Enterocolitis, Necrotizing, Infection, Ventilator-associated Pneumonia
Conditions
Keywords
oropharyngeal, colostrum, mother's milk, premature, neonate, infection, necrotizing enterocolitis, ventilator-associated pneumonia, breastmilk, human milk, late-onset sepsis, microbiome, antioxidant, enteral feeds
Brief summary
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
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.
Interventions
OTHERoropharyngeal mother's milk
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
OTHERoropharyngeal sterile water
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
Sponsors
The Gerber Foundation
Fundacion Para La Investigacion Hospital La Fe
University of Chicago
Endeavor Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Days to 4 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of of late-onset sepsis | at 40 wks CGA | positive blood cultures (not deemed contaminated) collected after 72 hours of age, and 2 clinical symptoms |
| Incidence of necrotizing enterocolitis | at 40 weeks CGA | defined according to modified Bell's criteria stage \>2 with clinical signs and radiological evidence of pneumatosis intestinalis or portal venous gas |
| Incidence of ventilator-associated pneumonia | at 40 weeks CGA | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in stool microbiome | 3 days, 2 weeks, 32 weeks CGA | — |
| Time to reach full enteral feeds | at 40 wks CGA | defined as # days to reach a 120kcal/kg/day |
| Changes in urinary biomarkers of oxidative stress | 3 days, | 1 day, 3 days, 1 week, 32 weeks CGA |
| Length of hospital stay | at 40 wks CGA | — |
| Concentrations of lactoferrin in urine | 1 day, 3 days, 32 weeks CGA | — |
Countries
United States
Outcome results
None listed