Integrated enhanced cognitive behavioural (I-CBTE) therapy significantly improves effectiveness of inpatient treatment of anorexia nervosa in real life settings.

BACKGROUND: Inpatient treatment of anorexia nervosa can be lifesaving but is associated with high rates of relapse and poor outcomes. To address this, the Oxford service has adapted the enhanced cognitive behavioural treatment (CBTE) model, first developed for inpatients in Italy to a UK national health service (NHS) setting. In this study, we compared the outcomes from treatment as usual (TAU), integrated CBTE (I-CBTE), and alternative treatment models in routine UK clinical practice. METHODS: This is a longitudinal cohort study, using routinely collected data between 2017 and 2020 involving all adults with anorexia nervosa admitted to specialist units from a large geographical area in England covering a total population of 3.5 million. We compared TAU with (1) I-CBTE (13 weeks inpatient CBTE, restoration to a healthy weight, combined with 7 weeks day treatment followed by 20 weeks of outpatient CBTE; (2) standalone inpatient CBTE (due to insufficient resources since the pandemic; and (3) 6-8 weeks admission with partial weight restoration as crisis management. Primary outcome measures (min. 1 year after discharge from hospital) were defined as: (1) good outcome: Body Mass Index (BMI) > 19.5 and no abnormal eating or compensatory behaviours; (2) poor outcome: BMI < 19.5 and/or ongoing eating disorder behaviours; (3) readmission; or (4) deceased. Secondary outcomes were BMI on discharge, and length of stay. RESULTS: 212 patients were admitted to 15 specialist units in the UK depending on bed availability. The mean age was 28.9 (18-60) years, mean admission BMI was 14.1 (10-18.3), 80% were voluntary. At minimum 1-year follow up after discharge, 70% of patients receiving I-CBTE and 29% standalone inpatient CBTE maintained good outcomes, in contrast with < 5% TAU and crisis management admission. Readmission rates of I-CBTE were 14.3% vs ~ 50% (χ2 < 0.0001) in the other groups. The main predictors of good outcome were reaching healthy BMI by discharge, I-CBTE and voluntary status. Age, psychiatric comorbidity and length of stay did not predict outcomes. BMI on discharge and length of stay were significantly better in the CBTE groups than in TAU. CONCLUSIONS: Our main finding is that in a real-life setting, I-CBTE has superior short- and minimum 1 year outcomes as compared with alternative inpatient treatment models. Dissemination of I-CBTE across the care pathway has the potential to transform outcomes of inpatient treatment for this high-risk patient population and reduce personal and societal costs.

Outcomes for adults requiring inpatient treatment for anorexia nervosa are poor. The aim of this work was to evaluate a recently introduced Integrated Cognitive Behavioural Therapy (I-CBTE) in Oxford, adapted from a model first developed for inpatients in Italy, compared with alternative inpatient treatment programmes in the UK. I-CBTE is an innovative approach which combines a time limited, planned admission of 13-weeks with the goal of full weight restoration, 7-weeks day treatment and ongoing outpatient CBTE. Treatment as usual includes an eclectic multidisciplinary approach, which is often unplanned and poorly coordinated across the care pathway in routine practice.Between 2017 and 2020, we systematically analysed routinely collected data for patients admitted to 15 specialist units from a population of 3.5million in England. We looked at outcomes between admission and discharge, and at one year follow up. 70% of patients receiving I-CBTE, maintained healthy weight at one year after discharge from hospital (without binging or purging), in contrast with less than 5% of those in alternative programmes that result in partial weight restoration. Readmission rates were 14.3% and ~ 50% respectively. Partial weight restoration resulted in high readmission rates and therefore should be discouraged.Our findings show that continuity and consistency of the I-CBTE approach are fundamental for maintaining good outcomes.

Risk, demand, capacity and outcomes in adult specialist eating disorder services in South-East of England before and since COVID-19.

