Effect of Targeted vs Standard Fortification of Breast Milk on Growth and Development of Preterm Infants (≤ 32 Weeks): a Randomised Controlled Trial
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 200
- 试验地点
- 4
- 主要终点
- Growth
研究概览
简要总结
BACKGROUND:
Human milk (HM) is recommended for all very low birth infants (VLBW)). Breast-milk is highly variable in nutrient content, failing to meet the nutritional demands of VLBW. Fortification of HM is recommended to prevent extra-uterine growth retardation and associated poor neurodevelopmental outcome. However, standard fortification with fixed dose multicomponent fortifier does not account for the variability in milk composition. Targeted fortification is a promising alternative and needs further investigation.
The aim of the study is to evaluate if targeted fortification of human milk may optimize growth and development in preterm infants.
STUDY DESIGN:
Randomized single blind controlled trial.
METHODS & ANALYSIS:
We will recruit preterm infants (≤ 32 weeks of gestation) within the first 7 days of life. After reaching 80 ml/kg/day of enteral feeding, patients will be randomised to receive standard fortification (HMF, Nutricia) or targeted fortification (modular components: Bebilon Bialko, Nutricia - protein, Fantomalt, Nutricia - carbohydrates, Calogen, Nutricia - lipids). The intervention will continue until 37 weeks of post-conception age, or hospital discharge. Parents and outcome assessors will be blinded to the intervention.
The primary outcome - weight gain velocity will be measured starting from the day infants regain their birth weight up to 4 weeks, then weekly until discharge.
Secondary outcomes such as neurodevelopment at 12 months of corrected age (CA) will be assessed with Bayley Scale of Development III, repeated at 36 months of CA. Additionally a Wescheler Preschool and Primary Scale of Intelligence IV test will be applied at 3,5 years of CA. Secondary outcomes such as length and head growth, body composition will be assesed at discharge and at 4 months. Incidence of necrotizing enterocolitis (NEC), sepsis, retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) will also be followed.
详细描述
Study design and setting This is a multi-centre superiority randomised parallel group, 1:1 allocation study. Patients will be recruited at three departments of neonatology and intensive care units: Department of Neonatology and Neonatal Intensive Care, Division of Neonatal Intensive Care (Medical University of Warsaw), and the Institute of Mother and Child. Follow up will be carried out at the Department of Paediatrics.
The study is lead by the Department of Neonatology and Neonatal Intensive Care (KAROWA) with approximately 3000 (100 ≤ 32 weeks of gestation) deliveries per year and 12 intensive care and 40 high dependency neonatal beds.
Recruitment Recruitment will take place between June 2019 and December 2020. Parents of infants born at less than 32 weeks of gestation will be approached within the first week of life.
Randomisation After reaching 80 ml/kg/day of enteral feeding, patients will be randomised to receive standard fortification (SF) or targeted fortification (TF) (proteins, lipids, carbohydrates). Allocation will be performed electronically.
Interventions Human milk fortification procedure Milk fortification will be done twice a day (8 am and 8 pm) for each following 12 hour nursing shift (Appendix 1).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The decision to start fortification will be made by the attending physician blinded to the intervention allocated. An employee outside the research team will feed data into the computer in separate datasheets so that the researchers can analyse data without having access to information about the allocation.
入排标准
- 年龄范围
- — 至 32 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients eligible for the trial must comply with all of the following at randomization:
- •Gestational age at birth ≤ 32 weeks
- •Enteral feeding of at least 80ml/kg/day
- •Donor or maternal milk based enteral feeding (at least 50%)
- •Parenteral/legal guardian consent
排除标准
- •>50% formula based enteral feeding
- •Small for gestational age (birth weight < 3rd percentile)
- •Congenital abnormalities which increase the risk of NEC
- •Withdrawal of feeding > 7 days
结局指标
主要结局
Growth
时间窗: from birth at postmentrual age <32 to up to 37 weeks of post-conceptional age
weight will be assessed every day.
Velocity of weight gain in grams
时间窗: from birth at postmentrual age <32 to up to 37 weeks of post-conceptional age
weight will be assessed every day.
次要结局
- Late onset sepsis (LOS)(from 72 hours of life at postmentrual age <32 up to 37 weeks of post gestational age)
- Necrotizing enterocolitis (NEC)(from birth at postmentrual age <32 to up to 37 weeks of post-gestational age)
- Retinopathy of prematurity (ROP)(from 3 weeks of life at postmentrual age <32 to 37 weeks of post gestational age)
- Neurodevelopmental outcome(at 12 and 36 weeks of corrected age.)
- Bronchopulmonary dysplasia (BPD)(from 28 days at postmentrual age <32 to up to 37 weeks of post gestational age)
研究者
Joanna Seliga-Siwecka
Principal Investigator
Princess Anna Mazowiecka Hospital, Warsaw, Poland