Does maternal vitamin D status influence placental weight or vascular and inflammatory pathology? Secondary analysis from the Kellogg Pregnancy Study.

INTRODUCTION: Positive effects of vitamin D (vitD) supplementation on comorbidities of pregnancy (COP) have been explored; however, few studies have elucidated the pathophysiology behind the development of these COP and the potential relationship with derangements in placental development and morphology. Additionally, it is known that placentas weighing 10th-90th % for gestational age are associated with better outcomes. Therefore, the objective of this study was to assess the impact of resulting circulating serum 25(OH)D concentrations associated with intake of high or low doses of supplementary vitD on placental development and morphology in women who participated in a randomized double blind, placebo-controlled trial of vitD supplementation. We hypothesized that if maternal serum 25(OH)D concentration (vitD status marker) is insufficient/deficient, then placental weight and % for gestational age (GA) will be smaller and will correlate with increased vascular and inflammatory placental pathologic findings. METHODS: The findings of the present study are a secondary analysis of data generated from a previously reported randomized controlled trial (RCT), the Kellogg Vitamin D Pregnancy Study. Pregnant women (n = 297) in this RCT (January 2013 - April 2018) were randomly assigned to 400 IU vs. 4400 IU vitD/day (10-14 weeks' gestational age) and followed to delivery. 132 placentas were analyzed by pathologists blinded to treatment, and the 2016 Amsterdam Consensus Criteria were used to categorize grouping/grading of placental pathology and weight. Total [25(OH)D] was measured using radioimmunoassay (ng/mL). Chi-square and Student's t-test were used to show the difference in maternal characteristics by treatment group and by placental weight. Chi-square analysis was used to determine differences between the percent pathology findings by treatment group. Students t-test was used to determine the differences in vitD status and the frequency of placental lesions. Association between [25(OH)D] area under the curve (AUC) and placental morphology were determined in a regression model that included maternal BMI ≥ 30 kg/m2, race/ethnicity, and vitD treatment group allocation. Data were analyzed using SAS v9.4 (Cary, NC) and statistical significance was indicated by p < 0.05. RESULTS: The percent pathology findings by treatment group were not significantly different for each of the placental pathology categories as defined by the 2016 Amsterdam Consensus Criteria including placental weight. However, when using 25(OH)D as a biomarker for vitD status, linear regression model showed maternal serum [25(OH)D] AUC was significantly associated with greater placental weight (p = 0.023). Logistic regression models showed mothers with BMI ≥ 30 kg/m2 had larger placental weight (p = 0.046), and Hispanic and white/Caucasian mothers had greater placental weights than Black American mothers (p = 0.025). When placentas ≥ 90th % for GA, n = 7, were removed from the placental pool, Pearson correlation still showed a positive association between maternal serum 25(OH)D AUC and placental weight (p = 0.011). In a second linear regression model of placentas ≥ 90th % for GA (n = 7) vs. placentas < 90th % (n = 108), maternal serum 25(OH)D AUC was significantly greater in those placentas ≥ 90th % (p = 0.03); however, this was not associated with increased perinatal mortality. CONCLUSION FINDINGS: suggest increasing maternal serum [25(OH)D] via vitamin D supplementation during pregnancy did not adversely affect placental morphology; trends showed those in the treatment group had fewer placental lesions. Placental weight was found to be significantly associated with [25(OH)D] AUC, which represents maternal vitamin D status over the course of pregnancy; 7 placentas ≥ 90th % for GA were not associated with perinatal mortality.

Reducing hospital-acquired pressure ulcers using bundle methodology in pediatric and neonatal patients receiving extracorporeal membrane oxygenation therapy: An integrative review and call to action.

PURPOSE: This review focuses on identifying (1) evidence of the effectiveness of care bundle methodology to reduce hospital-acquired pressure ulcers (HAPUs) in pediatric and neonatal patients receiving extracorporeal membrane oxygenation (ECMO) therapy and (2) barriers to implementing HAPU care bundles in this at-risk population. DESIGN AND METHODS: An integrative review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search of the scientific literature was performed. Studies included were published between January 2011 and February 2016. A total of seven articles met inclusion criteria. Data were extracted from each published article and analyzed to identify common themes, specifically bundle methodology and barriers to implementing HAPU bundles, in this population. RESULTS: There is limited research on effectiveness of care bundle methodology in reducing HAPUs in children, and no research specific to its effectiveness in pediatric or neonatal ECMO patients. No research was identified studying barriers to implementation of HAPU care bundles in this population. PRACTICE IMPLICATIONS: Nurses are well poised to test innovative strategies to prevent HAPUs. Nurses should consider implementing and testing bundle methodology to reduce HAPU in this at-risk population, and conduct research to identify any barriers to implementing this strategy. There is literature to support the use of nurses as unit-based skin care champions to facilitate teamwork and reliable use of the bundle, both critical components to the success of bundle methodology.

