Prenatal Opioid Exposure Linked to Increased Mortality Risk


Opioid-exposed infants diagnosed with neonatal opioid withdrawal syndrome present with various comorbidities but a prolonged survival rate.


JoAnna Leyenaar, MD, PhD, MPH

A new study reports that opioid-exposed infants may be at a significantly increased risk for mortality.

However, infants with neonatal opioid withdrawal syndrome (NOWS) have a lower risk for mortality compared with exposed infants without NOWS.

The population-based, retrospective cohort study was led by JoAnna Leyenaar, MD, PhD, MPH, Department of Pediatrics, Children's Hospital at Dartmouth-Hitchcock Medical Center. The team used data from the Texas Neonatal Intensive Care Project to determine outcomes related to prenatal opioid exposure.

“Infant mortality is a widely accepted indicator of population health but has been the focus of very few studies in opioid-exposed infants,” the investigators wrote.

The Population

Leyenaar and colleagues linked Medicaid claims to vital records for births from January 1, 2010-December 31, 2014. Their analysis included follow-up of infants through 1 year of age.

Mother-child dyads were included for analysis if the infant was born in Texas at 22 – 43 weeks’ gestational age, and if the mother was 15 – 44 years of age.

The investigators used Kaplan-Meier and log-rank tests to assess risk of infant mortality, defined as death occurring at <365 days.

“A series of logistic regression models was estimated to determine associations between prenatal opioid exposure and mortality, adjusting for maternal and neonatal characteristics and clustering infants at the maternal level to account for statistical dependence owing to multiple births during the study period,” they explained.

Overall, the analysis included a total of 1,129,032 maternal-infant dyads, of which 7207 were considered prenatally exposed to opioids. Of those exposed, 4238 were diagnosed with NOWS.

In terms of demographics, 62.0% of the maternal cohort was Hispanic, 21.0% was non-Hispanic White, and 14.1% was non-Hispanic Black. The mean age of the mothers was 25.4.

The investigators noted that opioid exposure was observed most frequently in women who were non-Hispanic White (42.5%), unmarried (74.7%), and had smoked during pregnancy (34.0%).

Additionally, women with prenatal opioid exposure were significantly more likely to have a mental illness (81.2%) and suffer from substance use disorders (77.9%), compared with the reference group.

Infants diagnosed with NOWS had higher rates of preterm delivery, small for gestational age, and congenital abnormalities—compared with exposed infants without NOWS.

Infant Mortality

Leyenaar and team reported that infant mortality occurred in 20 per 1000 live births for opioid-exposed infants not diagnosed with NOWS, 11 per 1000 live births for infants with NOWS, and 6 per 1000 live births in non-exposed infants (P < .001).

“After adjusting for maternal and neonatal characteristics, mortality in infants with a NOWS diagnosis was not significantly different from the reference population (odds ratio [OR], 0.82; 95% CI, 0.58-1.14),” the investigators wrote. “In contrast, the odds of mortality in opioid-exposed infants not diagnosed with NOWS was 72% greater than the reference population (odds ratio, 1.72; 95% CI, 1.25-2.37)”

The investigators particularly highlighted these increased odds in exposed infants without NOWS despite having lower risk for premature birth and abnormalities compared to the NOWS population.

Therefore, they hypothesized that enhanced health and social services for NOWS inftants may in fact play a role in improving survival rate for that population.

“Clinical interventions, public health programs, and health policy to support women with opioid use disorder and their infants appear to be warranted, regardless of the perceived severity of neonatal opioid withdrawal,” the investigators concluded.

The study, “Infant Mortality Associated With Prenatal Opioid Exposure,” was published online in JAMA Pediatrics.

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