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Child Psychiatrist /Adult Psychiatrist

Prescription Opioid Exposure During Pregnancy Elevates Preterm Delivery Risk

Keypoint: Opioids during pregnancy increase the risk for spontaneous preterm birth.


During Pregnancy

Prescription opioid exposure during pregnancy is positively associated with increased odds of spontaneous preterm birth in a dose-dependent manner. These findings, published in JAMA Network Open, emphasize the importance of prescribing the lowest necessary dose of opioids for pain management during pregnancy.


For pregnant individuals, there are limited options beyond acetaminophen for managing moderate to severe pain during pregnancy due to the fetal risks associated with nonsteroidal anti-inflammatory drugs. Despite the high opioid prescription rates among pregnant individuals in the United States, the effect of short-term opioid exposure on perinatal outcomes remains inadequately characterized.


To this aim, investigators conducted a retrospective, nested case-control study that examined pregnant patients enrolled in Tennessee Medicaid between 2007 and 2019. Eligible participants were comprised of pregnant individuals aged 15 to 44 years without a diagnosed opioid use disorder who gave birth to a single fetus at 24 weeks gestation or later. The primary exposure of interest was the total opioid morphine milligram equivalents (MMEs) filled within the 60 days preceding the delivery date. The investigators documented instances of spontaneous preterm birth and matched these cases with up to 10 controls by pregnancy commencement date, race, ethnicity, age at delivery within a 2-year range, and previous history of preterm birth.


The investigators included 25,391 cases involving spontaneous preterm birth and 225,696 paired controls, for a pooled sample of 251,087 patients. On average, patients were 23 years of age and were mostly non-Hispanic White (cases, 58.1%; controls, 58.5%). Overall, 18,702 patients (7.4%) filled an opioid prescription in the 60 days before the index date.


The investigators found that higher opioid MME doses were associated with increased odds of spontaneous preterm birth in a dose-dependent manner, as each doubling of MME was associated with a 4% increase in spontaneous preterm delivery risk (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.08). Elevated odds of preterm delivery began at 150 MME (aOR, 1.08; 95% CI, 1.03-1.14), and reached a 21% increased risk at 900 MME. The odds remained relatively consistent across different opioid types after accounting for confounding factors and opioid MME.


These results indicate that even low doses of prescription opioids during pregnancy increase the risk for spontaneous preterm delivery. The investigators noted, “We also caution against the conclusion that lower doses especially those below 100 MME are safe; the confidence bands over the low dose range still include odds ratios that are consistent with meaningful harm.” In conclusion, study authors stated, “These findings support guidance to prescribe the lowest opioid dose necessary in pregnancy to manage pain.”


Study limitations include potential residual confounding in the case-control design, reliance on opioid dispensing data, lack of nonprescription analgesics information, potential protopathic concerns, focus on births at 24 weeks or later, and representation from Medicaid-enrolled individuals limiting generalizability.


Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Note: This article originally appeared on Psychiatry Advisor

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