Preliminary Results of the Adoption and Application of the Integrated Comprehensive Care Bundle Care Program When Treating Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: St. Joseph's Health System has implemented an integrated comprehensive care bundle care (ICC) program with the hopes that it would improve patients' care while reducing overall costs. The aim of this analysis was to evaluate the performance of the ICC program within patients admitted with chronic pulmonary obstructive disease (COPD). METHODS: We conducted a retrospective observational cohort study comparing ICC patients to non-ICC patients admitted to St. Joseph's Healthcare Hamilton for COPD being discharged with support services between June 2012 and March 2015, using administrative data. Confounding adjustment was achieved through the use of propensity score matching. Medical resource utilizations during the initial hospitalization and within the 60 days following discharge were compared using regression models. RESULTS: All 76 patients who entered the ICC program (100.0%) were matched 1 : 1 to 76 eligible non-ICC patients (28.4%). Length of stay (6.47 [7.29] versus 9.55 [10.21] days) and resource intensity weights (1.16 [0.80] versus 1.64 [1.69]) were lower in the ICC group within the initial hospitalization but, while favoring the ICC program, healthcare resource use tended not to differ statistically following discharge. INTERPRETATION: The ICC program was able to reduce initial medical resource utilization without increasing subsequent medical resource use.

Fetal blood sampling.

OBJECTIVE: We sought to review indications, technical aspects, risks, and recommendations for fetal blood sampling (FBS). METHODS: A systematic review was performed using MEDLINE, PubMed, EMBASE, and Cochrane Library using the terms "fetal blood sampling," "percutaneous umbilical blood sampling," and "cordocentesis." The search was restricted to English-language articles published from 1966 through July 2012. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Evidence reports and guidelines published by organizations or institutions such as the National Institutes of Health, Agency for Health Research and Quality, American Congress of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. Grade (Grading of Recommendations Assessment, Development, and Evaluation) methodology was employed for defining strength of recommendations and rating quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence. RESULTS AND RECOMMENDATIONS: Ultrasound-guided FBS is the only procedure that provides direct access to the fetal circulation. When invasive testing is planned for suspected severe fetal anemia or thrombocytopenia, we recommend FBS as the procedure of choice, with availability of immediate transfusion if confirmed. We recommend against the use of FBS for indications in which other less invasive, and therefore lower risk, alternatives are available. The overall success rate of FBS is high, and blood samples can be obtained in >98% of patients. We suggest that counseling for FBS include discussion about the potential risk of FBS that may include, but may not be limited to: bleeding from puncture site (20-30%); fetal bradycardia (5-10%); pregnancy loss (≥1.3%, depending on indication, gestational age, and placental penetration); and vertical transmission of hepatitis or human immunodeficiency virus. We recommend that FBS be performed by experienced operators at centers with expertise in invasive fetal procedures when feasible.

Health characteristics and outcomes of two randomized vitamin D supplementation trials during pregnancy: a combined analysis.

OBJECTIVE: To assess the safety and health effects of vitamin D supplementation during pregnancy. METHODS AND DESIGN: Datasets from two randomized clinical trials were first analyzed separately then combined for this analysis using a common data dictionary. In the NICHD trial, women were randomized to 400, 2000, or 4000IU vitamin D3/day, stratified by race. In the Thrasher Research Fund trial, participants were randomized to 2000 or 4000IU vitamin D3/day. Study drugs were from the same manufacturing lot for both trials. Identical questionnaires were given for comparable sociodemographics & clinical characteristics. Outcome measures were: [1] maternal and neonatal 25(OH)D achieved, and [2] maternal comorbidities of pregnancy (COP). SAS 9.3 was used for all analyses. RESULTS: In the combined cohort, there were 110 controls, 201 in the 2000IU group, and 193 in the 4000IU group. No differences between groups in baseline 25(OH)D were found; however, delivery and cord blood values were greater in the 4000IU group (p<0.0001), an effect that persisted even after controlling for race and study. A greater percent were vitamin D replete in the 4000IU group (p<0.0001). There was a trend where the 4000IU group had decreased rates of comorbidities of pregnancy. There was a strong association between COP and final maternal 25(OH)D; an effect that persisted even after controlling for race and study (p=0.006). CONCLUSIONS: Supplementation with 4000IU/day was associated with lower risk of hypovitaminosis D than Control and 2000IU groups. While not statistically significant, there was a trend toward lower rates of COP as supplementation dose increased. Maternal delivery 25(OH)D was inversely associated with any comorbidity of pregnancy, with fewer events as 25(OH)D increased. Future studies are needed to confirm these findings and determine the mechanisms of action of such effects. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

Vitamin D and its role during pregnancy in attaining optimal health of mother and fetus.

Despite its discovery a hundred years ago, vitamin D has emerged as one of the most controversial nutrients and prohormones of the 21st century. Its role in calcium metabolism and bone health is undisputed but its role in immune function and long-term health is debated. There are clear indicators from in vitro and animal in vivo studies that point to vitamin D's indisputable role in both innate and adaptive immunity; however, the translation of these findings to clinical practice, including the care of the pregnant woman, has not occurred. Until recently, there has been a paucity of data from randomized controlled trials to establish clear cut beneficial effects of vitamin D supplementation during pregnancy. An overview of vitamin metabolism, states of deficiency, and the results of recent clinical trials conducted in the U.S. are presented with an emphasis on what is known and what questions remain to be answered.

