Utero opioid exposure increases risk of neonatal opioid withdrawal syndrome


Investigators found that opioid use during pregnancy increases the relative risk of neonatal opioid withdrawal syndrome in newborns.

In utero exposure to strong agonists and long half-life prescription opioids increases risk of neonatal opioid withdrawal syndrome (NOWS) in newborns, according to a recent study.

Although opioid use during pregnancy often leads to NOWS, opioids are often prescribed to relieve pain in pregnant mothers. Past studies of adverse events of opioid use have collected data on class-wide outcomes, though opioids vary in pharmacodynamic and pharmacokinetic factors.

NOWS can lead to irritability, mild tremors, seizures, fevers, and excessive weight loss. Newborns may face extended hospitalization, birth complications, intensive care unit admission, and disrupted bonding when afflicted with NOWS. From 2000 to 2016, cases of NOWS in newborns had risen from 1.2 to 8.8 per hospital births. This coincides with increased use of opioids during pregnancy.

Investigators gathered data from 48,202 Medicaid-insured mothers whose newborns were exposed to opioids during pregnancy. Mothers included in the study had been given 2 or more dispensed opioid prescriptions in the 90 days before the newborn’s birth and were enrolled in Medicaid for at least 270 before delivery and at least 30 days after.

Strong and weak agonist strength and half-life were compared between various opioid medications. NOWS was then identified in newborns, using a diagnostic from the International Classification of Diseases, Ninth Revision, Clinical Modification.

In the newborns, 1069 were diagnosed with NOWS, 559 of which were severe. There were 25,710 exposures to hydrocodone during pregnancy, 16,202 to codeine,4540 to oxycodone, 1244 to tramadol, 260 to methadone, 90 to hydromorphone, and 63 to morphine. 

Relative risk (RR) was calculated through 4 different factors: unadjusted, adjusted for confounding variables, adjusted for opioid characteristics, and adjusted for both opioid characteristics and confounding variables. Codeine had a lower relative risk than hydrocodone, with tramadol seeing a similar RR. Oxycodone, hydromorphone, morphine, and methadone saw an increased RR in comparison.

Newborns of mothers who received strong agonists saw an increased RR, along with newborns of mothers who received half-life opioids. While more variation in results from half-life opioids was found, long half-life opioids led to a greater risk of NOWS compared to short half-life opioids. Investigators concluded that there are important differences between different types of opioids, which should be considered during clinical decision making.


Esposito DB, Huybrechts KF, Werler MM, Straub L, Hernández-DíazS, Mogun H, et al. Characteristics of prescription opioid analgesics in pregnancy and risk of neonatal opioid withdrawal syndrome in newborns. JAMA Netw Open. 2022;5(8):e2228588. doi:10.1001/jamanetworkopen.2022.28588

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