Vaginal Microbiome Seeding and Health Outcomes in Cesarean-delivered Neonates.

NCT ID: NCT03298334

Last Updated: 2025-06-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

600 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-01

Study Completion Date

2029-04-30

Brief Summary

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Neonates delivered by scheduled Cesarean Section will be randomized to receive vaginal seeding (exposing the infant to Mother's vaginal flora) or sham. Infants will be followed for three years to examine health outcomes including microbiome development, immune development, metabolic outcomes, and any adverse events.

Detailed Description

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Cesarean section (CS) delivery is a common surgical procedure intended to increase the chances of successful delivery and to protect the health of the mother and baby. Yet this intervention is overused and has been associated with higher risk of immune and metabolic disorders in the offspring. It is hypothesized that these associations are due to CS-delivered newborns not receiving the full inoculum of maternal microbes at birth.

While restoring labor is not possible, restoring the microbes that colonize infants during birth through exposure to vaginal flora, is feasible, and has been shown in a small pilot study, to normalize the microbiota of the intestine, skin and mouth during the first month of life.

The investigators hypothesize that the restoration of the vaginal microbiota to the infant at birth will restore the infant microbiome and decrease the risk of obesity and other immune-mediated diseases linked with CS. The investigators aim to test this hypothesis in a randomized controlled trial by first examining the effect of vaginal seeding, in CS-delivered newborns, on the gut microbiota composition, structure and function (Phase I of study; first 50 infants) and then on the BMI z score and other immune-mediated outcomes (Phase II of study; 600 infants).

Methods: CS-delivered neonates will be randomized to either an experimental arm with exposure to the maternal vaginal microbiota at birth, or a control arm with no exposure. Feces, skin, saliva, breast milk, and vaginal swabs will be collected for microbiome analysis. The investigators will obtain clinical information from in-person visits, surveys and the electronic health record.

Implications: this randomized controlled clinical study will provide evidence of whether the "vaginal seeding" procedure can safely transfer microbes from mom-to-baby, and whether these microbes are beneficial for the metabolic and immune health of the child.

Conditions

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Cesarean Delivery Affecting Newborn Obesity, Childhood Intestinal Microbiome Microbiota Host Microbial Interactions Gastrointestinal Microbiome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Receives Vaginal Seeding

Group Type ACTIVE_COMPARATOR

Vaginal Seeding

Intervention Type BIOLOGICAL

A gauze containing the Mother's vaginal flora will be swabbed over the face and body of the neonate shortly after cesarean delivery.

No Vaginal Seeding

Group Type SHAM_COMPARATOR

No Vaginal Seeding

Intervention Type OTHER

A gauze carrying sterile saline will be swabbed over the face and body of the neonate shortly after cesarean delivery.

Interventions

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Vaginal Seeding

A gauze containing the Mother's vaginal flora will be swabbed over the face and body of the neonate shortly after cesarean delivery.

Intervention Type BIOLOGICAL

No Vaginal Seeding

A gauze carrying sterile saline will be swabbed over the face and body of the neonate shortly after cesarean delivery.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Scheduled for cesarean delivery at ≥ 37 weeks
* Pregnant with single fetus, in good general health, age 18 years or older
* Negative maternal testing for infections transmitted through vaginal and/or other body fluids performed as standard of care tests in early pregnancy
* Negative testing for Group B strep at 35-37 weeks gestation
* Vaginal pH ≤ 4.5 indicative of Lactobacillus-dominated vaginal microbiota
* No maternal or fetal complications that may inhibit the ability to perform microbiome restoration per protocol
* English or Spanish speaking
* Negative maternal testing for Gonorrhea, Chlamydia, Hepatitis B, Hepatitis C, Syphilis, and HIV at 35 weeks gestation or later
* Women aged 18-29 years must have a normal Pap test within 3 years
* Women aged 30-65 years must have a normal Pap test and an HPV test (co-testing) within 5 years or FDA-approved primary hrHPV testing alone within 5 years or a normal Pap test alone within 3 years
* Negative maternal testing for SARS-CoV-2 for the delivery admission performed as standard of care test at the Inova Health System.


