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

NCT ID: NCT07274527

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 320 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-30
• Study Completion Date: 2030-01-30

Brief Summary

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.

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.

Conditions

Neonatal Respiratory Distress Related Conditions; Meconium; Perinatal Morbidity; Neonatal Acidosis; Cord Blood; Neonatal Brain Injury; Maternal Morbidity; Mechanical Ventilation; CPAP; Surfactant; Perinatal Death; Amnioinfusion; NICU Admission

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Intrauterine pressure catheter

Intervention Type: DEVICE

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.

Standard of Care

Standard obstetric care will be at the discretion of the delivery provider.

Group Type: PLACEBO_COMPARATOR

Standard obstetric care at discretion of delivery provider

Intervention Type: OTHER

Route obstetric care at discretion of delivery provider

Interventions

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.

Intervention Type: DEVICE

Standard obstetric care at discretion of delivery provider

Route obstetric care at discretion of delivery provider

Intervention Type: OTHER

Other Intervention Names

Amnioinfusion

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Gerber Foundation

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Brock E. Polnaszek MD MPH(c)

Assistant Professor and Clinical Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Froedtert Hospital and Medical College of Wisconsin Birth Center

Milwaukee, Wisconsin, United States

Countries

United States

Facility Contacts

Polnaszek Assistant Professor and Principal Investigator, MD MPH

Role: primary

bpolnaszek@mcw.edu

414-805-6600

References

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.

Reference Type: BACKGROUND

PMID: 37164492 (View on PubMed)

Other Identifiers

PRO00054878

Identifier Type: -

Identifier Source: org_study_id