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The AMNIO-BRAIN Trial is a research study looking at whether a simple treatment during labor can help protect a baby's brain.
Some newborns develop a condition called hypoxic-ischemic encephalopathy (HIE), which happens when the brain does not get enough oxygen or blood flow. This can lead to serious health problems, including developmental delays and lifelong disabilities. While there is a cooling treatment after birth that can help, it starts only after delivery and may come too late to prevent the earliest stages of injury.
Research suggests that some brain injury may actually begin during labor, especially when there is an infection in the uterus called chorioamnionitis. This infection can cause inflammation and fever in the mother, which may increase stress on the baby and affect the baby's brain.
This study is testing whether a commonly used labor procedure called amnioinfusion can help. Amnioinfusion involves placing fluid similar to your biologic amniotic fluid into the uterus during labor. It is already used safely in many deliveries for other reasons. In prior research, this treatment slightly lowered the temperature inside the uterus and improved signs that the baby was no longer under stress.
In this study, 80 pregnant subjects with chorioamnionitis will be randomly assigned to receive amnioinfusion during labor or receive standard care without amnioinfusion. All patients will continue to receive normal treatment for infection.
After delivery, researchers will collect a small sample of blood from the umbilical cord. This blood will be tested for markers that can show whether the baby may have experienced stress or injury to the brain.
The AMNIO-BRAIN Trial is designed to investigate whether intrapartum amnioinfusion, administered during labor, for patients with clinical chorioamnionitis can reduce molecular biomarkers of neonatal brain injury at birth. This study builds upon pilot randomized trial data demonstrating that room-temperature amnioinfusion lowers intrauterine temperature and is associated with reductions in umbilical artery lactate, a validated marker of anaerobic metabolism and tissue injury.
Current understanding of neonatal brain injury suggests that neurologic injury evolves through several biologic phases. During the initial or "priming" phase: inflammatory signaling, oxidative stress, mitochondrial dysfunction, and excitotoxicity contribute to neuronal injury before the latent and secondary injury phases occur. Clinical chorioamnionitis and maternal intrapartum fever are strongly associated with activation of these inflammatory pathways and may significantly worsen fetal neurologic injury.
Experimental animal data and translational studies suggest that early cooling during the priming phase may attenuate downstream neuronal injury. However, currently available neuroprotective therapies are initiated only after birth. Therefore, interventions capable of modulating intrauterine temperature and inflammation during labor may represent an important opportunity for earlier neuroprotection.
This prospective, randomized, controlled trial will enroll 80 maternal-infant dyads at ≥36 weeks' gestation with clinical chorioamnionitis. Participants will be randomized to either intrapartum amnioinfusion using room-temperature lactated Ringer's solution or standard obstetric care without amnioinfusion. The primary outcome will be umbilical artery cord blood concentration of S100B. S100D is a validated astroglia-specific biomarker associated with hypoxic-ischemic encephalopathy, MRI-confirmed neonatal brain injury, and adverse long-term neurodevelopmental outcomes. Secondary analyses will evaluate additional biomarkers of neurologic injury and inflammation, including GFAP, Tau, and IL-6, in addition to neonatal and maternal clinical outcomes.
Cord blood samples will undergo advanced proteomic analysis using the NULISAseq CNS Disease Panel, an innovative platform capable of attomolar -level biomarker detection. This study seeks to establish biologic plausibility for intrapartum neuroprotection and generate critical preliminary data for future definitive trials targeting neonatal neurologic outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of Care | Placebo Comparator | Standard obstetric care will be at the discretion of the delivery provider. |
|
| Room Temperature Lactated Ringer Amnioinfusion | Experimental | Standardized room temperature amnioinfusion consisting of a 500 mL bolus of (24°C) lactated ringer's infused over 30 minutes through an intrauterine pressure catheter (IUPC), followed by a continuous maintenance infusion of 125 mL/hour. Infusion continues until 1L is infused or delivery occurs. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intrauterine Pressure Catheter | Device | Standardized room temperature amnioinfusion consisting of a 500mL bolus of (24°C) lactated ringer's infused over 30 minutes through an intrauterine pressure catheter (IUPC), followed by a continuous maintenance infusion of 125 mL/hour. Infusion continues until 1L is infused or delivery occurs. |
| Measure | Description | Time Frame |
|---|---|---|
| S100B measured through NULISAseq CNS Disease Panel 120 | Panel 120 enables ultrasensitive, multiplexed quantification of 120+ neuro-specific and inflammatory proteins from just 10 µL (25 µL input) of umbilical cord blood. Panel 120 can detect and track key biomarkers of amyloid and tau pathologies, synaptic function, neurodegeneration, and inflammation in a single panel with unmatched precision and reproducibility. With assays specific the brain-derived Tau isoforms (pTau217, pTau181, pTau231, and tTau), the panel provides a comprehensive view of tau pathology from blood with unprecedented sensitivity and specificity, as well as S100B for brain specific brain injury. | At delivery and/or part of routine childhood care through the first year of life. |
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of umbilical cord gas values | Umbilical cord gases including pH, lactate, base excess will be assessed. | At delivery |
| Number of participants with composite neonatal respiratory morbidity |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Brock E Polnaszek, MD,MPH | Contact | (414)-805-6600 | bpolnaszek@mcw.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Froedtert Hospital and Medical College of Wisconsin Birth Center | Milwaukee | Wisconsin | 53045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39117278 | Background | Polnaszek BE, Rossen J, Scarpaci M, Murphy LM, Whelan AR, Hamel M, Rouse DJ, Tuuli MG, Lewkowitz AK. Amnioinfusion for reducing umbilical artery lactate among fetuses at risk of neurologic injury: a pilot randomized clinical trial. Am J Obstet Gynecol MFM. 2024 Oct;6(10):101446. doi: 10.1016/j.ajogmf.2024.101446. Epub 2024 Aug 8. No abstract available. |
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IPD data at this time is not a part of our consent process but may be considered on a case-by-case basis with contacting the principal investigator (e.g. a metanalysis) with de-identified data.
