Retinol and Pro-Vitamin A Carotenoid Nutritional Status during Pregnancy Is Associated with Newborn Hearing Screen Results.

The prenatal period is critical for auditory development; thus, prenatal influences on auditory development may significantly impact long-term hearing ability. While previous studies identified a protective effect of carotenoids on adult hearing, the impact of these nutrients on hearing outcomes in neonates is not well understood. The purpose of this study is to investigate the relationship between maternal and umbilical cord plasma retinol and carotenoid concentrations and abnormal newborn hearing screen (NHS) results. Mother-infant dyads (n = 546) were enrolled at delivery. Plasma samples were analyzed using HPLC and LC-MS/MS. NHS results were obtained from medical records. Statistical analysis utilized Mann-Whitney U tests and logistic regression models, with p ≤ 0.05 considered statistically significant. Abnormal NHS results were observed in 8.5% of infants. Higher median cord retinol (187.4 vs. 162.2 µg/L, p = 0.01), maternal trans-ß-carotene (206.1 vs. 149.4 µg/L, p = 0.02), maternal cis-ß-carotene (15.9 vs. 11.2 µg/L, p = 0.02), and cord trans-ß-carotene (15.5 vs. 8.0 µg/L, p = 0.04) were associated with abnormal NHS. Significant associations between natural log-transformed retinol and ß-carotene concentrations and abnormal NHS results remained after adjustment for smoking status, maternal age, and corrected gestational age. Further studies should investigate if congenital metabolic deficiencies, pesticide contamination of carotenoid-rich foods, maternal hypothyroidism, or other variables mediate this relationship.

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.

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.

Plasma Concentrations and Maternal-Umbilical Cord Plasma Ratios of the Six Most Prevalent Carotenoids across Five Groups of Birth Gestational Age.

Carotenoids are antioxidant nutrients with the potential to provide protection against oxidative stress. Plasma carotenoid concentrations are lower in newborn infants compared to their mothers; however, limited information is available regarding how concentrations differ by gestational age. The objective of this research is to assess maternal and umbilical cord plasma carotenoid concentrations and maternal-umbilical cord plasma ratios across five groups of birth gestational age. Mother-infant dyads were enrolled at delivery for collection of maternal and umbilical cord blood. Plasma carotenoids were analyzed by HPLC and LC-MS/MS. Birth gestational age was categorized into five groups, and the Kruskal-Wallis test compared carotenoid concentrations and maternal-umbilical cord plasma ratios between these groups. A p-value of < 0.05 was considered statistically significant. 370 mother-infant dyads were included, with most infants delivered at early term (20.3%) or term (64.6%). Though maternal plasma concentrations increased with birth gestational age, we observed less variability in umbilical cord plasma concentrations, thus the maternal-umbilical cord plasma ratio also increased with birth CGA groups for lutein + zeaxanthin (p = 0.008), ß-cryptoxanthin (p = 0.027), α-carotene (p = 0.030); ß-carotene approached significance (p = 0.056). Additional research is needed to determine if carotenoid concentrations were physiologic to varying gestational ages or if they were impacted by factors associated with preterm birth.

Intrauterine Transfer of Polyunsaturated Fatty Acids in Mother-Infant Dyads as Analyzed at Time of Delivery.

Polyunsaturated fatty acids (PUFAs) are essential for fetal development, and intrauterine transfer is the only supply of PUFAs to the fetus. The prevailing theory of gestational nutrient transfer is that certain nutrients (including PUFAs) may have prioritized transport across the placenta. Numerous studies have identified correlations between maternal and infant fatty acid concentrations; however, little is known about what role maternal PUFA status may play in differential intrauterine nutrient transfer. Twenty mother-infant dyads were enrolled at delivery for collection of maternal and umbilical cord blood, and placental tissue samples. Plasma concentrations of PUFAs were assessed using gas chromatography (GC-FID). Intrauterine transfer percentages for each fatty acid were calculated as follows: ((cord blood fatty acid level/maternal blood fatty acid level) × 100). Kruskal-Wallis tests were used to compare transfer percentages between maternal fatty acid tertile groups. A p-value < 0.05 was considered significant. There were statistically significant differences in intrauterine transfer percentages of arachidonic acid (AA) (64% vs. 65% vs. 45%, p = 0.02), eicosapentaenoic acid (EPA) (41% vs. 19% vs. 17%, p = 0.03), and total fatty acids (TFA) (27% vs. 26% vs. 20%, p = 0.05) between maternal plasma fatty acid tertiles. Intrauterine transfer percentages of AA, EPA, and TFA were highest in the lowest tertile of respective maternal fatty acid concentration. These findings may indicate that fatty acid transfer to the fetus is prioritized during gestation even during periods of maternal nutritional inadequacy.

