Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 130
- 试验地点
- 2
- 主要终点
- Weight
研究概览
简要总结
This study is a randomized trial comparing 2 methods of human milk fortification for preterm infants in the neonatal intensive care unit (NICU). All participating infants will receive a human milk diet comprising maternal and/or donor milk plus multi-component and modular fortifiers. In one group (control), the milk will be fortified according to routine standard of care. In the other group (intervention), the fortification will be individually targeted based on the results of point-of-care human milk analysis. Outcomes include physical growth in the NICU and after discharge, brain structure by magnetic resonance imaging at term equivalent age, and neurodevelopment at 2 years.
详细描述
Human milk is the recommended diet for preterm infants and it requires fortification to meet their high nutrient requirements. This study addresses a gap in knowledge about the optimal strategy for human milk fortification in the neonatal intensive care unit (NICU).
Infants will be recruited from a single site (Brigham and Women's Hospital, Boston MA). Eligible infants are NICU inpatients born <31 weeks' gestation and enrolled within 21 days of birth, whose mothers are providing breast milk. Exclusion criteria include major congenital anomalies, severe fetal growth restriction (weight <3rd percentile), clinically significant gastrointestinal pathology, triplets or higher order multiples, and expected death or transfer. Infants who require fluid restriction <140 mL/kg/day will also be excluded.
The study period begins when infants have reached full volume (150-160 mL/kg/day) human milk feedings fortified to 24 kcal per ounce. Participants will be randomized to one of two diet groups; twins will be randomized separately. The study diet will continue until 36 weeks' postmenstrual age or hospital discharge, whichever comes first.
Available maternal milk will be pooled with donor milk (if needed) to reach the total daily fluid volume; this "base" milk will be analyzed with a point-of-care human milk analyzer (Miris, AB). All infants will receive at minimum the standard human milk fortification (multicomponent fortifier to 24 kcal/oz plus liquid protein 0.27 g/dL). In one group (control), we will follow the standard of care for milk fortification, only adding more protein and/or energy if weight gain is lagging. In the other group (intervention), we will individually target fortification with additional protein and/or energy so that the "base" milk always contains protein 1 g/dL and energy 67 kcal/dL.
Outcome measures will include physical growth during the diet intervention period, including gain in weight, length, and head circumference and body composition with air displacement plethysmography at the end of the diet intervention. At term equivalent age, participants will undergo brain magnetic resonance imaging. At 2 years corrected age, outcomes include standard and novel neurodevelopmental tests including the Bayley-III and tests of emerging executive function; and physical size.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Parents, clinical, and research staff apart from the study milk technician will be unaware of the treatment group.
入排标准
- 年龄范围
- 1 Day 至 21 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inpatient in Brigham and Women's Hospital NICU
- •Gestational age 24 0/7 to 30 6/7 weeks
- •Chronologic age <21 days
- •Mother providing breast milk
排除标准
- •Major congenital anomaly
- •Severe fetal growth restriction (birth weight <3rd percentile by Olsen reference)
- •Necrotizing enterocolitis, intestinal perforation, other major gastrointestinal pathology
- •Triplets or higher order multiples
- •Plan for redirection of care and/or anticipated death
- •Clinically significant renal or hepatic dysfunction
- •Inborn error of metabolism
- •Fluid restriction <140 mL/kg/day for 3 or more days
- •Grade 3 or 4 intraventricular hemorrhage detected prior to enrollment
- •Anticipated transfer <36 weeks' postmenstrual age
- •Parents do not consent to use of pasteurized donor human milk
- •Infant in non-parental custody
结局指标
主要结局
Weight
时间窗: at study endpoint (36 weeks' postmenstrual age or discharge)
Weight z-score
Length
时间窗: at study endpoint (36 weeks' postmenstrual age or discharge)
Length z-score
Fat free mass
时间窗: at study endpoint (36 weeks' postmenstrual age or discharge)
Fat free mass estimated with air displacement plethysmography (z-score)
Total brain volume
时间窗: at term equivalent age (38 to 41 weeks' postmenstrual age)
Total brain volume by MRI
Cerebellar volume
时间窗: at term equivalent age (38 to 41 weeks' postmenstrual age)
Cerebellar volume by MRI
Bayley-III cognitive score
时间窗: at 2 years' corrected age
Scaled composite score (continuous), higher score indicates better performance, range of possible scores 55-145
Bayley-III motor score
时间窗: at 2 years' corrected age
Scaled composite score (continuous), higher score indicates better performance, range of possible scores 46-154
次要结局
- Low Bayley-III cognitive score(At 2 years' corrected age)
- Fat mass(at study endpoint (36 weeks' postmenstrual age or discharge))
- Weight(at 2 years' corrected age)
- Height(at 2 years' corrected age)
- Low Bayley-III motor score(At 2 years' corrected age)
- Spacial working memory(at 2 years' corrected age)
- Executive function(at 2 years' corrected age)
- Behavioral inhibition(at 2 years' corrected age)
- Behavioral difficulties(at 2 years' corrected age)
- Bayley-III language score(At 2 years' corrected age)
研究者
Mandy Brown Belfort, MD MPH
Attending physician
Brigham and Women's Hospital