A Randomized Controlled Trial Investigating if Antibiotic Use in the First 48 Hours of Life Adversely Impacts the Preterm Infant Microbiome

Study Overview
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Brief Summary
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The purpose of this study is to determine whether antibiotics given immediately after birth alter the development of the developing preterm infant's microbiome, which may further alter overall clinical outcomes.

Official Title
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A Randomized Controlled Trial Investigating if Antibiotic Use in the First 48 Hours of Life Adversely Impacts the Preterm Infant Microbiome

Conditions
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Premature Birth of Newborn, Enterocolitis, Necrotizing

Intervention / Treatment
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* Drug: Ampicillin
* Drug: Gentamicins
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for antibiotic randomization: Infant must be born between the gestational ages of 28 0/7 weeks and 34 6/7 weeks -AND- Infant must be born at investigator's home institution. -AND- Infant must be considered to have a low risk of infection by one of the following criteria: Delivered for maternal indications (Cesarean section or induction of labor for maternal health, including pre-eclampsia, placental abruption, history of intrauterine fetal demise (IUFD)/abruption, multiple gestation requiring preterm delivery, etc) -OR- Delivered due to preterm labor to a mother without the diagnosis of chorioamnionitis/maternal fever or prolonged rupture of membranes >18 hours Exclusion Criteria for antibiotic randomization: Signs of clinical illness within the first 3 hours of life: 5-minute Apgar <5 Requiring vasoactive drugs Seizures Significant respiratory distress requiring supplemental oxygen >40% Immature:Total (I:T) Ratio of >0.2 on initial complete blood count (CBC) Congenital anomalies, including renal anomalies requiring serum antibiotic level monitoring ANY infant born between the gestational ages of 28 0/7 weeks and 34 6/7 weeks who do not meet inclusion criteria, with parental consent, can participate in the stool analysis only arm of the study.

Ages Eligible for Study
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Maximum Age: 6 Hours

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Randomized & Blinded - Receiving Antibiotics<br>The infants within this arm of the study meet the inclusion criteria as being low risk. They will be randomized to receive routine ampicillin and gentamicin for the initial 48 hours of their life as a routine rule-out sepsis. Stool samples will be collected throughout hospitalization and at 18 months of life. | Drug: Ampicillin<br>* Ampicillin will be given as routine antibiotic coverage for those in the active arm, as the standard initial antibiotic used within the neonatal unit. It may also be used for patients who are not eligible for randomization.<br>Drug: Gentamicins<br>* Gentamicin will be given as routine antibiotic coverage for those in the active arm, as the standard initial antibiotic used within the neonatal unit. It may also be used for patients who are not eligible for randomization.<br>|
| Placebo Comparator: Randomized & Blinded - Receiving Placebo<br>The infants within this arm of the study meet the inclusion criteria as being low risk. They will be randomized to receive placebo (saline) in place of ampicillin and gentamicin for the initial 48 hours of their life as a routine rule-out sepsis. Stool samples will be collected throughout hospitalization and at 18 months of life. | Drug: Placebo<br>* Normal saline will be given as placebo for those in the placebo comparator group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Richness of the Preterm Infant Microbiome | Number of 16S rRNA gene amplicon sequence variants (i.e., proxy for prokaryote species-like groupings) detected in each sample. A higher richness means that a higher number of species of archaea and bacteria was detected in a sample. | 2 weeks | 
| Shannon Diversity of the Preterm Infant Microbiome | Function of richness and evenness of 16S rRNA gene amplicon sequence variants (i.e., proxy for prokaryote species-like groupings) within each sample. A higher Shannon diversity means that a sample had a combination of a higher number of species of archaea and bacteria, and/or a more even relative abundance of those species within a sample. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic Lung Disease of Infancy (CLD) | Premature infants who require > 21% FiO2 for at least 28 days and/or at 36 weeks corrected gestation | 4-12 weeks | 
| Necrotizing Enterocolitis (NEC) | Any patient showing signs/symptoms of this acute neonatal gastrointestinal disease, including abdominal distension, bloody stools, systemic illness, and radiographic changes (pneumatosis intestinalis, portal venous gas, free intraperitoneal gas). | 4-12 weeks | 
| Retinopathy of Prematurity (ROP) | Cases of ROP as diagnosed by the pediatric ophthalmologist | 4-12 weeks | 
| Intraventricular Hemorrhage (IVH) | Cases of IVH present on any head ultrasound obtained during patient's hospitalization | 4-12 weeks | 
| Death |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microbiome, Antibiotics