718 - Safety Events for Pharmacologically Treated and Non-Pharmacologically Treated Infants with Neonatal Opioid Withdrawal in the ESC-NOW Trial

Publication Number: 1695.718

Leslie Young, The University of Vermont Children's Hospital, Burlington, VT, United States; Zhuopei Hu, University of Arkansas for Medical Sciences College of Medicine, Little Rock, AR, United States; Stephanie L. Merhar, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; song Ounpraseuth, UAMS, Little Rock, AR, United States; Lillian Trochinski, RTI International, Brookfield, WI, United States; Abhik Das, RTI, Gaithersburg, MD, United States; Lori A. Devlin, University of Louisville School of Medicine, Louisville, KY, United States; for the Eunice Kennedy Shriver NICHD Neonatal Research Network and the, RTI International, Durham, NC, United States

Background: Infants pharmacologically treated for neonatal opioid withdrawal syndrome (NOWS) are often transferred to the neonatal intensive care unit (NICU) to monitor for clinical instability (i.e. seizures, respiratory insufficiency, somnolence). The NICU is not an ideal environment for infants with NOWS as it hinders optimal nonpharmacologic care, the first line of treatment for NOWS. Additionally, NICU admissions interrupt maternal-infant bonding and rooming in and may require transfer to another hospital. To optimize care, some have advocated for and started treating infants pharmacologically in non-ICU settings without cardiopulmonary monitoring. Though evidence for continuous monitoring is lacking, this has been common practice since the 1970s, and to date there is insufficient evidence to support the safety of providing pharmacologic treatment without such monitoring in place. The shift in practice despite a lack of safety data highlights the critical importance of additional and timely evidence to inform this practice.

Objective: To evaluate the incidence of safety events in infants with NOWS who receive and do not receive pharmacologic treatment with an opioid (i.e. morphine, methadone, or buprenorphine).

Design/Methods: All infants from the Eating, Sleeping, Consoling for Neonatal Opioid Withdrawal (ESC-NOW) trial were included. Safety events were defined as those currently used to justify ICU monitoring of infants, including seizures, respiratory insufficiency, somnolence, escalation of care, and death. Adverse and serious adverse events (AE/SAEs) reported during ESC-NOW were used to identify such events. AE/SAEs deemed unrelated to NOWS or NOWS management were excluded (fIg.1). Pharmacologic and nonpharmacologic treatment hours were calculated to quantify the duration over which events were reported.

Results: This analysis included 1305 infants (473 pharm treated, 832 non-pharm treated). Across the study infants received in-hospital care for 331,488 total hours; 160,753 hours (48%) were pharmacologic treatment hours. There were 27 in hospital AE/SAEs reported across the study (Fig.1). No study-defined safety events were reported for either pharmacologically or non-pharmacologically treated infants.

Conclusion(s): Across the study cohort, including >160,000 hours of prospective observation during pharmacologic treatment, no safety events related to NOWS or NOWS management were reported. This suggests that oft-cited safety events are exceedingly rare. These results should be considered alongside existing literature as we look to determine the appropriate location of care for infants with NOWS.

Maternal and Infant Characteristics for the ESC-NOW Trial Cohort
** Medication for opioid use disorder (MOUD); rural-urban commuting area codes (RUCA);
†Other includes: American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, Asian, and more than one race
††Polysubstance exposure included exposure to opioids and an additional psychotropic agent, excluding nicotine. Additional exposures included: amphetamines, barbiturates, benzodiazepines, kratom, cocaine, gabapentin, marijuana, methamphetamines, phencyclidine, and selective serotonin reuptake inhibitors

Safety Events During the ESC-NOW Trial