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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called vaginal seeding, which involves exposing babies delivered via C-section to their mother's vaginal bacteria. The goal is to determine if this exposure improves the baby's health in areas like immune and metabolic development over three years. Participants will receive either the actual treatment or a placebo (a sham treatment). Moms scheduled for a C-section who are generally healthy and free from certain infections or complications may qualify to participate.

As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking health advancements.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vaginal seeding can alter the gut bacteria of babies born by C-section, potentially benefiting their health. However, the safety of this procedure remains under investigation. Some studies have suggested a risk of transmitting infections from mother to baby, but there is insufficient data on the frequency or severity of such occurrences. As this trial is in its early stages, scientists continue to assess the safety of this treatment. Further research is necessary to fully understand both the benefits and risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about vaginal seeding for cesarean-delivered infants because it has the potential to expose newborns to beneficial bacteria that they would normally encounter during vaginal delivery. Unlike the standard practice of cesarean sections, which may limit early exposure to these microbes, vaginal seeding involves swabbing the infant with the mother’s vaginal fluids. This could help mimic the natural transfer of microbiota, potentially supporting the infant's immune system and gut health from birth. By exploring this method, researchers hope to understand if it can bridge the microbiome gap often seen in C-section deliveries, potentially leading to improved long-term health outcomes for the infants.

What evidence suggests that vaginal seeding might be an effective treatment for Cesarean-delivered infants?

This trial will compare the effects of vaginal seeding with no vaginal seeding in cesarean-delivered infants. Research suggests that vaginal seeding might help align the community of tiny organisms, such as bacteria, in C-section babies with those in vaginally born babies. Some studies have shown small changes in gut bacteria after vaginal seeding, but more research is needed to confirm these effects. The procedure transfers bacteria from the mother to the baby to potentially improve health. However, other research indicates there might not be a significant impact on gut health, growth, or allergy risks. Overall, while the idea is promising, the current evidence remains mixed, necessitating further studies. ^{1 2 3 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12195427/

Can Vaginal Seeding at Birth Improve Health Outcomes of ... Studies have shown that vaginal seeding at birth partially restores the infant microbiome towards that of a vaginally delivered infant. More ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0163445324002834

Impact of vaginal seeding on the gut microbiome of infants ... Current evidence indicates modest changes in the gut microbiome of CS-born infants following VS. However, further clinical studies are necessary.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03298334

Vaginal Microbiome Seeding and Health Outcomes in ... This randomized controlled clinical study will provide evidence of whether the vaginal seeding procedure can safely transfer microbes from mom-to-baby.

4. sarawickham.com sarawickham.com/research-updates/microbiome-seeding/

Microbiome seeding - what's the evidence? “For infants born through cesarean delivery, vaginal seeding has no significant impacts on the gut microbiota, growth, or allergy risks during ...

5. journals.asm.org journals.asm.org/doi/10.1128/mbio.00491-23

Maternal Bacterial Engraftment in Multiple Body Sites of ... Observational data support the hypothesis that vaginal seeding may partially restore the microbiota of C-section delivered infants (22, 23). In ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9237654/

Can maternal-child microbial seeding interventions ... Therefore, vaginal seeding in an infant scheduled for C-section may possibly increase the risk of transmission of infection that they may not ...

7. jaci-global.org jaci-global.org/article/S2772-8293(25)00159-6/fulltext

Exposure to vaginal microbiome in cesarean-delivered ... The safety profile or effects of vaginal seeding in immune development and allergic outcomes has not yet been assessed, and its use in clinical practice is ...