* Infant condition after delivery requires no more than standard neonatal resuscitation\* or is otherwise medically unable to receive the full VMT procedure

\[\*\] Standard neonatal resuscitation may include: tactile stimulation, bulb suction, oxygen without positive pressure, or drying

Exclusion Criteria

* Delivery at a hospital other than Inova Health System
* Cesarean delivery scheduled for active infection that would have interfered with vaginal delivery such as genital herpetic lesions
* Rupture of membranes prior to scheduled cesarean delivery
* Bacterial vaginosis within 30 days of cesarean delivery
* Symptomatic urinary tract infection within 30 days of cesarean delivery
* Antibiotic therapy within 30 days of cesarean delivery (exclusive of medication use for prophylaxis at the time of surgery)
* Symptoms on admission suggesting Chorioamnionitis, e.g. maternal fever, fundal tenderness
* Symptoms on delivery admission of possible vaginal infection such as genital herpetic lesions
* History of genital HSV
* History positive testing for Group B strep infection
* History of a child with a diagnosis of Group B strep sepsis
* Pregnancy a result of donor egg or surrogacy
* Preexisting history of Type I or Type II Diabetes
* Maternal history of documented genital HPV infection, positive HPV testing or genital warts on physician examination
* Positive maternal testing for SARS-CoV-2 within 30 days of delivery or symptoms on admission suggesting potential Covid-19 infection
Minimum Eligible Age

0 Days

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Johns Hopkins University

OTHER

Sponsor Role collaborator

Rutgers University

OTHER

Sponsor Role collaborator

Inova Health Care Services

OTHER

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Suchitra Hourigan, MD, Chief, Clinical Microbiome Unit, NIAID, Pediatric Gastroenterologist

Role: PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID), Inova Children's Hospital

Noel Mueller, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Maria Gloria Dominguez Bello, PhD

Role: PRINCIPAL_INVESTIGATOR

Rutgers University

Lawrence Appel, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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Inova Health System

Falls Church, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Suchitra Hourigan, MD

Role: CONTACT

Shira Levy

Role: CONTACT

703-776-8489

Facility Contacts

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Suchitra Hourigan, MD

Role: primary

General Information

Role: backup

References

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Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, Bokulich NA, Song SJ, Hoashi M, Rivera-Vinas JI, Mendez K, Knight R, Clemente JC. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med. 2016 Mar;22(3):250-3. doi: 10.1038/nm.4039. Epub 2016 Feb 1.

Reference Type BACKGROUND
PMID: 26828196 (View on PubMed)

Song SJ, Wang J, Martino C, Jiang L, Thompson WK, Shenhav L, McDonald D, Marotz C, Harris PR, Hernandez CD, Henderson N, Ackley E, Nardella D, Gillihan C, Montacuti V, Schweizer W, Jay M, Combellick J, Sun H, Garcia-Mantrana I, Gil Raga F, Collado MC, Rivera-Vinas JI, Campos-Rivera M, Ruiz-Calderon JF, Knight R, Dominguez-Bello MG. Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding. Med. 2021 Aug 13;2(8):951-964.e5. doi: 10.1016/j.medj.2021.05.003. Epub 2021 Jun 17.

Reference Type BACKGROUND
PMID: 35590169 (View on PubMed)

Hourigan SK, Dominguez-Bello MG, Mueller NT. Can maternal-child microbial seeding interventions improve the health of infants delivered by Cesarean section? Cell Host Microbe. 2022 May 11;30(5):607-611. doi: 10.1016/j.chom.2022.02.014.

Reference Type BACKGROUND
PMID: 35550663 (View on PubMed)

Namasivayam S, Tilves C, Ding H, Wu S, Domingue JC, Ruiz-Bedoya C, Shah A, Bohrnsen E, Schwarz B, Bacorn M, Chen Q, Levy S, Dominguez Bello MG, Jain SK, Sears CL, Mueller NT, Hourigan SK. Fecal transplant from vaginally seeded infants decreases intraabdominal adiposity in mice. Gut Microbes. 2024 Jan-Dec;16(1):2353394. doi: 10.1080/19490976.2024.2353394. Epub 2024 May 14.

Reference Type DERIVED
PMID: 38743047 (View on PubMed)

Other Identifiers

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17-2694

Identifier Type: -

Identifier Source: org_study_id

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