Clinical trial NCT04484441: Maternal-fetal Immune Responses to Fetal Surgery
Official title: Maternal-fetal Immune Responses to Fetal Surgery
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Spina Bifida
Congenital Diaphragmatic Hernia
Lower Urinary Tract Obstructive Syndrome
Myelomeningocele
Keywords: Fetal Surgery
Fetal Intervention
In Utero Surgery
In Utero Intervention
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2020-07-23
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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.

Eligibility criteria: Inclusion Criteria for study group:

* Maternal age ≥18 years
* Pregnant with a congenital anomaly diagnosis AND undergoing fetal intervention in utero
* Delivery planned at Mayo Clinic, Rochester MN

Inclusion Criteria for control group:

* Maternal age ≥18 years
* Pregnant with normal ultrasound findings
* Delivery planned at Mayo Clinic, Rochester MN

Exclusion Criteria:

* Delivery planned elsewhere
* Abnormal fetal karyotype

Primary outcomes:
measure: Maternal T cell activation following in utero intervention.
timeFrame: Baseline, 1-2 days post intervention, 1 week post intervention, delivery
Secondary outcomes:
measure: Placental histology in the maternal-fetal interface in term and preterm fetal intervention cases
timeFrame: Delivery
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester, Minnesota
state: Minnesota
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Houston
country: United States
facility: University of Texas Houston
state: Texas
Study officials:
affiliation: Mayo Clinic
name: Mauro Schenone, MD
role: PRINCIPAL_INVESTIGATOR
References: