The Effect of Maternal Diet on Fetal Outcomes

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 \u3e30. 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.https://digitalcommons.unmc.edu/com_students_pres/1000/thumbnail.jp

Randomized trial of two doses of vitamin D3 in preterm infants \u3c32 weeks: Dose impact on achieving desired serum 25(OH)D3 in a NICU population.

BACKGROUND: Recommendations for vitamin D supplementation for preterm infants span a wide range of doses. Response to vitamin D supplementation and impact on outcomes in preterm infants is not well understood. OBJECTIVE: Evaluate serum 25(OH)D3 concentration changes after 4 weeks in response to two different doses of vitamin D3 supplementation in a population of premature infants and quantify the impact on NICU outcomes. DESIGN: 32 infants born at 24-32 weeks gestation were prospectively randomized to receive 400 or 800 IU/day vitamin D3 supplementation. Serum 25(OH)D3 levels were measured every 4 weeks. The Wilcoxon signed rank test was used to compare serum levels of 25(OH)D3 at 4 weeks and each subsequent time point. A p-value of RESULTS: Serum 25(OH)D3 levels at birth were 41.9 and 42.9 nmol/l for infants in the 400 IU group and 800 IU group, respectively (p = 0.86). Cord 25(OH)D3 concentrations significantly correlated with gestational age (r = 0.40, p = 0.04). After 4 weeks of D3 supplementation, median 25(OH)D3 levels increased in both groups (84.6vs. 105.3 nmol/l for 400 vs. 800 IU/day respectively, with significantly more improvement in the higher dose (p = 0.048). Infants in the 400 IU group were significantly more likely to have dual energy x-ray absorptiometry (DEXA) bone density measurements(56% vs 16%, p = 0.04). CONCLUSIONS: Improvement in 25(OH)D3 levels at 4 weeks, bone density, and trends towards improvement in linear growth support consideration of a daily dose of 800 IU of vitamin D for infantsNICU

Effect of Maternal Retinol Status at Time of Term Delivery on Retinol Placental Concentration, Intrauterine Transfer Rate, and Newborn Retinol Status

Retinol (vitamin A) is essential, so the objective of this Institutional Review Board approved study is to evaluate retinol placental concentration, intrauterine transfer, and neonatal status at time of term delivery between cases of maternal retinol adequacy, insufficiency, and deficiency in a United States population. Birth information and biological samples were collected for mother-infant dyads (n = 260). Maternal and umbilical cord blood retinol concentrations (n = 260) were analyzed by HPLC and categorized: deficient (≤0.7 umol/L), insufficient (\u3e0.7-1.05 umol/L), adequate (\u3e1.05 umol/L). Intrauterine transfer rate was calculated: (umbilical cord blood retinol concentration/maternal retinol concentration) × 100. Non-parametric statistics used include Spearman\u27s correlations, Mann-Whitney U, and Kruskal-Wallis tests. p-values \u3c0.05 were statistically significant. Only 51.2% of mothers were retinol adequate, with 38.4% insufficient, 10.4% deficient. Only 1.5% of infants were retinol adequate. Placental concentrations (n = 73) differed between adequate vs. deficient mothers (median 0.13 vs. 0.10 μg/g; p = 0.003). Umbilical cord blood concentrations were similar between deficient, insufficient, and adequate mothers (0.61 vs. 0.55 vs. 0.57 μmol/L; p = 0.35). Intrauterine transfer increased with maternal deficiency (103.4%) and insufficiency (61.2%) compared to adequacy (43.1%), p \u3c 0.0001. Results indicate that intrauterine transfer rate is augmented in cases of maternal retinol inadequacy, leading to similar concentrations in umbilical cord blood at term delivery

Evaluation of Vitamin E Isoforms in Placental Tissue and Their Relationship with Maternal Dietary Intake and Plasma Concentrations in Mother-Infant Dyads

