Spina BifidaNCT04484441
Maternal-fetal Immune Responses to Fetal Surgery
An observational study of Spina Bifida and Congenital Diaphragmatic Hernia, run by Mayo Clinic at 3 sites in United States.
Trial summary
Performing surgery in utero on fetuses with certain birth defects has led to significant improvements in outcomes after birth; however, many of these infants are born preterm which can decrease the effectiveness of these procedures. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Spina Bifida, Congenital Diaphragmatic Hernia, Lower Urinary Tract Obstructive Syndrome
- What is being tested?
- Blood and placenta specimen collection.
- How many people
- 21 participants
- Where
- 3 sitesUnited States
- Study dates
- 24 Mar 2022to 1 Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Study population: The study population will compare two groups of pregnant women. Each group will be comprised of maternal, paternal, fetal trios. The study cohort will be comprised of adult women carrying a fetus with a diagnosed congenital anomaly and scheduled to undergo fetal surgical intervention. The control cohort will enroll pregnant women with normal ultrasound findings that will be matched with the subjects enrolled in the study cohort for parity, maternal age, ethnicity, fetal sex and gestational age at time of surgical intervention.
Who may be able to join
- Maternal age ≥18 years
- Pregnant with a congenital anomaly diagnosis AND undergoing fetal intervention in utero
- Delivery planned at Mayo Clinic, Rochester MN
- Maternal age ≥18 years
- Pregnant with normal ultrasound findings
- Delivery planned at Mayo Clinic, Rochester MN
Who cannot join
- Delivery planned elsewhere
- Abnormal fetal karyotype
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of Texas Houston
Houston, Texas, 77030
Mayo Clinic in Rochester, Minnesota
Rochester, Minnesota, 55905
About this study
Performing surgery in utero on fetuses with certain birth defects has led to significant improvements in outcomes after birth; however, many of these infants are born preterm which can decrease the effectiveness of these procedures. The investigators aim to understand the effects of surgery on the maternal and fetal immune system and whether immune activation may be causing some of these infants to be born prematurely.
Read the detailed description
Over 300,000 neonates worldwide die in their first month of life due to a congenital birth defect. Thanks to advancements in diagnostic technology and imaging, the field of fetal surgery was developed to treat some of these conditions in utero. Results have demonstrated improved short and long-term outcomes following surgery, especially for those fetuses diagnosed with congenital diaphragmatic hernia, lower urinary tract obstruction and spina bifida. However, over 30% of the surgical cases will have preterm labor, leading to complications related to neonatal prematurity. The cause of this surgery-induced preterm birth is unknown; however, disruption in fetal-maternal tolerance may lead to immune activation and inflammation of the maternal and fetal immune systems. Maintaining immunologic tolerance is essential during pregnancy, as a women shares only half of her genetic material with the fetus. Previous work has demonstrated that fetal surgery leads to an increase in maternal cells identified in cord blood. Animal studies have also shown that in utero intervention leads to the activation of maternal cells against fetal (paternal) antigen. Based on this previous data, it is hypothesized that surgical trauma following in utero intervention results in mixing of maternal and fetal cells leading to activation of systemic (adaptive maternal immunity) and regional (fetal placental macrophages) immune responses that disrupt fetal-maternal tolerance, which can result in preterm birth. Blood will be collected from pregnant women and their partners. Blood and placental tissue will be collected from infants that do and do not undergo in utero surgery to determine whether maternal T cells specific to fetal antigen are activated and expand after in utero intervention; and 2) to determine whether placental macrophages (Hofbauer Cells) and histology in the maternal-fetal interface exhibit increased activation and inflammation in surgical cases born preterm (<37 weeks) compared to term. Should this exploratory study reveal activation of maternal and/or fetal immune responses following in utero surgery, modalities aimed at therapeutically suppressing these acute responses may prolong gestation, significantly benefiting newborns diagnosed with a congenital anomaly.