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.

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 (>0.7-1.05 umol/L), adequate (>1.05 umol/L). Intrauterine transfer rate was calculated: (umbilical cord blood retinol concentration/maternal retinol concentration) × 100. Non-parametric statistics used include Spearman's correlations, Mann-Whitney U, and Kruskal-Wallis tests. p-values <0.05 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 < 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.

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.

Erratum: Status of Retinoids and Carotenoids and Associations with Clinical Outcomes in Maternal-Infant Pairs in Nigeria. Nutrients 2018, 10, 1286.

Due to a mistake during the production process, there were spelling errors in four of the author names in the original published version [...].

Quantification of Lutein + Zeaxanthin Presence in Human Placenta and Correlations with Blood Levels and Maternal Dietary Intake.

Lutein + zeaxanthin (L + Z) are carotenoids recognized in eye health, but less is known about their status during pregnancy. While quantified in maternal and umbilical cord blood, they have never been analyzed in placenta. The purpose of this study is to quantify combined L + Z concentrations in human placenta and correlate with levels in maternal dietary intake, maternal serum, and umbilical cord blood. The proportions of combined L + Z were compared within diet, placenta, maternal serum, and umbilical cord blood among additional carotenoids (lycopene, ß-cryptoxanthin, α-carotene, and ß-carotene). This Institutional Review Boardapproved cross-sectional study enrolled 82 mother-infant pairs. Placenta, maternal serum, and umbilical cord blood samples were analyzed for carotenoids concentrations. Mothers completed a food frequency questionnaire and demographic/birth outcome data were collected. L + Z were present in placenta, median 0.105 micrograms/gram (mcg/g) and were significantly correlated with maternal serum (r = 0.57; p < 0.001), umbilical cord blood levels (r = 0.49; p = 0.001), but not dietary intake (p = 0.110). L + Z were the most prevalent in placenta (49.1%) umbilical cord blood (37.0%), but not maternal serum (18.6%) or dietary intake (19.4%). Rate of transfer was 16.0%, the highest of all carotenoids. Conclusively, L + Z were identified as the two most prevalent in placenta. Results highlight unique roles L + Z may play during pregnancy.

Omega-3 Fatty Acid Supplementation, Pro-Resolving Mediators, and Clinical Outcomes in Maternal-Infant Pairs.

Omega (n)-3 fatty acids are vital to neonatal maturation, and recent investigations reveal n-3 fatty acids serve as substrates for the biosynthesis of specialized pro-resolving lipid mediators (SPM) that have anti-inflammatory and immune-stimulating effects. The role SPM play in the protection against negative maternal-fetal health outcomes is unclear, and there are no current biomarkers of n-3 fatty acid sufficiency. We sought to ascertain the relationships between n-3 fatty acid intake, SPM levels, and maternal-fetal health outcomes. We obtained n-3 fatty acid intake information from 136 mothers admitted for delivery using a food frequency questionnaire and measured docosahexaenoic acid (DHA)-derived SPMs resolvin D1 (RvD1) and RvD2 in maternal and cord plasma. We found significantly elevated SPM in maternal versus cord plasma, and increased SPM levels were associated with at-risk outcomes. We also identified that increased DHA intake was associated with elevated maternal plasma RvD1 (p = 0.03; R² = 0.18) and RvD2 (p = 0.04; R² = 0.20) in the setting of neonatal intensive care unit (NICU) admission. These findings indicate that increased n-3 fatty acid intake may provide increased substrate for the production of SPM during high-risk pregnancy/delivery conditions, and that increased maternal plasma SPM could serve as a biomarker for negative neonatal outcomes.

Vitamin E status and associations in maternal-infant Dyads in the Midwestern United States.

BACKGROUND: Oxidative stress has been associated with adverse neonatal outcomes, and vitamin E has powerful anti-oxidant properties. Vitamin E occurs in several different isoforms which differ in their ability to modulate inflammation and oxidative stress. Therefore, the purpose of this study was to evaluate the status of α-, γ- and δ-tocopherol in maternal-infant pairs, and the impact on maternal-newborn outcomes. METHODS: Vitamin E status was evaluated in 189 mother-infant pairs. Concentrations of α-, γ- and δ-tocopherol were measured using HPLC. Descriptive statistics were calculated and Spearman coefficients were used to assess correlations between maternal and cord measurements. Linear and logistic regression models were used to adjust for relevant confounders. A p < 0.05 was considered statistically significant. RESULTS: Maternal and cord serum tocopherol concentrations were positively correlated for γ-tocopherol (r = 0.32, p Ë‚ 0.001) and δ-tocopherol (r = 0.46, p Ë‚ 0.001) but not for α-tocopherol. After adjustment for confounders, maternal concentrations of tocopherols were positively associated with Apgar scores (p = 0.02) and infant growth parameters at birth. Conversely, cord tocopherol levels were inversely associated with Apgar scores (p = 0.02) and infant growth. Cord concentrations of α-tocopherol were higher in infants born to mothers with a diagnosis of pre-eclampsia (p = 0.04). CONCLUSION: Maternal-fetal transfer of γ- and δ-tocopherols is higher than α-tocopherol and may be mediated by either different or more efficient methods, conversely tissue uptake of α-tocopherol by the developing fetus may be higher. As serum levels of maternal tocopherols are positively associated with outcomes while higher cord levels show a negative impact, uptake and tissue deposition of vitamin E by the fetus may be crucial in growth and development. More research into the role of maternal diet, placental regulation, and fetal uptake of vitamin E tocopherols in relation to clinical outcomes is warranted.

Status of Retinoids and Carotenoids and Associations with Clinical Outcomes in Maternal-Infant Pairs in Nigeria.

Vitamin A is an essential nutrient in pregnancy, and other carotenoids have been independently associated with maternal-infant outcomes. The objective of this study was to quantify the status of vitamin A and carotenoids in Nigerian maternal-infant pairs at delivery, compare these to a cohort from a developed nation, and determine the impact on clinical outcomes. Maternal and cord blood samples were collected in 99 Nigerian mother-infant pairs. Concentrations of lutein + zeaxanthin, ß-cryptoxanthin, lycopene, α- and ß-carotenes, and retinol were measured using HPLC. Descriptive statistics were calculated and Spearman coefficients were used to assess correlations between maternal and cord measurements; Mann-Whitney tests were used to compare median plasma values between dichotomous variables. Linear regression models were used to adjust for relevant confounders. A p < 0.05 was considered statistically significant. Thirty-five percent of mothers had plasma retinol concentrations ≤0.70 µmol/L; 82% of infants had plasma retinol concentrations ≤0.70 µmol/L at delivery. Maternal and infant concentrations of vitamin A compounds were highly correlated and were associated with newborn growth and Apgar scores. Despite plasma concentrations of pro-vitamin A carotenoids higher than those reported in other populations, pregnant Nigerian women have a high prevalence of vitamin A deficiency. As vitamin A related compounds are modifiable by diet, future research determining the clinical impact of these compounds is warranted.

A Comparison of Vitamin E Status and Associated Pregnancy Outcomes in Maternal⁻Infant Dyads between a Nigerian and a United States Population.

