Placental disease/preterm delivery and opioid use during pregnancy


“Opioids affect placental development and function in animal models, but human data on their association with ischemic placental disease are limited,” wrote the authors.

A study in the American Journal of Epidemiology has found that women who had at least 2 opioid prescriptions filled during early pregnancy were 34% more likely to experience placental abruption, 21% more likely to have preterm delivery, and 13% more likely to deliver a child of small for gestational age (SGA), compared to pregnant women who were not exposed to opioids.

The risk of preeclampsia was similar between the 2 groups.

“Opioids affect placental development and function in animal models, but human data on their association with ischemic placental disease are limited,” wrote the authors.

The researchers evaluated a large cohort of pregnant women contained in the United States nationwide Medicaid Analytic eXtract (MAX) from 2000 to 2014.

Within a mother-infant linked dataset, the women started Medicaid enrollment at least 3 months prior to the estimated date of their last menstrual period (LMP) and continued enrollment for more than 30 days after delivery. The women also had no supplemental insurance or restricted benefits.

Because the focus of the study was on the impact of prescription opioid use, women were also excluded if they had 1 or more of the following 3 conditions from 3 months prior to LMP through delivery: greater than 1 pharmacy dispensing of naltrexone, naloxone or buprenorphine; a charge code for methadone given for opioid maintenance therapy for dependence; and at least 1 diagnosis of opioid use disorder (OUD) or opioid poisoning.

Of 1,833.871 eligible pregnancies, greater than 2 prescriptions of opioids were filled by 6.5% of the women. More specifically, 5.1% had at least 2 opioid dispensings in early pregnancy (irrespective of late exposure); 1.6% had at least 2 dispensings in late but not early pregnancy; and 1.8% had at least 2 dispensings in both early and late pregnancy.

Combined, early and late pregnancy exposure to more than 2 prescriptions of opioids resulted in a 62% increase for placental abruption, a 21% increase for preterm delivery, and a 13% increase for SGA, compared to pregnant women who were unexposed to opioids. But as with early opioid exposure alone, there was no meaningful difference for preeclampsia.

Women taking opioids were more likely to be White, multiparous, reside in the southern region of the U.S. and have documented tobacco use.

Pain conditions were also more frequent among opioid users, with the most common pains being abdominal and back/neck. In addition, opioid users more often had psychiatric disorders such as depression, and conditions associated with ischemic placental disease (IPD), like hypertension.

The stronger likelihood of opioid exposure both early and late in pregnancy versus early pregnancy alone might be attributed to different mechanisms leading to placental insufficiency being influenced by accumulated opioid exposure across early and late pregnancy, according to the authors. Sustained opioid use could also reflect chronic pain.

“Prescription opioids may modestly increase risk of placental abruption, preterm birth and SGA, but they do not appear to be associated with preeclampsia,” concluded the authors, adding that the benefits of pain management during pregnancy should be considered in light of the study’s findings.



Esposito DB, Bateman B, Werler M, et al. Ischemic placental disease, preterm delivery, and their association with opioid use during pregnancy. Am J Epidemiol. Published online June 24, 2021.


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