Impact of Docosahexaenoic Acid Supplementation on Proinflammatory Cytokines Release and the Development of Necrotizing Enterocolitis in Preterm Neonates: A Randomized Controlled Study

Abstract Introduction Preterm neonates have under-developed immune-regulatory system; consequently, there is a risk for developing chronic inflammation. Necrotizing enterocolitis (NEC) is an acute devastating neonatal intestinal inflammatory disorder. Due to the obscure multifactorial etiology, early diagnosis and effective treatment of NEC are limited. Consequently, effective strategies in the prevention of NEC, including nutritional approaches, are critically needed. The current study was conducted to assess the potential immunomodulatory effect of Docosahexaenoic Acid (DHA) supplementation in preterm neonates at neonatal intensive care unit (NICU) and subsequently its effect on preventing or reducing NEC incidence. Methods This was a prospective randomized controlled study. A total of 67 neonates, with gestational age equal or less than 32 weeks at birth and weight less than or equal 1500 grams, were randomly assigned to either DHA group or the control group. Modified Bell’s staging criteria for NEC was used as an objective tool for diagnosis and staging of NEC. Levels of Interleukin 1 beta (IL-1β) were measured at baseline and after 10 days. Mortality and NICU length of stay (LOS) were also monitored. Results Thirty neonates of each group completed the study. A statistically significant difference was observed between the two groups regarding diagnosis and staging of NEC (p =0.0001). There was also a statistically significant difference between DHA group 22(73.3), 95% CI [55.9, 86.5] and the control group 8 (26.7), 95% CI [13.5, 44.1] in the percentage change in IL-1β levels (p =0.0001). A statistically significant association was found between IL-1 β change and NEC diagnosis (p = 0.001). NICU LOS was significantly lower among DHA group 21.63±6.67 compared to the control group 25.07±4.67 (p= 0.025). Mortality n (%) among the control group 4 (11.8) was higher than DHA group 3 (9.1), however, no significant difference was detected (p = 1.0). Conclusion Findings of this study suggest that enteral DHA supplementation can reduce NEC incidence in preterm neonates through its immunoregulatory effect that modulates production of regulatory cytokines. Trial registration registered at clinical trials.gov (NCT03700957), 6 October 2018.