Randomized Clinical Trial of High vs. Standard-Calorie Formula for Methadone-Expo

美沙酮博览会高热量配方奶粉与标准热量配方奶粉的随机临床试验

• 批准号: 7875607
• 负责人: DEBRA L BOGEN
• 金额: $ 23.37万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7875607
• 关键词: Address; Age; Birth; Birth Weight; Body Weight decreased; Calories; Crying; Data; Development; Diarrhea; Dietary Intervention; Dose; Double-Blind Method; Energy Intake; Enrollment; Etiology; Feasibility Studies; Funding; Hospitalization; Hour; Infant; Infant formula; Intervention; Lead; Length of Stay; Life; Low Birth Weight Infant; Measures; Metabolic; Methadone; Methods; Morphine; Mothers; Muscle Hypertonia; Muscle Tonus; NIH Program Announcements; National Institute of Drug Abuse; Neonatal Abstinence Syndrome; Newborn Infant; Opiates; Outcome; Outpatients; Pattern; Performance; Pharmaceutical Preparations; Pilot Projects; Postpartum Women; Pregnancy; Preventive; Protocols documentation; Randomized; Randomized Clinical Trials; Recruitment Activity; Severities; Sleep; Substance-Related Disorders; Sweat; Sweating; Symptoms; Time; Uterus; Visit; Vomiting; Weight; Weight Gain; Woman; design; experience; feeding; high risk infant; improved; in utero; infant outcome; neonate; pregnant; pressure; prevent; primary outcome; public health relevance; standard of care; sucking; therapy development

DESCRIPTION (provided by applicant): Background: Infants exposed to methadone during pregnancy experience high rates of neonatal abstinence syndrome (NAS). Common NAS symptoms (tremulousness, increased muscle tone, sweating, excessive crying, vomiting and diarrhea) increase infants' metabolic needs. Another frequent NAS symptom, weak and uncoordinated suckling, impairs infants' ability to take in adequate calories. These combined problems compromise infant weight gain. The current standard of care for opiate-exposed infants requires evidence of poor weight gain or excessive weight loss before initiating high-calorie formula. We hypothesize that inadequate caloric intake among methadone exposed infants may result in excessive weight loss, slow weight regain and exacerbation of NAS. These factors lead to the newborn's requirement for higher morphine doses and longer duration of hospitalization. Therefore, methadone exposed infants may benefit from early caloric enhancement. A nutritional intervention for opiate-exposed infants has not been previously evaluated. This application will provide data on adequacy of recruitment, protocol feasibility, performance of selected measures, and preliminary estimates of efficacy for a comprehensive R01 submission. Specific Aims: 1. For methadone exposed infants, compare infants randomized to high (24 kcal/oz) versus standard (20 kcal/oz) formula for the following outcomes: Weight loss and gain patterns. The primary dependent measure will be days until the infant returns to birth weight. Secondary measures will be maximum percent weight loss and days to weight nadir. NAS severity measured by: a) total length of hospital stay for NAS; b) duration of NAS treatment; c) mean Finnegan scores on days 2-10; d) maximum concentration of morphine used to treat NAS. 2. Describe the suck quality at 4-6 days of age among methadone exposed infants. Evaluate the association between the infant suck quality and infant weight loss and gain patterns and measures of NAS severity. Design: Women on methadone will be recruited during pregnancy and will attend a single brief visit late in pregnancy. After delivery, infants will be randomized in a double blind trial of either high-calorie or standard- calorie formula which will be started at 72 hours after birth and be continued through 21 days of age. Infants will be weighed daily and will have outpatient study visits at 1 and 3 months. For this pilot study, up to 70 mothers will be enrolled over 18 months. This pilot study is needed to establish the feasibility of the study methods and to better estimate differences that can be observed between the groups. For the primary outcome variable, days until the infant returns to birth weight, discrete survival methods will be used. Potential Impact: Early caloric enhancement for methadone-exposed infants is inexpensive, readily available, easy to implement and could improve outcomes of these high-risk infants. High-calorie formula could result in a more normal pattern of weight loss and gain, less severe NAS symptoms and shorter hospital stays. PUBLIC HEALTH RELEVANCE: Neonatal abstinence syndrome (NAS) symptoms contribute to poor infant weight gain. Early caloric enhancement for infants exposed to methadone is inexpensive, readily available, easy to implement and could improve early outcomes for these high-risk infants. We will conduct a preliminary randomized clinical trial of high-calorie vs. standard-calorie formula for methadone exposed infants to evaluate the adequacy of recruitment, protocol feasibility and estimates of whether high-calorie formula results in more normal patterns of weight loss and gain, less severe NAS symptoms and shorter hospital stays.

