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

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.