38Background and Aim: Retinopathy of prematurity (ROP) is a disorder of the retina of low-39 birth-weight preterm infants that potentially leads to blindness. Docosahexaenoic acid 40 (DHA), a component of fish oil, is protective in experimental models. Administration of 41 fish oil as part of parenteral nutrition has shown inconsistent results. We aimed to test the 42 effect of enteral DHA to prevent ROP development and/or severity, and to reduce hospital 43 stay. 44 Methods: This was a double-blind, parallel clinical-trial. Preterm infants (n = 110; 55 per 45 group) with birth weight <1500g but >1000g were recruited in a level 3 NICU. Infants were 46 randomized to receive 75 mg of DHA/kg/day (DHA-group) or high oleic sunflower oil 47 (control-group) for 14 days by enteral feeding. The effect of DHA was evaluated on any 48 stage of ROP, severe ROP (stage ≥3) incidence, and hospital stay. Groups were compared 49 with relative risk and 95% CI, Fisher's Exact, Student's t or Mann-Whitney U tests, as 50 appropriate. Logistic regression was applied to adjust for confounders.51Results: There was no difference between the DHA and control groups in ROP risk (RR for 52 DHA= 0.79; 95% CI, 0.49-1.27, P= 0.33). However, patients who received DHA showed 53 lower risk for stage 3 ROP than controls (RR for DHA= 0.66; 95% CI, 0.44-0.99, P= 0.03).
54After adjusting for confounders, enteral DHA decreased the risk of stage 3 ROP (OR adj. = 55 0.10; 95% CI, 0.011-0.886; P= 0.04). Hospital stay was not different between groups.
56Conclusion: Enteral DHA may reduce the incidence of stage 3 ROP. 57 58
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.
Necrotizing enterocolitis (NEC) is an inflammatory bowel disease and a leading cause of morbidity and mortality in preterm infants. In this study, a randomized double-blind parallel-group (1:1) trial was carried out in two neonatal intensive care units of two tertiary hospitals. Two hundred and twenty-five preterm newborns with an expected functional gastrointestinal tract were recruited and received an enteral dose of 75 mg of docosahexaenoic acid (DHA)/kg body weight or high-oleic sunflower oil daily for 14 days from the first enteral feed after birth. Confirmed NEC was evaluated with Bell’s scale from stage ≥ IIa. Two hundred and fourteen randomized infants were analyzed in terms of the intent-to-treat (DHA-group: n = 105; control-group: n = 109); data for two hundred infants were analysed per protocol. Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100; p = 0.007), with RR = 0.93 (95% CI 0.881 to 0.981), risk difference = −7%, (95% CI −12.00 to −1.99), and number needed-to-treat = 15 (95% CI 8.3 to 50). Intent-to-treat analysis showed a lower level of treatment failure in the DHA-group compared with the control-group (6/105 (6%) vs. 16/109 (15%); p = 0.03, RR = 0.905, (95% CI 0.826 to 0.991)). The results after multivariate-regression analysis remained significant. Adverse events (apart from the incidence of NEC) were not different between groups. A daily dose of DHA for 14 days starting with the first enteral feed may prevent NEC in preterm infants.
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