Gut Priming With Oral Bovine Colostrum for Preterm Neonates; Randomized Control Trial

Effect of Bovine Colostrum On T-Regulatory Cells, Prevention Of Late Onset Sepsis And Necrotizing Enterocolitis In Preterm Neonates

The aim was to assess the ability of bovine colostrum concentrate to reduce the incidence of late-onset sepsis episodes and necrotizing enterocolitis in artificially fed preterm neonates and its effect on T regulatory cells. And to evaluate the effect of bovine colostrum concentrate on feeding tolerance, growth, hospital stay and mortality in preterm neonates.

Study Overview

• Status: Completed
• Conditions: Feeding; Difficult, Newborn; Necrotizing Enterocolitis of Newborn; Late Onset Neonatal Sepsis
• Intervention / Treatment: Dietary supplement: Bovine colostrum

Detailed Description

The study was interventional, double blinded and randomized trial ، performed on preterm neonates( <34 week) admitted on Ain ShamsUniversity (ASU) neonatal intensive care units (NICU) after considering exclusion criteria.

The enrolled patients was subdivided into two groups; group A are infants with non bovine colstrum and group B with bovine colostrum All infants received the standard neonatal care and underwent follow-up from birth until reach 37 week corrected gestational age, discharge or death whichever came first.

I. Data Collection: Careful history taking

1. Antenatal history including: rupture of membrane, Chorioamnionitis, history of urinary tract infection.
2. Natal history including: mode of delivery, place of delivery, the need for resuscitation, recorded Apgar score at 1minute and 5 minutes.
3. Postnatal history including: age of admission in neonatal intensive care unit, symptoms suggest infection.

II. Thorough clinical assessment:

1. Weight and Occiptofrontal circumference (twice weekly).
2. Complete examination including cardiovascular, respiratory, abdominal and neurological examination.

III. Laboratory investigations:

1. Complete blood picture, C-reactive protein on admission and repeated twice weekly
2. Blood culture before starting treatment and with any suspected sepsis.
3. In first 24 hours and the end of second week : Collecting peripheral blood mononuclear cells to be analyzed for cellular parameters by flow cytometry (CD4 T cells, CD25 L, FOXP3). Three subsets of CD4+ T cells will be defined according to CD25 staining: CD25- , CD25 low, and CD25 high. Cells expressing CD25 high will be chosen and gated for the detection of FOXP3+ T cells.

IV. Radiological investigations:

Chest X-ray (It was done on admission and repeated when needed). Abdominal X-ray (when necrotizing enterocolitis is suspected). Abdominal ultrasound (when necrotizing enterocolitis is suspected).

V. Follow-up and end-point of the study:

All infant underwent follow-up from birth until reach 37 week corrected gestational age, discharge or death whichever came first.NPO for more than 24 hours

The following primary outcome data was recorded:

• Clinical examination and laboratory investigations when clinically indicated for evidence of sepsis.
• Clinical examination and radiological investigations when clinically indicated for evidence of NEC.

A secondary outcome measure includes weight increment per kg per week, duration of hospitalization, mortality if any, monitoring adverse effects of treatment (if any); such as emesis, increased gastric residuals, increased abdominal girth, diarrhea, skin rash. Long term outcome includes necrotizing enterocolitis, and intracranial hemorrhage.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Abasseya
    • Giza, Abasseya, Egypt, 05000
      • MEDICIN

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• • Preterm Neonate having a gestational age equal or less than 34 weeks at birth, admitted in Ain-Shams University NICUs

Exclusion Criteria:

• • Maternal risk factor of early onset sepsis, chorioamnionitis.

  • Proved early onset sepsis.
  • Life-threatening congenital abnormalities.
  • Inborn error of metabolism.
  • Chromosomal aberrations.
  • Neonates with underlying gastrointestinal problems (such as GIT anomalies) that prevent enteral feeding.
  • Perinatal asphyxia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Non bovine colostrun; Preterm received preterm formula
Active Comparator: Bovine colostrum group; Preterm received bovine colostrum as trophic feeding	Dietary supplement: Bovine colostrum; bovine colostrum for first 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Late Onset Sepsis in the three groups	Incidence of Late Onset Sepsis in the studied group measured by rodwell and tollner sepsis scoring system	From time of randomization to discharge from nicu or death whichever comes first
The incidence of Necrotizing Enterocolitis in the three groups	Incidence of Necrotizing Enterocolitis in the three groups diagnosed according to bell's staging	From time of randomization to discharge from nicu or death whichever comes first
The change of Active T regulatory cells In the three groups	Active T regulatory cells diagnosed by cell CD 4 expressing CD 25 high or simultaneously CD 25 plus FOXP3	Change from base line at randomization and after intervention by 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feeding intolerance is defined as presence of at least 3 consecutive days of any of the following:emesis, gastric residuals, diarrhea, blood in stools or abnormally enlarged bowel loops	Feeding intolerance	From time of randomization to discharge from nicu or death whichever comes first
Neonatal mortality	Number of deaths in the study group	From time of randomization to discharge from nicu or death whichever comes first
Duration of hospital stay	Duration of hospital stay	From time of randomization to discharge from nicu or death whichever comes first

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: Hisham Awad, professor of pediatrics Ain Shams university

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2018
• Primary Completion (Actual): June 15, 2019
• Study Completion (Actual): September 15, 2019

Study Registration Dates

• First Submitted: November 8, 2018
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (Actual): April 24, 2019

Study Record Updates

• Last Update Posted (Actual): June 23, 2020
• Last Update Submitted That Met QC Criteria: June 21, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Gastrointestinal Diseases; Infant, Newborn, Diseases; Gastroenteritis; Intestinal Diseases; Sepsis; Enterocolitis; Enterocolitis, Necrotizing; Neonatal Sepsis
• Other Study ID Numbers: FMASU 50 / 2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: research protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No