PediatricsORIGINAL ARTICLE

Association of prenatal substance exposure and the development of the amygdala, hippocampus, and parahippocampus

Micah Hartwell, PhD; Molly Bloom, BS; Covenant Elenwo, MPH; Trey Gooch, BS; Kelly Dunn, MD; Florence Breslin, MS; and Julie M. Croff, PhD
Notes and Affiliations
Notes and Affiliations

Received: December 17, 2023

Accepted: April 22, 2024

Published: June 26, 2024

  • Micah Hartwell, PhD, 

    Director of Office of Medical Student Research, Office of Medical Student Research,
    12373
    Oklahoma State University College of Osteopathic Medicine at Cherokee Nation
    , Tahlequah, OK, USA

  • Molly Bloom, BS, 

    Oklahoma State University Center for Health Sciences, Tulsa, OK, USA

  • Covenant Elenwo, MPH, 

    Office of Medical Student Research,
    12373
    Oklahoma State University College of Osteopathic Medicine at Cherokee Nation
    , Tahlequah, OK, USA

  • Trey Gooch, BS, 

    Office of Medical Student Research,
    12373
    Oklahoma State University College of Osteopathic Medicine at Cherokee Nation
    , Tahlequah, OK, USA

  • Kelly Dunn, MD, 

    Clinical Assistant Professor of Psychiatry and Behavioral Science, Department of Psychiatry and Behavioral Sciences, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA

  • Florence Breslin, MS, 

    Program Director of Clinical Registry Systems, Department of Rural Health, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA

  • Julie M. Croff, PhD, 

    Professor, Department of Rural Health, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA

Abstract

Context: Prenatal substance exposure (PSE) can lead to various harmful outcomes for the developing fetus and is linked to many emotional, behavioral, and cognitive difficulties later in life. Therefore, examination of the relationship between the development of associated brain structures and PSE is important for the development of more specific or new preventative methods.

Objectives: Our study’s primary objective was to examine the relationship between the physical development of the amygdala, hippocampus, and parahippocampus following prenatal alcohol, tobacco, and prescription opioid exposure.

Methods: We conducted a cross-sectional analysis of the Adolescent Brain and Cognitive Development (ABCD) Study, a longitudinal neuroimaging study that measures brain morphometry from childhood throughout adolescence. Data were collected from approximately 12,000 children (ages 9 and 10) and parents across 22 sites within the United States. Prenatal opioid, tobacco, and alcohol use was determined through parent self-report of use during pregnancy. We extracted variables assessing the volumetric size (mm3) of the amygdala, hippocampus, and parahippocampal gyrus as well as brain volume, poverty level, age, sex, and race/ethnicity for controls within our adjusted models. We reported sociodemographic characteristics of the sample overall and by children who had PSE. We calculated and reported the means of each of the specific brain regions by substance exposure. Finally, we constructed multivariable regression models to measure the associations between different PSE and the demographic characteristics, total brain volume, and volume of each brain structure.

Results: Among the total sample, 24.6% had prenatal alcohol exposure, 13.6% had prenatal tobacco exposure, and 1.2% had prenatal opioid exposure. On average, those with prenatal tobacco exposure were found to have a statistically significant smaller parahippocampus.

Conclusions: We found a significant association between prenatal tobacco exposure and smaller parahippocampal volume, which may have profound impacts on the livelihood of individuals including motor delays, poor cognitive and behavioral outcomes, and long-term health consequences. Given the cumulative neurodevelopmental effects associated with PSE, we recommend that healthcare providers increase screening rates, detection, and referrals for cessation. Additionally, we recommend that medical associations lobby policymakers to address upstream barriers to the effective identification of at-risk pregnant individuals, specifically, eliminating or significantly reducing punitive legal consequences stemming from state laws concerning prenatal substance use.

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