Amnioinfusion for Chorioamnionitis: Targeting Neonatal Brain Injury Biomarkers

Official title

The AMNIO-BRAIN Trial: A Randomized Trial of Amnioinfusion for Chorioamnionitis Targeting Neonatal Brain Injury Biomarkers

Overview

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.

Detailed description

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.

Interventions

• Device Intrauterine Pressure Catheter
  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.
• Other Standard obstetric care at discretion of delivery provider
  Route obstetric care at the discretion of delivery provider.

Primary outcome measures

• S100B measured through NULISAseq CNS Disease Panel 120 [Time frame: At delivery and/or part of routine childhood care through the first year of life.]

Secondary outcome measures (12)

• Concentration of umbilical cord gas values [Time frame: At delivery]
• Number of participants with composite neonatal respiratory morbidity [Time frame: After delivery though 6 weeks postpartum]
• Time to defervesence [Time frame: At delivery/birth]
• Feasibility metrics [Time frame: From consent to 1 year postpartum]
• Scores on developmental screening [Time frame: 1 year after delivery]
• Number of participants with composite maternal morbidity [Time frame: 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 [Time frame: During labor and delivery]
• Decisional Self Efficacy (DSE) [Time frame: At delivery/birth]
• Labor Agentry Scale (LAS) [Time frame: At delivery/birth]
• Value of neonatal temperature [Time frame: At delivery/birth]
• Number of childhood participants with healthcare utilization [Time frame: 1 year after delivery]
• Maternal intraamniotic infection treatment success [Time frame: Delivery hospitalization until 6 weeks postpartum]

Eligibility criteria

Inclusion criteria

• Maternal age ≥18 years
• Singleton gestation
• Gestational age ≥36 weeks
• Labor at time of enrollment
• Clinical chorioamnionitis or intra-amniotic infection defined according to ACOG criteria, including: Maternal temperature ≥38.0°C At least one associated clinical finding, including:
• 1\. Maternal leukocytosis
• 2\. Purulent cervical drainage
• 3\. Fetal tachycardia
• Cervical dilation sufficient for intrauterine pressure catheter placement
• Ability to provide informed consent

Exclusion criteria

• Multifetal gestation
• Known major fetal anomaly
• Contraindication to vaginal delivery
• Placenta previa
• Category III fetal heart tracing requiring immediate delivery
• Non-English-speaking

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Froedtert Hospital and Medical College of Wisconsin Birth Center — Milwaukee

Publications

• 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. PMID 39117278

Identifiers

NCT: NCT07610642 · PRO00059233

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