AIMS AND METHOD: This is a longitudinal cohort study describing the demand, capacity and outcomes of adult specialist eating disorder in-patient services covering a population of 3.5 million in a South-East England provider collaborative before and since the COVID-19 pandemic, between July 2018 and March 2021. RESULTS: There were 351 referrals for admission; 97% were female, 95% had a diagnosis of anorexia nervosa and 19% had a body mass index (BMI) <13. Referrals have increased by 21% since the start of pandemic, coinciding with reduced capacity. Waiting times have increased from 33 to 46 days. There were significant differences in outcomes between providers. A novel, integrated enhanced cognitive behaviour theapy treatment model showed a 25% reduction in length of stay and improved BMI on discharge (50% v. 16% BMI >19), compared with traditional eclectic in-patient treatment. CLINICAL IMPLICATIONS: Integrated enhanced cognitive behaviour theapy reduced length of stay and improved outcomes, and can offer more effective use of healthcare resources.

Practice What We Preach: Beginning a Journey to Embrace Patient-Centered Outcomes Research.

BACKGROUND: Patient-centered outcomes research seeks to answer patient-centered questions. The process includes varied locations and individuals throughout the care continuum to address individual differences and constraints in implementation and dissemination. PROBLEM: This paper intends to answer this question: do academic nurses practice what they preach by assisting patient-centered outcomes research and researchers through their engagement with patients, caregivers, and other community stakeholder partners in nursing research? APPROACH: This paper provides an overview of how academic nurses in a single institution (the University of Texas Medical Branch at Galveston School of Nursing) began to embrace patient-centered outcomes research. CONCLUSION: Whether academic nurses are practicing what they preach in terms of patient-centered outcomes research remains uncertain. More examples from academia are required to make that determination. Academic nurses worldwide have embarked on a steep learning curve to embrace patient-centered outcomes research. This journey will require patience and a systematic strategy.

Applying Ethical Principles When Discussing Alcohol Use During Pregnancy.

Over the past 2 decades, more women in the United States are engaging in excessive alcohol use, including women of reproductive age. Consuming alcohol in amounts greater than recommended limits is associated with an increased risk for adverse health effects, such as breast cancer, hypertension stroke, spontaneous abortion, and infertility. No safe time, safe amount, or safe type of alcohol to consume during pregnancy has been identified. Contradictory beliefs about alcohol use, fear of stigmatization, and potential legal consequences can provide challenges for health care providers who communicate these risks to clients. Health care providers can help to prevent alcohol-related health issues, including alcohol-exposed pregnancies, by providing their clients with factual information about alcohol and health and client-centered options for reducing their health risks. Clinicians can use alcohol screening and brief intervention as a framework for applying the ethical principles of autonomy, veracity, beneficence, and nonmaleficence when talking with women in ways that are nonstigmatizing and supportive to help reduce their health risks and prevent alcohol-exposed pregnancies.

Maternal Vitamin D Deficiency Causes Sustained Impairment of Lung Structure and Function and Increases Susceptibility to Hyperoxia-induced Lung Injury in Infant Rats.

Vitamin D deficiency (VDD) during pregnancy is associated with increased respiratory morbidities and risk for chronic lung disease after preterm birth. However, the direct effects of maternal VDD on perinatal lung structure and function and whether maternal VDD increases the susceptibility of lung injury due to hyperoxia are uncertain. In the present study, we sought to determine whether maternal VDD is sufficient to impair lung structure and function and whether VDD increases the impact of hyperoxia on the developing rat lung. Four-week-old rats were fed VDD chow and housed in a room shielded from ultraviolet A/B light to achieve 25-hydroxyvitamin D concentrations <10 ng/ml at mating and throughout lactation. Lung structure was assessed at 2 weeks for radial alveolar count, mean linear intercept, pulmonary vessel density, and lung function (lung compliance and resistance). The effects of hyperoxia for 2 weeks after birth were assessed after exposure to fraction of inspired oxygen of 0.95. At 2 weeks, VDD offspring had decreased alveolar and vascular growth and abnormal airway reactivity and lung function. Impaired lung structure and function in VDD offspring were similar to those observed in control rats exposed to postnatal hyperoxia alone. Maternal VDD causes sustained abnormalities of distal lung growth, increases in airway hyperreactivity, and abnormal lung mechanics during infancy. These changes in VDD pups were as severe as those measured after exposure to postnatal hyperoxia alone. We speculate that antenatal disruption of vitamin D signaling increases the risk for late-childhood respiratory disease.

Maternal vitamin D deficiency induces transcriptomic changes in newborn rat lungs.

