Analytical Validation and Clinical Testing of the Preemie System for Analysis and Calculation of Targeted Fortification of Mother's Breast Milk for Preterm Infants
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Enrollment
- 180
- Locations
- 1
- Primary Endpoint
- Phase 1: Accuracy of the Preemie system against reference laboratory International Standards Organization (ISO) methods.
Study Overview
Brief Summary
This study aims to test and validate the Preemie Ecosystem- a new device and associated software package for measuring the nutrient (fat, protein and carbohydrate) content of the breast milk of the mothers of premature babies. This is potentially useful, as premature babies have higher nutritional requirements than babies born at term near their due date. At the moment, a nutritional supplement called breast milk fortifier is added to breast milk in standard amounts to improve its nutritional content and help premature babies grow. However, we know that each mother's breast milk is different, and varies from day to day, so each mother's milk may require more or less of such supplements in order to meet European recommendations for the nutrient intake.
The aim of this study is to first test and validate the accuracy of the Preemie device for measuring the nutritional content of mother's breast milk, using milk donated to the local donor milk bank and from mothers of babies currently on the neonatal unit. Next, once this is complete, the aim is to demonstrate it is feasible to use the Preemie device to enable fortification of mother's milk on an individualised basis for a small group of premature babies. The growth and nutrient intakes of these babies will be compared to another group who are cared for using the standard fortification approach.
The results of this study will be used to gain "Conformité Européenne" (CE) certification of the Preemie device and software.
Detailed Description
This is a single centre study taking place in a neonatal intensive care unit which is a regional referral centre for neonatal surgery and other tertiary specialities. The centre has well established policies for nutritional care, inducing the routine use of breast milk fortifier, and a track record in research into the nutrition and growth of preterm infants. It will have 2 phases:
Phase 1: Validation of the Preemie sensor, encompassing 2 different analytical studies for assessing the accuracy (1) and the precision/reproducibility (2) of the system
Phase 2: Open label randomised controlled trial to test use of Preemie ecosystem in clinical practice for the delivery of targeted individualised breast milk fortification
The methods used in each phase are as follows:
PHASE 1: Validation of Preemie Sensor Part A - Mothers currently expressing breast milk and meeting the inclusion criteria will be approached to take part in the study. They will be asked to provide 120ml of their breast milk which will be divided into a 20ml sample for use with the Preemie system and a 100ml sample for formal laboratory testing. The 20ml will be divided into ten smaller 2ml samples, and these will have their nutrient content (energy, fat, carbohydrate/sugar and protein) measured each day (in triplicate) using the Preemie sensor over a five day period and results recorded. The 100ml sample will be sent away to an independent third-party external laboratory to have its nutrient content (energy, fat, carbohydrate and protein) measured using standardised laboratory methods and results returned back to the study team. The results from the 2 systems will then be compared and the Preemie sensor assessed for accuracy.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 0 Days to 50 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Phase 1A For University Hospital Southampton (UHS) milk bank donors
- •Approved as a donor for the UHS milk bank through the usual process
- •Be providing milk to UHS donor milk bank For mothers of infant inpatients
- •Have an infant who is currently an inpatient in the neonatal unit, paediatric wards, paediatric cardiac ward, or paediatric intensive care unit
- •Be providing breastmilk for their preterm or term born infant
- •Have sufficient breast milk available such that providing 120ml breast milk for the study does not impact on the needs of their infant.
- •Inclusion criteria Phase 1B
- •Approved as a donor for the UHS milk bank through the usual process
- •Be providing milk to UHS donor milk bank
Exclusion Criteria
- •Phase 1A and 1B For mothers of infant inpatients
- •- Mothers whose infants are inpatients and where there is a concern about adequacy of maternal milk supply to feed their infant
- •Inclusion Criteria Phase 2
- •Birth weight ≥1kg and <1.8 kg (so meet the ESPGHAN criteria for breast milk fortification)
- •Be taking fully fortified enteral breast milk feeds (≥150 ml/kg/day of mothers or donor breast milk containing breast milk fortifier as per the manufacturer's instructions)
- •Tolerating fully fortified breast milk feeds≥150 ml/kg/day for 48 hours
- •No longer on parenteral nutrition.