描述（由申请人提供）：背景：婴儿暴露于美沙酮在怀孕期间的经验，新生儿戒断综合征（NAS）的高利率。常见的NAS症状（颤抖，肌张力增加，出汗，过度哭泣，呕吐和腹泻）增加了婴儿的代谢需求。另一个常见的NAS症状，虚弱和不协调的吸吮，损害婴儿吸收足够热量的能力。这些综合问题损害了婴儿体重的增加。目前对阿片类药物暴露婴儿的护理标准要求在开始高热量配方奶粉之前有体重增加不佳或体重过度减轻的证据。我们推测，美沙酮暴露婴儿的热量摄入不足可能会导致体重过度减轻，体重恢复缓慢和NAS恶化。这些因素导致新生儿需要更高的吗啡剂量和更长的住院时间。因此，美沙酮暴露的婴儿可能受益于早期热量增加。对阿片类药物暴露婴儿的营养干预以前没有进行过评估。该申请将提供关于招募充分性、方案可行性、选定指标的性能以及全面R 01提交资料的疗效初步估计的数据。具体目标：1。对于美沙酮暴露的婴儿，比较随机分配到高（24千卡/盎司）与标准（20千卡/盎司）配方奶粉的婴儿的以下结果： 体重减轻和增加模式。主要的依赖性指标是婴儿恢复出生体重的天数。次要指标将是最大体重减轻百分比和体重最低值的天数。 NAS严重性衡量标准：a）NAS的住院总时间; B）NAS治疗的持续时间; c）第2-10天的平均Finnegan评分; d）用于治疗NAS的吗啡的最大浓度。2.描述接触美沙酮的婴儿在4-6日龄时的吸吮质量。评估婴儿吸吮质量与婴儿体重减轻和增加模式以及NAS严重程度测量之间的相关性。设计：在怀孕期间招募接受美沙酮治疗的妇女，并在怀孕后期进行一次简短的访视。分娩后，婴儿将随机参加高热量或标准热量配方奶粉的双盲试验，该试验将在出生后72小时开始，并持续到21天。婴儿将每天称重，并在1个月和3个月时进行门诊研究访视。对于这项试点研究，将在18个月内招募多达70名母亲。需要进行这项试点研究，以确定研究方法的可行性，并更好地估计各组之间可以观察到的差异。对于主要结局变量，即婴儿恢复出生体重的天数，将使用离散生存方法。潜在的影响：早期增加美沙酮暴露婴儿的热量是廉价的，容易获得，易于实施，并可以改善这些高危婴儿的结果。高热量配方奶粉可以导致更正常的体重减轻和增加模式，不太严重的NAS症状和更短的住院时间。 公共卫生相关性：新生儿禁欲综合征（NAS）症状导致婴儿体重增加不良。暴露于美沙酮的婴儿的早期热量增加是廉价的，容易获得，易于实施，并可以改善这些高危婴儿的早期结果。我们将对接触美沙酮的婴儿进行一项高热量与标准热量配方奶粉的初步随机临床试验，以评估招募的充分性、方案的可行性以及高热量配方奶粉是否会导致更正常的体重减轻和增加模式、更不严重的NAS症状和更短的住院时间。