The Influence of Mediators on the Relationship Between Antenatal Opioid Agonist Exposure and the Severity of Neonatal Opioid Withdrawal Syndrome

Authors

Lori A Devlin, Department of Pediatrics, University of Louisville School of Medicine, 571 South Floyd Street Suite 342, Louisville, KY, 40202, USA
Zhuopei Hu, Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Songthip Ounpraseuth, Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Alan E. Simon, Environmental Influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health, Rockville, MD, USA
Robert D. Annett, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA; University of New Mexico Health Sciences Center, Albuquerque, NM, USA
Abhik Das, Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, NC, USA
Janell F. Fuller, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
Rosemary D. Higgins, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA; Florida Gulf Coast University, Fort Meyers, FL, USA
Stephanie L. Merhar, Division of Neonatology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA
P Brian Smith, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
Margaret M. Crawford, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
Lesley E. Cottrell, Department of Pediatrics, West Virginia University Medical Center, Morgantown, WV, USA
Adam J. Czynski, Department of Pediatrics, Connecticut Children's Medical Center, Hartford, CT, USA
Sarah Newman, Nebraska Medical Center, Omaha, NE, USA
David A. Paul, Department of Pediatrics, ChristianaCare Health Systems, Newark, DE, USA
Pablo J. Sánchez, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA
Erin O. Semmens, School of Public and Community Health Sciences, University of Montana, Missoula, MT, USA
M Cody Smith, Department of Pediatrics, West Virginia University Medical Center, Morgantown, WV, USA
Bonny L. Whalen, Department of Pediatrics, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
Jessica N. Snowden, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Leslie W. Young, Department of Pediatrics, University of Vermont Larner College of Medicine, Burlington, VT, USA
Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and the NIH Environmental influences on Child Health Outcomes (ECHO) Program Institutional Development Awards States Pediatric Clinical Trials Network

Document Type

Article

Publication Date

3-11-2023

Abstract

OBJECTIVES: (1) To evaluate the direct (un-mediated) and indirect (mediated) relationship between antenatal exposure to opioid agonist medication as treatment for opioid use disorder (MOUD) and the severity of neonatal opioid withdrawal syndrome (NOWS), and (2) to understand the degree to which mediating factors influence the direct relationship between MOUD exposure and NOWS severity.

METHODS: This cross-sectional study includes data abstracted from the medical records of 1294 opioid-exposed infants (859 MOUD exposed and 435 non-MOUD exposed) born at or admitted to one of 30 US hospitals from July 1, 2016, to June 30, 2017. Regression models and mediation analyses were used to evaluate the relationship between MOUD exposure and NOWS severity (i.e., infant pharmacologic treatment and length of newborn hospital stay (LOS)) to identify potential mediators of this relationship in analyses adjusted for confounding factors.

RESULTS: A direct (un-mediated) association was found between antenatal exposure to MOUD and both pharmacologic treatment for NOWS (aOR 2.34; 95%CI 1.74, 3.14) and an increase in LOS (1.73 days; 95%CI 0.49, 2.98). Delivery of adequate prenatal care and a reduction in polysubstance exposure were mediators of the relationship between MOUD and NOWS severity and as thus, were indirectly associated with a decrease in both pharmacologic treatment for NOWS and LOS.

CONCLUSIONS FOR PRACTICE: MOUD exposure is directly associated with NOWS severity. Prenatal care and polysubstance exposure are potential mediators in this relationship. These mediating factors may be targeted to reduce the severity of NOWS while maintaining the important benefits of MOUD during pregnancy.

Publisher

Kluwer Academic/Plenum Publishers

Publication Title

Maternal and child health journal

ISSN

1573-6628

DOI

10.1007/s10995-022-03521-3

Language (ISO)

English

Recommended Citation

Devlin LA, Hu Z, Ounpraseuth S, Simon AE, Annett RD, Das A, Fuller JF, Higgins RD, Merhar SL, Smith PB, Crawford MM, Cottrell LE, Czynski AJ, Newman S, Paul DA, Sánchez PJ, Semmens EO, Smith MC, Whalen BL, Snowden JN, Young LW; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and the NIH Environmental influences on Child Health Outcomes (ECHO) Program Institutional Development Awards States Pediatric Clinical Trials Network. The Influence of Mediators on the Relationship Between Antenatal Opioid Agonist Exposure and the Severity of Neonatal Opioid Withdrawal Syndrome. Matern Child Health J. 2023 Mar 11. doi: 10.1007/s10995-022-03521-3. Epub ahead of print. PMID: 36905529.