α-tocopherol is a vitamin E isoform with potent antioxidant activity, while the γ-tocopherol isoform of vitamin E exerts more pro-inflammatory effects. In maternal-fetal environments, increased plasma α-tocopherol concentrations are associated with positive birth outcomes, while higher γ-tocopherol concentrations are linked with negative pregnancy outcomes. However, little is known about tocopherol concentrations in placental tissue and their role in modulating placental oxidative stress, a process that is implicated in many complications of pregnancy. The objectives of this research are to evaluate the concentrations of α- and γ-tocopherol in placental tissue and assess relationships with maternal and umbilical cord plasma concentrations. A total of 82 mother-infant dyads were enrolled at the time of delivery, and maternal and umbilical cord blood samples and placenta samples were collected. α- and γ-tocopherol concentrations in these samples were analyzed by high-performance liquid chromatography (HPLC). γ-tocopherol concentrations demonstrated significant, positive correlations among all sample types (p-values \u3c 0.001). Placental tissue had a significantly lower ratio of α:γ-tocopherol concentrations when compared to maternal plasma and umbilical cord plasma (2.9 vs. 9.9 vs. 13.2, respectively; p \u3c 0.001). Additional research should explore possible mechanisms for tocopherol storage and transfer in placental tissue and assess relationships between placental tocopherol concentrations and measures of maternal-fetal oxidative stress and clinical outcomes of pregnancy

Comparing Intrauterine Transfer Rates and Maternal Plasma Levels of Carotenoids In Maternal-Infant Pairs Between Gestational Age Groups

Background: Carotenoids are recognized as potential antioxidants with a wide range of functions in humans, such as protecting eye health. Carotenoid levels in infant cord blood are generally lower than in maternal serum. Still, little research has assessed on the intrauterine transfer rate of carotenoids between mothers and infants at varying gestational ages. Objective: This study aimed to identify differences in intrauterine transfer rates of carotenoids between five gestational age groups. Experimental Design: An IRB-approved study enrolled 308 maternal-infant pairs at delivery. Gestational age was categorized into five groups: extremely preterm (\u3c28 weeks), very preterm (28 to \u3c32 weeks), moderately to late preterm (32 to \u3c37 weeks), early term (37 to \u3c39 weeks), and term (\u3e39 weeks). Maternal blood and umbilical cord samples were collected at birth and analyzed for carotenoid nutrient levels using high-performance liquid chromatography. Demographic and clinical outcome data were collected from the electronic health record. Intrauterine transfer rates were calculated as [(umbilical cord blood nutrient level/maternal serum level)*100]. Descriptive statistics were generated. The Kruskal-Wallis test was used to compare the intrauterine transfer rates of carotenoids between the gestational age groups. Post-hoc pairwise comparisons were used to assess specific inter-group differences. A p-value of \u3c0.05 was considered significant. Results: Median birth gestational age was 39 2/7 weeks with 3 (1%) infants in the extremely preterm group, 9 (2.9%) in very preterm, 33 (10.7%) in moderately to late preterm, 70 (22.7%) in early term, and 193 (62.7%) born term. There was a significant difference in intrauterine transfer rate between gestational age groups for lutein + zeaxanthin (L+Z), a-carotene, and total B-carotene (Table 1). Post-hoc pairwise comparisons showed significant differences between term and moderately preterm for L+Z (p=0.016), term and extremely preterm for L+Z (p=0.041), and term and moderately preterm for a-carotene (p=0.003). Table 1. Comparison of Median Intrauterine Transfer Rates in Maternal-Infant Pairs Between Gestational Age Groups Transfer Rate p-value between all groups lutein + zeaxanthin 15.6% 0.001 total lycopene 4.4% 0.070 β-cryptoxanthin 11.0% 0.112 ⍺-carotene 8.6% 0.03 β-carotene 6.1% 0.037 Conclusion: There may be a relationship between intrauterine transfer rates of carotenoids and gestational age groups. Further research is needed to fully understand the clinical significance of this observed relationship and ascertain what interventions, if any, are ideal for maternal-fetal health. This study is limited by the low number of participants in the extremely preterm and very preterm groups.https://digitalcommons.unmc.edu/surp2020/1007/thumbnail.jp

Plasma Retinol Concentrations and Dietary Intakes of Mother-Infant Sets in Singleton versus Twin Pregnancy

Vitamin A (retinol) is essential for normal fetal development, but the recommendation for maternal dietary intake (Retinol Activity Equivalent, RAE) does not differ for singleton vs. twin pregnancy, despite the limited evaluation of retinol status. Therefore, this study aimed to evaluate plasma retinol concentrations and deficiency status in mother-infant sets from singleton vs. twin pregnancies as well as maternal RAE intake. A total of 21 mother-infant sets were included (14 singleton, 7 twin). The HPLC and LC-MS/HS evaluated the plasma retinol concentration, and data were analyzed using the Mann-Whitney U test. Plasma retinol was significantly lower in twin vs. singleton pregnancies in both maternal (192.2 vs. 312.1 vs. mcg/L, p = 0.002) and umbilical cord (UC) samples (102.5 vs. 154.4 vs. mcg/L, p = 0.002). The prevalence of serum-defined vitamin A deficiency (VAD) \u3c200.6 mcg/L was higher in twins vs. singletons for both maternal (57% vs. 7%, p = 0.031) and UC samples (100% vs. 0%, p \u3c 0.001), despite a similar RAE intake (2178 vs. 1862 mcg/day, p = 0.603). Twin pregnancies demonstrated a higher likelihood of vitamin A deficiency in mothers, with an odds ratio of 17.3 (95% CI: 1.4 to 216.6). This study suggests twin pregnancy may be associated with VAD deficiency. Further research is needed to determine optimal maternal dietary recommendations during twin gestation

Something Smells Fishy: How Lipid Mediators Impact the Maternal–Fetal Interface and Neonatal Development

Normal pregnancy relies on inflammation for implantation, placentation, and parturition, but uncontrolled inflammation can lead to poor maternal and infant outcomes. Maternal diet is one modifiable factor that can impact inflammation. Omega-3 and -6 fatty acids obtained through the diet are metabolized into bioactive compounds that effect inflammation. Recent evidence has shown that the downstream products of omega-3 and -6 fatty acids may influence physiology during pregnancy. In this review, the current knowledge relating to omega-3 and omega-6 metabolites during pregnancy will be summarized

Impact of COVID-19 Infection During Pregnancy on Neonatal Birth Outcomes

Approximately 116 million births have been reported worldwide in the nine months following the start of the COVID-19 pandemic. Currently, the effects of COVID-19 infection during pregnancy on birth outcomes are not fully understood. An IRB-approved study enrolled 115 mothers since March 2020, 5 of whom had a confirmed history of COVID-19 infection during pregnancy. For each COVID-19-infected mother, two mothers of similar age, gestation period, and race who were not infected with COVID-19 during pregnancy were matched 2-to-1 for a case-control analysis. Descriptive statistics were generated, and the Mann-Whitney U test was used to compare continuous variables between the two groups. Fisher’s Exact test was used to evaluate categorical outcomes between the groups. Phttps://digitalcommons.unmc.edu/surp2021/1007/thumbnail.jp

Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities

Omega-3 fatty acids are important to pregnancy and neonatal development and health. One mechanism by which omega-3 fatty acids exert their protective effects is through serving as substrates for the generation of specialized pro-resolving lipid mediators (SPM) that potently limit and resolve inflammatory processes. We recently identified that SPM levels are increased in maternal blood at delivery as compared to umbilical cord blood, suggesting the placenta as a potential site of action for maternal SPM. To explore this hypothesis, we obtained human placental samples and stained for the SPM resolvin D2 (RvD2) receptor GPR18 via immunohistochemistry. In so doing, we identified GPR18 expression in placental vascular smooth muscle and extravillous trophoblasts of the placental tissues. Using in vitro culturing, we confirmed expression of GPR18 in these cell types and further identified that stimulation with RvD2 led to significantly altered responsiveness (cytoskeletal changes and pro-inflammatory cytokine production) to lipopolysaccharide inflammatory stimulation in human umbilical artery smooth muscle cells and placental trophoblasts. Taken together, these findings establish a role for SPM actions in human placental tissue

Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities

Omega-3 fatty acids are important to pregnancy and neonatal development and health. One mechanism by which omega-3 fatty acids exert their protective effects is through serving as substrates for the generation of specialized pro-resolving lipid mediators (SPM) that potently limit and resolve inflammatory processes. We recently identified that SPM levels are increased in maternal blood at delivery as compared to umbilical cord blood, suggesting the placenta as a potential site of action for maternal SPM. To explore this hypothesis, we obtained human placental samples and stained for the SPM resolvin D2 (RvD2) receptor GPR18 via immunohistochemistry. In so doing, we identified GPR18 expression in placental vascular smooth muscle and extravillous trophoblasts of the placental tissues. Using in vitro culturing, we confirmed expression of GPR18 in these cell types and further identified that stimulation with RvD2 led to significantly altered responsiveness (cytoskeletal changes and pro-inflammatory cytokine production) to lipopolysaccharide inflammatory stimulation in human umbilical artery smooth muscle cells and placental trophoblasts. Taken together, these findings establish a role for SPM actions in human placental tissue