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

Abstract

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 (β = -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 (β = -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.

Keywords: Infant neurodevelopment; Medication-assisted treatment; Opioids; Parental stress; Pregnancy; Substance use disorder.

Figure 1:. Flowchart of ENRICH Study Participants Included in the Analysis

*The most common reasons for disqualifications include disqualifying drug use among any study groups and being positive for alcohol biomarkers among HC group.