LAUSR

Little is known about the impact of dose, duration and timing of prenatal prescription opioid exposure on the risk of neonatal opioid withdrawal syndrome (NOWS). Using a cohort of 18,869 pre-pregnancy chronic opioid users nested in the 2000-2014 Medicaid Analytic eXtract, we assessed average opioid dosage within bi-weekly gestational age intervals, created group-based trajectory models and evaluated the association between trajectory groups and NOWS risk. Women were grouped into 6 distinct trajectories which, based on observed patterns, were categorized as (1) continuous very low dose use, (2) continuous low use, (3) initial moderate use with gradual decrease to very low/no use, (4) initial high use with gradual decrease to very low use, (5) continuous moderate use, and (6) continuous high use. Absolute risk of NOWS per 1,000 livebirths was 7.7 for group 1 (=reference group); 28.8 for group 2 (relative risk [RR]: 3.7, 95% CI 2.8-5.0), 16.5 for group 3 (RR=2.2, 1.5-3.1), 64.9 for group 4 (RR=8.4, 5.6-12.6), 77.3 for group 5 (RR=10.0, 7.5-13.5), and 172.4 for group 6 (RR=22.4, 16.1-31.2). Trajectory models - which capture dose, duration and timing of exposure - are useful to gain insight into clinically relevant groupings to evaluate the risk of prenatal opioid exposure.