Bioactive metabolites of OMEGA-6 and OMEGA-3 fatty acids are associated with inflammatory cytokine concentrations in maternal and infant plasma at the time of delivery.

BACKGROUND & AIMS: Inflammation is necessary for a healthy pregnancy. However, unregulated or excessive inflammation during pregnancy is associated with severe maternal and infant morbidities, such as pre-eclampsia, abnormal infant neurodevelopment, or preterm birth. Inflammation is regulated in part by the bioactive metabolites of omega-6 (n-6) and omega-3 (n-3) fatty acids (FAs). N-6 FAs have been shown to promote pro-inflammatory cytokine environments in adults, while n-3 FAs have been shown to contribute to the resolution of inflammation; however, how these metabolites affect maternal and infant inflammation is still uncertain. The objective of this study was to predict the influence of n-6 and n-3 FA metabolites on inflammatory biomarkers in maternal and umbilical cord plasma at the time of delivery. METHODS: Inflammatory biomarkers (IL-1ß, IL-2, IL-6, IL-8, IL-10, and TNFα) for maternal and umbilical cord plasma samples in 39 maternal-infant dyads were analyzed via multi-analyte bead array. Metabolites of n-6 FAs (arachidonic acid and linoleic acid) and n-3 FAs (eicosapentaenoic acid and docosahexaenoic acid) were assayed via liquid chromatography-mass spectrometry. Linear regression models assessed relationships between maternal and infant inflammatory markers and metabolite plasma concentrations. RESULTS: Increased plasma concentrations of maternal n-6 metabolites were predictive of elevated pro-inflammatory cytokine concentrations in mothers; similarly, higher plasma concentrations of umbilical cord n-6 FA metabolites were predictive of elevated pro-inflammatory cytokine concentrations in infants. Higher plasma concentrations of maternal n-6 FA metabolites were also predictive of elevated pro-inflammatory cytokines in infants, suggesting that maternal n-6 FA status has an intergenerational impact on the inflammatory status of the infant. In contrast, maternal and cord plasma concentrations of n-3 FA metabolites had a mixed effect on inflammatory status in mothers and infants, which may be due to the inadequate maternal dietary intake of n-3 FAs in our study population. CONCLUSIONS: Our results reveal that maternal FA status may have an intergenerational impact on the inflammatory status of the infant. Additional research is needed to identify how dietary interventions that modify maternal FA intake prior to or during pregnancy may impact maternal and infant inflammatory status and associated long-term health outcomes.

The impact of iron supplementation on the preterm neonatal gut microbiome: A pilot study.

OBJECTIVE: The gastrointestinal microbiome in preterm infants exhibits significant influence on optimal outcomes-with dysbiosis shown to substantially increase the risk of the life-threatening necrotizing enterocolitis. Iron is a vital nutrient especially during the perinatal window of rapid hemoglobin production, tissue growth, and foundational neurodevelopment. However, excess colonic iron exhibits potent oxidation capacity and alters the gut microbiome-potentially facilitating the proliferation of pathological bacterial strains. Breastfed preterm infants routinely receive iron supplementation starting 14 days after delivery and are highly vulnerable to morbidities associated with gastrointestinal dysbiosis. Therefore, we set out to determine if routine iron supplementation alters the preterm gut microbiome. METHODS: After IRB approval, we collected stool specimens from 14 infants born <34 weeks gestation in the first, second, and fourth week of life to assess gut microbiome composition via 16S rRNA sequencing. RESULTS: We observed no significant differences in either phyla or key genera relative abundance between pre- and post-iron timepoints. We observed notable shifts in infant microbiome composition based on season of delivery. CONCLUSION: Though no obvious indication of iron-induced dysbiosis was observed in this unique study in the setting of prematurity, further investigation in a larger sample is warranted to fully understand iron's impact on the gastrointestinal milieu.

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 (>30 kg/m2) and smoking status (never vs. current/former smoker) using linear regression modeling. A p-value < 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.

Early Enteral Feeding in Preterm Infants: A Narrative Review of the Nutritional, Metabolic, and Developmental Benefits.

Enteral feeding is the preferred method of nutrient provision for preterm infants. Though parenteral nutrition remains an alternative to provide critical nutrition after preterm delivery, the literature suggests that enteral feeding still confers significant nutritional and non-nutritional benefits. Therefore, the purpose of this narrative review is to summarize health and clinical benefits of early enteral feeding within the first month of life in preterm infants. Likewise, this review also proposes methods to improve enteral delivery in clinical care, including a proposal for decision-making of initiation and advancement of enteral feeding. An extensive literature review assessed enteral studies in preterm infants with subsequent outcomes. The findings support the early initiation and advancement of enteral feeding impact preterm infant health by enhancing micronutrient delivery, promoting intestinal development and maturation, stimulating microbiome development, reducing inflammation, and enhancing brain growth and neurodevelopment. Clinicians must consider these short- and long-term implications when caring for preterm infants.

Concentrations of fat-soluble nutrients and blood inflammatory compounds in mother-infant dyads at birth.