Vitamin D deficiency (VDD) during pregnancy is common and related to several maternal and fetal morbidities. Vitamin D (VD) plays a role in normal lung development and VDD causes abnormal airway, alveolar, and vascular growth in newborn rats. Here we use an unbiased transcriptomic approach to identify pathways altered in the lungs of offspring from VDD dams. The lungs of newborn offspring from VD replete and VDD dams were removed and RNA from these samples were analyzed using Affymetrix microarrays. Data were RMA normalized, differential gene expression was determined using Significance Analysis of Microarrays (5 % FDR) and pathway enrichment analysis was assessed. There were 2233 differentially expressed transcripts between the VDD and control lungs (1889 up, 344 down). Consistent with the suppression of lung growth in the VDD group, there were significant suppression of signal transduction pathways related to vascular biology and anabolic signaling pathways, e.g. the insulin-like growth factor-1 receptor (IGF-1R), fibroblast growth factor (FGF), cell cycle control. A major, enriched functional category was upregulation of pathways related to the innate immune system, including pathways for granulocyte and macrophage development, chemotaxis, and activation of cytokine signaling through Jak/Stat (e.g. resulting in higher IL1 α and ß). We conclude that VDD during fetal development alters multiple pathways beyond the predicted angiogeneic alterations. These changes either contribute to, or reflect, the abnormal airway, alveolar, and vascular growth seen in the neonatal lung resulting from maternal VDD. The pattern also suggests abnormal lung development caused by maternal VDD creates a proinflammatory milieu that could contribute to the suppression of lung growth and development.

Antenatal Endotoxin Impairs Lung Mechanics and Increases Sensitivity to Ventilator-Induced Lung Injury in Newborn Rat Pups.

Perinatal inflammation due to chorioamnionitis and ventilator-induced lung injury (VILI) at birth is independent risk factors for the development of bronchopulmonary dysplasia (BPD). We have previously shown that antenatal endotoxin (ETX) causes abnormal lung structure and function in 2-week-old rats, but whether ETX impairs lung mechanics at birth and increases risk for VILI is unknown. Fetal rats were exposed to 10 µg endotoxin or saline via intra-amniotic injection. At birth (D0) or 7 days (D7), rats received 90 min of lung protective ventilation [PROTECT group; tidal volume (Vt) = 6 ml/kg with positive end expiratory pressure (PEEP) = 2 cmH2O]; P20 ventilation [plateau pressure (Pplat) = 20 cmH2O, PEEP = 0]; or P24 ventilation (Pplat = 24 cmH2O, PEEP = 0, only applied to D7). Prior to prolonged ventilation at D0, endotoxin-exposed rats had decreased compliance and inspiratory capacity (IC) compared to controls. At D7, endotoxin was associated with reduced compliance. High-pressure ventilation (P20 and P24) tended to increase IC and compliance in all saline-treated groups. Ventilation at D0 with P20 increased IC and compliance when applied to saline-treated but not endotoxin-exposed pups. At D7, P24 ventilation of endotoxin-exposed pups increased elastance, bronchoalveolar lavage protein content, and IL-1b and TEN-C mRNA expression in comparison to the saline group. In summary, antenatal endotoxin exposure alters lung mechanics at birth and 1 week of life and increases susceptibility to VILI as observed in lung mechanics, alveolocapillary barrier injury, and inflammatory mRNA expression. We speculate that antenatal inflammation primes the lung for a more marked VILI response, suggesting an adverse synergistic effect of antenatal and postnatal exposures.

Do safety briefings improve patient safety in the acute hospital setting? A systematic review.

AIMS: To synthesize current knowledge about the impact of safety briefings as an intervention to improve patient safety. BACKGROUND: Improving safety in health care remains an ongoing challenge. There is a lack of evidence underpinning safety enhancing interventions. DESIGN: Mixed method multi-level synthesis. DATA SOURCES: Four health literature databases were searched (Cinahl, Medline, Scopus and Health Business Elite) from January 2002 - March 2017. REVIEW METHODS: Thomas and Harden approach to mixed method synthesis. RESULTS: Following quality appraisal, 12 studies were included. There was significant heterogeneity in study aims, measures, and outcomes. Findings showed that safety briefings achieved beneficial outcomes and can improve safety culture. Outcomes included improved risk identification, reduced falls, enhanced relationships, increased incident reporting, ability to voice concerns, and reduced length of stay. CONCLUSION: Healthcare leaders should embrace the potential of safety briefings by promoting their effective use whilst allowing for local adaptation.

