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Association Between Prenatal Opioid Exposure and Neurodevelopmental Outcomes in Early Childhood: A Retrospective Cohort Study

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Abstract

Introduction

Several studies have reported increasing prevalence of prescription opioid use among pregnant women. However, little is known regarding the effects of maternal opioid use on neurodevelopmental disorders in early childhood in pregnant women with no evidence of opioid use disorders or drug dependence.

Objective

The aim of this study was to quantify the association between prenatal opioid exposure from maternal prescription use and neurodevelopmental outcomes in early childhood.

Methods

This retrospective study included pregnant women aged 12–55 years and their live-birth infants born from 2010 to 2012 present in Optum’s deidentified Clinformatics® Data Mart database. Eligible infants born to mothers without opioid use disorders or drug dependence were followed till occurrence of neurodevelopmental disorders, loss to follow-up, or study end (December 31, 2017), whichever came first. Propensity score by fine stratification was applied to adjust for confounding by demographic characteristics, obstetric characteristics, maternal comorbid mental and pain conditions, and measures of burden of illnesses and to obtain adjusted hazard ratios (HR) and 95% confidence intervals (CI). Exposed and unexposed infants were compared on the incidence of neurodevelopmental disorders.

Results

Of 24,910 newborns, 7.6% (1899) were prenatally exposed to prescription opioids. Overall, 1562 children were diagnosed with neurodevelopmental disorders, with crude incidence rates of 2.9 per 100 person-years in exposed children versus 2.5 per 100 person-years in unexposed children. After adjustment, we observed no association between fetal opioid exposure and the risk of neurodevelopmental disorders (HR 1.10; 95% CI 0.92–1.32). However, increased risk of neurodevelopmental disorders were observed in children with longer cumulative exposure duration (HR 1.70; 95% CI 1.05–2.96) or high cumulative opioid doses (HR 1.22; 95% CI 1.01–1.54).

Conclusion and Relevance

In pregnant women without opioid use disorders or drug dependence, maternal opioid use was not associated with increased risk of neurodevelopmental disorders in early childhood. However, increased risks of early neurodevelopmental disorders were observed in children born to women receiving prescription opioids for longer duration and at higher doses during pregnancy.

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Authors and Affiliations

  1. Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Suite 265F, Kingston, RI, 02881, USA

    Xuerong Wen, Oluwadolapo D. Lawal, Nicholas Belviso, Kelly L. Matson & Shuang Wang

  2. College of Health Sciences, University of Rhode Island, Kingston, RI, USA

    Brian J. Quilliam

  3. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, California, CA, USA

    Kimford J. Meador

Authors
  1. Xuerong Wen
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  2. Oluwadolapo D. Lawal
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  3. Nicholas Belviso
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  4. Kelly L. Matson
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  5. Shuang Wang
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  6. Brian J. Quilliam
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Correspondence to Xuerong Wen.

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Author contributions

All authors were responsible for critical revision of the manuscript for intellectual content. All authors read and approved the final version. Wen, Lawal and Meador conceptualized and designed this study, and drafted the initial version of the manuscript. Wen, Meador, Lawal and Belviso contributed to data preparation, statistical analyses, and interpretation. Wang contributed to statistical analyses and interpretation. Matson and Quilliam provided clinical and technical support, and contribution to interpretation of study findings.

Funding/support

Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number R15HD097588. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Principal Investigator: Wen X. The funding source had no role in the design or conduct of the study; collection, management, analysis, or the interpretation of the data preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Conflicts of interest and financial disclosures

Dr Meador has received research support from the National Institutes of Health and Sunovion Pharmaceuticals, and travel support from Eisai. The Epilepsy Study Consortium pays Dr Meador’s university for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, and UCB Pharma. The other authors have no conflicts of interests to declare.

Ethics approval

This study uses deidentified data, hence was considered exempt by the University of Rhode Island Institutional Review Board.

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Availability of data and material

A data use agreement exists between The University of Rhode Island College of Pharmacy and Optum. The Optum Clinformatics Data Mart database cannot be shared by authors with parties external to this agreement.

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Wen, X., Lawal, O.D., Belviso, N. et al. Association Between Prenatal Opioid Exposure and Neurodevelopmental Outcomes in Early Childhood: A Retrospective Cohort Study. Drug Saf 44, 863–875 (2021). https://doi.org/10.1007/s40264-021-01080-0

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