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

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

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.

Study Overview

• Status: Completed
• Conditions: Enterocolitis, Necrotizing; Infection; Ventilator-associated Pneumonia
• Intervention / Treatment: Other: oropharyngeal mother's milk; Other: oropharyngeal sterile water

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.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33143-4679
      • South Miami Hospital
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Northshore University Health System
    • Park Ridge, Illinois, United States, 60068
      • Advocate Children's Hospital-Park Ridge
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
  • North Carolina
    • Wilmington, North Carolina, United States, 28403-6024
      • Betty Cameron Women & Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 4 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oropharyngeal mother's milk; 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; 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
Placebo Comparator: oropharyngeal sterile water; 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; 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

What is the study measuring?

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,

Collaborators and Investigators

• Sponsor: NorthShore University HealthSystem
• Collaborators: University of Chicago; The Gerber Foundation; Fundacion Para La Investigacion Hospital La Fe
• Investigators: Principal Investigator: Nancy A Garofalo (previously Rodriguez), PhD APN NNP, NorthShore University HealthSystem

Publications and helpful links

General Publications

• Rodriguez NA, Vento M, Claud EC, Wang CE, Caplan MS. Oropharyngeal administration of mother's colostrum, health outcomes of premature infants: study protocol for a randomized controlled trial. Trials. 2015 Oct 12;16:453. doi: 10.1186/s13063-015-0969-6.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2013
• Primary Completion (Actual): October 30, 2021
• Study Completion (Actual): January 4, 2022

Study Registration Dates

• First Submitted: April 11, 2014
• First Submitted That Met QC Criteria: April 16, 2014
• First Posted (Estimate): April 17, 2014

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: infection; colostrum; microbiome; neonate; premature; necrotizing enterocolitis; antioxidant; ventilator-associated pneumonia; human milk; breastmilk; mother's milk; oropharyngeal; late-onset sepsis; enteral feeds
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Cross Infection; Iatrogenic Disease; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Healthcare-Associated Pneumonia; Pneumonia; Premature Birth; Enterocolitis; Enterocolitis, Necrotizing; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: EH11-360

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF