Oropharyngeal Administration of Colostrum to Extremely Low Gestational Age Newborns

Study Overview
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Brief Summary
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Colostrum is rich in cytokines and other immune agents that may provide immunomodulatory protection against nosocomial infection in extremely premature infants. However, most of them could not proceed enteral feedings due to clinical instability in the first few days. Recent studies supports oropharyngeal administration as a potentially safe and effective delivery method for immunologic benefits and only small amount of colostrum could be administrated for immune therapy for extremely premature babies. The purpose of this study is to determine the beneficial effects of oropharyngeal administration of colostrum for immunologic aspects in extremely low gestational age infants and evaluated the safety of this method to extremely premature infants in the first few days of life.

Conditions
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Extremely Low Gestational Age Newborn, Premature Infant

Intervention / Treatment
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* Other: oropharyngeal administration of own mother's colostrum
* Other: oropharyngeal administration of sterile water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: premature infant with a gestational age less than 28 weeks born at Seoul National University Hospital and admit to the Seoul National University Children's Hospital NICU immediately after birth parents of the infant signed to the informed consent form with voluntary agreement Exclusion Criteria: infants with major congenital anomalies or chromosomal syndromes infants of mothers not willing to provide colostrum in the first week of life infants of mothers with known infectious diseases that may be transmitted through the breast milk such as HIV, hepatitis C or active TB

Ages Eligible for Study
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Minimum Age: 48 Hours
Maximum Age: 96 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colostrum<br>oropharyngeal administration of own mother's colostrum | Other: oropharyngeal administration of own mother's colostrum<br>* application of 0.2 mL of colostrum to the infant's oropharyngeal mucosa every 3 hours for 3 days from the postnatal 48 to 96 hours.<br>|
| Placebo Comparator: Placebo<br>oropharyngeal administration of sterile water | Other: oropharyngeal administration of sterile water<br>* application of 0.2 mL of sterile water to the infant's oropharyngeal mucosa every 3 hours for 3 days from the postnatal 48 to 96 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Secretary IgA Concentration at 2 Weeks of Age |  | 2 weeks of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Secretary IgA Concentration at 1 Week of Age |  | 1 week of age | 
| Salivary TGF-beta 1 Concentration at 2 Week of Age |  | 2 week of age | 
| Salivary IL-8 Concentration at 2 Weeks of Age |  | 2 weeks of age | 
| Concentration of Urinary Lactoferrin |  | 1 week of age | 
| Concentration of Urinary IL-1 Beta |  | 2 weeks of age | 
| Concentration of Salivary Lactoferrin, Lysozyme, Alpha-lactalbumin and Cytokines |  | 1 week of age | 
| Concentration of Salivary Lactoferrin, Lysozyme, Alpha-lactalbumin and Cytokines |  | 2 weeks of age | 
| Time to Reach Full Feeding | day of life when the baby reaches full enteral feeding, defined as a volume above 120 130mL/kg/day | up to 2 months of age | 
| Total Hospital Admission Duration | days from admission to discharge from NICU | up to 4 months of age | 
| Episodes of Culture Positive Sepsis | numbers of documented sepsis events defined as isolation of the microorganism from ≥ 1 blood culture + ≥ 1 clinical symptoms or sign (fever, hypothermia, apnea, bradycardia, hypo-/hyperglycemia) | from date of randomization up to 4 months of age | 
| Episodes of Necrotizing Enterocolitis ≥ Bell's Stage 2 |  | from date of randomization up to 4 months of age | 
| Episodes of Pneumonia | numbers of documented pneumonia events those accompanied with increased tracheal secretion, increased ventilatory setting and treated with antibiotics | from date of randomization up to 4 months of age | 
| Development of Bronchopulmonary Dysplasia ≥ Moderate |  | up to 4 months of age | 
| Development of Intraventricular Hemorrhage ≥ Grade 3 |  | up to 4 months of age | 
| In-hospital Death |  | up to 4 months of age | 
| Development of Adverse Effects | category of adverse effects general - fever or hypothermia, rash respiratory & cardiovascular - apnea, tachypnea, desaturation, hypotension, bradycardia, tachycardia gastrointestinal - abdominal distension, bilious gastric remain, vomiting, bloody stool, necrotizing enterocolitis renal - oliguria (urine output < 1.0cc/kg/day) laboratory - hypo-/hyper-natremia, acidosis, hypercarbia | from the start date of oropharyngeal administration of colostrum or sterile water to 1 week of age |