O2062: Neurodevelopmental Trajectories After Neonatal Opioid Withdrawal Syndrome in a Prospective Longitudinal Cohort

Background: Neonatal opioid withdrawal syndrome (NOWS) is a significant public health problem in the United States. Children with prenatal opioid exposure are at higher risk for developmental and behavioral concerns and poorer school performance. However, the complex socioeconomic, environmental, and genetic and epigenetic factors complicate interpretation and prediction in this population. Typical neonatal follow-up research uses a single assessment at 2 years of age with inconsistent predictive validity for long-term outcomes. In comparison, developmental trajectories provide a more comprehensive evaluation with potential for more accurate prediction of long-term outcomes.

Methods: Prospective observational cohort of 205 subjects with NOWS. Inclusion criteria: birth gestational age ≥34 weeks with in-utero opioid exposure and pharmacologic treatment for NOWS. We excluded infants with significant congenital or genetic anomalies known to affect neurodevelopment (e.g., Trisomy 21). Developmental outcomes were assessed at 1, 2, and 3 years with the Bayley Scales of Infant and Toddler Development (Bayley, 3rd, or 4th edition). Cognitive, language, and motor composite scores (standardized population mean [M] =100, standard deviation [SD] =15) and receptive language, expressive language, cognitive, fine motor, and gross motor scaled scores (M=10, SD=3) were derived. For the single timepoint outcome, the oldest age Bayley assessment performed was used for analysis (either 2- or 3-year-old assessment). We compared Bayley scores to population means using one-sample Z tests. We report estimates, 95% confidence intervals (CI), and two-sided p values. Linear mixed models were used to estimate scores and 95% CIs across time, accounting for repeated measures. The study was IRB approved (IRB18-00703); informed consent was obtained from the legal guardian.

Results: We enrolled 205 infants from October 2018 to March 2020. Pregnant person and infant characteristics are presented in Table 1. All infants in the cohort had in utero exposure to opioids. Although the majority (64%) of mothers participated in a medication for opioid use disorder treatment program at some point during pregnancy, polysubstance use was common (74%), with only 20% in an MOUD program without other nonprescribed substance use for the duration of their pregnancy. One-hundred sixty-seven infants (81%) completed at least a partial 2 or 3-year developmental visit. Infants with NOWS had lower Bayley scores at 2-3 years compared to published norms in the cognitive, language, and motor domains (Figure 1A). Bayley trajectories showed scores at all time points are below the population mean and decline over time for all subtests (Figure 1B,C,D).

Conclusion: Infants with pharmacologically treated NOWS have significantly lower cognitive, language, and motor scores on standardized developmental testing compared to population means at 2-3 years of age. Bayley trajectories indicate a possible decline in scores over time, however, differential loss to follow-up could impact these estimates.