Oxidative stress is associated with adverse pregnancy outcomes, and vitamin E has powerful anti-oxidant properties with the potential to impact health outcomes. Tocopherol isomers of vitamin E differ in their ability to modulate inflammation and vary in concentration in diets containing high proportions of processed versus unprocessed foods. The purpose of this study was to compare vitamin E status and associated pregnancy outcomes (mode of delivery, chorioamnionitis, APGARs (measure of appearance, pulse, grimace, activity, respiration), gestational age at delivery, and fetal growth) between maternal⁻infant dyads in a developed and a developing nation to identify potentially modifiable differences that may impact pregnancy and neonatal outcomes and provide a way to improve maternal and neonatal health. Plasma tocopherol levels were evaluated in 189 Midwestern United States (US) mother⁻infant pairs and 99 Central Nigerian mother⁻infant pairs. Maternal and infant concentrations of α-, γ-, and δ-tocopherol were measured using HPLC with diode-array detection. Descriptive statistics were calculated and tocopherol concentrations were associated with clinical outcomes such as mode of delivery, chorioamnionitis, APGARS, and fetal growth. Alpha- and γ-tocopherol levels were higher in the US mothers, (alpha: 12,357.9 (175.23⁻34,687.75) vs. 8333.1 (1576.59⁻16,248.40) (mcg/L); p < 0.001) (gamma: 340.7 (224.59⁻4385.95) vs. 357.5 (66.36⁻1775.31) (mcg/L); p < 0.001), while δ-tocopherol levels were higher in the Nigerian mothers (delta: 261.7 (24.70⁻1324.71) vs. 368.9 (43.06⁻1886.47) (mcg/L); p < 0.001). US infants had higher γ-tocopherol levels than Nigerian infants (203.1 (42.53⁻1953.23) vs. 113.8 (0.00⁻823.00) (mcg/L); p < 0.001), while both the Nigerian mothers and infants had higher α:γ-tocopherol ratios (8.5 vs. 26.2, and 8.9 vs. 18.8, respectively; p < 0.001). Our results in both populations show associations between increased circulating γ-tocopherol and negative outcomes like Caesarian sections, in contrast to the associations with positive outcomes such as vaginal delivery seen with increased α:γ-tocopherol ratios. Growth was positively associated with α- and γ-tocopherols in cord blood in the US population, and with cord blood δ-tocopherols in the Nigerian population. Tocopherol levels likely impact health outcomes in pregnancy in a complicated metabolism across the maternal⁻fetal axis that appears to be potentially influenced by culture and available diet.

Fat-soluble vitamins A and E and health disparities in a cohort of pregnant women at delivery.

The objective of the present study was to evaluate intakes and serum levels of vitamin A, vitamin E, and related compounds in a cohort of maternal-infant pairs in the Midwestern USA in relation to measures of health disparities. Concentrations of carotenoids and tocopherols in maternal serum were measured using HPLC and measures of socio-economic status, including food security and food desert residence, were obtained in 180 mothers upon admission to a Midwestern Academic Medical Center labour and delivery unit. The Kruskal-Wallis and independent-samples t tests were used to compare measures between groups; logistic regression models were used to adjust for relevant confounders. P < 0·05 was considered statistically significant. The odds of vitamin A insufficiency/deficiency were 2·17 times higher for non-whites when compared with whites (95 % CI 1·16, 4·05; P = 0·01) after adjustment for relevant confounders. Similarly, the odds of being vitamin E deficient were 3·52 times higher for non-whites (95 % CI 1·51, 8·10; P = 0·003). Those with public health insurance had lower serum lutein concentrations compared with those with private health insurance (P = 0·05), and living in a food desert was associated with lower serum concentrations of ß-carotene (P = 0·02), after adjustment for confounders. Subjects with low/marginal food security had higher serum levels of lutein and ß-cryptoxanthin compared with those with high food security (P = 0·004 and 0·02 for lutein and ß-cryptoxanthin). Diet quality may be a public health concern in economically disadvantaged populations of industrialised societies leading to nutritional disadvantages as well.

Serum Lycopene Concentrations and Associations with Clinical Outcomes in a Cohort of Maternal-Infant Dyads.