- Conditions
- Spina Bifida, Congenital Diaphragmatic Hernia, Lower Urinary Tract Obstructive Syndrome, Myelomeningocele
- Being tested
- Blood and placenta specimen collection.
- Keywords
- Fetal Surgery, Fetal Intervention, In Utero Surgery, In Utero Intervention
- Medical subject headings
- Spinal Dysraphism, Hernias, Diaphragmatic, Congenital, Meningomyelocele
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood and placenta specimen collection.Other
Collection of maternal and paternal blood. Collection of infant cord blood and placenta.
| Study group | Role | What they receive |
|---|---|---|
| Fetal surgical intervention group | Pregnant adult women carrying a fetus with a diagnosed congenital anomaly and scheduled to undergo fetal surgical intervention at Mayo Clinic. Receives: Other: Blood and placenta specimen collection. | |
| Control group - normal pregnancy | Pregnant adult women with normal ultrasound findings. These women will be matched with the subjects enrolled in the intervention cohort for parity, maternal age, ethnicity, fetal sex and gestational age at time of surgical intervention. Receives: Other: Blood and placenta specimen collection. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maternal T cell activation following in utero intervention.
T cells from maternal blood will be isolated and CDR3 spectra typing will be completed. These samples will be compared to each other to identify high frequency T cell clones as well as longitudinal changes in the dynamics of clones.
Blood collected at the four time points above will be profiled for changes in immune activation using mass cytometry (CyTOF) and plasma collected to measure changes in cytokine responses pre- and post-surgery by multiplex.
Measured: Baseline, 1-2 days post intervention, 1 week post intervention, delivery
Secondary outcomes (1)
Placental histology in the maternal-fetal interface in term and preterm fetal intervention cases
Placental macrophages will be phenotyped for subtypes (M1 classical versus M2 repair), activation (CD25 and CD40), and apoptosis status by CyTOF. Comparisons will be made between those born before 37 weeks and those born after 37 weeks in the surgical group, as well as to those who didn't undergo surgery.
From each placenta, 5 sections will be dissected and submitted for histological evaluation of placental villitis. Toxoplasmosis, Other [syphilis, varicella-zoster, parvovirus B19], Rubella, Cytomegalovirus and Herpes (TORCH) infection panels will be completed to distinguish infectious villitis from immune-mediated villitis.
Measured: Delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2020
- Study start24 Mar 2022
- Primary completion31 Dec 2024
- Study completion1 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spina BifidaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mauro H. Schenone, Mayo Clinic
- Investigators
- Mauro Schenone, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04484441
- Sponsor's protocol ID
- 19-011382
- Status last verified
- Feb 2026
- First submitted
- 20 Jul 2020
- Last updated
- 10 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maternal-fetal Immune Responses to Fetal Surgery
- ClinicalTrials.gov ID
- NCT04484441
- Acronym / sponsor ID
- 19-011382
- Conditions
- Spina Bifida, Congenital Diaphragmatic Hernia, Lower Urinary Tract Obstructive Syndrome, Myelomeningocele
- Keywords
- Fetal Surgery, Fetal Intervention, In Utero Surgery, In Utero Intervention
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 24 Mar 2022 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 1 Dec 2025 (actual)
- First posted
- 23 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Performing surgery in utero on fetuses with certain birth defects has led to significant improvements in outcomes after birth; however, many of these infants are born preterm which can decrease the effectiveness of these procedures. The investigators aim to understand the effects of surgery on the maternal and fetal immune system and whether immune activation may be causing some of these infants to be born prematurely.
