Clinical trial NCT05513690: Amnioinfusion for Intrauterine Neuroprotection
Official title: Amnioinfusion for Intrauterine Neuroprotection: A Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Lactic Acidemia
Keywords: Umbilical cord gases
Neonatal neurologic morbidity
Amnioinfusion
Lead sponsor: Women and Infants Hospital of Rhode Island
Sponsor class: OTHER
Collaborators: name: Foundation for Society of Maternal-Fetal Medicine
First posted: 2022-08-24
Enrollment: 26
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Amnioinfusion for intrapartum risk factors for neurologic morbidity versus no amnioinfusion.
Primary purpose: TREATMENT

Brief summary: Hypoxic ischemic encephalopathy (HIE), a serious brain injury in infants, occurs in 2-9 per 1,000 infants after delivery. Up to 60% of infants diagnosed with HIE die and 25% of the survivors have long-term neurologic deficits. Risk factors for HIE include abnormal fetal heart tracings and intrauterine infection. Therapeutic whole-body cooling of infants with HIE is standard of care after delivery, with only 7-9 at-risk infants needing to be treated to prevent one infant from suffering long-term neurologic deficits. However, animal studies show that therapeutic cooling may be more beneficial when given in utero at the time of an insult, rather than after delivery. Though therapeutic cooling in utero has yet to be explored in humans, an established in utero fluid delivery system during labor-amnioinfusion-provides a unique opportunity for in utero intervention. We propose a pilot randomized controlled trial to test the feasibility and preliminary effects of room temperature amnioinfusion on tissue injury including HIE.

Detailed description: Hypoxic ischemic encephalopathy (HIE), a serious brain injury in infants, occurs in 2-9 per 1,000 infants after delivery. Up to 60% of infants diagnosed with HIE die and 25% of the survivors have long-term neurologic deficits. Risk factors for HIE include abnormal fetal heart tracings and intrauterine infection. In addition, maternal fever is associated with a four to five-fold increased risk of HIE. Two phases leading to HIE are recognized: neuronal death from cellular hypoxia and further injury from exhaustion of energy stores.

Therapeutic cooling of infants with HIE provides neuroprotection by reducing metabolic demands and suppressing toxic processes. Studies show that whole-body cooling of infants reduces the risk of neurologic motor and cognitive deficits with brain imaging suggesting that human infants who are cooled earlier have a greater benefit. Moreover, animal studies show that brain cooling may be more beneficial when given in utero at the time of an insult during the first phase of cellular hypoxia, rather than after delivery. Though therapeutic cooling in utero has yet to be explored in humans, an established in utero fluid delivery system-amnioinfusion- provides a unique opportunity for in utero intervention.

Amnioinfusion (AI), the administration of fluid via an intrauterine catheter inserted through the cervix, is a common intervention during labor to improve fetal heart tracings and reduce cesarean delivery. Introduced in 1983, it used warm saline due to a theoretical concern for fetal shock from cold fluids. Subsequent studies showed no advantage of warm fluids, and fluids at room temperature (\~25oC) have become standard. AI can lower in utero temperature by 1.0°C (36.4°C versus 37.4°C, P\<0.01). This 1.0°C degree of cooling has been associated a 6% reduction in brain energy utilization which could be protective against neurological injury. This suggests that AI can be leveraged to lower in utero and fetal temperatures to protect against neurologic injury.

Expanding the indication for AI is a novel approach to reduce neurologic injury in utero. However, there is a gap in the acceptability and efficacy of amnioinfusion for this indication. To fill this gap, we propose a pilot randomized controlled trial to test the feasibility and effects of amnioinfusion with fluids at room temperature on infants at high risk for neurologic injury including HIE.

Eligibility criteria: Inclusion Criteria:

* Maternal age \>18 years old
* Singleton
* Term gestational age at time of admission (\>37 weeks 0 days);

Exclusion Criteria:

* Major fetal anomaly
* Active substance or alcohol use
* Contraindications to intrauterine pressure catheter placement (e.g. placental previa, human immunodeficiency virus, Hepatitis C)
* Fetal growth restriction
* Inability to consent

Primary outcomes:
measure: Umbilical artery lactate
timeFrame: Within 15 minutes of delivery
Secondary outcomes:
measure: Number of eligible patients who consent to study
timeFrame: Throughout study completion, an average of 1 year
measure: Ottawa Decisional self-efficacy scale
timeFrame: Scale collected once from date of delivery following randomization until hospital discharge but within the first week
measure: Labour Agentry Scale
timeFrame: Scale collected once from date of delivery following randomization until hospital discharge but within the first week
measure: Intrauterine temperature
timeFrame: 10-minute intervals from date/time of randomization until date/time of delivery, assessed only until fetus is delivered or end of second stage of labor.
measure: Neonatal core temperature
timeFrame: Within 10 minutes of birth
Other outcomes:
measure: Electronic fetal monitoring
timeFrame: 10-minute intervals from date/time of randomization until date/time of delivery, assessed only until fetus is delivered or end of second stage of labor.
measure: Montevideo units
timeFrame: 10-minute intervals from date/time of randomization until date/time of delivery, assessed only until fetus is delivered or end of second stage of labor.
measure: Number of patients with composite and individual neonatal morbidity
timeFrame: Collected following delivery and/or within 6 weeks postpartum
measure: Number of patients with composite and individual maternal morbidity
timeFrame: Collected following delivery and/or within 6 weeks postpartum
measure: Number of patients with placental pathology available
timeFrame: For all patients who are randomization until date/time of delivery of placenta up to 6 weeks or 36 days after delivery.
Locations:
city: Providence
country: United States
facility: Women and Infant's Hospital of Rhode Island
state: Rhode Island
Study officials:
affiliation: Waren Alpert Medical School of Brown University, Women and Infant's Hospital
name: Brock Polnaszek, MD
role: PRINCIPAL_INVESTIGATOR
References: