Vaginal Seeding for Cesarean-Delivered Infants

Overseen By Shira Levy

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Antibiotics

Disqualifiers: Diabetes, Genital HSV, Group B strep, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: At birth

600 Participants Needed

Trial Summary

What is the purpose of this 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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude mothers who have taken antibiotics within 30 days of delivery, except for those used during surgery. It's best to discuss your specific medications with the trial team.

Is vaginal seeding safe for C-section-delivered infants?

Currently, there is not enough evidence to confirm the safety of vaginal seeding for C-section-delivered infants, and it should only be done as part of approved research studies. ^{1 2 3 4 5}

How is the treatment Vaginal Seeding different from other treatments for cesarean-delivered infants?

Vaginal Seeding is unique because it involves swabbing cesarean-delivered infants with their mother's vaginal fluids to transfer beneficial bacteria, aiming to mimic the natural exposure that occurs during vaginal birth. This approach is novel as it focuses on restoring the infant's microbiome (the community of microorganisms living in the body), which is not addressed by other treatments for cesarean-delivered infants. ^{6 7 8 9 10}

Research Team

Noel Mueller, PhD

Principal Investigator

Johns Hopkins University

Lawrence Appel, MD, MPH

Principal Investigator

Johns Hopkins University

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

Principal Investigator

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

Maria Gloria Dominguez Bello, PhD

Principal Investigator

Rutgers University

Eligibility Criteria

This trial is for healthy English or Spanish-speaking women aged 18+ scheduled for a Cesarean delivery at ≥37 weeks with a single fetus and normal vaginal flora. They must test negative for various infections including STIs, Group B strep, and COVID-19 close to the time of delivery. Women can't join if they have certain infections, history of genital herpes or HPV, diabetes, or are on recent antibiotics.

Inclusion Criteria

Mother: Negative testing for Group B strep at 35-37 weeks gestation

Mother: Negative maternal testing for SARS-CoV-2 for the delivery admission performed as standard of care test at the Inova Health System

My newborn needed standard help after birth or can't undergo the full VMT procedure due to health reasons.

Exclusion Criteria

Mother: Pregnancy a result of donor egg or surrogacy

My mother had a confirmed genital HPV infection or genital warts.

Mother: Cesarean delivery scheduled for active infection that would have interfered with vaginal delivery such as genital herpetic lesions

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Neonates are randomized to receive either vaginal seeding or a sham procedure at birth

At birth

1 visit (in-person)

Follow-up

Participants are monitored for microbiome development, immune and metabolic outcomes, and adverse events

3 years

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• No Vaginal Seeding
• Vaginal Seeding

Trial Overview The study tests whether exposing Cesarean-delivered babies to their mother's vaginal bacteria (vaginal seeding) affects their health outcomes over three years compared to those who don't get this exposure (sham). It looks at microbiome development, immune response, metabolic effects, and any adverse events.

Participant Groups

Group I: Receives Vaginal Seeding Active Control 1 Intervention

Group II: No Vaginal Seeding Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Inova Health Care Services

Collaborator

Trials

80

Recruited

22,700+

Rutgers University

Collaborator

Trials

127

Recruited

2,814,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Findings from Research

Children born via Cesarean section may face higher risks for health issues like allergies, asthma, and obesity, leading to interest in vaginal seeding as a potential solution.

Vaginal seeding aims to transfer the mother's vaginal microbiome to C-section infants, showing some promise in restoring microbial exposure, but there is currently insufficient evidence to confirm its health benefits, with ongoing studies needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacterial Baptism: Scientific, Medical, and Regulatory Issues Raised by Vaginal Seeding of C-Section-Born Babies. Mueller, NT., Hourigan, SK., Hoffmann, DE., et al.[2021]

In a study of 1358 pregnant women undergoing labor induction, adverse events (AEs) were more common with the misoprostol vaginal insert (MVI), prompting retrieval in 11.4% of cases compared to 4.0% for the dinoprostone vaginal insert (DVI).

The most frequent AEs were uterine tachysystole with fetal heart rate involvement, but retrieval of the inserts did not delay delivery times, and the rates of neonatal intensive care unit admissions were similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of labour with retrievable prostaglandin vaginal inserts: outcomes following retrieval due to an intrapartum adverse event. Rugarn, O., Tipping, D., Powers, B., et al.[2021]

The practice of 'vaginal seeding' aims to establish a baby's microbiome by transferring vaginal bacteria after a cesarean delivery, but it raises potential health risks that need to be carefully considered.