Detailed description
Over 300,000 neonates worldwide die in their first month of life due to a congenital birth defect. Thanks to advancements in diagnostic technology and imaging, the field of fetal surgery was developed to treat some of these conditions in utero. Results have demonstrated improved short and long-term outcomes following surgery, especially for those fetuses diagnosed with congenital diaphragmatic hernia, lower urinary tract obstruction and spina bifida. However, over 30% of the surgical cases will have preterm labor, leading to complications related to neonatal prematurity. The cause of this surgery-induced preterm birth is unknown; however, disruption in fetal-maternal tolerance may lead to immune activation and inflammation of the maternal and fetal immune systems. Maintaining immunologic tolerance is essential during pregnancy, as a women shares only half of her genetic material with the fetus. Previous work has demonstrated that fetal surgery leads to an increase in maternal cells identified in cord blood. Animal studies have also shown that in utero intervention leads to the activation of maternal cells against fetal (paternal) antigen. Based on this previous data, it is hypothesized that surgical trauma following in utero intervention results in mixing of maternal and fetal cells leading to activation of systemic (adaptive maternal immunity) and regional (fetal placental macrophages) immune responses that disrupt fetal-maternal tolerance, which can result in preterm birth. Blood will be collected from pregnant women and their partners. Blood and placental tissue will be collected from infants that do and do not undergo in utero surgery to determine whether maternal T cells specific to fetal antigen are activated and expand after in utero intervention; and 2) to determine whether placental macrophages (Hofbauer Cells) and histology in the maternal-fetal interface exhibit increased activation and inflammation in surgical cases born preterm (<37 weeks) compared to term. Should this exploratory study reveal activation of maternal and/or fetal immune responses following in utero surgery, modalities aimed at therapeutically suppressing these acute responses may prolong gestation, significantly benefiting newborns diagnosed with a congenital anomaly.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fetal surgical intervention group | – | Other: Blood and placenta specimen collection.Pregnant adult women carrying a fetus with a diagnosed congenital anomaly and scheduled to undergo fetal surgical intervention at Mayo Clinic. |
| Control group - normal pregnancy | – | Other: Blood and placenta specimen collection.Pregnant adult women with normal ultrasound findings. These women will be matched with the subjects enrolled in the intervention cohort for parity, maternal age, ethnicity, fetal sex and gestational age at time of surgical intervention. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- The study population will compare two groups of pregnant women. Each group will be comprised of maternal, paternal, fetal trios. The study cohort will be comprised of adult women carrying a fetus with a diagnosed congenital anomaly and scheduled to undergo fetal surgical intervention. The control cohort will enroll pregnant women with normal ultrasound findings that will be matched with the subjects enrolled in the study cohort for parity, maternal age, ethnicity, fetal sex and gestational age at time of surgical intervention.
Key inclusion criteria (6 listed)
- Maternal age ≥18 years
- Pregnant with a congenital anomaly diagnosis AND undergoing fetal intervention in utero
- Delivery planned at Mayo Clinic, Rochester MN
- Maternal age ≥18 years
- Pregnant with normal ultrasound findings
Key exclusion criteria (2 listed)
- Delivery planned elsewhere
- Abnormal fetal karyotype
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood and placenta specimen collection.Collection of maternal and paternal blood. Collection of infant cord blood and placenta. | Other | Control group - normal pregnancy, Fetal surgical intervention group |
Primary outcome
Maternal T cell activation following in utero intervention.
Time frame: Baseline, 1-2 days post intervention, 1 week post intervention, delivery
T cells from maternal blood will be isolated and CDR3 spectra typing will be completed. These samples will be compared to each other to identify high frequency T cell clones as well as longitudinal changes in the dynamics of clones. Blood collected at the four time points above will be profiled for changes in immune activation using mass cytometry (CyTOF) and plasma collected to measure changes in cytokine responses pre- and post-surgery by multiplex.
1 secondary outcome
Placental histology in the maternal-fetal interface in term and preterm fetal intervention cases
Time frame: Delivery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2026.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mauro Schenone, MD principal investigator
Mayo Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Spina Bifida and Congenital Diaphragmatic Hernia, run by Mayo Clinic at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maternal T cell activation following in utero intervention. (time frame: Baseline, 1-2 days post intervention, 1 week post intervention, delivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2026.