Infant Mortality Associated With Prenatal Opioid Exposure

JAMA Pediatr. 2021 Jul 1;175(7):706-714. doi: 10.1001/jamapediatrics.2020.6364.


Importance: Knowledge of health outcomes among opioid-exposed infants is limited, particularly for those not diagnosed with neonatal opioid withdrawal syndrome (NOWS).

Objectives: To describe infant mortality among opioid-exposed infants and identify how mortality risk differs in opioid-exposed infants with and without a diagnosis of NOWS compared with infants without opioid exposure.

Design, setting, and participants: A retrospective cohort study of maternal-infant dyads was conducted, linking health care claims with vital records for births from January 1, 2010, to December 31, 2014, with follow-up of infants until age 1 year (through 2015). Maternal-infant dyads were included if the infant was born in Texas at 22 to 43 weeks' gestational age to a woman aged 15 to 44 years insured by Texas Medicaid. Data analysis was performed from May 2019 to October 2020.

Exposure: The primary exposure was prenatal opioid exposure, with infants stratified by the presence or absence of a diagnosis of NOWS during the birth hospitalization.

Main outcomes and measures: Risk of infant mortality (death at age <365 days) was examined using Kaplan-Meier and log-rank tests. 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.

Results: Among 1 129 032 maternal-infant dyads, 7207 had prenatal opioid exposure, including 4238 diagnosed with NOWS (mean [SD] birth weight, 2851 [624] g) and 2969 not diagnosed with NOWS (mean [SD] birth weight, 2971 [639] g). Infant mortality was 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 the reference group (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, 0.82; 95% CI, 0.58-1.14). 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).

Conclusions and relevance: In this study, opioid-exposed infants appeared to be at increased risk of mortality, and the treatments and supports provided to those diagnosed with NOWS may be protective. Interventions to support opioid-exposed maternal-infant dyads are warranted, regardless of the perceived severity of neonatal opioid withdrawal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Humans
  • Infant
  • Infant Mortality*
  • Infant, Newborn
  • Male
  • Neonatal Abstinence Syndrome / mortality*
  • Opioid-Related Disorders / mortality*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / mortality*
  • Retrospective Studies
  • Texas / epidemiology