权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Antenatal Betamethasone in Late Preterm Gestation Lambs

晚期早产羔羊的产前倍他米松

基本信息

批准号：
7826658
负责人：
Satyanarayana Lakshminrusimha
金额：
$ 7.93万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-06 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7826658
关键词：
Accounting Adenylate Cyclase Adrenergic Receptor Affect Air American College of Obstetricians and Gynecologists Animal Model Antibiotic A23187 Apical Arginine Arteries Atrial Natriuretic Factor Bathing Betamethasone Biochemical Pathway Birth Blinded Blood Circulation Blood Vessels Blood gas Breathing Calcium Catheters Cesarean section Choline Clinical Protocols Cyclic AMP Cyclic GMP Dilution Techniques Discipline of obstetrics Disease Dose Drops Environmental air flow Enzymes Epoprostenol Epoprostenol Receptors Evaluation Event Fetal Lung Fetus Forskolin Freezing Generations Gestational Age Glucocorticoids Guanylate Cyclase Histology Hour Human Incidence Incubated Infant Injection of therapeutic agent Intervention Intramuscular Ionophores Isoproterenol Lipids Liquid substance Lung Lung Compliance Measurement Measures Mediating Mediator of activation protein Medical Mesenteric Arteries Messenger RNA Monitor Morbidity - disease rate Mothers Muscle relaxation phase Natriuretic Peptides Newborn Infant Nitric Oxide Nitric Oxide Donors Norepinephrine North America Particulate Pathway interactions Penicillamine Peptide Receptor Phospholipids Physiological Physiology Placebos Practice Guidelines Pregnancy Premature Birth Premature Infant Premature Labor Production Prolonged Pregnancy Prostacyclin synthase Prostaglandins Prostaglandins I Proteins Protocols documentation Pulmonary Hypertension Pulmonary Surfactant-Associated Protein A Pulmonary Vascular Resistance Pulmonary artery structure Pulmonary function tests Randomized Relaxation Reporting Research Design Respiratory distress Risk Saline Sampling Secondary to Severities Smooth Muscle Soluble Guanylate Cyclase Source Steroids Structure of parenchyma of lung Surface Tension Terbutaline Testing Third Pregnancy Trimester Time Tissues Tocolysis Trachea Type II Epithelial Receptor Cell Vasodilation Ventilator Woman Work absorption alveolar type II cell atrial natriuretic factor receptor A beta adrenergic agent beta-adrenergic receptor blue dextran constriction fetal hemodynamics high risk human NOS3 protein improved in utero in vivo insight instrument intraventricular hemorrhage lung lobe mortality neonatal morbidity postnatal pregnant pressure prevent public health relevance receptor research study respiratory respiratory distress syndrome response surfactant wet lung

项目摘要

DESCRIPTION (provided by applicant): The incidence of late preterm births (defined as births at 34 0/7 to 36 6/7 wk gestation) have been steadily increasing over the past decade and account for the ~ 75% of all preterm births. Respiratory morbidity from disorders of transition including pulmonary hypertension (impaired pulmonary vasodilation), transient tachypnea of newborn (inadequate lung liquid clearance) and respiratory distress syndrome (inadequate surfactant production and release) affect late preterm infants at a higher rate than infants of more advanced gestational age. Practice guidelines of the American College of Obstetricians and Gynecologists (ACOG) recommend tocolysis and glucocorticoids to women in preterm labor up to 34 wk gestation. However, beyond 34 wk efforts are no longer directed at prolonging pregnancy or enhancing fetal maturity. Moreover, because of the inherent inaccuracy of pregnancy dating with margins of error up to 3 wk in the third trimester, inductions of labor and elective cesarean section performed at "presumed term" might inadvertently contribute to the increasing incidence of late preterm birth. The Antenatal Steroids for Term Cesarean Section study reported that two doses of antenatal betamethasone significantly reduced respiratory morbidity in > 37 wk infants born by elective cesarean section. Administration of antenatal glucocorticoids to < 34 wk gestation mothers in preterm labor undoubtedly reduces a number of neonatal morbidities including respiratory distress and intraventricular hemorrhage. Given the promising results in infants > 37 wk in a single study, research evaluating the pulmonary physiological effects and benefits (or lack there of) of antenatal glucocorticoids for preterm labor between 34 and 36 6/7 wk is important. We propose to gain such insight by administering betamethasone to pregnant ewes prior to elective cesarean section. It may not be possible to prevent delivery for 48 h after initiation of an antenatal steroid course. Hence we plan to test two protocols: one dose of betamethasone administered 24 h prior to delivery and two doses administered 48 h and 24 h prior to delivery in this proposal. Late preterm lambs (134 d gestation, term ~ 145 d) delivered by elective cesarean section following two, one or no doses of antenatal betamethasone will either be sacrificed at birth (for evaluation of pulmonary vascular reactivity, lung liquid status, compliance and surfactant production and release) or instrumented for evaluation of pulmonary vascular resistance, oxygenation and ventilation for 6 h. We will study the changes in important mediators of pulmonary transition at birth such as nitric oxide, beta adrenergic agents, natriuretic peptides and prostaglandins secondary to antenatal glucocorticoid use. We hypothesize that antenatal administration of either one or two doses of betamethasone will enhance pulmonary vasodilation, lung liquid reabsorption and surfactant production in late preterm lambs delivered by cesarean section. These studies are likely to have an impact on the clinical protocol for use of antenatal steroids, changing current practice. PUBLIC HEALTH RELEVANCE: The number of births at 34 to 37 weeks of gestation, often referred to as late preterm births, delivered by cesarean section is rapidly increasing in North America. Treating late preterm pregnant mothers in labor with betamethasone (a steroid) may reduce the risk of respiratory complications and mortality in their infants. We intend to administer betamethasone to late preterm gestation ewes to study the benefit and mechanism of this treatment in fetal lambs delivered by cesarean section.

