
Prescription opioid use during pregnancy was associated with higher odds of spontaneous preterm birth (sPTB), while antidepressant use showed no significant association. This nested case-control study analyzed Tennessee Medicaid data from 2007–2019, involving 25,406 sPTB cases and 225,771 matched controls. Opioid-only exposure was linked to a 29% increased risk of sPTB (adjusted OR 1.29, 95% CI 1.23–1.35), whereas antidepressant-only exposure had no significant impact (adjusted OR 1.04, 95% CI 0.96–1.12). Combined opioid and antidepressant exposure also increased risk (adjusted OR 1.22, 95% CI 1.06–1.40), but no additive interaction was identified. Findings underscore the need for cautious opioid use during pregnancy to mitigate preterm birth risk.
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