Clinical Impact of Donor Milk Pasteurized by HTST Treatment in Preterm Infants

Study Overview
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Brief Summary
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Randomized double-blind clinical trial to compare the incidence of microbiological proven late onset sepsis in extremely preterm infants (<1000 grams) that are supplemented with donor milk pasteurized by High Temperature Short Time (HTST) method versus the Holder method.

Detailed Description
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Donor milk pasteurized by an innovative High Temperature Short Time (HTST) system (patented by researchers) retains more immune and trophic compounds than pasteurized milk by traditional Holder method. These compounds are related to the protection conferred by breast milk against nosocomial sepsis and necrotizing enterocolitis in preterm infants, so it would be of interest to study if there is a clinical benefit in these patients when health professionals are supplementing with donor milk pasteurized by both methods. The purpose of this study is to compare the incidence of microbiological proven late onset sepsis in newborns under 1000 grams that in the first 28 days of life need to be supplemented with donor milk pasteurized by HTST method versus the Holder method. This is a randomized double-blind clinical trial with parallel assignment. A total of 305 premature babies with a birth weight of less than 1000 grams will be recruited, admitted to the Neonatology Services of the Hospital 12 de Octubre and the Hospital de La Paz and meet the inclusion criteria. Half of the patients will be supplemented exclusively with donor milk pasteurized by the HTST system and the other half with pasteurized milk by the Holder method. Linear generalized models will be used for longitudinal data analysis.

Official Title
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Clinical and Economic Impact of Supplementation With Donor Milk Pasteurized by HTST Method Versus Holder Method in Extremely Birth Weight Preterm Infants. Randomized Clinical Trial

Conditions
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Late-Onset Neonatal Sepsis

Intervention / Treatment
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* Other: donor milk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (all criteria are necessary) : Infants weighing 1000 grams or less at birth Infants born or transferred before the third day of life to the participating centers Start enteral feeding in the first week of life Receive any amount of donor milk in the first 28 days of life Informed consent signed by parents or legal guardians Exclusion Criteria: Language barrier Infants with chromosomopathies Infants with major congenital malformations Infants with severe asphyxiation (cord pH or first arterial pH <7) Infants included in another clinical trial that modifies nutritional management Infants who previously fed with formula Post-randomization exclusion criteria: - Randomized infant who do not fulfill inclusion criteria

Ages Eligible for Study
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Maximum Age: 28 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Holder pasteurization<br>Donor milk pasteurized by Holder method (62.5ºC, 30 minutes) | Other: donor milk<br>* pasteurized donor milk<br>|
| Experimental: HTST pasteurization<br>Donor milk pasteurized by High Temperature Short Time (HTST) method (72ºC, 15 seconds) | Other: donor milk<br>* pasteurized donor milk<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiological proven late onset sepsis rate | Incidence of Microbiological proven late onset sepsis expressed as a percentage | From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central line associated bloodstream infections (CLABSI) rate | Number of CLABSI events per 1000 catheter-days | From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks | 
| Necrotizing enterocolitis (NEC) and/or microbiological proven late onset sepsis rate | Incidence of NEC nad late onset sepsis as a percentage | From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks | 
| Mortality rate | Percentage of preterm infant died during the study | From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks | 
| Oxygen supplementation | Percentage of infants with respiratory assistance with fraction of inspired oxygen greater than 0.21 at 36 weeks postmenstrual age | Assessed up to 24 weeks | 
| Stage 3-5 Retinopathy | Percentage of infants diagnosed with retinopathy by the ophthalmologist | From the time and day of randomization until the date of discharge from the neonatal unit, assessed up to 24 weeks | 
| Growth velocity | Growth calculated as the weight gain in g/kg/day | Assessed up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neonatal sepsis, extremely low birth weight infant, donor milk, HTST pasteurization, Holder pasteurization