描述（由申请人提供）：在过去十年中，晚期早产（定义为妊娠34 0/7至36 6/7周的出生）的发生率稳步增加，约占所有早产的75%。过渡期疾病包括肺动脉高压（肺血管舒张受损）、新生儿一过性呼吸急促（肺液体清除不足）和呼吸窘迫综合征（表面活性物质产生和释放不足）导致的呼吸系统疾病对晚期早产儿的影响率高于更晚胎龄的婴儿。美国妇产科医师学会（ACOG）的实践指南建议对妊娠34周内的早产妇女使用安胎药和糖皮质激素。然而，超过34周的努力不再针对延长妊娠或提高胎儿成熟度。此外，由于固有的不准确的妊娠日期的误差幅度高达3周的第三个三个月，引产和选择性剖宫产在“推定期限”可能会无意中导致晚期早产的发生率增加。足月剖腹产孕妇使用类固醇研究报告称，产前使用两剂倍他米松可显著降低37周以上择期剖腹产婴儿的呼吸系统发病率。在一项研究中，产前糖皮质激素给药至< 34 wk gestation mothers in preterm labor undoubtedly reduces a number of neonatal morbidities including respiratory distress and intraventricular hemorrhage. Given the promising results in infants >37周，评价34至36 6/7周之间产前糖皮质激素对早产的肺生理作用和益处（或缺乏）的研究是重要的。我们建议通过在择期剖宫产前对妊娠母羊进行倍他米松给药来获得这种认识。在开始产前类固醇疗程后48小时内可能无法阻止分娩。因此，我们计划测试两种方案：在本提案中，在分娩前24小时给予一剂倍他米松，在分娩前48小时和24小时给予两剂倍他米松。在两次、一次或不给药产前倍他米松后通过选择性剖宫产分娩的晚期早产羔羊（妊娠134 d，足月~ 145 d）将在出生时处死（用于评价肺血管反应性、肺液体状态、顺应性和表面活性物质产生和释放）或进行仪器检测，用于评价肺血管阻力、氧合和通气6 h。我们将研究出生时肺转变的重要介质的变化，如一氧化氮、β肾上腺素能药物、利钠肽和继发于产前糖皮质激素使用的肾上腺素。我们推测，产前给予一剂或两剂倍他米松将增强通过剖宫产分娩的晚期早产羔羊的肺血管舒张、肺液体重吸收和表面活性物质的产生。这些研究可能会对产前使用类固醇的临床方案产生影响，改变目前的做法。公共卫生相关性：在北美，妊娠34至37周时通过剖腹产分娩的分娩（通常称为晚期早产）数量正在迅速增加。用倍他米松（一种类固醇）治疗晚期早产孕妇可能会降低婴儿呼吸系统并发症和死亡率的风险。我们打算对晚期早产母羊给予倍他米松，以研究这种治疗对剖腹产胎羊的益处和机制。