Randomized controlled trial of early arachidonic acid and docosahexaenoic acid enteral supplementation in very preterm infants

[Objective]: To evaluate changes in blood long-chain polyunsaturated fatty acid (LCPUFA) and oxylipin concentrations in very preterm infants from birth to 36 weeks’ postmenstrual age (WPA) after providing an emulsified arachidonic acid (ARA):docosahexaenoic acid (DHA) supplement at two different concentrations.[Study design]: This prospective, randomized trial assigned infants to receive a supplement (1) 80:40 group (80 mg/kg/day ARA and 40 mg/kg/day DHA, n = 9) or (2) 120:60 group (120 mg/kg/day ARA and 60 mg/kg/day DHA, n = 9). Infants received supplement daily from birth until 36 WPA. At baseline, 21 days of life and 36 WPA, the LCPUFAs were measured in plasma by gas chromatography/mass spectrophotometry. Additionally, LCPUFAs and oxylipins were analyzed in whole blood by ultra-high-performance liquid chromatography-tandem mass spectrometry. Furthermore, a sample of oral mucosa was obtained to analyze single-nucleotide polymorphism located in the FADS1 gene by PCR.[Results]: Gestational age was similar between groups (80:40 = 28+6 [27+3; 30+3] completed weeks+days; 120:60 = 29+6 [27+3; 30+5] completed weeks+days, p = 0.83). At 36 WPA, the change in plasma ARA was significantly different between groups (80:40 group = 0.15 [−0.67; 0.69] %nmol, 120:60 = 1.68 [1.38; 3.16] %nmol, p = 0.031). In whole blood, the levels of ARA-derived oxylipins (5-, 8-, 9-, 11-, 15-HETE and 8,9-EET) and EPA-derived oxylipins (18-HEPE) significantly increase from baseline to 36 WPA in the 120:60 group than the 80:40 group.[Conclusion]: Supplementation at high doses (120:60 mg/kg/day) increased levels of ARA, and EPA- and ARA-derived oxylipins compared to low doses (80:40 mg/kg/day). Differences were detected in EPA metabolites without a significant increase in plasma DHA.This article was supported by the 20th National Grants for Research in Life Sciences 2021/2021 from Ramón Areces Foundation (Spain), the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) networking grant 2021, and Spanish Programs for the generation of Knowledge and Scientific and Technological strengthening of the system and oriented to the challenges of Society (PID2020-119084RB-C21 and PID2020-114821RB-I00 funded by MCIN/AEI/10.13039/501100011033) from the Ministry of Science and Innovation (Spain).Peer reviewe