Antenatal Vitamin D Preserves Placental Vascular and Fetal Growth in Experimental Chorioamnionitis Due to Intra-amniotic Endotoxin Exposure.

BACKGROUND: Chorioamnionitis (CA) is associated with a high risk for the development of bronchopulmonary dysplasia (BPD) after preterm birth, but mechanisms that increase susceptibility for BPD and strategies to prevent BPD are uncertain. As a model of CA, antenatal intra-amniotic (IA) endotoxin (ETX) exposure alters placental structure, causes fetal growth restriction, increases perinatal mortality, and causes sustained cardiorespiratory abnormalities throughout infancy. Vitamin D (Vit D) has been shown to have both anti-inflammatory and proangiogenic properties. Antenatal IA treatment with Vit D (1,25-(OH)2D3) during IA ETX exposure improves survival and increases vascular and alveolar growth in infant rats. Whether IA ETX causes decreased placental vascular development and if the protective effects of prenatal Vit D treatment are due to direct effects on the fetus or to improved placental vascular development remain unknown. OBJECTIVE: The objective of this study was to determine if IA ETX impairs placental vascular development and Vit D metabolism, and whether 1,25-(OH)2D3 treatment improves placental vascularity after IA ETX exposure during late gestation in pregnant rats. DESIGN/METHODS: Fetal rats were exposed to ETX (10 mg), ETX + 1,25-(OH)2D3 (1 ng/mL), 1,25-(OH)2D3 (1 ng/mL), or saline (control) via IA injection at E20 and delivered 2 days later. To assess placental vascular development, histologic sections from the placenta were stained for CD31 and vessel density per high power field (HPF) was determined and analyzed using Matlab software. To determine the effects of ETX on placental Vit D metabolism, Vit D receptor (VDR) and activity of the Vit D conversion enzyme, CYP27B1, were assayed from placental homogenates. Angiogenic mediators were measured by reverse transcription polymerase chain reaction by RNA extracted from placental tissue. RESULTS: IA ETX reduced placenta and newborn birth weights by 22 and 20%, respectively, when compared with controls (placental weight: 0.60 vs. 0.47 g; p < 0.0001; birth weight: 4.68 vs. 5.88 g; p < 0.0001). IA 1,25-(OH)2D3 treatment increased birth weight by 12% in ETX-exposed pups (5.25 vs. 4.68 g; p < 0.001). IA ETX decreased placental vessel density by 24% in comparison with controls (1,114 vs. 848 vessels per HPF; p < 0.05). Treatment with IA 1,25-(OH)2D3 increased placenta vessel density twofold after ETX exposure (1,739 vs. 848); p < 0.0001), and increased vessel density compared with saline controls by 56% (1,739 vs. 1,114; p < 0.0001). IA ETX decreased both VDR and CYP27B1 expression by 83 and 35%, respectively (p < 0.01). CONCLUSION: IA ETX decreases placental growth and vessel density and decreases placental VDR and CYP27B1 protein expression, and that antenatal 1,25-(OH)2D3 restores placental weight and vessel density, as well as birth weight. We speculate that 1,25-(OH)2D3 treatment preserves placental function in experimental CA and that these effects may be mediated by increased vascular growth.

Likelihood of cesarean delivery after applying leading active labor diagnostic guidelines.

