Importance: Prescription opioids are often used during pregnancy even though they are associated with neonatal opioid withdrawal syndrome (NOWS). Most studies of adverse outcomes of opioid use for pain have assessed only the class-wide outcome despite the pharmacodynamic and pharmacokinetic heterogeneity across opioid medications.

Question: Does risk of neonatal opioid withdrawal syndrome (NOWS) after in utero exposure to prescription opioids vary across commonly prescribed types of opioids?

Findings: In this cohort study of 48 202 opioid-exposed pregnancies with live-born neonates, strong agonists were associated with a higher risk of NOWS compared with weak agonists, and long half-life opioids were associated with an increased risk compared with short half-life products. These associations were independent of morphine milligram equivalents.

Meaning: The study suggests that knowing the varying opioid-specific risk of NOWS associated with in utero exposure may help prescribers select opioids for pain management in late stages of pregnancy.