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

Primary Purpose

Cesarean Delivery Affecting Newborn, Obesity, Childhood, Intestinal Microbiome

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Vaginal Seeding

No Vaginal Seeding

About this trial

This is an interventional prevention trial for Cesarean Delivery Affecting Newborn

Eligibility Criteria

0 Days - 50 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for Mother:

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 21-29 years should have a normal Pap test within 3 years
Women aged 30-65 years should have a normal Pap test and an HPV test (co-testing) 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.

Inclusion Criteria for Infant:

-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 for Mother:

Delivery at a hospital other than Inova Health System
Systemic medication for immunosuppression including biological agent within 3 months of cesarean delivery (exclusive of medications used for non-immunosuppressive purposes - e.g. betamethasone for fetal lung maturation)
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 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

Sites / Locations

Inova Health SystemRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Receives Vaginal Seeding

No Vaginal Seeding

Arm Description

Outcomes

Primary Outcome Measures

Adiposity

E.g. Body mass index z-score

Secondary Outcome Measures

Adverse events

Monitoring for adverse events

Intestinal microbiota

Intestinal microbiota development over the first three years of life

Immune and inflammatory regulation

E.g. Monitoring for immune and inflammatory mediated conditions

Full Information

NCT ID

NCT03298334

First Posted

September 27, 2017

Last Updated

January 18, 2023

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Johns Hopkins University, Rutgers University, Inova Health Care Services

1. Study Identification

Unique Protocol Identification Number

NCT03298334

Brief Title

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

Official Title

Vaginal Microbiome Seeding and Health Outcomes in Cesarean-delivered Neonates: a Randomized Controlled Trial

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 1, 2018 (Actual)

Primary Completion Date

April 2027 (Anticipated)

Study Completion Date

April 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Johns Hopkins University, Rutgers University, Inova Health Care Services

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

600 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Receives Vaginal Seeding

Arm Type

Active Comparator

Arm Title

No Vaginal Seeding

Arm Type

Sham Comparator

Intervention Type

Biological

Intervention Name(s)

Vaginal Seeding

Intervention Description

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

Other

Intervention Name(s)

No Vaginal Seeding

Intervention Description

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

Primary Outcome Measure Information:

Title

Adiposity

Description

E.g. Body mass index z-score

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Adverse events

Description

Monitoring for adverse events

Time Frame

3 years

Title

Intestinal microbiota

Description

Intestinal microbiota development over the first three years of life

Time Frame

3 years

Title

Immune and inflammatory regulation

Description

E.g. Monitoring for immune and inflammatory mediated conditions

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

0 Days

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria for Mother: 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. Inclusion Criteria for Infant: 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 for Mother: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Suchitra Hourigan, MD

Phone

703-776-8489

suchitra.hourigan@inova.org, suchitra.hourigan@nih.gov

First Name & Middle Initial & Last Name or Official Title & Degree

Shira Levy

Phone

703-776-8489

shira.levy@inova.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Noel Mueller, PhD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Maria Gloria Dominguez Bello, PhD

Organizational Affiliation

Rutgers University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Lawrence Appel, MD, MPH

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Inova Health System

City

Falls Church

State/Province

Virginia

ZIP/Postal Code

22042

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Suchitra Hourigan, MD

Phone

703-776-8489

suchitra.hourigan@inova.org, suchitra.hourigan@nih.gov

First Name & Middle Initial & Last Name & Degree

General Information

microbiome@inova.org

First Name & Middle Initial & Last Name & Degree

Ankit Shah, MD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual participant data will be shared with co-principal investigators (Maria Gloria Dominguez-Bello at Rutgers University and Noel Mueller at Johns Hopkins School of Medicine).

Citations:

PubMed Identifier

26828196

Citation

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.

Results Reference

background

PubMed Identifier

35590169

Citation

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.

Results Reference

background

PubMed Identifier

35550663

Citation

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.

Results Reference

background

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

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