BACKGROUND: Friedman, the United Kingdom's National Institute for Health and Care Excellence (NICE), and the American College of Obstetricians and Gynecologists/Society for Maternal-Fetal Medicine (ACOG/SMFM) support different active labor diagnostic guidelines. Our aims were to compare likelihoods for cesarean delivery among women admitted before vs in active labor by diagnostic guideline (within-guideline comparisons) and between women admitted in active labor per one or more of the guidelines (between-guideline comparisons). DESIGN: Active labor diagnostic guidelines were retrospectively applied to cervical examination data from nulliparous women with spontaneous labor onset (n = 2573). Generalized linear models were used to determine outcome likelihoods within- and between-guideline groups. RESULTS: At admission, 15.7%, 48.3%, and 10.1% of nulliparous women were in active labor per Friedman, NICE, and ACOG/SMFM diagnostic guidelines, respectively. Cesarean delivery was more likely among women admitted before vs in active labor per the Friedman (AOR 1.75 [95% CI 1.08-2.82] or NICE guideline (AOR 2.55 [95% CI 1.84-3.53]). Between guidelines, cesarean delivery was less likely among women admitted in active labor per the NICE guideline, as compared with the ACOG/SMFM guideline (AOR 0.55 [95% CI 0.35-0.88]). CONCLUSION: Many nulliparous women are admitted to the hospital before active labor onset. These women are significantly more likely to have a cesarean delivery. Diagnosing active labor before admission or before intervention to speed labor may be one component of a multi-faceted approach to decreasing the primary cesarean rate in the United States. The NICE diagnostic guideline is more inclusive than Friedman or ACOG/SMFM guidelines and its use may be the most clinically useful for safely lowering cesarean rates.

Hepatocyte growth factor as a downstream mediator of vascular endothelial growth factor-dependent preservation of growth in the developing lung.

Impaired vascular endothelial growth factor (VEGF) signaling contributes to the pathogenesis of bronchopulmonary dysplasia (BPD). We hypothesized that the effects of VEGF on lung structure during development may be mediated through its downstream effects on both endothelial nitric oxide synthase (eNOS) and hepatocyte growth factor (HGF) activity, and that, in the absence of eNOS, trophic effects of VEGF would be mediated through HGF signaling. To test this hypothesis, we performed an integrative series of in vitro (fetal rat lung explants and isolated fetal alveolar and endothelial cells) and in vivo studies with normal rat pups and eNOS(-/-) mice. Compared with controls, fetal lung explants from eNOS(-/-) mice had decreased terminal lung bud formation, which was restored with recombinant human VEGF (rhVEGF) treatment. Neonatal eNOS(-/-) mice were more susceptible to hyperoxia-induced inhibition of lung growth than controls, which was prevented with rhVEGF treatment. Fetal alveolar type II (AT2) cell proliferation was increased with rhVEGF treatment only with mesenchymal cell (MC) coculture, and these effects were attenuated with anti-HGF antibody treatment. Unlike VEGF, HGF directly stimulated isolated AT2 cells even without MC coculture. HGF directly stimulates fetal pulmonary artery endothelial cell growth and tube formation, which is attenuated by treatment with JNJ-38877605, a c-Met inhibitor. rHGF treatment preserves alveolar and vascular growth after postnatal exposure to SU-5416, a VEGF receptor inhibitor. We conclude that the effects of VEGF on AT2 and endothelial cells during lung development are partly mediated through HGF-c-Met signaling and speculate that reciprocal VEGF-HGF signaling between epithelia and endothelia is disrupted in infants who develop BPD.

Labor Dystocia: Uses of Related Nomenclature.

INTRODUCTION: Labor dystocia (slow or difficult labor or birth) is the most commonly diagnosed aberration of labor and the most frequently documented indication for primary cesarean birth. Yet, dystocia remains a poorly specified diagnostic category, with determinations often varying widely among clinicians. The primary aims of this review are to 1) summarize definitions of active labor and dystocia, as put forth by leading professional obstetric and midwifery organizations in world regions wherein English is the majority language and 2) describe the use of dystocia and related terms in contemporary research studies. METHODS: Major national midwifery and obstetric organizations from qualifying United Nations-member sovereign nations and international organizations were searched to identify guidelines providing definitions of active labor and dystocia or related terms. Research studies (2000-2013) were systematically identified via PubMed, MEDLINE, and CINAHL searches to describe the use of dystocia and related terms in contemporary scientific publications. RESULTS: Only 6 organizational guidelines defined dystocia or related terms. Few research teams (n = 25 publications) defined dystocia-related terms with nonambiguous clinical parameters that can be applied prospectively. There is heterogeneity in the nomenclature used to describe dystocia, and when a similar term is shared between guidelines or research publications, the underlying definition of that term is sometimes inconsistent between documents. DISCUSSION: Failure to define dystocia in evidence-based, well-described, clinically meaningful terms that are widely acceptable to and reproducible among clinicians and researchers is concerning at both national and global levels. This failure is particularly problematic in light of the major contribution of this diagnosis to primary cesarean birth rates.

Labor Dystocia: A Common Approach to Diagnosis.

Contemporary labor and birth population norms should be the basis for evaluating labor progression and determining slow progress that may benefit from intervention. The aim of this article is to present guidelines for a common, evidence-based approach for determination of active labor onset and diagnosis of labor dystocia based on a synthesis of existing professional guidelines and relevant contemporary publications. A 3-point approach for diagnosing active labor onset and classifying labor dystocia-related labor aberrations into well-defined, mutually exclusive categories that can be used clinically and validated by researchers is proposed. The approach comprises identification of 1) an objective point that strictly defines active labor onset (point of active labor determination); 2) an objective point that identifies when labor progress becomes atypical, beyond which interventions aimed at correcting labor dystocia may be justified (point of protraction diagnosis); and 3) an objective point that identifies when interventions aimed at correcting labor dystocia, if used, can first be determined to be unsuccessful, beyond which assisted vaginal or cesarean birth may be justified (earliest point of arrest diagnosis). Widespread adoption of a common approach for diagnosing labor dystocia will facilitate consistent evaluation of labor progress, improve communications between clinicians and laboring women, indicate when intervention aimed at speeding labor progress or facilitating birth may be appropriate, and allow for more efficient translation of safe and effective management strategies into clinical practice. Correct application of the diagnosis of labor dystocia may lead to a decrease in the rate of cesarean birth, decreased health care costs, and improved health of childbearing women and neonates.

Antenatal endotoxin disrupts lung vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase expression in the developing rat.

Vitamin D [vit D; 1,25-(OH)2D] treatment improves survival and lung alveolar and vascular growth in an experimental model of bronchopulmonary dysplasia (BPD) after antenatal exposure to endotoxin (ETX). However, little is known about lung-specific 1,25-(OH)2D3 regulation during development, especially regarding maturational changes in lung-specific expression of the vitamin D receptor (VDR), 1α-hydroxylase (1α-OHase), and CYP24A1 during late gestation and the effects of antenatal ETX exposure on 1,25-(OH)2D3 metabolism in the lung. We hypothesized that vit D regulatory proteins undergo maturation regulation in the late fetal and early neonatal lung and that prenatal exposure to ETX impairs lung growth partly through abnormal endogenous vit D metabolism. Normal fetal rat lungs were harvested between embryonic day 15 and postnatal day 14. Lung homogenates were assayed for VDR, 1α-OHase, and CYP24A1 protein contents by Western blot analysis. Fetal rats were injected on embryonic day 20 with intra-amniotic ETX, ETX + 1,25-(OH)2D3, or saline and delivered 2 days later. Pulmonary artery endothelial cells (PAECs) from fetal sheep were assessed for VDR, 1α-OHase, and CYP24A1 expression after treatment with 25-(OH)D3, 1,25-(OH)2D3, ETX, ETX + 25-(OH)D3, or ETX + 1,25-(OH)2D3. We found that lung VDR, 1α-OHase, and CYP2741 protein expression dramatically increase immediately before birth (P < 0.01 vs. early fetal values). Antenatal ETX increases CYP24A1 expression (P < 0.05) and decreases VDR and 1α-OHase expression at birth (P < 0.001), but these changes are prevented with concurrent vit D treatment (P < 0.001). ETX-induced reduction of fetal PAEC growth and tube formation and lung 1α-OHase expression are prevented by vit D treatment (P < 0.001). We conclude that lung VDR, 1α-OHase, and CYP24A1 protein content markedly increase before birth and that antenatal ETX disrupts lung vit D metabolism through downregulation of VDR and increased vit D catabolic enzyme expression, including changes in developing endothelium. We speculate that endogenous vitamin D metabolism modulates normal fetal lung development and that prenatal disruption of vit D signaling may contribute to impaired postnatal lung growth at least partly through altered angiogenic signaling.

Outcomes of nulliparous women with spontaneous labor onset admitted to hospitals in preactive versus active labor.

