124 Prescription Opioid Exposure and Risk of Spontaneous Preterm Delivery

Prior studies that reported associations between opioid exposure during pregnancy and preterm birth did not differentiate between spontaneous and indicated preterm birth or fully investigate a potential dose-dependent relationship with opioid exposure. We investigated the association between prescription opioid exposure proximate to delivery and spontaneous preterm birth, and whether the association is dose-dependent. We performed a nested case-control study of pregnant patients enrolled in TN Medicaid. Enrollment files were linked to healthcare encounters, hospital discharge data, birth certificate data, and prescription fill records. We included patients aged 15-44 years with a singleton livebirth at 24 weeks or greater between 2007 and 2019 with linked birth certificate data in the parent cohort. We identified cases of spontaneous preterm birth using a validated algorithm and matched up to 10 controls on case delivery date (index date), conception date, race, ethnicity, maternal age at delivery (±2 years), and preterm birth history. The exposure was total opioid morphine milligram equivalents (MME) filled within the 60 days prior to the index date. We used conditional logistic regression to estimate adjusted odds ratios (aOR) and obtained 95% confidence intervals (95% CI). We identified 25,383 patients with spontaneous preterm birth (cases) and matched them to 225,436 controls (N=250,819 total). Overall, 8.8% of case patients filled an opioid prescription (median MME 150, IQR 75-338) versus 7.3% of controls (median MME 135, IQR 72-270). Total opioid MME prescribed within 60 days prior to index date was continuously associated with higher odds of spontaneous preterm birth, adjusting for relevant confounders (aOR=1.03 95% CI: [1.07-1.13] per opioid MME). Total opioid doses >98.7 MME were significantly associated with spontaneous preterm birth. We identified an association between higher total opioid exposure and spontaneous preterm birth. Our findings support guidance to minimize opioid exposure proximate to delivery and prescribe the lowest dose necessary.