Cesarean Delivery Affecting NewbornPhase 1/2NCT03298334
Vaginal Microbiome Seeding and Health Outcomes in Cesarean-delivered Neonates.
A Phase 1/2 study testing Vaginal Seeding and No Vaginal Seeding in people with Cesarean Delivery Affecting Newborn and Obesity, Childhood, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 days to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cesarean Delivery Affecting Newborn, Obesity, Childhood, Intestinal Microbiome
- What is being tested?
- Vaginal Seeding and No Vaginal Seeding
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 600 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2018to Apr 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 days to 50 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Inova Health System
Falls Church, Virginia, 22042
Suchitra Hourigan, MD, 703-776-8489, suchitra.hourigan@inova.org, suchitra.hourigan@nih.gov
General Information, microbiome@inova.org
About this study
Official title: Vaginal Microbiome Seeding and Health Outcomes in Cesarean-delivered Neonates: a Randomized Controlled Trial
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.
Read the 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.
- Conditions
- Cesarean Delivery Affecting Newborn, Obesity, Childhood, Intestinal Microbiome, Microbiota, Host Microbial Interactions, Gastrointestinal Microbiome
- Being tested
- Vaginal Seeding, No Vaginal Seeding
- Medical subject headings
- Pediatric Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vaginal SeedingBiological
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 SeedingOther
A gauze carrying sterile saline will be swabbed over the face and body of the neonate shortly after cesarean delivery.
| Study group | Role | What they receive |
|---|---|---|
| Receives Vaginal Seeding | Active comparator | Not described Receives: Biological: Vaginal Seeding |
| No Vaginal Seeding | Sham comparator | Not described Receives: Other: No Vaginal Seeding |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adiposity
E.g. Body mass index z-score
Measured: 2 years
Secondary outcomes (3)
Adverse events
Monitoring for adverse events
Measured: 3 years
Intestinal microbiota
Intestinal microbiota development over the first three years of life
Measured: 3 years
Immune and inflammatory regulation
E.g. Monitoring for immune and inflammatory mediated conditions
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2017
- Study start1 Jul 2018
- Primary completionApr 2027 (estimated)
- Study completionApr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cesarean Delivery Affecting NewbornStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Johns Hopkins University, Rutgers University, Inova Health Care Services
- Responsible party
- Sponsor
- Investigators
- Suchitra Hourigan, MD, Chief, Clinical Microbiome Unit, NIAID, Pediatric Gastroenterologist, Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID), Inova Children's HospitalNoel Mueller, PhD, Principal investigator, Johns Hopkins UniversityMaria Gloria Dominguez Bello, PhD, Principal investigator, Rutgers UniversityLawrence Appel, MD, MPH, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03298334
- Sponsor's protocol ID
- 17-2694
- Status last verified
- Jun 2025
- First submitted
- 27 Sep 2017
- Last updated
- 8 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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).
Publications
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.
PubMed 26828196Song 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.
PubMed 35590169Hourigan 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.
PubMed 35550663Namasivayam 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.
PubMed 38743047