INTRODUCTION: The timing of when a woman is admitted to the hospital for labor care following spontaneous contraction onset may be among the most important decisions that labor attendants make because it can influence care patterns and birth outcomes. The aims of this study were to estimate the percentage of low-risk, nulliparous women at term who are admitted to labor units prior to active labor and to evaluate the effects of the timing of admission (ie, preactive vs active labor) on labor interventions and mode of birth. METHODS: Data from low-risk, nulliparous women with spontaneous labor onset at term gestation were merged from 2 prospective studies conducted at 3 large Midwestern hospitals. Baseline characteristics, labor interventions, and outcomes were compared between groups using Fisher's exact and Mann-Whitney U tests, as appropriate. Likelihoods for oxytocin augmentation, amniotomy, and cesarean birth were assessed by logistic regression. RESULTS: Of the sample of 216 low-risk nulliparous women, 114 (52.8%) were admitted in preactive labor and 102 (47.2%) were admitted in active labor. Women who were admitted in preactive labor were more likely to undergo oxytocin augmentation (84.2% and 45.1%, respectively; odds ratio [OR], 6.5; 95% confidence interval [CI], 3.43-12.27) but not amniotomy (55.3% and 61.8%, respectively; OR, 0.8; 95% CI, 0.44-1.32) when compared to women admitted in active labor. The likelihood of cesarean birth was higher for women admitted before active labor onset (15.8% and 6.9%, respectively; OR, 2.6; 95% CI, 1.02-6.37). DISCUSSION: Many low-risk nulliparous women with regular, spontaneous uterine contractions are admitted to labor units before active labor onset, which increases their likelihood of receiving oxytocin and giving birth via cesarean. An evidence-based, standardized approach for labor admission decision making is recommended to decrease inadvertent admissions of women in preactive labor. When active labor cannot be diagnosed with relative certainty, observation before admission to the birthing unit is warranted.

Cord blood endothelial colony-forming cells from newborns with congenital diaphragmatic hernia.

Endothelial colony-forming cells (ECFCs) are decreased in the cord blood of preterm infants with moderate-to-severe bronchopulmonary dysplasia. We quantified ECFCs from infants with congenital diaphragmatic hernia, a neonatal disorder with severe lung hypoplasia. Unlike newborns who develop bronchopulmonary dysplasia, those with congenital diaphragmatic hernia had increased and highly-proliferative cord blood ECFCs.

Endothelial colony-forming cell conditioned media promote angiogenesis in vitro and prevent pulmonary hypertension in experimental bronchopulmonary dysplasia.

Late-outgrowth endothelial colony-forming cells (ECFCs), a type of circulating endothelial progenitor cell (EPC), may contribute to pulmonary angiogenesis during development. Cord blood ECFCs from preterm newborns proliferate more rapidly than term ECFCs but are more susceptible to the adverse effects of hyperoxia. Recent studies suggest that bone marrow-derived EPCs protect against experimental lung injury via paracrine mechanisms independent of vascular engraftment. To determine whether human umbilical cord blood ECFCs from preterm and term newborns have therapeutic benefit in experimental neonatal lung injury, we isolated cord blood ECFCs from full-term and preterm newborns and prepared ECFC-conditioned medium (CM) to test its therapeutic benefit on fetal pulmonary artery endothelial cell (PAEC) proliferation and function as well as alveolar type 2 (AT2) cell growth. PAECs and AT2 cells were isolated from late-gestation fetal sheep. Additionally, we administered both ECFCs and ECFC-CM to bleomycin-exposed newborn rats, an experimental model of bronchopulmonary dysplasia (BPD). Both term ECFC-CM and preterm ECFC-CM promoted cell growth and angiogenesis in vitro. However, when ECFC-CM was collected during exposure to mild hyperoxia, the benefit of preterm ECFC-CM was no longer observed. In the bleomycin model of BPD, treatment with ECFC-CM (or CM from mature EC) effectively decreased right ventricular hypertrophy but had no effect on alveolar septation. We conclude that term ECFC-CM is beneficial both in vitro and in experimental BPD. During oxidative stress, preterm ECFC-CM, but not term ECFC-CM, loses its benefit. The inability of term ECFC-CM to promote alveolarization may limit its therapeutic potential.

Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is associated with impaired vascular and alveolar growth. Antenatal factors contribute to the risk for developing BPD by unclear mechanisms. Endothelial progenitor cells, such as angiogenic circulating progenitor cells (CPCs) and late-outgrowth endothelial colony-forming cells (ECFCs), may contribute to angiogenesis in the developing lung. We hypothesise that cord blood angiogenic CPCs and ECFCs are decreased in preterm infants with moderate and severe BPD. We quantified ECFCs and the CPC/nonangiogenic-CPC ratio (CPC/non-CPC) in cord blood samples from 62 preterm infants and assessed their relationships to maternal and perinatal risk factors as well as BPD severity. The CPC/non-CPC ratio and ECFC number were compared between preterm infants with mild or no BPD and those with moderate or severe BPD. ECFC number (p<0.001) and CPC/non-CPC ratio (p<0.05) were significantly decreased in cord blood samples of preterm infants who subsequently developed moderate or severe BPD. Gestational age and birth weight were not associated with either angiogenic marker. Circulating vascular progenitor cells are decreased in the cord blood of preterm infants who develop moderate and severe BPD. These findings suggest that prenatal factors contribute to late respiratory outcomes in preterm infants.

Bone marrow-derived angiogenic cells restore lung alveolar and vascular structure after neonatal hyperoxia in infant mice.

Neonatal hyperoxia impairs vascular and alveolar growth in mice and decreases endothelial progenitor cells. To determine the role of bone marrow-derived cells in restoration of neonatal lung structure after injury, we studied a novel bone marrow myeloid progenitor cell population from Tie2-green fluorescent protein (GFP) transgenic mice (bone marrow-derived angiogenic cells; BMDAC). We hypothesized that treatment with BMDAC would restore normal lung structure in infant mice during recovery from neonatal hyperoxia. Neonatal mice (1-day-old) were exposed to 80% oxygen for 10 days. BMDACs (1 x 10(5)), embryonic endothelial progenitor cells, mouse embryonic fibroblasts (control), or saline were then injected into the pulmonary circulation. At 21 days of age, saline-treated mice had enlarged alveoli, reduced septation, and a reduction in vascular density. In contrast, mice treated with BMDAC had complete restoration of lung structure that was indistinguishable from room air controls. BMDAC comprised 12% of distal lung cells localized to pulmonary vessels or alveolar type II (AT2) cells and persist (8.8%) for 8 wk postinjection. Coculture of AT2 cells or lung endothelial cells (luEC) with BMDAC augmented AT2 and luEC cell growth in vitro. We conclude that treatment with BMDAC after neonatal hyperoxia restores lung structure in this model of bronchopulmonary dysplasia.

Hyperoxia disrupts vascular endothelial growth factor-nitric oxide signaling and decreases growth of endothelial colony-forming cells from preterm infants.

Exposure of preterm infants to hyperoxia impairs vascular growth, contributing to the development of bronchopulmonary dysplasia and retinopathy of prematurity. Disruption of vascular endothelial growth factor (VEGF)-nitric oxide (NO) signaling impairs vascular growth. Endothelial progenitor cells (EPCs) may play an important role in vascular growth. Endothelial colony-forming cells (ECFCs), a type of EPC, from human preterm cord blood are more susceptible to hyperoxia-induced growth impairment than term ECFCs. Therefore, we hypothesized that hyperoxia disrupts VEGF-NO signaling and impairs growth in preterm ECFCs and that exogenous VEGF or NO preserves growth in hyperoxia. Growth kinetics of preterm cord blood-derived ECFCs (gestational ages, 27-34 wk) were assessed in room air (RA) and hyperoxia (40-50% oxygen) with or without VEGF, NO, or N(omega)-nitro-l-arginine. VEGF, VEGF receptor-2 (VEGFR-2), and endothelial NO synthase (eNOS) protein expression and NO production were compared. Compared with RA controls, hyperoxia significantly decreased growth, VEGFR-2 and eNOS expression, and NO production. VEGF treatment restored growth in hyperoxia to values measured in RA controls and significantly increased eNOS expression in hyperoxia. NO treatment also increased growth in hyperoxia. N(omega)-nitro-l-arginine treatment inhibited VEGF-augmented growth in RA and hyperoxia. We conclude that hyperoxia decreases growth and disrupts VEGF-NO signaling in human preterm ECFCs. VEGF treatment restores growth in hyperoxia by increasing NO production. NO treatment also increases growth during hyperoxia. Exogenous VEGF or NO may protect preterm ECFCs from the adverse effects of hyperoxia and preservation of ECFC function may improve outcomes of preterm infants.