Abstract
Background
Methamphetamine (MA) use during pregnancy is a significant public health concern in the United States and affects long-term brain and behavioral development in children. We hypothesized that prenatal MA exposure would be related to greater DNA methylation of HSD11B2 and postnatal environmental stress.
Methods
The Infant Development, Environment, and Lifestyle Study (IDEAL), a longitudinal study of prenatal MA exposure enrolled mother−infant dyads in California, Hawaii, Iowa, and Oklahoma. Prenatal exposure was defined by maternal self-report and/or meconium toxicology screening. At ages 10–11 years, 100 children were assessed for drug exposure and DNA methylation of HSD11B2. Hierarchical linear models were used to determine the association between prenatal MA exposure and methylation of HSD11B2 at four CpG sites.
Results
Prenatal MA exposure (1.4% vs 0.31%, P < 0.01) and early childhood adversity (3.0 vs 2.0, P < 0.01) were associated with greater DNA methylation of HSD11B2 at the CpG2 site. The statistically significant effects of early childhood adversity (B = 0.11, P < 0.01) and prenatal MA exposure (B = 0.32, P = 0.03) on DNA methylation remained after adjusting for covariates.
Conclusions
Prenatal MA exposure is related to postnatal childhood adversity and epigenetic alterations in HSD11B2, an important gene along the stress response pathway suggesting prenatal and postnatal programming effects.
Impact
-
Prenatal methamphetamine exposure has been associated with developmental issues in newborns, yet little is known about the stress pathophysiology of methamphetamine on neurobehavior.
-
This is the first evidence that prenatal methamphetamine exposure acts as a stressor, confirming the third pathophysiology of methamphetamine exposure.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Hedegaard, H., Warner, M. & Minino, A. M. Drug Overdose Deaths in the United States, 1999−2015 (National Center for Health Statistics, Hyattsville, MD, 2017).
World Drug Report 2018 (United Nations Office on Drugs and Crime, Vienna, 2018).
Center for Behavioral Health Statistics and Quality. 2014 National Survey on Drug Use and Health: Detailed Tables (Substance Abuse and Mental Health Services Administration, Rockville, MD, 2015).
Center for Behavioral Health Statistics and Quality. 2015 National Survey on Drug Use and Health: Detailed Tables (Substance Abuse and Mental Health Services Administration, Rockville, MD, 2016).
Shonkoff, J. P., Boyce, T. & McEwen, B. S. Neuroscience, molecular biology, and the childhood roots of health disparities: building a new framework for health promotion and disease prevention. JAMA 301, 2252–2259 (2009).
Lester, B. M. & Padbury, J. Third pathophysiology of prenatal cocaine exposure. Dev. Neurosci. 31, 23–35 (2009).
Seckl, J. R. & Walker, B. R. Minireview: 11beta-hydroxysteroid dehydrogenase type 1—a tissue-specific amplifier of glucocorticoid action. Endocrinology 142, 1371–1376 (2001).
Appleton, A. A., Lester, B. M., Armstrong, D. A., Lesseur, C. & Marsit, C. J. Examining the joint contribution of placental NR3C1 and HSD11B2 methylation for infant neurobehavior. Psychoneuroendocrinology 52, 32–42 (2015).
Smith, L. M. et al. Developmental and behavioral consequences of prenatal methamphetamine exposure: a review of the Infant Development, Environment, and Lifestyle (IDEAL) study. Neurotoxicol Teratol. 51, 35–44 (2015).
Marsit, C. J., Maccani, M. A., Padbury, J. F. & Lester, B. M. Placental 11-beta hydroxysteroid dehydrogenase methylation is associated with newborn growth and a measure of neurobehavioral outcome. PLoS ONE 7, e33794 (2012).
Abar, B. et al. Examining the relationships between prenatal methamphetamine exposure, early adversity, and child neurobehavioral disinhibition. Psychol. Addict. Behav. 27, 662–673 (2013).
Fisher, P. A. et al. The combined effects of prenatal drug exposure and early adversity on neurobehavioral disinhibition in childhood and adolescence. Dev. Psychopathol. 23, 777–788 (2011).
Himes, S. K. et al. Risk of neurobehavioral disinhibition in prenatal methamphetamine-exposed young children with positive hair toxicology results. Ther. Drug Monit. 36, 535–543 (2014).
Raul, J. S., Cirimele, V., Ludes, B. & Kintz, P. Detection of physiological concentrations of cortisol and cortisone in human hair. Clin. Biochem. 37, 1105–1111 (2004).
