Plasma oxylipins and unesterified precursor fatty acids are altered by DHA supplementation in pregnancy: Can they help predict risk of preterm birth?

Abstract

A B S T R A C TBackground: Oxidized derivatives of polyunsaturated fatty acids, collectively known as oxylipins, are labile bioactive mediators with diverse roles in human physiology and pathology. Oxylipins are increasingly being measured in plasma collected in clinical studies to investigate biological mechanisms and as pharmacodynamic biomarkers for nutrient-based and drug-based interventions. Whole blood is generally stored either on ice or at room temperature prior to processing. However, the potential impacts of delays in processing, and of temperature prior to processing, on oxylipin concentrations are incompletely understood. Objective: To evaluate the effects of delayed processing of blood samples in a timeframe that is typical of a clinical laboratory setting, using typical storage temperatures, on concentrations of representative unesterified oxylipins measured by liquid chromatography-tandem mass spectrometry. Design: Whole blood (drawn on three separate occasions from a single person) was collected into 5 mL purpletop potassium-EDTA tubes and stored for 0, 10, 20, 30, 60 or 120 min at room temperature or on wet ice, followed by centrifugation at 4°C for 10 min with plasma collection. Each sample was run in duplicate, therefore there were six tubes and up to six data points at each time point for each oxylipin at each condition (ice/room temperature). Representative oxylipins derived from arachidonic acid, docosahexaenoic acid, and linoleic acid were quantified by liquid chromatography tandem mass spectrometry. Longitudinal models were used to estimate differences between temperature groups 2 h after blood draw. Results: We found that most oxylipins measured in human plasma in traditional potassium-EDTA tubes are reasonably stable when stored on ice for up to 2 h prior to processing, with little evidence of auto-oxidation in either condition. By contrast, in whole blood stored at room temperature, substantial time-dependent increases in the 12-lipoxygenase-derived (12-HETE, 14-HDHA) and platelet-derived (thromboxane B2) oxylipins were observed. Conclusion: These findings suggest that certain plasma oxylipins can be measured with reasonable accuracy despite delayed processing for up to 2 h when blood is stored on ice prior to centrifugation. 12-Lipoxygenaseand platelet-derived oxylipins may be particularly sensitive to post-collection artifact with delayed processing at room temperature. Future studies are needed to determine impacts of duration and temperature of centrifugation on oxylipin concentrations.

Omega-6 and Omega-3 Fatty Acid-Derived Oxylipins from the Lipoxygenase Pathway in Maternal and Umbilical Cord Plasma at Delivery and Their Relationship with Infant Growth

“…Goveia-Figueira et al found that 5- and 15-HETE levels were associated with premature labor [ 27 ]. Similarly, Ramsden et al showed that above-median 5-HETE and 15-HETE concentrations were associated with a higher risk of preterm delivery when assessed at gestational week 14 [ 28 ]. Maternal plasma samples from women with pre-eclampsia had significantly higher 5-, 8-, 12-, 15-HETE, and LTB4 levels compared with women having normal pregnancies and nonpregnant women.…”

Polyunsaturated Fatty Acids and Their Metabolites in Hyperemesis Gravidarum

“…However, there is limited knowledge about how the effects are mediated. Bioactive lipids have been proposed as key mediators and studied in response to omega-3 supplementation in healthy volunteers [78], during pregnancy [79], in placenta [80] and in maternal and cord plasma [59,81], but never in omega-3 supplementation studies of HG.…”

Prediction of Spontaneous Preterm Birth : Clinical and Immunological Aspects

“…It has been suggested that a subset of oxylipins might serve as potential early biomarkers for sPTB 152 , and that low circulating levels of omega-3 PUFAs (EPA and DHA) are a risk factor for early PTB 153 . The authors hypothesised that several underlying mechanisms are plausible, such as the impact of dietary long chain fatty acids on the production of eicosanoids involved in the parturition process, on the myometrial activity, and on inflammatory pathways 153 .…”

“…It was included in the study of Aung et al 207 but was not associated with PTB. In the study by Ramsden et al 8-HETE was not included 152 . To our knowledge there are no previous reports on an association between 8-HETE and PTB.…”