Severity of neonatal opioid withdrawal syndrome with prenatal exposure to serotonin reuptake inhibitors.

OBJECTIVE: To evaluate the severity of neonatal opioid withdrawal syndrome (NOWS) in infants prenatally exposed to medications for opioid use disorder (MOUD) and serotonin reuptake inhibitors (SRI). METHODS: A prospective cohort included 148 maternal-infant pairs categorized into MOUD (n = 127) and MOUD + SRI (n = 27) groups. NOWS severity was operationalized as the infant's need for pharmacologic treatment with opioids, duration of hospitalization, and duration of treatment. The association between prenatal SRI exposure and the need for pharmacologic treatment (logistic regression), time-to-discharge, and time-to-treatment discontinuation (Cox proportional hazards modeling) was examined after adjusting for the type of maternal MOUD, use of hydroxyzine, other opioids, benzodiazepines/sedatives, alcohol, tobacco, marijuana, gestational age, and breastfeeding. RESULTS: Infants in the MOUD + SRI group were more likely to receive pharmacologic treatment for NOWS (OR = 3.58; 95% CI: 1.31; 9.76) and had a longer hospitalization (median: 11 vs. 6 days; HR = 0.54; 95% CI: 0.33; 0.89) compared to the MOUD group. With respect to time-to-treatment discontinuation, no association was observed in infants who received treatment (HR = 0.59; 95% CI: 0.26, 1.32); however, significant differences were observed in the entire sample (HR = 0.55; 95% CI: 0.34, 0.89). CONCLUSIONS: Use of SRIs among pregnant women on MOUD might be associated with more severe NOWS. IMPACT: A potential drug-drug interaction between maternal SRIs and opioid medications that inhibit the reuptake of serotonin has been hypothesized but not carefully evaluated in clinical studies. Results of this prospective cohort indicate that the use of SRIs among pregnant women on MOUD is associated with more severe neonatal opioid withdrawal syndrome. This is the first prospective study which carefully examined effect modification between the type of maternal MOUD and SRI use on neonatal outcomes. This report lays the foundation for treatment optimization in pregnant women with co-occurring mental health and substance use disorders.

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Association between prenatal opioid exposure, neonatal opioid withdrawal syndrome, and neurodevelopmental and behavioral outcomes at 5-8 months of age.

BACKGROUND: While use of prescription opioids and medication assisted therapy (MAT) for opioid use disorder in pregnancy, as well as the incidence of neonatal opioid withdrawal syndrome (NOWS) continue to rise, little is known about outcomes for children with NOWS beyond the newborn period. METHODS: We examined 1) prenatal MAT exposure vs. unexposed healthy controls [HC]; and 2) treatment for NOWS and NOWS severity on infant neurodevelopmental and behavioral outcomes at 5-8 months of age in 78 maternal-infant pairs from the ENRICH prospective cohort study. Data were obtained from 3 study visits: prenatal, delivery, and neurodevelopmental evaluation at 5-8 months of age. Neurodevelopmental outcomes included the Bayley Scales of Infant Development [BSID-III], caregiver questionnaires (Parenting Stress Index [PSI-SF], Infant Behavior Questionnaire [IBQ-R], Sensory Profile), and the experimental Still-Face Paradigm (SFP). RESULTS: No differences in the BSID-III, PSI-SF, or IBQ-R scores were observed between MAT and HC groups; however, MAT-exposed and HC infants differed with respect to SFP self-regulation (ß = -18.9; p = 0.01) and Sensory Profile sensation seeking (OR = 4.87; 95% CI: 1.55; 15.30) after adjusting for covariates. No significant differences between Treated-for-NOWS vs. not-Treated-for-NOWS were observed. Shorter timing to NOWS treatment initiation was associated with higher Total Stress (ß = -9.08; p = 0.035), while longer hospitalization was associated with higher Parent-child dysfunctional interaction (p = 0.018) on PSI-SF. CONCLUSIONS: Our results provide additional evidence of little-to-no effect of MAT and pharmacological treatment of NOWS on infant neurodevelopmental and behavioral outcomes at 5-8 months of age. However, prolonged hospitalization might increase family psychosocial stress and requires further examination.