Amnioinfusion's Protective Effects on Respiratory and Longitudinal Pediatric Outcomes After Intrapartum Thick Meconium Exposure (PEARL)

The PEARL Trial: A Randomized Trial of Amnioinfusion's Protective Effects on Respiratory and Longitudinal Pediatric Outcomes After Intrapartum Thick Meconium Exposure

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.

Study Overview

• Status: Recruiting
• Conditions: Mechanical Ventilation; Perinatal Death; Maternal Morbidity; Neonatal Respiratory Distress Related Conditions; CPAP; Cord Blood; Surfactant; Perinatal Morbidity; Meconium; Neonatal Acidosis; Neonatal Brain Injury; Amnioinfusion; NICU Admission
• Intervention / Treatment: Device: Intrauterine pressure catheter; Other: Standard obstetric care at discretion of delivery provider

Detailed Description

Thick meconium-stained amniotic fluid is a common intrapartum finding and is associated with increased newborn respiratory morbidity, NICU admission, and long-term developmental concerns. Prior research on amnioinfusion for meconium produced mixed results, largely because earlier trials included all meconium consistencies, used different fluid types and temperatures, did not monitor adherence to infusion protocols, and did not study biologic markers or long-term child outcomes. Because of these limitations, clinicians lack clear evidence about whether modern, standardized amnioinfusion can benefit infants exposed to thick meconium.

The PEARL Trial is designed to address these gaps using a methodologically rigorous, implementation-science-informed approach. The study enrolls maternal-infant dyads at ≥ 36 weeks' gestation with confirmed thick meconium, defined both visually and using an objective "meconium-crit" method that measures the proportion of meconium in the amniotic fluid. After eligibility is confirmed, participants are randomized to receive either a structured warm lactated Ringer's (LR) amnioinfusion protocol or standard obstetric care with no amnioinfusion.

The intervention consists of a 500-mL bolus of warmed LR infused over 30 minutes through an intrauterine pressure catheter, followed by a maintenance infusion until the meconium clears or delivery occurs. Ultrasound checks, infusion parameters, and fluid characteristics are recorded using a fidelity checklist to ensure consistent delivery of the intervention.

The primary outcome is a composite measure of neonatal respiratory morbidity within 72 hours of birth, including need for oxygen, continuous positive airway pressure (CPAP), intubation, inhaled nitric oxide, surfactant therapy, NICU admission, or perinatal death. At birth, umbilical cord blood is collected for gases and for a multiplex panel of inflammatory cytokines and S100B, a biomarker associated with neurologic injury, to better understand biologic pathways linking thick meconium exposure to newborn outcomes. The investigators will also track long-term childhood respiratory morbidity including asthma treatment and severity, reactive airway disease, persistent pulmonary hypertension, bronchopulmonary dysplasia, health care utilization outcomes including but not limited to subspecialty referral, ancillary referrals, emergency room and rehospitalizations.

Long-term follow-up occurs at 12 months corrected age using the Ages and Stages Questionnaire (ASQ-3), a validated tool that screens for communication, motor, problem-solving, and social-emotional development. This allows the trial to explore whether improved intrapartum intervention translates into better developmental outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53045
      • Recruiting
      • Froedtert Hospital and Medical College of Wisconsin Birth Center
      • Contact: Polnaszek Assistant Professor and Principal Investigator, MD MPH; Phone Number: 414-805-6600; Email: bpolnaszek@mcw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• Cercial dilation between 2-10 centimeters
• Meconium

Exclusion Criteria:

• 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
• Prelabor premature ruptuore of membranes before 36 weeks 0 days gestation, - Inability to consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Warm Lactated Ringer Amnioinfusion; Standardized 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. Re-administration is permitted if thick meconium persists or the deepest amniotic fluid pocket is <2 cm by ultrasound.	Device: Intrauterine pressure catheter; Standardized 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.; Other Names: Amnioinfusion
Placebo Comparator: Standard of Care; Standard obstetric care will be at the discretion of the delivery provider.	Other: Standard obstetric care at discretion of delivery provider; Route obstetric care at discretion of delivery provider

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	72 hours after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of umbilical cord gas values	Umbilical cord gases including pH, lactate, base excess will be assessed.	At delivery
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.	At delivery and if measured in the neonate as a part of usual care
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.	1 year after delivery
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.	Through 6 weeks postpartum

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	1 year after delivery
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.	During labor and delivery
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	Randomization to 48 hours after birth
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	1 year of life
Number of participants with placental pathology	Using contemporary placental pathology recommended and endorse by the College of American Pathologists, we will examine the categories of findings on pathologic examination fo the placenta	Following delivery
Number of participants with composite childhood respiratory morbidity	A composite of childhood respiratory morbidity will including tracking for diagnoses realted to respiratory complications such as airway disease, asthma, bronchopulmonary dysplasia, and persistent pulmonary hypertension	1 year of life

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Collaborators: The Gerber Foundation

Publications and helpful links

General Publications

• Davis JD, Sanchez-Ramos L, McKinney JA, Lin L, Kaunitz AM. Intrapartum amnioinfusion reduces meconium aspiration syndrome and improves neonatal outcomes in patients with meconium-stained fluid: a systematic review and meta-analysis. Am J Obstet Gynecol. 2023 May;228(5S):S1179-S1191.e19. doi: 10.1016/j.ajog.2022.07.047. Epub 2023 Mar 18.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2026
• Primary Completion (Estimated): April 15, 2029
• Study Completion (Estimated): April 15, 2030

Study Registration Dates

• First Submitted: November 27, 2025
• First Submitted That Met QC Criteria: November 27, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Amnioinfusion; Healthcare Utilization; Meconium; Maternal Morbidity; Neonatal morbidity; Neonatal respiratory morbidity; Developmental Screening; Umbilical cord gas and biomarkers
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Death; Pathological Conditions, Signs and Symptoms; Perinatal Death; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Ringer's Lactate
• Other Study ID Numbers: PRO00054878

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No