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

Infant Mortality Associated With Prenatal Opioid Exposure

JoAnna K Leyenaar  1   2 , Andrew P Schaefer  2 , Jared R Wasserman  2 , Erika L Moen  2   3 , A James O'Malley  2   3 , David C Goodman  1   2
Affiliations

Infant Mortality Associated With Prenatal Opioid Exposure

JoAnna K Leyenaar et al. JAMA Pediatr. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Leyenaar reported receiving a grant from Dartmouth-Hitchcock Medical Center Hearst Foundation endowment award in Maternal and Child Health during the conduct of the study. Dr O'Malley reported receiving grants from the National Institutes of Health outside the submitted work. Dr Goodman reported receiving grants from the Texas Health and Human Services Commission during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Factors Examined in Regression Models Given Hypothesized Associations With Infant Mortality
Figure 2.
Figure 2.. Probability of Survival During Infancy
Probability of survival beginning at birth (A) and beginning at age 5 days (B) in opioid-exposed infants with and without a history of neonatal opioid withdrawal syndrome (NOWS) diagnosis and in the reference population. Log-rank P < .001 for both analyses. Because the availability of mortality data from vital records did not depend on Medicaid enrollment, there was no observable censoring of infants at risk. Mortality among infants who moved out of the state may not be identified, but this variable was not available in the data set.
See this image and copyright information in PMC

References

    1. Substance Abuse and Mental Health Services Administration . Key substance use and mental health National Survey on Drug Use and Health (HHS publication No. PEP20-07-01-001, NSDUH series H-55). Published 2020. Accessed February 4, 2021. https://www.samhsa.gov/data/
    1. Reddy UM, Davis JM, Ren Z, Greene MF; Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes Workshop invited speakers . Opioid use in pregnancy, neonatal abstinence syndrome, and childhood outcomes: executive summary of a joint workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, American College of Obstetricians and Gynecologists, American Academy of Pediatrics, Society for Maternal-Fetal Medicine, Centers for Disease Control and Prevention, and the March of Dimes Foundation. Obstet Gynecol. 2017;130(1):10-28. doi: 10.1097/AOG.0000000000002054 - DOI - PMC - PubMed
    1. Jansson LM, Patrick SW. Neonatal abstinence syndrome. Pediatr Clin North Am. 2019;66(2):353-367. doi: 10.1016/j.pcl.2018.12.006 - DOI - PMC - PubMed
    1. Opioid use and opioid use disorder in pregnancy: Committee Opinion No. 711. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2017;130(2):e81-e94. doi: 10.1097/AOG.0000000000002235 - DOI - PubMed
    1. Winkelman TNA, Villapiano N, Kozhimannil KB, Davis MM, Patrick SW. Incidence and costs of neonatal abstinence syndrome among infants with Medicaid: 2004-2014. Pediatrics. 2018;141(4):e20173520. doi: 10.1542/peds.2017-3520 - DOI - PMC - PubMed

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