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）：早产晚期（定义为34 0/7至36 6/7周妊娠的出生）在过去十年中一直在稳步增加，占所有早产出生的约75％。过渡疾病的呼吸发病率，包括肺动脉高压（肺部血管舒张受损），新生儿的短暂性tachypnea（肺液体清除不足）和呼吸窘迫综合征（表面表面活性剂的产生不足和释放）会影响比婴儿更高的遗传年龄更高的先生率的早期婴儿。美国产科医生学院的实践指南（ACOG）建议对早产的女性进行糖酵解和糖皮质激素，最高34周妊娠。但是，超过34周的努力不再针对延长怀孕或增强胎儿成熟。此外，由于妊娠的固有不准确性，在三个月的误差缘高达3周，劳动和选修剖宫产的诱导在“推定的术语”上进行的术语可能会无意中促成早产后期的发病率的增加。剖宫产术语的产前类固醇研究报告说，两种产前倍替米松在> 37周的婴儿中显着降低了由选举剖宫产的婴儿。在早产中给予<34周妊娠母亲的产前糖皮质激素无疑会减少许多新生儿病毒，包括呼吸窘迫和脑室内出血。鉴于在一项研究中，婴儿> 37周的婴儿> 37周的结果，研究评估肺部生理作用和益处（或缺乏）产前糖皮质激素在34至36 6/7周之间对早产的研究很重要。我们建议通过在选修剖宫产前向怀孕的母羊替当米松来获得这种见解。启动产前类固醇病程后，可能无法防止48小时内交付。因此，我们计划测试两种方案：交付前24小时给药的一剂替当米松，并在此提案中交付前48小时和24小时给药。在剖宫产片中，晚期早产羔羊（134 d妊娠，〜145 d）之后，将在出生时牺牲两剂，一剂或没有剂量的产盘倍他米松（用于评估肺血管反应性，肺液体状态，合规性和表面活性和释放的肺部反应性，并释放的肺部反应和释放），以评估6个阳性抗体的阳极抗性和释放的阳性抗体量和阳性式阳极抗性，并具有6个阳性式阳性式阳极抗性。我们将研究出生时肺过渡的重要介质的变化，例如一氧化氮，β肾上腺素能，亚钠肽和继发于产前糖皮质激素使用的前列腺素。我们假设在剖宫产分段提供的早产羔羊中，产前给药一种或两剂替米斯米松将增强肺血管舒张，肺液体吸收和表面活性剂的产生。这些研究可能会影响使用产前类固醇的临床方案，从而改变了当前的实践。公共卫生相关性：妊娠34至37周时的出生人数，通常称为早产分子，剖宫产分区迅速增加。用倍他米松（类固醇）治疗早产孕妇在劳动中的晚期孕妇可以降低婴儿呼吸并发症和死亡的风险。我们打算将替伯斯米松施用到早产妊娠母羊，以研究剖宫产分区送达的胎儿羔羊的好处和机制。