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

Patricia Álvarez; David Ramiro-Cortijo; María Teresa Montes; Bárbara Moreno; María V Calvo; Ge Liu; Ana Esteban Romero; Marta Ybarra; Malaika Cordeiro; Marina Clambor Murube; Eva Valverde; Aurora Sánchez-Pacheco; Javier Fontecha; Robert Gibson; Miguel Saenz de Pipaon

doi:10.3389/fped.2022.947221

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

Front Pediatr. 2022 Aug 25:10:947221. doi: 10.3389/fped.2022.947221. eCollection 2022.

Authors

Patricia Álvarez¹, David Ramiro-Cortijo², María Teresa Montes¹, Bárbara Moreno¹, María V Calvo³, Ge Liu⁴, Ana Esteban Romero¹, Marta Ybarra¹, Malaika Cordeiro¹, Marina Clambor Murube⁵, Eva Valverde¹, Aurora Sánchez-Pacheco⁵, Javier Fontecha³, Robert Gibson^{6

7}, Miguel Saenz de Pipaon¹

Affiliations

¹ Department of Neonatology, La Paz University Hospital, Universidad Autónoma de Madrid, Madrid, Spain.
² Department of Physiology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
³ Food Lipid Biomarkers and Health Group, Instituto de Investigación en Ciencias de la Alimentación (CIAL, CSIC-UAM), Madrid, Spain.
⁴ South Australian Health and Medical Research Institute, SAHMRI Women and Kids, Adelaide, SA, Australia.
⁵ Department of Biochemistry, Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain.
⁶ SAHMRI Women and Kids, South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
⁷ School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, SA, Australia.

Abstract

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.

Keywords: ARA; DHA; emulsion; long-chain polyunsaturated fatty acids; oxylipins; single-nucleotide polymorphisms; supplementation.