ORCID ID

0000-0003-2609-9355

Graduation Date

Winter 12-17-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Ann Anderson Berry

Second Advisor

Corrine Hanson

Third Advisor

Tara Nordgren

Fourth Advisor

Sathish Kumar Natarajan

MeSH Headings

Omega-6 Fatty Acid Metabolites, Omega-3 Fatty Acid Metabolites, Infant Growth, Oxylipins, Pregnancy, Prematurity, Neonatal Intensive Care Unit

Abstract

Normal pregnancy relies on inflammation for implantation, placentation, and parturition, but uncontrolled it can lead to poor infant outcomes. Maternal diet is one modifiable factor that can impact inflammation. Omega-3 and omega-6 fatty acids have been shown to be metabolized into bioactive metabolites that effect inflammation. The presence and importance of these metabolites at the time of delivery are not well understood. Therefore, the purpose of this dissertation was to first quantify omega-3 and omega-6 metabolites in maternal plasma, cord plasma, and placental tissue. Then the relationships between metabolites and infant outcomes, including birth weight percentile, length percentile, head circumferences percentile, prematurity and admission to the Neonatal Intensive Care Unit were explored. Lastly, the associations of GPR18 receptor expression and prematurity were explored. An IRB-approved cross-sectional study enrolled 120 maternal-infant pairs for infants born at Nebraska Medicine Hospital. Placental tissue, maternal blood and umbilical cord blood samples were collected and analyzed for metabolite concentrations. Mothers completed a food frequency questionnaire to identify usual intake. Demographic and birth outcome data were collected from the electronic medical record. Omega-3 and Omega-6 metabolites from the enzymatic lipoxygenase pathway are present at delivery. Birth length percentile was positively associated with cord metabolites 9-hydroxyoctadecadienoic acid (HODE), 13-HODE, 13-ketooctadecadienoic acid (KODE), and 5-hydroxyeicosapentaenoic acid (HEPE). Birth weight percentiles were negatively predicted by maternal 5,15-dihydroxyeicosatetraenoic acid (DiHETE), maternal 7-hydroxydocosahexaenoic acid (HDHA), and placental leukotriene B4 (LTB4). Further, maternal lipoxin A4 (LXA4) reduced the odds of admission to the neonatal intensive care unit (NICU), while cord 14,15-dihydroxyeicosatrienoic acid (DiHET) reduced the odds of prematurity. In the setting of prematurity, the expression of specialized pro-resolving mediator resolvin D2’s G-coupled-protein receptor was lower in in placental vascular smooth muscle cells relative to term placentas. Conclusively from this study, a diverse group of omega-3 and omega-6 metabolites were identified at delivery. Further, these results highlight roles of oxylipins in fetal growth, with potential benefits conferred to the developing infant.

Available for download on Sunday, December 04, 2022

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