Odds for spontaneous preterm birth rise as opioid exposure increases

Key takeaways:

• Each doubling of opioid morphine milligram equivalents (MME) vs. no exposure was tied to increasing spontaneous preterm birth odds.
• One hundred or more MME significantly increased spontaneous preterm birth odds.

Pregnant women who were prescribed opioid drugs had increased likelihood of spontaneous preterm delivery, and odds increased as total dose increased, according to case-control study results published in JAMA Network Open.

“Multiple studies have reported an association between opioid exposure during pregnancy and preterm birth, although the mechanism of this association is poorly defined. Some studies suggest this association is due to effects on placental development early in pregnancy, which leads to iatrogenic preterm birth due to maternal or fetal indications for delivery such as fetal growth restriction, placental abruption or preeclampsia,” Olivia M. Bosworth, BA, undergraduate research assistant at Vanderbilt University, and colleagues wrote. “Importantly, previous studies on prenatal opioid exposure have not distinguished between indicated and spontaneous preterm birth, which impacts clinicians’ ability to adequately counsel patients about the potential risks of opioid use, especially sporadic use, during pregnancy.”

Bosworth and colleagues conducted a retrospective case-control study with data from a cohort of pregnant patients enrolled in Tennessee Medicaid aged 15 to 44 years who had a singleton birth at 24 weeks gestation or later from 2007 to 2019. Researchers linked enrollment files with health care encounters, hospital discharge information, birth certificate data and opioid prescription records. Researchers matched spontaneous preterm birth cases with up to 10 control cases based on pregnancy start date, race, ethnicity, age at delivery and preterm birth history.

Primary outcome was spontaneous preterm birth and its association with total opioid morphine milligram equivalents (MME) filled in the 60 days before the index date.

Overall, 25,391 patients (median age, 23 years) had spontaneous preterm birth and were matched with 225,696 controls (median age, 23 years). Of patients with spontaneous preterm birth, 58.1% were white, 38.7% were Black, 2.6% were Hispanic and 0.5% were Asian.

Overall, 7.4% of patients filled an opioid prescription within 60 days before the index date. Researchers noted that each doubling of nonzero opioid MME was associated with a 4% increase in spontaneous preterm birth odds compared with no opioid exposure (adjusted OR = 1.04; 95% CI, 1.01-1.08). In addition, compared with no opioid prescriptions, the most commonly filled opioid MME prescriptions were associated with statistically significantly higher spontaneous preterm birth odds, with evidence showing significantly increased spontaneous preterm birth odds above 100 MME, the researchers wrote.

“We found a continuous positive association between total prescription opioid MME dose exposure and the odds of spontaneous preterm birth,” they wrote. “Our findings support guidance to prescribe the lowest dose necessary to manage pain.”