Study reveals link between opioid dosage and spontaneous preterm birth risk

Total prescription opioid dose dispensed is positively associated with spontaneous preterm birth risk, according to a recent study published in JAMA Network Open.

Despite the common application of acute pain management in pregnant patients, there are few options besides acetaminophen to manage moderate to severe pain. This leaves opioid medications as the primary pharmaceutical option for pain management, which may be associated with high opioid prescription rates during pregnancy in the United States.

Preterm birth impacts up to 10.5% of pregnancies and is associated with neurodevelopmental impairment, chronic disease, and infant death. While data has indicated an association between opioid use during pregnancy and preterm birth, this data has not differentiated between indicated and spontaneous preterm birth.

Investigators conducted a nested case-control study to evaluate a potential dose-dependent association between opioid prescription exposure during pregnancy and spontaneous preterm birth risk. Participants were identified through enrollment in Tennessee Medicaid (TennCare).

TennCare files were linked to health care encounters, hospital discharge data, vital records, and prescription fills. Tennessee birth certificate data was also assessed to determine maternal demographics and clinical characteristics, gestational age, and obstetric procedures.

Participants included pregnant individuals aged 15 to 44 years with a single fetus born from 2007 to 2019 at 24 weeks’ gestation or greater. Spontaneous birth was determined by premature rupture of membranes, forceps or vacuum use or attempted use, prolonged or precipitous labor, and no induction for delivery.

The date of delivery was defined as the index date for cases, who were matched to controls with an index date within 4 days of their start date. Ninety days of continuous enrollment before the index data was necessary for cases and controls.

Cases and controls were matched based on risk factors including race and ethnicity, prior preterm birth history, and age at delivery. Patients missing data on these factors were excluded from the analysis.

Total opioid morphine milligram equivalent (MME) filled in the 60 days before the index date was the primary exposure of the analysis. Pharmacy data was used to determine opioid strength, type, and dispensed quantity. Covariates included prepregnancy body mass index (BMI), parity, hepatitis B and C infections, tobacco use, and pain indications.

There were 25,391 cases of spontaneous preterm birth reported, 58.1% from non-Hispanic White patients, 38.7% Black, 2.6% Hispanic, and 0.5% Asian. Cases were matched to 225,696 controls with similar characteristics. Both groups were aged a mean 23 years.

A lower BMI and education level, as well as increased risk of medical conditions associated with acute or chronic pain, were reported among cases. An opioid prescription was reported in 8.8% of cases and 7.3% of controls.

A significant association was found between opioid MME dose prescribed in the 60 days before the index date and spontaneous preterm birth. The risk of spontaneous preterm birth was increased 4% with each doubling of nonzero opioid MME, with an adjusted odds ratio of 1.04.

Spontaneous preterm birth odds were significantly increased by being prescribed the most common opioid prescriptions, with an 8% increase from a 150-MME opioid prescription, a 16% increase from a 450-MME prescription, and a 21% increase from a 900-MME prescription.

These results indicated a significant association between total prescription opioid MME dose exposure and spontaneous preterm birth risk. Investigators concluded the lowest dose necessary for pain management should be prescribed.

Reference

Bosworth OM, Padilla-Azain MC, Adgent MA, et al. Prescription opioid exposure during pregnancy and risk of spontaneous preterm delivery. JAMA Netw Open. 2024;7(2):e2355990. doi:10.1001/jamanetworkopen.2023.55990