A harm minimization approach is recommended for managing women who request vaginal microbiome transfer, emphasizing the importance of informed decision-making and safety in this controversial practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manipulating the baby biome: What are the issues? Lee, LY., Garland, SM., Giles, ML., et al.[2017]

Vaginal seeding is a practice aimed at transferring maternal vaginal bacteria to newborns to promote healthy gut colonization and potentially reduce the risk of asthma and immune disorders, especially in infants born via cesarean delivery.

Currently, vaginal seeding should only be conducted within approved research protocols, as there is insufficient data on its safety and efficacy for widespread clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Committee Opinion No. 725: Vaginal Seeding. [2022]

Vaginal seeding is a practice aimed at transferring maternal vaginal bacteria to newborns to promote healthy gut colonization and potentially reduce the risk of asthma and immune disorders, especially in infants born via cesarean delivery.

Currently, vaginal seeding should only be conducted within approved research protocols, as there is insufficient data on its safety and efficacy for widespread clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Committee Opinion No. 725 Summary: Vaginal Seeding. [2018]

In a study of 87 pregnant women with previous cesarean sections, 91.95% successfully achieved vaginal deliveries, indicating that vaginal delivery is feasible for this group under appropriate conditions.

There were no deaths reported, and while one case experienced a partial uterine rupture that was surgically repaired, the overall safety profile was positive, with most newborns scoring above 8 on the Apgar scale, suggesting good health at birth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical management of vaginal delivery with previous cesarean section]. Huang, P., Liu, GB.[2008]

In a study of 346 preterm breech infants, those delivered vaginally had better arterial cord blood pH and base excess compared to those delivered by cesarean section, suggesting a potentially better fetal outcome for vaginal deliveries.

The findings indicate that there is no clear advantage of routine cesarean section over vaginal delivery for preterm breech infants, as many parameters were comparable, and the data do not support a policy favoring cesarean delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of fetal outcome in premature vaginal or cesarean breech delivery at 24-37 gestational weeks. Vidovics, M., Jacobs, VR., Fischer, T., et al.[2018]

Vacuum-assisted vaginal delivery (VA-VBAC) in women with a previous cesarean delivery is associated with a higher risk of maternal complications, including postpartum hemorrhage (10.5% vs. 7.2%), blood transfusions, and retained placenta compared to primigravid women delivering vaginally.

Despite the increased maternal risks, neonatal outcomes such as Apgar scores and NICU admissions were similar between the VA-VBAC group and primigravid group, suggesting that while maternal safety may be compromised, the procedure does not adversely affect newborn health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vacuum extraction delivery at first vaginal birth following cesarean: maternal and neonatal outcome. Rottenstreich, M., Rotem, R., Katz, B., et al.[2022]

In a study of 210 women with previous cesarean sections who delivered twins, 44% successfully attempted a trial of labor without any uterine ruptures, indicating a safe option for these patients.

The trial of labor did not lead to increased maternal or perinatal complications, suggesting that it is an effective alternative to routine repeat cesarean delivery for women with twins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaginal birth after cesarean section in twin gestation. Miller, DA., Mullin, P., Hou, D., et al.[2019]

A retrospective study of 1253 women with a previous cesarean section found that 54% successfully had a normal vaginal delivery, supporting vaginal delivery as a safe option for these patients when properly screened.

Importantly, there were no recorded cases of uterine scar rupture among the participants, indicating that with appropriate selection, vaginal delivery can be performed safely after a cesarean section.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Indications and contraindications for normal labor in patients who previously underwent cesarean section]. Cappa, F., D'Alfonso, A., Di Luzio, F., et al.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

Bacterial Baptism: Scientific, Medical, and Regulatory Issues Raised by Vaginal Seeding of C-Section-Born Babies. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Induction of labour with retrievable prostaglandin vaginal inserts: outcomes following retrieval due to an intrapartum adverse event. [2021]

3. Australia pubmed.ncbi.nlm.nih.gov

Manipulating the baby biome: What are the issues? [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Committee Opinion No. 725: Vaginal Seeding. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Committee Opinion No. 725 Summary: Vaginal Seeding. [2018]

6. China pubmed.ncbi.nlm.nih.gov

[Clinical management of vaginal delivery with previous cesarean section]. [2008]

7. Germany pubmed.ncbi.nlm.nih.gov

Comparison of fetal outcome in premature vaginal or cesarean breech delivery at 24-37 gestational weeks. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Vacuum extraction delivery at first vaginal birth following cesarean: maternal and neonatal outcome. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Vaginal birth after cesarean section in twin gestation. [2019]

10. Italy pubmed.ncbi.nlm.nih.gov

[Indications and contraindications for normal labor in patients who previously underwent cesarean section]. [2017]