The Efficacy and Mechanisms of Oral Probiotics in Preventing Necrotizing Enterocolitis

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and its mechanisms of oral mixture probiotics in preventing necrotizing enterocolitis among the preterm very low birth weight infants.

Detailed Description
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Necrotizing enterocolitis (NEC) remains the most catastrophic gastrointestinal emergencies in preterm very low birth weight (VLBW) infants.Although study showed it is a multifactorial disease, its pathogenesis is still not yet unclear currently. Prematurity and formula feeding is considered as the main risk factors.Gut microbiota disturbance and immature immune system is associated with NEC. A lot of studies had showed that oral probiotics can alter gut microbiota flora colonization and reduce the incidence of NEC,but the exact mechanism remains unclear.The aim of this study is to elucidate the clinical efficacy and possible molecular mechanism of oral mixture probiotics in preventing NEC among preterm VLBW infants. Patient Registry procedures: First,randomized numbers was generated by the computer and sent to the principal investigator(PI) at each center when an infant was eligible for enrollment.Second, patient will be assigned randomly to experimental group or control group by PI.Finally,the PI at each center will be responsible for the accuracy,completeness or representativeness of medical records, registry forms,data collection. Sample size determination: The incidence of death and NEC was around 20% recently.To reduce the incidence of NEC and death to 10% at discharge would require a 50% improvement.At 80% power at P = 0.05 (two-sided),the loss rate of 0.2, this would require 135 subjects per arm. Statistical analysis:The two groups were compared by a Χ2-test for categorical variables,Mann-Whitney U Test were used when reporting medians.A P value of <0.05 was considered statistically significant.

Official Title
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The Efficacy and Mechanisms of Oral Probiotics in Preventing Necrotizing Enterocolitis Among Very Low Birth Weight Infants With Formula-feeding

Conditions
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Necrotizing Enterocolitis, Death

Intervention / Treatment
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* Dietary Supplement: probiotics
* Dietary Supplement: glucose solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm infants ≦ 34 weeks gestational age and birth weight below 1500 gm and who survive to NICU are eligible for the trial. Exclusion Criteria: severe asphyxia (stage III), fetal chromosomal anomalies, cyanotic congenital heart disease, congenital intestinal atresia, gastroschisis, omphalocele, active upper gastric intestinal bleeding, lacking/refused of parental consent, those who are fasted for >3 weeks during the study period.

Ages Eligible for Study
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Maximum Age: 3 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: probiotics group<br>Administration of probiotics 500mg begins by mouth within 4 hours of life with 1-3 consecutive doses; the frequency depends on the feeding times. Study is continuous until preterm infants grow up to 36 weeks post menstrual age. | Dietary Supplement: probiotics<br>* Administration of mixture probiotics 500mg by mouth, one time or divided into 2-4 times depends on the feeding volume until to 36 weeks post menstrual age.<br>|
| Placebo Comparator: control group<br>control group received 1 mL of a 5% glucose solution. Administration of control group begins by mouth within 4 hours of life with 1-3 consecutive doses; the frequency depends on the feeding times. Study is also continuous until preterm infants grow up to 36 weeks post menstrual age. | Dietary Supplement: glucose solution<br>* Administration of 1 mL of a 5% glucose solution by mouth, one time or divided into 2-4 times depends on the feeding volume until to 36 weeks post menstrual age.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the incidence of combined death and necrotizing enterocolitis |  | at 36 weeks correct gestational age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the incidence of sepsis,intraventricular hemorrhage(IVH)(grade 3-4),feeding intolerance(FI),bronchopulmonary dysplasia(BPD),parenteral nutrition associated liver disease(PNALD)and retinopathyof prematurity(ROP). |  | participants will be followed for the duration of hospital stay, an expected average of 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotics, preterm very low birth weight infants, necrotizing enterocolitis, gut microflora, TLR, NF-KB, inflammatory factors