Thick meconium in the amniotic fluid occurs in about one out of seven pregnancies and increases the chance that a newborn may have breathing problems after birth. These problems can include the need for oxygen, breathing support, admission to the neonatal intensive care unit (NICU), or, in severe cases, meconium aspiration syndrome or persistent pulmonary hypertension.
Although amnioinfusion or placing sterile fluid into the uterus during labor was previously studied as a way to reduce these complications, earlier research had major limitations. Past studies included all types of meconium, used different fluid types and temperatures, had inconsistent protocols, and did not measure biomarkers of inflammation or look at long-term outcomes. As a result, it is still unclear whether a modern, standardized approach to amnioinfusion can meaningfully improve newborn health when the meconium is truly thick.
The PEARL Trial is a randomized clinical trial designed to answer this question. The study will enroll pregnant individuals at or beyond 36 weeks of gestation who develop thick meconium-stained amniotic fluid, confirmed using a simple, objective measurement ("meconium-crit"). Participants will be randomly assigned to receive either:
Warm lactated Ringer's (LR) amnioinfusion through an intrauterine pressure catheter (IUPC), following a standardized protocol, or standard care without amnioinfusion.
The main goal is to determine whether warm LR amnioinfusion reduces short-term breathing problems in newborns. The study also collects umbilical cord blood at birth to evaluate markers of inflammation and potential brain injury, which may help explain why some infants develop complications. Families will also be contacted when their child is 12 months old to complete a developmental questionnaire that is widely used in pediatric practice.
By using a clear definition of thick meconium, a warm LR infusion protocol, fidelity checklists, and long-term follow-up, this trial aims to provide high-quality evidence to guide care in labor and delivery units nationwide.
Maternal age greater than or equal to 18 years old
Singleton pregnancy
Gestational age of greater than or equal to 36 weeks 0 days gestation
Cephalic presentation
Major fetal anomaly
Multiple gestation
Eunice Kennedy Shrive National Institute of Child Health and Human Developmet (NICHD) Category III fetal heart tracing
Contraindication to internal monitors
Parallel
Intrauterine pressure catheter
DeviceStandardized warm amnioinfusion consisting of a 500 mL bolus of warmed (37°C) lactated ringer's infused over 30 minutes through an intrauterine pressure catheter (IUPC), followed by a continuous maintenance infusion of 125 mL/hour until the amniotic fluid clears or delivery.
Standard obstetric care at discretion of delivery provider
Other interventionRoute obstetric care at discretion of delivery provider
Number of participants with composite neonatal respiratory morbidity
Composite neonatal respiratory morbidity including continuous positive airway pressure (CPAP) \>6 hours, oxygen \>24 hours, intubation, persistent pulmonary hypertension (PPHN), surfactant use, inhaled nitric oxide, extracorporeal membrane oxygenation (ECMO), neonatal intensive care unit (NICU) admission, or perinatal death.
Concentration of umbilical cord gas values
Umbilical cord gases including pH, lactate, base excess will be assessed.
Concentration of umbilical cord blood biomarkers
Human Cytokine/Chemokine Panel A 48-Plex Discovery Assay® (HD48A; Eve Technologies) and other novel markers such as sCD40L, G-CSF, and IFNα2. Additionally, S100B as a validated marker for brain injury will be collected.
Scores on developmental screening
Predominantly will capture standard developmental screening including the Ages and Stages Questionaires through 1 year of life. Additional information on developmental screening including Sarnat score and referral to subspecialists will be tracked.
Number of participants with composite maternal morbidity
Composite morbidity will collect processes related to meconium including postpartum hemorrhage requiring intervention such as estimated blood loss \>1000 mililiters (mL) or uterotonics, transexamic acid, blood transfusion or surgical interventions (dilation and curettage, Bakri, Jadha, laparotomy, interventional radiology), endometritis, intraamniotic infection, operative delivery (forceps, vaccum, cesarean), obstetric anal sphincter injury (OASIS), ICU admission, amniotic fluid embolism, and death.
Number of participants with healthcare utilization
Capturing all hospitalizatoins, emergency room visits, subspeciality referal, ancillary referrals, and follow-up visits in the first year of life
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 including things like rates of tachysystole after randomization including categories, declerations, total deceleration area, variablity, accelerations.
Number of participants experiencing pre-defined fidelity metrics
A protocol-specific fidelity checklist will be completed in real time by research staff including Quantification of meconium-crit, Confirmation of cervical dilation ≥ 2 cm, IUPC placement time and verification, Volume and rate of bolus and maintenance infusion, Ultrasound measurements pre- and post-infusion, Fluid color tracking and clearance time, any deviations or complications
Number of participants with neonatal morbidity
NICU admission, seizures, hypoxic-ischemic encephalopathy, intracranial hemorrhage and grade, electrolyte abnormalities, hypoglycemia requiring treatment, hyperbilirubinemia requiring phototherapy, neonatal temperature categorized into hypothermia and hyperthermia, suspected and culture proven sepsis, antibiotic administration
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Medical College of Wisconsin
Lead sponsor
The Gerber Foundation
Collaborator
