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

Quantifying Breast Milk Retinol Inadequacy and the Impact on Neonatal Outcomes in a Midwestern United States Population of Postpartum Women

Background: Low serum antioxidant concentrations at birth can lead to oxidative stress, bronchopulmonary dysplasia, retinopathy, and necrotizing colitis in infants. Specifically, low retinol (Vitamin A1) levels can cause night blindness and impaired immune system function. Retinol inadequacy is a well-documented nutritional issue in developing countries. According to World Health Organization survey data, low Vitamin A serum levels (less than 300 mcg/L) impact approximately one third of pre-school aged children and more than 15% of pregnant woman in at-risk populations. However, there is a lack of understanding about the prevalence of breast milk retinol inadequacy in developed countries. For vitamin A deficiency to constitute a moderate public health problem by WHO biochemical standards, population retinol must reach between 10-25% for breast milk inadequacy or 10-20% for maternal serum deficiency. Objective: The purpose of this study is to quantify the prevalence of breast milk retinol adequacy (greater than 300 mcg/L), insufficiency (between 200 – 300 mcg/L) and deficiency (less than 200 mcg/L) in a Midwestern United States population of postpartum women. A secondary aim is to identify the relationship amongst breast milk retinol concentrations and birth outcomes. Experimental Design: An IRB approved study enrolled 24 infant-mother pairs. Data analysis was performed on subjects with breast milk nutrient analyses available. Descriptive statistics were run for all variables, including maternal retinol activity equivalents. Spearman correlation coefficients were used to assess the relationship between maternal blood retinol and breast milk retinol, cord blood retinol and breast milk retinol, and breast milk retinol and birth outcomes. Median corrected gestational age statistics and breast milk retinol levels were compared amongst maternal serum retinol groups. Results: In our population of postpartum mothers, only 56% of participants had breast milk retinol adequacy, with 36.4% of participants achieving maternal serum retinol adequacy. Retinol category results are summed up in Table 1. Median maternal retinol activity equivalents was 1740 mcg/L (range=651mcg/L - 3436mcg/L). There was no significant correlation between maternal serum retinol level and breast milk retinol levels (R=0.24, p=0.915). Additionally, there was no significant correlation between maternal retinol activity equivalents and maternal serum retinol level (R=.008, p=0.973) or breast milk retinol level (R=-.192, p=0.381). There was a significant negative correlation between breast milk retinol level and the number of oxygen therapy days during infant admission (R=-0.483, p=0.017). Conclusion: Based on these results, breast milk and maternal serum retinol inadequacies may constitute a serious and moderate public health problem, respectively, for postpartum mothers in the Midwestern United States. These results suggest that breast milk retinol adequacy promotes healthy lung development in neonates. Further, breast milk retinol levels may be independent of maternal serum retinol levels and maternal retinol activity equivalents. Limitations of this study include a small sample size of mothers whose preterm skewed infants were all admitted to the NICU. Future studies should focus on replicating these results with a larger heterogenous sample size.https://digitalcommons.unmc.edu/surp2020/1020/thumbnail.jp

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

Differences in Maternal and Infant Cord Blood Vitamin D Between Racial/Ethnic Groups

Background: Vitamin D deficiency associated with lower 25-hydroxyvitamin D (25(OH)D) concentration is common among individuals with more melanin pigmentation. Low 25(OH)D levels in pregnant women may be related to increased risk of low birth weight and preterm delivery. Still, few studies have assessed how serum levels of 25(OH)D vary between maternal and infant race/ethnicity. Objective: This study aimed to investigate the relationship between 25(OH)D levels in maternal blood and infant cord blood within certain ethnic groups, prematurity status, and low birth weight. Experimental Design:An IRB-approved study enrolled 86 mother-infant pairs. Maternal blood samples and infant cord blood samples were analyzed for 25(OH)D serum levels. Descriptive statistics and Kruskal-Willis tests comparisons were conducted with the use of IBM SPSS Statistics 28 software to assess the relationship between maternal and cord blood 25(OH)D levels in other race/ethnicity groups, birthweight, and preterm birth. Prematurity was categorized into two groups: premature (weeks) and term (≥37 weeks). Birth weight was categorized into two groups: low birth weight (\u3c 2500 g weeks) and not low birth weight (≥2500 g weeks). A p-value of Results:Median levels of 25(OH)D serum were lower in infant’s cord blood (22.52 ng/mL) than maternal blood (38.06 ng/mL). White participants had significantly higher 25(OH)D levels than African American participants in both maternal blood (40.76 ng/mL vs 27.79, p = Conclusion: Our findings suggest a possible association with lower serum 25-hydroxyvitamin D concentration in darker skin pigmentation, even in a small sample size. These results suggest that prematurity and birth weight should be replicated in larger sample sizes of different Race/Ethnic groups, limiting this finding. Further studies should focus on examining differences with larger and more diverse sample sizes. Such research should include measuring Vitamin D intake in pregnancy and clinical outcomes.https://digitalcommons.unmc.edu/surp2021/1008/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

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

Omega-3 and omega-6 fatty acids are important for neonatal development and health. One mechanism by which omega-3 and omega-6 fatty acids exert their effects is through their metabolism into oxylipins and specialized pro-resolving mediators. However, the influence of oxylipins on fetal growth is not well understood. Therefore, the objective of this study was to identify oxylipins present in maternal and umbilical cord plasma and investigate their relationship with infant growth. Liquid chromatography–tandem mass spectrometry was used to quantify oxylipin levels in plasma collected at the time of delivery. Spearman’s correlations highlighted significant correlations between metabolite levels and infant growth. They were then adjusted for maternal obesity (normal body mass index (BMI: ≤30 kg/m2) vs. obese BMI (\u3e30 kg/m2) and smoking status (never vs. current/former smoker) using linear regression modeling. A p-value \u3c 0.05 was considered statistically significant. Our study demonstrated a diverse panel of oxylipins from the lipoxygenase pathway present at the time of delivery. In addition, both omega-3 and omega-6 oxylipins demonstrated potential influences on the birth length and weight percentiles. The oxylipins present during pregnancy may influence fetal growth and development, suggesting potential metabolites to be used as biomarkers for infant outcomes

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

Omega-3 and omega-6 fatty acids are important for neonatal development and health. One mechanism by which omega-3 and omega-6 fatty acids exert their effects is through their metabolism into oxylipins and specialized pro-resolving mediators. However, the influence of oxylipins on fetal growth is not well understood. Therefore, the objective of this study was to identify oxylipins present in maternal and umbilical cord plasma and investigate their relationship with infant growth. Liquid chromatography-tandem mass spectrometry was used to quantify oxylipin levels in plasma collected at the time of delivery. Spearman\u27s correlations highlighted significant correlations between metabolite levels and infant growth. They were then adjusted for maternal obesity (normal body mass index (BMI: ≤30 kg/m2) vs. obese BMI (\u3e30 kg/m2) and smoking status (never vs. current/former smoker) using linear regression modeling. A p-value \u3c 0.05 was considered statistically significant. Our study demonstrated a diverse panel of oxylipins from the lipoxygenase pathway present at the time of delivery. In addition, both omega-3 and omega-6 oxylipins demonstrated potential influences on the birth length and weight percentiles. The oxylipins present during pregnancy may influence fetal growth and development, suggesting potential metabolites to be used as biomarkers for infant outcomes

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