(282) Opioid Analgesic and Antidepressant Use During Pregnancy and the Risk of Spontaneous Preterm Birth: A Nested Case-Control Study

Background: Mental health and pain conditions are common in pregnancy, often requiring use of antidepressants and opioids during this vulnerable period. However, it is unclear whether the single and combined use of these medications is associated with severe adverse pregnancy outcomes, such as spontaneous preterm birth (sPTB).

Objectives: To investigate the association between prenatal exposure to antidepressants or opioids, alone or in combination, and sPTB.

Methods: We used linked Tennessee Medicaid (2007-2019) and birth certificate data to conduct a nested case-control study of pregnant patients 15-44 years of age with singleton live births. We identified cases of sPTB at 24 to < 37 weeks of gestation using a validated algorithm. We matched each case with up to 10 randomly selected controls based on the estimated start date of pregnancy, history of prior preterm birth, maternal age, race, and ethnicity. We used pharmacy data to identify antidepressant or opioid prescription fills during the 60 days before the index date (calendar date for case delivery) and derived four mutually exclusive exposure categories: 1) unexposed, 2) opioid only, 3) antidepressant only, and 4) combined. We estimated odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression to account for matching, and adjusted for maternal demographics, preterm birth risk factors, and clinical indications for medication use. We estimated measures of additive biological interaction, e.g., relative excess risk due to interaction. In a secondary analysis, we limited antidepressant exposure to selective serotonin reuptake inhibitors (SSRIs).

Results: We identified 25,406 cases of sPTB and 225,771 matched controls. The proportion of cases and controls exposed to opioids-only, antidepressant-only, and combined were 11.6% and 8.0%; 3.5% and 2.9%; and 1.1% and 0.6%, respectively. After adjustment, opioid exposure (aOR: 1.29 [95% CI: 1.23-1.35]) and combined exposure (aOR: 1.22 [95% CI: 1.06-1.40]) were associated with higher odds of sPTB, relative to the unexposed group, while antidepressant only use was not (aOR: 1.04 [95% CI: 0.96-1.12]). There was no statistically significant additive interaction found for combined exposure to opioids and antidepressants. Similar results were observed in the secondary analysis of SSRIs.

Conclusions: Opioid use during pregnancy was associated with a higher risk of sPTB. Co-exposure to opioids and antidepressants did not elevate the odds of sPTB above what we observed for opioid exposure alone and antidepressant use alone showed no association with sPTB. Clinicians should consider these findings relative to risks associated with untreated maternal mood disorders and pain when making treatment decisions during pregnancy.