- •Exclusion Criteria Phase 2
- •Infants where there is a concern about mother's supply of breast milk being insufficient to meet demands (where donor milk is not being used to make up any shortfall);
- •Known congenital metabolic disorder;
- •Infant formula fed;
- •Bilateral grade III or IV intraventricular haemorrhage;
- •Any infant who has had gastrointestinal tract surgery;
- •Refusal of consent;
- •Refusal for the use of breast milk fortifier
- •Birthweight <1 kg
Arms & Interventions
Targeted breast milk fortification using preemie device
Mother's breast milk (MBM) or Donor Breast Milk (DBM) for use in a day's milk feeds will be measured using the Preemie sensor every 2-3 days, results recorded, and the amounts of breast milk fortifier (BMF), protein supplement, carbohydrate supplement and fat supplements needed to be added in order for that sample of milk to meet current 2022 European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) enteral nutrient intake recommendations calculated by the Preemie Sensor NutriNTrack software. Feeds will be made up in batches of 24hrs worth of feeds each day based on these calculations and the resulting supplement amounts used for the next 2-3 days until another sample of MBM is analysed, in line with previous work by Rochow et al
Intervention: Targeted breast milk fortification using preemie device (Device)
Targeted breast milk fortification using preemie device
Mother's breast milk (MBM) or Donor Breast Milk (DBM) for use in a day's milk feeds will be measured using the Preemie sensor every 2-3 days, results recorded, and the amounts of breast milk fortifier (BMF), protein supplement, carbohydrate supplement and fat supplements needed to be added in order for that sample of milk to meet current 2022 European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) enteral nutrient intake recommendations calculated by the Preemie Sensor NutriNTrack software. Feeds will be made up in batches of 24hrs worth of feeds each day based on these calculations and the resulting supplement amounts used for the next 2-3 days until another sample of MBM is analysed, in line with previous work by Rochow et al
Intervention: Standard Breast milk fortification (Dietary Supplement)
Standard Fortification
Mother's breast milk (MBM) or Donor Breast Milk (DBM) for use in a day's milk feeds will be measured using the Preemie sensor every 2-3 days and results recorded. Breast milk will then be fortified in the standard way according to the manufacturer's recommendations, which assume a standard macronutrient content of the milk.
Intervention: Standard Breast milk fortification (Dietary Supplement)
Outcomes
Primary Outcomes
Phase 1: Accuracy of the Preemie system against reference laboratory International Standards Organization (ISO) methods.
Time Frame: 6 months
Establish accuracy of the Preemie system in measuring the macronutrient content of human milk (fat in g/L, fatty acids in g/L, protein in g/L, carbohydrate in g/L, and energy in g/L) carried out using the Preemie system and determining the bias against the same measurements performed through validated reference laboratory methods; Accuracy study of the Preemie system by paired testing of at least 100 human breast milk samples using both the Preemie system and reference laboratory ISO methods As per the Clinical and Laboratory Standards (CLSI) reference standard EP09c, Measurement Procedure Comparison and Bias Estimation Using Patient Samples - 3rd Edition, 2018, the accuracy of the Preemie system compared to the reference laboratory will be assessed through regression analysis, method comparison (R2, slope, intercept calculations), and bias estimations at low, medium, and high levels of each analyte.
Phase 2: Feasibility of recruiting infants to a study using Preemie system and associated NutriNTrack software to provide targeted individualised breast milk fortification in line with European recommendations.
Time Frame: 1 year
Measure ability to recruit infants to study (recruitment success rates given as the percentage of parents giving consent of the total number approached)
Phase 1: Precision of the Preemie system against reference laboratory ISO methods.
Time Frame: 6 months
Establish precision/reproducibility of the Preemie sensor by assessing the standard deviation of measures of the macronutrient content of human breast milk (protein in g/L, Fat in g/L, carbohydrate in g/l) related to measurements collected by different operators and units Precision/reproducibility study of the Preemie system by paired testing of at least 5 human milk samples. As per the CLSI reference standard EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - 3rd Edition, 2014, the Preemie system precision/reproducibility will be assessed by measuring the standard deviation between day, within run, between run, and in total, at each site, for each analyte.
Phase 2: Feasibility of using Preemie system and associated NutriNTrack software to provide targeted individualised breast milk fortification in line with European recommendations.
Time Frame: 1 year
Measure ability to deliver intervention successfully (intervention compliance given as a percentage of infants randomised to targeted individualised breast milk fortification who received the intervention as intended)
Secondary Outcomes
- Phase 2: Head Growth(36 weeks corrected gestational age)
- Phase 2: Enteral macronutrient intakes(36 weeks corrected gestational age)
- Phase 2: Enteral wate-soluble vitamin intakes(36 weeks corrected gestational age)
- Phase 2: Ease of use of Preemie device(1 year (end of study))
- Phase 2: Enteral fat-soluble vitamin intakes(36 weeks corrected gestational age)
- Phase 2: Length Growth(36 weeks corrected gestational age)
- Phase 2: Neonatal morbidities(36 weeks corrected gestational age)
- Phase 2: Weight Gain(36 weeks corrected gestational age)
- Phase 2: Albumin as a serum marker of nutritional status(36 weeks corrected gestational age)
- Phase 2: Alkaline Phosphatase (ALP) as a serum marker of nutritional status(36 weeks corrected gestational age)
- Phase 2: Enteral trace element intakes(36 weeks corrected gestational age)
- Phase 2: Enteral electrolyte intakes(36 weeks corrected gestational age)
- Phase 2: Feed intolerance(36 weeks corrected gestational age)
- Phase 2: Urea as a serum marker of nutritional status(36 weeks corrected gestational age)