577 - Intrauterine Exposure to Psychotropic Medications as a Risk Factor for Neonatal Opioid Withdrawal Syndrome

Publication Number: 577.5261

Jessie Maxwell, University of New Mexico School of Medicine, Albuquerque, NM, United States; Zhuopei Hu, UAMS, 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; Lori A.. Devlin, University of Louisville School of Medicine, Louisville, KY, United States; Leslie Young, Larner College of Medicine at the University of Vermont, Burlington, VT, United States; NICHD Neonatal Research Network, National Institute of Child Health and Human Development, Bethesda, MD, United States; ECHO IDeA States Pediatric Clinical Trials Network, n/a, North Bethesda, MD, United States

Background: The incidence of neonatal opioid withdrawal syndrome (NOWS) following intrauterine exposure to opioids continues to increase. Co-exposure to psychotropic medications has been associated with an increase in NOWS severity for infants managed with Finnegan, but it is unknown if use of the ESC care approach modifies this relationship.

Objective: To evaluate the association between antenatal exposure to psychotropic medication and receipt of pharmacologic treatment for infants with NOWS in a contemporary cohort managed with ESC versus usual care.

Design/Methods: In this subgroup analysis we used data from the Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) ESC trial to compare outcomes from infants with NOWS who had concomitant antenatal exposure to psychotropic medication, including selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines, to those without these co-exposures. For the outcomes of length of stay and length of treatment, we used a generalized linear mixed model (GLMM) with a negative binomial distribution and a log link function and reported incidence rate ratios (IRRs). For the outcome of percentage of pharmacologically treated infants, we used a mixed-effects Poisson regression with robust error variance, reporting relative risks (RRs). We adjusted for the trial design and demographic variables previously associated with NOWS severity.

Results: Of the 1,305 infants included in the ESC-NOW study, 297 (22.8%) had antenatal co-exposure to psychotropic medications. The mean length of stay was 1.6 days longer for infants with psychotropic exposure compared to those without exposure (12.1 vs. 10.5 days, respectively; p < 0.001) (Table 2). Infants with exposure to psychotropic medications were more likely to receive pharmacologic treatment, 39.3% vs 33.7% (absolute difference 5.5%, 95%CI 0.1%-11.0%). For infants treated for NOWS with postnatal opioids, there was no difference in the mean length of pharmacologic treatment in those with antenatal psychotropic exposure compared to those without psychotropic exposure (16.8 vs 14.6 days, respectively) (Table 2). Those with exposure to psychotropic medication were more likely to also have exposure to other substances (i.e., alcohol, nicotine, marijuana, and methamphetamine) (84% vs. 69%; p< 0.05; Table 1).

Conclusion(s): Infants with NOWS and antenatal exposure to psychotropic medication had longer lengths of stay and were more likely to require pharmacologic treatment, indicating that antenatal exposure to psychotropic medication is associated with more severe withdrawal.

Descriptive statistics of infant and maternal characteristics
PAS ESC Psychotropic Meds Maxwell 2025 FINAL 2.pdfa MOUD: Medication for Opioid Use Disorder
b Other substance exposure included exposure to alcohol, nicotine, marijuana and methamphetamines
* p < 0.05 with two independent t-test
** p < 0.05 using Chi-square test


Outcome measures by psychotropic exposure
PAS ESC Psychotropic Meds Maxwell 2025 FINAL 3.pdf* The adjusted analysis was performed without demographic covariates, but still accounted for the study design (i.e., fixed period/time effect and random site effect, intervention arms), randomization scheme stratification indicator (proportion of infants with NOWS treated pharmacologically at each site: lowest 3rd, middle 3rd, highest 3rd)
** The adjusted analysis accounts for the trial design (i.e. a fixed effect for the trial period, intervention group, and random site effect), randomization stratification indicator as fixed effect and adjusted by MOUD, sex, birth weight, gestational age, breastmilk feeding during hospital stay, and other substance exposures

a Reported as incidence rate ratio (IRR) based on a generalized linear mixed model (GLMM) with negative binomial distribution and log link function
b Reported as relative risk (RR) based on mixed effect Poisson regression model with robust error variance


Psychotropic Medication Exposure (N = 1305)
PAS ESC Psychotropic Meds Maxwell 2025 FINAL 4.pdf*SSRI: Selective Serotonin Reuptake Inhibitors
^The other Psychotropic medication includes Adderall, Alprazolam, Ambien, Amitriptyline, Amoxapine, Aripiprazole, Buspirone, Carisoprodol, Clonazepam, Clonidine, Desipramine, Doxepin, Fluoxetine, Hydroxyzine, Imipramine, Lamotrigine, Nortriptyline, Olanzapine, Pregabalin, Protriptyline, Quetiapine, Risperidone, Trazodone, Trimipramine, Venlafaxine, Xylazine, Zolpidem