Oxidative stress has been associated with adverse neonatal outcomes, and many carotenoids, including lycopene, potentially have antioxidant properties. The objective of this analysis was to explore the associations between serum lycopene concentrations, including lycopene isomers, and maternal-newborn outcomes. Maternal and cord blood samples were collected in 180 mother-infant pairs. Serum of total lycopene as well as the cis- and trans-isomers concentrations were measured using HPLC (High Performance Liquid Chromatography). Descriptive statistics were calculated; Spearman coefficients were used to assess correlations between maternal and cord concentrations. The relationship between lycopene concentration and outcomes were evaluated with linear and logistic regression models, with adjustment for relevant confounders. A p ≤ 0.05 was considered statistically significant. Maternal and cord serum lycopene concentrations were positively correlated for total lycopene (r = 0.30, p < 0.0001), cis-lycopene (r = 0.29, p = 0.0002); and trans-lycopene (r = 0.32, p < 0.0001). Maternal concentrations of cis-lycopene were significantly lower in mothers whose infants developed respiratory distress syndrome compared to those who did not (0.336 ± 0.171 vs. 0.445 ± 0.238 µmol/L, p = 0.04) and also in mothers whose babies were admitted to the newborn intensive care unit compared to those who were not (0.380 ± 0.202 vs. 0.458 ± 0.244 µmol/L, p = 0.04). Conversely, cord concentrations of trans-lycopene were significantly higher in infants who developed RDS (Respiratory Distress Syndrome) (0.023 ± 0.012 vs. 0.016 ± 0.012, p = 0.007 for RDS vs. no RDS), and a similar pattern was seen NICU admission (0.023 ± 0.016 vs. 0.015 ± 0.009 µmol/L for NICU (Newborn Intensive Care Unit) admission vs. no NICU admission, p = 0.007). Maternal concentrations of total and cis-lycopene were positively associated with infant birth weight, length and head circumference after adjustment for relevant confounders. As serum carotenoids, including lycopene, are modifiable by diet, future research determining the clinical impact of these compounds is warranted.

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.

Status of Vitamin A and Related Compounds and Clinical Outcomes in Maternal-Infant Pairs in the Midwestern United States.

BACKGROUND: Vitamin A is an essential nutrient for pregnant women, and other vitamin A-related compounds, including lutein and lycopene, have been associated with maternal-infant outcomes. The objective of this study was to quantify the status of vitamin A and related compounds in maternal-infant pairs at the time of delivery, and to determine its impact on clinical outcomes. METHODS: Maternal and cord blood samples were collected in 189 mother-infant pairs. Concentrations of lutein + zeaxanthin, ß-cryptoxanthin, lycopene, carotenes, and retinol were measured using high-performance liquid chromatography. Descriptive statistics was calculated and Spearman coefficients were used to assess correlations between maternal and cord measurements. Kruskal-Wallis and independent samples t test were used to compare measures between retinol groups. Linear and logistic regression models were used to adjust for relevant confounders. p < 0.05 was considered statistically significant. RESULTS: Ten percent of mothers had serum retinol concentrations ≤0.70 µmol/L; 80% of infants had serum retinol concentrations ≤0.70 µmol/L. Low maternal retinol concentrations were associated with maternal anemia (p = 0.04) and a trend toward low birth weight (p = 0.06). Maternal and infant concentrations of vitamin A compounds were highly correlated. After adjustment for confounders, maternal lutein was associated with a C-section (p = 0.03) and a diagnosis of respiratory distress syndrome in the infant (p = 0.02). Maternal lycopene was associated with growth parameters in the infant. CONCLUSIONS: As vitamin A-related compounds are modifiable by diet, future research determining the clinical impact of these compounds is warranted.

A Comparison of Nutritional Antioxidant Content in Breast Milk, Donor Milk, and Infant Formulas.

Human milk is the optimal food for human infants, including infants born prematurely. In the event that a mother of a hospitalized infant cannot provide breast milk, donor milk is considered an acceptable alternative. It is known that the macronutrient composition of donor milk is different than human milk, with variable fat content and protein content. However, much less is known about the micronutrient content of donor milk, including nutritional antioxidants. Samples of breast milk from 12 mothers of infants hospitalized in the Newborn Intensive Care Unit until were collected and analyzed for concentrations of nutritional antioxidants, including α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein + zeaxanthin, retinol, and α-tocopherol. Additionally, a homogenized sample of donor milk available from a commercial milk bank and samples of infant formulas were also analyzed. Concentrations of nutritional antioxidants were measured using high-performance liquid chromatography. Compared to breast milk collected from mothers of hospitalized infants, commercially available donor milk had 18%-53% of the nutritional antioxidant content of maternal breast milk. As donor milk is becoming a common nutritional intervention for the high risk preterm infant, the nutritional antioxidant status of donor milk-fed premature infants and outcomes related to oxidative stress may merit further investigation.