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|
| Standard obstetric care at discretion of delivery provider | Other | Route obstetric care at the discretion of delivery provider. |
|
Composite neonatal morbidity including NICU admission, fever >38 degree Celsius, therapeutic hypothermia, hypoxic-ischemic encephalopathy, seizures, intracranial hemorrhage and grade, hyperbilirubinemia requiring phototherapy, suspected and culture proven sepsis, antibiotics, respiratory distress, supplemental oxygen, mechanical ventilation, intubation, or neonatal death
| After delivery though 6 weeks postpartum |
| Time to defervesence | Evaluate the time of birthing person becoming afebrile from her maximum temperature collected intrapartum following the intervention. | At delivery/birth |
| Feasibility metrics | Evaluate feasibility metrics including number of patients approached, consented, randomized and followed to completion | From consent to 1 year postpartum |
| Scores on developmental screening | Will predominately capture standard developmental screening including the Ages and Stages Questionnaires through 1 year of life. Additional developmental screening including Sarnat score and referral to subspecialists will be tracked as well. | 1 year after delivery |
| Number of participants with composite maternal morbidity | Composite maternal morbidity consisting of amniotic fluid embolism, acute respiratory distress syndrome, pulmonary edema, intubation, PPH > 1000 milliliters including intervention such as estimated blood loss >1000 milliliters (mL) or uterotonics, tranexamic acid, blood transfusion or surgical interventions (dilation and curettage, Bakri, Jadha, laparotomy, interventional radiology), blood transfusion, hysterectomy, diffuse intravascular coagulation, endometritis, intraamniotic infection, maternal sepsis with culture, and death. | Hospitalization through 6 weeks postpartum |
| Number of participants in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Electronic (NICHD) Fetal Monitoring categories | Using standard NICHD data, we will collect and analyze standard electronic fetal monitoring data after randomization including things like rates of tachysystole, categories, declarations, total deceleration area, variability, and accelerations | During labor and delivery |
| Decisional Self Efficacy (DSE) | DSE measures self-confidence or belief in one's abilities in decision making, including shared-decision making for participating in trial. The 5-point scale, items are summed, divided by 11, multiplied by 25, and scores range from 0 [not at all confident] to 100 [very confident]. | At delivery/birth |
| Labor Agentry Scale (LAS) | The Labour Agentry Scale (LAS) is a validated, unifactorial, 29-item or 10-item instrument measuring a person's perceived control, confidence, and positive experiences during childbirth. It uses a 7-point Likert scale (1 = never to 7 = almost always) to assess personal agency, with higher scores reflecting higher levels of control. | At delivery/birth |
| Value of neonatal temperature | The temperature of the baby at the time of delivery and route of collection (axillary, oral, or rectal) will be collected and reported. | At delivery/birth |
| Number of childhood participants with healthcare utilization | Capturing all hospitalizations, emergency room visits, subspeciality referrals, ancillary referrals, and follow-up visits in the first year of life. | 1 year after delivery |
| Maternal intraamniotic infection treatment success | Defined as resolution of fever within 16 hours of antibiotic administration and the absence of endometritis through 6 weeks postpartum. | Delivery hospitalization until 6 weeks postpartum |
| Number of childhood participants with healthcare utilization | Capturing all hospitalizations, emergency room visits, subspeciality referrals, ancillary referrals, and follow-up visits in the first year of life | 1 year after delivery |
| Number of maternal participants with healthcare utilization | Capturing all hospitalizations, emergency room visits, subspeciality referrals, ancillary referrals, and follow-up visits in the first year of life. | From delivery until 1 year postpartum |
| ID | Term |
|---|---|
| D002821 | Chorioamnionitis |
| ID | Term |
|---|---|
| D005315 | Fetal Diseases |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005322 | Fetal Membranes, Premature Rupture |
| D007744 | Obstetric Labor Complications |
| D010922 | Placenta Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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