Maternal Opioid Use Disorder Raises Postneonatal Infant Mortality

Infants born to individuals with opioid use disorder (OUD) or with a neonatal opioid withdrawal syndrome (NOWS) diagnosis had a higher risk of postneonatal infant mortality compared with infants who didn't have these exposures, researchers found.

In a retrospective cohort study of 390,075 infants born to mothers enrolled in Tennessee Medicaid, there were 1,317 postneonatal deaths, corresponding to 3.67 deaths per 1,000 person-years (95% CI 3.48-3.87), Margaret Adgent, PhD, MSPH, of Vanderbilt University Medical Center in Nashville, and colleagues reported.

The incidence of postneonatal infant mortality was higher in any OUD/NOWS group compared with infants who were OUD negative/NOWS negative, the researchers wrote in JAMA Pediatrics.

Deaths per 1,000 person-years were 8.41 (95% CI 6.12-11.56) in the OUD positive/NOWS positive group, 8.95 (95% CI 6.93-11.54) in the OUD positive/NOWS negative group, and 9.25 (95% CI 5.90-14.50) in the OUD negative/NOWS positive group. In contrast, there were 3.47 (95% CI 3.28-3.67) in the OUD negative/NOWS negative group.

After full adjustment for maternal characteristics as well as infant and birth characteristics, the risk of postneonatal death remained elevated. For the OUD positive/NOWS positive group, adjusted HR was 1.54 (95% CI 1.07-2.21); for the OUD positive/NOWS negative group, adjusted HR was 1.62 (95% CI 1.21-2.17); and for OUD negative/NOWS positive, adjusted HR was 1.64 (95% CI 1.02-2.65).

"Prior studies show that rates of OUD among new mothers and NOWS have increased in recent years," Adgent noted.

"Rates of OUD and NOWS in Tennessee are among the highest in the country," she told MedPage Today in an email. "We conducted this study because we were interested in understanding the serious, long-term risks to infants associated with these conditions so that future efforts can provide the right kind of support for these infants and their parents, both before and after birth."

"Infants born to individuals with an OUD diagnosis, with or without a diagnosis of NOWS, were at increased risk of postneonatal mortality," Adgent observed. "Additionally, infants with NOWS for whom maternal OUD was not documented in our data also had an increased risk. It is notable that mortality risks were comparable across all of these scenarios. NOWS is a temporary and treatable condition and did not increase the risk of postneonatal mortality above what was observed in the other OUD-exposed pregnancies."

The study included infants born in Tennessee hospitals from 2017 through 2018 to individuals ages 15 to 44 years with continuous TennCare enrollment from 183 days prior to birth through 28 days post-birth.

Among dyads with any OUD/NOWS, the study team identified 4,922 (1.3%) as OUD positive/NOWS positive, 7,196 (1.8%) as OUD positive/NOWS negative, and 2,239 (0.6%) as OUD negative/NOWS positive.

Most deaths were due to ill-defined or unknown causes (43.1%), followed by external causes (27.6%), and congenital malformations/chromosomal abnormalities (13.8%).

Relative to deaths in OUD negative/NOWS negative infants, deaths with any OUD/NOWS had a higher proportion attributed to ill-defined causes (46.6% vs 42.8%) and external causes (33.6% vs 27.0%), including accidental suffocation or strangulation in bed. Deaths with any OUD/NOWS were less likely to have deaths attributed to congenital malformations or other causes combined (19.8% vs 30.2%).

Limitations of the study included some potential for misclassification, including the possibility that some infants classified as NOWS positive may have been exposed to nonopioid medications, Adgent and colleagues acknowledged. Some maintenance medications, such as buprenorphine or naltrexone, could have been used for pain management or alcohol addiction in addition to opioid drug use, they noted.

Certain covariates included in the research team's fully adjusted model could have a mediating role if prenatal OUD alone was considered as the primary exposure, they added.

Other reports have indicated that, across the country, pregnant and postpartum women with addiction face barriers to treatment.

"Our study focused on postneonatal mortality, or infant deaths occurring after 28 days of age, a time when most infants have been discharged from the hospital and are at home with their families," Adgent said.

"These are rare but tragic events," she continued. "Our findings suggest that comprehensive support for mothers with OUD and their babies should extend beyond pregnancy and delivery, into long-term pediatric care that offers a wide range of support services."

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