This is a single-center, parallel-arm, blind, sham-controlled, feasibility randomized controlled trial (RCT) to be conducted in healthy cesarean-born children. Eligible children will be randomized 1:1 to have their nose swabbed with either maternal vaginal secretions or a sterile swab (intervention vs. control group, respectively). The main hypothesis is that conducting an RCT assessing the utility of vaginal seeding in modifying the early-life upper respiratory tract (URT) microbiome of children born by cesarean section (C-section) is feasible and that the intervention is safe.
Eligible children will be randomized 1:1 to have their nose swabbed with either maternal vaginal secretions or a sterile swab (intervention vs. control group, respectively). The procedure will be performed following birth by C-section and immediately after the initial newborn care by the general pediatric team. The mother and child will then receive usual medical care as determined by their health care providers. Follow-up will occur at multiple time points during the child's first 6 months of life. One planned interim analysis to assess the safety of the procedure will be conducted. The intervention aims to transfer the maternal vaginal microbiome to the nasal cavity of cesarean-born children at birth (i.e., vaginal seeding of the URT). Hence, the intervention simply attempts to replicate the natural exposure to maternal vaginal secretions during vaginal delivery in children born by C-section.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
20
Following birth by C-section and immediately after the initial newborn care by the general pediatric team, children randomized to the intervention group will have their nasal cavity swabbed with maternal vaginal secretions.
Following birth by C-section and immediately after the initial newborn care by the general pediatric team, children randomized to the control group will have their nasal cavity swabbed with a sterile swab.
Vanderbilt University Medical Center
Nashville, Tennessee, United States
RECRUITINGFeasibility of the RCT
The study will be considered "definitively feasible as proposed," "possibly feasible as proposed," or "not feasible as proposed" based on eligibility, consent, enrollment, and loss to follow-up rates, which could be used as preliminary data to inform the design of a future phase II RCT. For this study, "enrolled" will be defined as consented and screened, with eligibility verified, and the eligibility, consent, enrollment, and loss to follow-up rates will be calculated using the following formulas: 1) eligibility rate = number of participants who are eligible\*100 / number of participants pre-screened, 2) consent rate = number of participants who provide consent\*100 / number of participants who are eligible, 3) enrollment rate = number of participants who are enrolled\*100 / number of participants consented and who complete screening procedures, and 4) loss to follow-up = number of participants who did not complete the end-of-study visit\*100 rate / number of participants randomized.
Time frame: Six months following randomization
Safety of the intervention
To be determined by the number of adverse events, serious adverse events, and unanticipated problems throughout the study, as defined using the standards set forth in the National Cancer Institute's - Common Terminology Criteria (NCI-CTCAE) for AEs version 4.0 and the United States Department of Health and Human Services - Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events: Office for Human Research Protections Guidance 2007
Time frame: Six months following randomization
Timing of the intervention
The number of minutes after birth when the intervention is performed.
Time frame: Immediately following administration of the intervention
Proportion of in-person study visits completed
The total number of in-person study visits completed by all participants\*100 / total number of in-person visits expected for all participants for each study time point.
Time frame: Six months following randomization
Common microbial ecology metrics of the maternal vaginal microbiome and of the early-life URT microbiome
The comparisons of the maternal vaginal microbiome on the day of delivery between study groups will be conducted using alpha-diversity (e.g., observed taxa, Shannon index, and Simpson indices), beta-diversity (e.g., Bray-Curtis, Jaccard, weighted UniFrac, and unweighted UniFrac indices), and differential abundance (at the amplicon sequence variant, genus, and/or family level) analyses. The early-life URT microbiome at each time point and over time will be compared between study groups using similar microbial ecology metrics. In pre-specified analyses, we will also compare the presence and abundance of the genus Lactobacillus and the predominant Lactobacillus amplicon sequence variants in the URT of children at each time point and over time between study groups, as this is the predominant taxa of the maternal vaginal microbiome during pregnancy.
Time frame: At each study time point (birth, ~2 days, ~5 days, ~4 weeks, and ~6 months of age) and over time (longitudinally from birth to age 6 months)
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