Trajectories of Prescription Opioid Utilization During Pregnancy Among Pre-Pregnancy Chronic Users and Risk of Neonatal Opioid Withdrawal Syndrome.

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.