Transforming Health and Resilience Via Individualized Nutrition in Very Preterm Infants for Extrauterine Growth and Development
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 2
- 主要终点
- Weight Gain Velocity
研究概览
简要总结
Human milk has several well-established benefits but does not adequately meet the increased nutritional demands of the growing preterm infant, necessitating additional nutrient supplementation in a process known as fortification. In U.S. neonatal intensive care units (NICUs), human milk is primarily supplemented using standardized fortification, in which a multicomponent fortifier is added to human milk to achieve assumed nutrient content based on standard milk reference values. However, this method does not account for the significant variability in human milk composition or in preterm infant metabolism, and up to half of all very premature infants experience poor growth and malnutrition using current nutritional practices. Poor postnatal growth has adverse implications for the developing preterm brain and long-term neurodevelopment.
Recent advances allow for individualized methods of human milk fortification, including adjustable and targeted fortification. Adjustable fortification uses laboratory markers of protein metabolism (BUN level) to estimate an infant's protein requirements. In targeted fortification, a milk sample is analyzed to determine its specific macronutrient and energy content, with additional macronutrient supplementation provided as needed to achieve goal values. Emerging data suggest that both methods are safe and effective for improving growth, however information on their comparable efficacy and neurodevelopmental implications are lacking, particularly using advanced quantitative brain MRI (qMRI) techniques.
Through this prospective, randomized-controlled trial, the investigators will compare the impact of individualized human milk fortification on somatic growth and neurodevelopment in preterm infants. Infants will be randomized to receive one of three nutritional interventions: standardized (control group), adjustable, or targeted human milk fortification. Infants will undergo their assigned nutritional intervention until term-equivalent age or discharge home, whichever is achieved first. Brain qMRI will be performed at term-corrected age, and neurodevelopmental follow-up will be performed through 5 years of age.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Outcomes Assessor)
盲法说明
Due to the nature of the nutritional interventions, the clinical and research teams will not be blinded to study intervention. The radiologist and research team members performing MRI interpretation, post-acquisition processing, and quantitative analysis will be blinded to study nutritional intervention arm. Similarly, teams performing neurodevelopmental follow-up will also be blinded to study nutritional intervention arm.
入排标准
- 年龄范围
- — 至 4 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Birth gestational age (GA) of ≤32 weeks
- •Postnatal age ≤4 weeks at time of enrollment
- •Maternal plan to provide human milk to infant, and consent to providing donor human milk if insufficient maternal milk supply
- •Maternal age > 18 years old
排除标准
- •Formula feeding prior to 36 weeks PMA or discharge home (whichever achieved first), either secondary to parental preference or medical necessity
- •Dysmorphic features or congenital anomalies suggestive of a genetic syndrome, metabolic disorder, chromosomal abnormality, or congenital infection
- •Dysgenetic or major destructive brain lesions detected by head ultrasound before enrollment
结局指标
主要结局
Weight Gain Velocity
时间窗: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Weight gain velocity (grams per kilogram per day)
Head Circumference Growth Velocity
时间窗: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Head circumference growth velocity (centimeters per week)
Total and Regional Brain Volumes
时间窗: Term-equivalent age (38 to 41 weeks postmenstrual age)
Total and regional (cortical and deep gray matter, white matter, amygdala-hippocampus, brainstem, cerebellum) brain volumes by MRI
Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS)
时间窗: Term-equivalent age (38 to 41 weeks postmenstrual age)
Summary scores in 13 different domains (habituation, attention, handling, self-regulation, arousal, excitability, lethargy, hypertonicity, hypotonicity, non-optimal reflex, asymmetric reflex, quality of movement, stress)
Differential Abilities Scale (2nd edition)-(DAS-II)
时间窗: 60 months (5 years) of age
\*For children with significant delays who may be unable to reach basal scores on the WPPSI-IV Early years core battery: verbal, nonverbal, and spatial reasoning subtests (higher score indicates better performance, score range 40-170)
Wechsler Preschool and Primary Scale of Intelligence (4th edition) (WPPSI-IV)
时间窗: 60 months (5 years) of age
Five primary indices: verbal comprehension, visual spatial, working memory, fluid reasoning, and processing speed (higher score indicates better performance, score range 40 to 160)
Length Growth Velocity
时间窗: Study enrollment through nutritional intervention endpoint (term-equivalent age (40 weeks PMA [postmenstrual age]) or discharge home, whichever is achieved first)
Length growth velocity (centimeters per week)
Mullen Scales of Early Learning (MSEL)
时间窗: 36 months (3 years) of age
Composite score as well as 5 subscores: gross motor, fine motor, visual reception, receptive language, and expressive language (reported as standardized t-scores, higher score indicates a better outcome, mean standardized t-score score of 50 with standard deviation of 10)
次要结局
未报告次要终点