BACKGROUND: Perinatal inflammation adversely affects health. Therefore, aims of this IRB-approved study are: (1) compare inflammatory compounds within and between maternal and umbilical cord blood samples at the time of delivery, (2) assess relationships between inflammatory compounds in maternal and cord blood with birth characteristics/outcomes, and (3) assess relationships between blood and placental fat-soluble nutrients with blood levels of individual inflammatory compounds. METHODS: Mother-infant dyads were enrolled (n = 152) for collection of birth data and biological samples of maternal blood, umbilical cord blood, and placental tissue. Nutrient levels included: lutein + zeaxanthin; lycopene; α-, ß-carotene; ß-cryptoxanthin; retinol; α-, γ-, δ-tocopherol. Inflammatory compounds included: tumor necrosis factor-α, superoxide dismutase, interleukins (IL) 1ß, 2, 6, 8, 10. RESULTS: Median inflammatory compound levels were 1.2-2.3 times higher in cord vs. maternal blood, except IL2 (1.3 times lower). Multiple significant correlations existed between maternal vs. infant inflammatory compounds (range of r = 0.22-0.48). While relationships existed with blood nutrient levels, the most significant were identified in placenta where all nutrients (except δ-tocopherol) exhibited relationships with inflammatory compounds. Relationships between anti-inflammatory nutrients and proinflammatory compounds were primarily inverse. CONCLUSION: Inflammation is strongly correlated between mother-infant dyads. Fat-soluble nutrients have relationships with inflammatory compounds, suggesting nutrition is a modifiable factor. IMPACT: Mother and newborn inflammation status are strongly interrelated. Levels of fat-soluble nutrients in blood, but especially placenta, are associated with blood levels of proinflammatory and anti-inflammatory compounds in both mother and newborn infant. As fat-soluble nutrient levels are associated with blood inflammatory compounds, nutrition is a modifiable factor to modulate inflammation and improve perinatal outcomes.

Fat-soluble nutrients and Omega-3 fatty acids as modifiable factors influencing preterm birth risk.

Preterm birth is a leading cause of child morbidity and mortality, so strategies to reduce early birth must remain a priority. One key approach to enhancing birth outcomes is improving maternal dietary intake. Therefore, the purpose of this review is to discuss mechanisms on perinatal status of fat-soluble nutrients (carotenoids, retinol, tocopherols) and omega-3 fatty acids and how they impact risk for preterm birth. Literature review demonstrates that maternal dietary intake and biological (blood and placental tissue) levels of fat-soluble nutrients during pregnancy may provide antioxidative, anti-inflammatory, and immunomodulatory health benefits. Omega-3 fatty acids also promote increased production of specialized pro-resolving mediators, subsequently mediating inflammation resolution. Combined effects of these nutrients support appropriate placental organogenesis and function. Consequently, fat-soluble nutrients and omega-3 fatty acids serve as strong influencers for preterm birth risk. As dietary intake remains a modifiable factor, future intervention would benefit from a focus on optimizing perinatal status of these specific nutrients.

Omega-3 Long-Chain Polyunsaturated Fatty Acids Intake by Ethnicity, Income, and Education Level in the United States: NHANES 2003-2014.

Although there are many recognized health benefits for the consumption of omega-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA), intake in the United States remains below recommended amounts. This analysis was designed to provide an updated assessment of fish and n-3 LCPUFA intake (eicosapentaenoic (EPA), docosahexaenoic acid (DHA), and EPA+DHA) in the United States adult population, based on education, income, and race/ethnicity, using data from the 2003-2014 National Health and Nutrition Examination Survey (NHANES) (n = 44,585). Over this survey period, participants with less education and lower income had significantly lower n-3 LCPUFA intakes and fish intakes (p < 0.001 for all between group comparisons). N-3 LCPUFA intake differed significantly according to ethnicity (p < 0.001), with the highest intake of n-3 LCPUFA and fish in individuals in the "Other" category (including Asian Americans). Supplement use increased EPA + DHA intake, but only 7.4% of individuals consistently took supplements. Overall, n-3 LCPUFA intake in this study population was low, but our findings indicate that individuals with lower educational attainment and income are at even higher risk of lower n-3 LCPUFA and fish intake.

Randomized trial of two doses of vitamin D3 in preterm infants <32 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 <0.05 was considered statistically significant. 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 <10 percentile (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 infants <32 weeks cared for in the NICU.

Response of vitamin D binding protein and free vitamin D concentrations to vitamin D supplementation in hospitalized premature infants.

OBJECTIVE: The objective of this study was to evaluate the relationship between 25(OH)D, Vitamin D Binding Protein (DBP), and free vitamin D in premature infants. METHODS: Thirty-two infants <32 weeks' gestation were randomized to two different levels of vitamin D3 supplementation (400 vs. 800 IU/day). 25(OH)D levels were measured by LC-MS/MS; DBP was measured by validated ELISA. Free vitamin D was calculated using molar ratios of 25(OH)D and DBP. The Wilcoxon signed rank test was used to compare DBP, free D and 25(OH)D levels; Spearman's correlation coefficients were used to assess correlations. RESULTS: The mean gestational age at birth was 30.5 weeks; mean birth weight was 1405 g. Mean 25(OH)D levels at birth were 17.3 ng/mL; DBP levels were 297 mg/L, and estimated free vitamin D levels were 18.9. There was a statistically significant change in 25(OH)D levels after 8 weeks (24.6 vs. 39.1 ng/mL in the 400 vs. 800 group, respectively, p=0.02). DBP levels from birth to 8 weeks showed a statistically significant decrease (267 vs. 208, p=0.04). Estimated free 25(OH)D concentrations increased over the study period, from 18.9 at birth to 64.7 at 8 weeks of age (p=0.0001). Free vitamin D levels at birth were associated with global DEXA bone mineral content at discharge from the NICU (r=0.58, p=0.05). CONCLUSION: Supplementation with vitamin D3 increased the free portion of the vitamin D metabolite, providing increased bioavailable substrate. Improved free vitamin D levels may improve measurable outcomes such as bone mineral content and deserve further evaluation.