Oropharyngeal Administration of Mother's Colostrum for Premature Infants (NS-72393-360)

Study Overview
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Brief Summary
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Extremely premature (BW<1250g) infants are at high risk for morbidity and mortality. Own mother's colostrum (OMC) and milk (OMM) protect against neonatal morbidity and are rich in immune factors which may provide immunostimulatory effects when administered oropharyngeally to extremely premature infants during the first weeks of life. The investigators hypothesize that infants who receive oropharyngeal mother's colostrum and milk will have significantly lower rates of infection and improved health outcomes, compared to infants who receive a placebo.

Detailed Description
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Extremely premature (BW<1250g) infants are at high risk for morbidity and mortality. Own mother's colostrum (OMC) and milk (OMM) protect against neonatal morbidity and are rich in immune factors which may provide immunostimulatory effects when administered oropharyngeally to extremely premature infants during the first weeks of life. This 5-year placebo-controlled, double-blind randomized controlled trial will evaluate the safety, efficacy and health outcomes of oropharyngeal administration of OMC/OMM in a sample of 622 (total patients enrolled) extremely premature infants with the following aims: Aim 1. To determine if oropharyngeal administration of OMC/OMM to extremely premature infants will reduce the risk of late-onset sepsis or death as the primary outcome, and necrotizing enterocolitis and ventilator-associated pneumonia as pre-planned secondary outcomes. Aim 2: To determine if extremely premature infants who receive OMC/OMM via the oropharyngeal route have a shorter time to reach full enteral feeds and a shorter length of hospital stay. Aim 3: To determine if oropharyngeal administration of OMC/OMM will have immunostimulatory effects for extremely premature infants, as measured by (A) enhancement of gastrointestinal (fecal) microbiota, (B) improvement in antioxidant defense maturation or reduction of pro-oxidant status, and (C) maturation of immunostimulatory effects as measured by changes in urinary lactoferrin. Results will confirm whether extremely premature infants demonstrate a host-immune response to this intervention and whether there is a beneficial effect on common morbidities in these high risk patients.

Official Title
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Oropharyngeal Administration of Mother's Colostrum: Health Outcomes of Premature Infants

Conditions
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Infection, Enterocolitis, Necrotizing, Ventilator-associated Pneumonia

Intervention / Treatment
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* Other: oropharyngeal mother's milk
* Other: oropharyngeal sterile water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Birthweight <1250g Mother plans to pump and provide breastmilk for at least 2 months Absence of severe congenital anomalies Admission to the neonatal intensive care unit within 24 hours after birth Ability to begin protocol within 96 hours of life Exclusion Criteria: Gastrointestinal anomaly pH < 7.0 on initial blood gas in NICU Maternal +HIV status Maternal drug or substance use that precludes infant from receiving mother's milk Tracheoesophageal fistula

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 4 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oropharyngeal mother's milk<br>0.2 mL every 2 hours for 48 hours beginning within 96 hours post-birth, followed by 0.2 mL every 3 hours until 32 weeks post conceptional age | Other: oropharyngeal mother's milk<br>* Application of 0.2 mL of own mother's milk onto the infant's oral mucosa, for an initial treatment period of every 2 hours for 48 hours, followed by an extended treatment period of every 3 hours until 32 weeks corrected gestational age<br>|
| Placebo Comparator: oropharyngeal sterile water<br>0.2 mL every 2 hours for 48 hours beginning within 96 hours post-birth, followed by 0.2 mL every 3 hours until 32 weeks post conceptional age | Other: oropharyngeal sterile water<br>* Application of 0.2 mL of sterile water onto the infant's oral mucosa, for an initial treatment period of every 2 hours for 48 hours, followed by an extended treatment period of every 3 hours until 32 weeks corrected gestational age<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of of late-onset sepsis | positive blood cultures (not deemed contaminated) collected after 72 hours of age, and 2 clinical symptoms | at 40 wks CGA | 
| Incidence of necrotizing enterocolitis | defined according to modified Bell's criteria stage >2 with clinical signs and radiological evidence of pneumatosis intestinalis or portal venous gas | at 40 weeks CGA | 
| Incidence of ventilator-associated pneumonia |  | at 40 weeks CGA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach full enteral feeds | defined as # days to reach a 120kcal/kg/day | at 40 wks CGA | 
| Length of hospital stay |  | at 40 wks CGA | 
| Concentrations of lactoferrin in urine |  | 1 day, 3 days, 32 weeks CGA | 
| Changes in stool microbiome |  | 3 days, 2 weeks, 32 weeks CGA | 
| Changes in urinary biomarkers of oxidative stress | 1 day, 3 days, 1 week, 32 weeks CGA | 3 days, | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breastmilk, neonate, oropharyngeal, colostrum, mother's milk, premature, infection, necrotizing enterocolitis, ventilator-associated pneumonia, human milk, late-onset sepsis, microbiome, antioxidant, enteral feeds