Zinc protoporphyrin-to-heme ratios in high-risk and preterm infants.

OBJECTIVES: To refine the reference range for the zinc protoporphyrin-to-heme ratio (ZnPP/H) of preterm infants, we assessed the impact of maternal risk factors on ZnPP/H and evaluated the impact of changes in iron supplementation on iron status. STUDY DESIGN: The reference range for neonatal ZnPP/H was refined using prospective data from 31 reference infants ≤ 35 weeks' postmenstrual age (PMA) plus retrospective data from 51 infants <30 weeks' PMA, and 59 infants 30-40 weeks' PMA. Cord blood and first week of life values were compared when both were available. The impact of maternal risk factors was assessed by examining prospectively collected ZnPP/H from 48 high-risk infants. The effect of changing iron supplementation guidelines was evaluated by retrospective chart review of serial ZnPP/H from 194 infants. RESULTS: Cord ZnPP/H was lower at 30-35 weeks' gestation than at 24-26 weeks' gestation (P = .01). Cord ZnPP/H values from insulin-dependent diabetic mothers were elevated compared with reference values. Changing the iron supplementation protocol was not associated with improved ZnPP/H measurements. CONCLUSIONS: Cord blood and postnatal reference ranges for ZnPP/H are defined. Iron balance depends on a complex interaction of prenatal and postnatal factors.

Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness.

The need, safety, and effectiveness of vitamin D supplementation during pregnancy remain controversial. In this randomized, controlled trial, women with a singleton pregnancy at 12 to 16 weeks' gestation received 400, 2000, or 4000 IU of vitamin D(3) per day until delivery. The primary outcome was maternal/neonatal circulating 25-hydroxyvitamin D [25(OH)D] concentration at delivery, with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] production. Of the 494 women enrolled, 350 women continued until delivery: Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different (p < 0.0001), and the percent who achieved sufficiency was significantly different by group, greatest in 4000-IU group (p < 0.0001). The relative risk (RR) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000- and the 400-IU groups (RR = 1.52, 95% CI 1.24-1.86), the 4000- and the 400-IU groups (RR = 1.60, 95% CI 1.32-1.95) but not between the 4000- and. 2000-IU groups (RR = 1.06, 95% CI 0.93-1.19). Circulating 25(OH)D had a direct influence on circulating 1,25(OH)(2)D(3) concentrations throughout pregnancy (p < 0.0001), with maximal production of 1,25(OH)(2)D(3) in all strata in the 4000-IU group. There were no differences between groups on any safety measure. Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels. It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race, whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations, especially in African Americans.

A selective androgen receptor modulator with minimal prostate hypertrophic activity restores lean body mass in aged orchidectomized male rats.

Androgens are required for the maintenance of normal sexual activity in adulthood and for enhancing muscle growth and lean body mass in adolescents and adults. Androgen receptor (AR) ligands with tissue selectivity (selective androgen receptor modulators, or SARMs) have potential for treating muscle wasting, hypogonadism of aging, osteoporosis, female sexual dysfunction, and other indications. JNJ-37654032 is a nonsteroidal AR ligand with mixed agonist and antagonist activity in androgen-responsive cell-based assays. It is an orally active SARM with muscle selectivity in orchidectomized rat models. It stimulated growth of the levator ani muscle with ED(50) 0.8 mg/kg, stimulating maximal growth at a dose of 3mg/kg. In contrast, it stimulated ventral prostate growth to 21% of its full size at 3mg/kg. At the same time, JNJ-37654032 reduced prostate weight in intact rats by 47% at 3mg/kg, while having no inhibitory effect on muscle. Using magnetic resonance imaging to monitor body composition, JNJ-37654032 restored about 20% of the lean body mass lost following orchidectomy in aged rats. JNJ-37654032 reduced follicle-stimulating hormone levels in orchidectomized rats and reduced testis size in intact rats. JNJ-37654032 is a potent prostate-sparing SARM with the potential for clinical benefit in muscle-wasting diseases.

Promoting family meals in WIC: lessons learned from a statewide initiative.

The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program in Washington State developed a module to be used at local WIC agencies to promote family meals. Needs assessment and formative evaluation ensured that the module met the needs of WIC staff and clients. The Promoting Family Meals module includes background information on family meals, tools for training WIC staff, outlines for group sessions, handouts tailored to each client's stage of change, children's coloring sheets, bookmarks, banners, and posters. After the first 6 months of use, there was a statistically significant (F = 26.17, df = 3, P < .001) increase in family meal participation in intervention agencies as compared to controls.

Synthesis and biological activities of novel beta-carbolines as PDE5 inhibitors.

A series of N(2)-furoyl and N(2)pyrimidinyl beta-carbolines was discovered to possess potent inhibitory activity against PDE5. During the synthesis we developed a tandem resin quenching protocol, which allowed us to synthesize large number of target compounds in a rapid fashion. Representative compounds exhibit superior selectivity to sildenafil versus other isozymes of PDEs, and demonstrated in vivo efficacy in increasing introcavernosal pressure in dogs.