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Midwest Student Biomedical Research Forum

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Maternal diet is critical for a successful pregnancy, as well as fetal health outcomes. Recent investigations reveal that dietary fats, such as omega-3 fatty acids, serve as substrates for the biosynthesis of specialized pro-resolving lipid mediators (SPM), which have anti-inflammatory and immune-stimulating effects. However, the relationship between maternal omega-3 fatty acid intake and maternal and cord plasma SPM levels in normal weight versus obese pre-pregnancy body mass index (BMI) deliveries is unclear.

Pre-pregnancy obesity is associated with serious adverse pregnancy outcomes, including an increased risk of miscarriage, caesarean section, pre-eclampsia, and thromboembolism. Along with maternal risk, these complications lead to a four-fold increase in neonatal mortality, attributed to prematurity and macrosomia. Obesity-associated inflammation in early development, from intrauterine, peri-partum, and early childhood insults, may have lifelong impacts on the offspring. Studies are needed to identify modifiable factors in the intrauterine environment and developing fetus that can reduce inflammation and limit the negative consequences of obesity during pregnancy. Recent studies reveal certain omega-3 fatty acid derivatives actively attenuate and resolve pro-inflammatory processes. These SPMs may be key to the beneficial effects of omega-3 fatty acids. While the association between inflammation and obesity is clear, the protective mechanisms of SPMs against complicated birth in maternal-fetal health are a gap in the field. Currently, it is known that SPM production is dependent on intermediates of the omega-3 fatty acid metabolic pathway. However, it is unknown how material SPM production is related to omega-3 fatty acid intake. In recent studies, the Anderson Berry Lab has found strikingly low intakes of omega-3 fatty acids in pregnant woman. Thus, understanding the therapeutic value of omega-3 fatty acid intake and the role of SPMs in maternal-fetal outcomes addresses an unmet need. We hope to achieve two specific aims: 1) to identify the relationship between maternal omega-3 fatty acid intake and maternal and cord plasma SPM levels in normal weight pre-pregnancy BMI and obese pre-pregnancy BMI deliveries and 2) to evaluate similarities and differences in intakes, food security, and transportation security. Dr. Anderson Berry will provide review of the pathophysiology of adverse pregnancy outcomes, teach and assist in a literature search for relevant manuscripts to study, and provide quality assurance for accuracy throughout the data collection process.

Over a 10-week period, the recruitment of additional subjects to augment current samples was successfully performed. Subject recruitment required the collection of informed consent, preparation of maternal and cord blood, preparation of placental tissue samples, and administration of a validated food frequency questionnaire. Over 100 new subjects were successfully enrolled in the study in this manner. Preliminary evaluation of differences in intakes, food security, and transportation security between obese and normal weight groups was completed. Due to technical equipment challenges and timing inconsistencies in data analysis, utilization of a targeted lipidomics approach to measure SPMs and determine the association between maternal omega-3 fatty acid dietary intake and maternal and cord plasma SPMs is in progress with the mass spectroscopy coil and protocol being fine-tuned on other, less valuable samples.

In the future, we hope to employ a targeted lipidomics approach to measure SPM levels and determine the association between maternal omega-3 fatty acid dietary intake and maternal and cord plasma SPM levels at the time of delivery. We plan to analyze 80 existing samples (40 mother-infant pairs) consisting of maternal, cord, placental, and neonatal blood and breast milk, 32% of which had a pre-pregnancy BMI >30. Clinical data from these subjects and dietary data measured via a validated food frequency questionnaire have been obtained. Dr. Nordgren will then determine SPM levels in plasma and placental samples via liquid chromatography-tandem mass spectrometry-mediated lipid identification. Key lipids and metabolites to be characterized will include 18- HEPE, 15-HETE, RvE1, RvD1, RvD2, RVD3, RvD5, 17(R)-RvD1, Maresin-1, and protectin-D1. This technique will also allow for determination of the association between maternal and cord serum concentrations of SPMs of obese pre-pregnancy BMI delivery. Levels and associations with clinical pregnancy outcomes will be analyzed. It is hypothesized that in the presence of obesity mediated inflammation, adequate omega-3 fatty acid intake provides a pool of substrates for increased SPM production, minimizing poor pregnancy outcomes.

The Effect of Maternal Diet on Fetal Outcomes