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

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.

Study Overview

• Status: Completed
• Conditions: Enterocolitis, Necrotizing; Premature Birth of Newborn
• Intervention / Treatment: Drug: Ampicillin; Drug: Gentamicins; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center - Comer Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 hours (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria for antibiotic randomization:

1. Infant must be born between the gestational ages of 28 0/7 weeks and 34 6/7 weeks

   -AND-

2. Infant must be born at investigator's home institution.

   -AND-

3. Infant must be considered to have a low risk of infection by one of the following criteria:

   1. 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-
   2. 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:

1. Signs of clinical illness within the first 3 hours of life:

   1. 5-minute Apgar <5
   2. Requiring vasoactive drugs
   3. Seizures
   4. Significant respiratory distress requiring supplemental oxygen >40%
2. Immature:Total (I:T) Ratio of >0.2 on initial complete blood count (CBC)
3. 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.

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
Active Comparator: Randomized & Blinded - Receiving Antibiotics; 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; 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.; Drug: Gentamicins; 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.
Placebo Comparator: Randomized & Blinded - Receiving Placebo; 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; Normal saline will be given as placebo for those in the placebo comparator group.

What is the study measuring?

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
Death		18 months
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

Collaborators and Investigators

• Sponsor: University of Chicago

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: June 19, 2015
• First Posted (Estimate): June 22, 2015

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Microbiome; Antibiotics
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Enterocolitis; Enterocolitis, Necrotizing; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Ampicillin; Gentamicins
• Other Study ID Numbers: IRB15-0053

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO