University of Maryland School of Medicine Researchers Find Medication Levels Measured in Umbilical Cord Tissue Not Associated with More Severe Withdrawal

Pregnant patients receiving medication to treat opioid use disorder should not reduce their medication dose out of fear that it will worsen withdrawal symptoms in their newborns, according to a new study led by researchers at the University of Maryland School of Medicine (UMSOM).

The findings suggest that lowering medication doses during pregnancy is not an effective strategy for preventing severe neonatal opioid withdrawal syndrome (NOWS) and reinforce the importance of maintaining treatment to protect mothers from relapse and overdose.

The research letter, published on October 29 in the journal JAMA Network Open examined whether doses of methadone and buprenorphine — the two medications commonly used to treat opioid use disorder during pregnancy — was associated with the severity of the withdrawal syndrome in newborns. They found that the levels of these medications measured in umbilical cord tissue after childbirth were not associated with the severity of this syndrome.

Opioid use disorder is a leading cause of death associated with pregnancy and the postpartum period, according to the American Medical Association. Mortality rates rose more than 80 percent between 2017 and 2020. Medication for opioid use disorder (MOUD) is an evidence-based treatment that helps stabilize the condition and reduce the risk of relapse and overdose, and has been shown to be safe in general to use during pregnancy. However, concerns that higher medication doses may cause more severe withdrawal in newborns can lead some patients and clinicians to consider lowering doses or stopping treatment during pregnancy.

The new findings challenge that approach.

“Our study shows that fear isn't supported,” said Courtney Townsel, MD, MS, an Associate Professor of Obstetrics, Gynecology and Reproductive Sciences at UMSOM and lead author of the study.  “We measured medication and metabolite levels directly in umbilical cord tissue, which is the most objective measure of what the baby was exposed to. Our results indicate higher exposure did not lead to worse withdrawal in newborns. Cutting the dose doesn't give the baby an easier withdrawal. It only puts the mother at risk.”

The study analyzed data from 92 pregnancies involving patients who received methadone or buprenorphine for at least 30 days before delivery. The team measured the medications and their metabolites in umbilical cord tissue collected at birth. Cord tissue provides an indicator of fetal drug exposure over the final trimester of pregnancy.

Severe withdrawal (which can include seizures vomiting, fever or hypothermia) occurred in approximately 44 percent of the newborns included in the study. Although severe withdrawal was more common among newborns exposed to methadone than among those exposed to buprenorphine, the researchers found no significant association between the mother's medication dose and withdrawal severity. They also found no significant differences in umbilical cord medication concentrations between newborns with severe withdrawal and those with less severe symptoms.

These findings suggest that the amount of medication reaching the fetus, as measured in cord tissue, does not explain which newborns will experience more severe withdrawal. NOWS is a complex condition, and additional factors—including differences in medication pharmacology, placental processes, fetal development, and individual newborn responses—may contribute to its severity.

The researchers said the results support an important distinction in clinical care: Medication doses should be individualized to effectively treat the pregnant patient's opioid use disorder, rather than reduced in an attempt to prevent or lessen NOWS.

“Clinicians should focus on maintaining effective treatment for the mother rather than lowering medication doses in an attempt to prevent neonatal withdrawal,” said study co-author Irina Burd, MD, PhD, Chair of Obstetrics, Gynecology, and Reproductive Sciences at UMSOM.

The authors noted that the study's relatively small sample size and limited racial and ethnic diversity are important limitations. The findings do not establish that medications have no effect on every aspect of newborn withdrawal, nor did it eliminate the need for appropriate monitoring and care for newborns exposed to opioids. However, the results do not support reducing maternal medication doses as a strategy to prevent severe NOWS.

The study underscores the need to balance newborn care with the health and safety of pregnant patients with opioid use disorder. Maintaining effective treatment throughout pregnancy can help reduce the risk of relapse and overdose, while newborns can receive appropriate assessment and treatment for withdrawal when needed.

Funding for the study was provided by The Society for Maternal Fetal Medicine Foundation, the American Association of Obstetricians and Gynecologists, and the Robert Wood Foundation.