cause adverse events; in addition, our ITT analysis on mortality also showed no difference between groups. Therefore, this DHA dose may be adequate for therapeutic purpose in neonates with additional beneficial impact on those neonates who did not receive human milk.…”

“…This review also reported a drug reduction in adults with inflammatory bowel disease and dysmenorrhea, with a higher beneficial effect with longer time of supplementation. Our findings are relevant because an acute and enteral administration of DHA may be an affordable strategy to obtain the modulation of the inflammatory response [17] , probably resulting in a reduction of analgesic need if a prolonged administration of DHA was not possible before surgery in neonates.…”

“…In fact, previous results from present sample of neonates who received DHA, demonstrated lower positive mononuclear cells to intracellular cytokines interleukin (IL)-1β, IL-6 after adjusting for confounders, indicating lower inflammatory response. They also presented lower development of organ dysfunctions and 4 days shorter length of NICU stay [17] . This is relevant because pro-inflammatory cytokines IL-1β, IL-6 and tumor necrosis factor-α (TNF-α) induce pain and hyperalgesia [18] .…”

“…A random numbers table was used to assign the treatment group, and they were placed into sealed opaque envelopes Bernabe-Garcia et al 152 consecutively numbered by one researcher who did not participate in patient recruitment. The daily dose was administered in 2 fractions by morning and evening through enteral feeding prior to formula or human milk feeding, stating 2 days before surgery and continued for 6 days after surgery, as was previously reported [17].…”

Impact of Docosahexaenoic acid supplementation on proinflammatory cytokines release and the development of Necrotizing enterocolitis in preterm Neonates: A randomized controlled study

“…Similarly, enteral DHA supplementation of preterm and term infants with confirmed sepsis, for 14 days resulted in an attenuation in IL-1β levels and a less severe course of sepsis ( López-Alarcón et al, 2012 ). Findings of an intervention study also revealed that enteral administration of DHA regulates the pro- and anti-inflammatory cytokines levels ( Bernabe-Garcia et al, 2016 ).…”