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

Study Overview
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Brief Summary
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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.

Detailed Description
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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 Antenatal history including: rupture of membrane, Chorioamnionitis, history of urinary tract infection. Natal history including: mode of delivery, place of delivery, the need for resuscitation, recorded Apgar score at 1minute and 5 minutes. Postnatal history including: age of admission in neonatal intensive care unit, symptoms suggest infection. II. Thorough clinical assessment: Weight and Occiptofrontal circumference (twice weekly). Complete examination including cardiovascular, respiratory, abdominal and neurological examination. III. Laboratory investigations: Complete blood picture, C-reactive protein on admission and repeated twice weekly Blood culture before starting treatment and with any suspected sepsis. 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.

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

Conditions
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Late Onset Neonatal Sepsis, Necrotizing Enterocolitis of Newborn, Feeding; Difficult, Newborn

Intervention / Treatment
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* Dietary Supplement: Bovine colostrum


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 24 Hours
Maximum Age: 28 Days

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Non bovine colostrun<br>Preterm received preterm formula | |
| Active Comparator: Bovine colostrum group<br>Preterm received bovine colostrum as trophic feeding | Dietary Supplement: Bovine colostrum<br>* bovine colostrum for first 2 weeks<br>|

What is the study measuring?
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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 |