Jensen Peña, C., Monk, C. & Champagne, F. A. Epigenetic effects of prenatal stress on 11beta-hydroxysteroid dehydrogenase-2 in the placenta and fetal brain. PLoS ONE 7, e39791 (2012).
Shonkoff, J. P., Garner, A. S. & Committee on Psychosocial Aspects of Child and Family Health. The lifelong effects of early childhood adversity and toxic stress. Pediatrics 129, e232–e246 (2012).
Felitti, V. J. et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am. J. Prev. Med 14, 245–258 (1998).
Appleton, A. A., et al. Patterning in placental 11-B hydroxysteroid dehydrogenase methylation according to prenatal socioeconomic adversity. PLoS ONE 8, e74691 (2013).
Marsit, C. J., Maccini, M. A., Padbury, J. F., & Lester, B. M. Placental 11-B hydroxysteroid dehydrogenase methylation is associated with newborn growth and a measure of neurobehavioral outcome. PLoS ONE 7, e33794 (2012).
Breton, C. V. et al. Small-magnitude effect sizes in epigenetic end points are important in children’s environmental health studies: the Children’s Environmental Health and Disease Prevention Research Center’s Epigenetics Working Group. Environ. Health Perspect. 125, 526 (2017).
Tiganescu, A., Walker, E. A., Hardy, R. S., Mayes, A. E. & Stewart, P. M. Localization, age- and site dependent expression, and regulation of 11beta-hydroxysteroid dehydrogenase type 1 in skin. J. Invest. Dermatol. 131, 30–36 (2011).
Maurer, N. et al. Salivary and hair glucocorticoids and sleep in very preterm children during school age. Psychoneuroendocrinology 72, 166–174 (2016).
Kirlic, N. et al. Cortisol reactivity in two-year-old children prenatally exposed to methamphetamine. J. Stud. Alcohol Drugs 74, 447–451 (2013).
Lester, B. et al. Prenatal cocaine exposure alters cortisol stress reactivity in 11 year old children. J. Pediatr. 157, 288–295 (2010).
Berko, E. R. et al. Mosaic epigenetic dysregulation of ectodermal cells in autism spectrum disorder. PLoS Genet. 10, e1004402 (2014).
Lowe, R. et al. Buccals are likely to be a more informative surrogate tissue than blood for epigenome-wide association studies. Epigenetics 8, 445–454 (2013).
Everson, T. M. et al. Epigenome-wide analysis identifies genes and pathways linked to neurobehavioral variation in preterm infants. Sci. Rep. 9, 6322 (2019).
Derogatis, L. R. Brief Symptom Inventory (BSI): Administration, Scoring and Procedures Manual, 3rd edn (National Computer Systems, Inc., Minneapolis, MN, 1993).
Beck, A. T., Steer, R. A. & Brown, G. K. The Beck Depression Inventory Manual, 2nd edn (Psychological Corporation, San Antonio, 1996).
Caldwell, B. M. & Bradley, R. H. HOME Inventory Administration Manual (Standard Edition) (University of Arkansas, Little Rock, AK, 2003).
Hollingshead, A. Four Factor Index of Social Status (Yale University, Department of Sociology, New Haven, CT, 1975) p. 247.
LaGasse, L. L., et al. The Maternal Lifestyle Study (MLS): the caretaking environment of infants exposed to cocaine/opiates. Pediatr. Res. 45, 247 (1999).
Acknowledgements
This work is supported by the National Institute on Drug Abuse (NIDA) Grant 1RO1DA014948 and in part by the National Center on Research Resources Grant 1UL1-TR000124 and 5P20 RR11091.
Author information
Authors and Affiliations
Contributions
O.O.O. designed the study, analyzed and interpreted data, drafted the article and revised critically for important intellectual content, and approved the final version as submitted. L.M.D. analyzed and interpreted data and reviewed and revised critically for important intellectual content and approved the final version as submitted. C.J.M. performed the laboratory studies, reviewed and revised critically for important intellectual content, and approved the final version as submitted. L.M.S. reviewed and revised critically for important intellectual content and approved the final version as submitted. C.R.N. reviewed and revised critically for important intellectual content and approved the final version as submitted. S.A.D.G. reviewed and revised critically for important intellectual content and approved the final version as submitted. J.F.P. reviewed and revised critically for important intellectual content, and approved the final version as submitted. B.M.L. conceptualized and designed the study, interpreted data, drafted the article and revised critically for important intellectual content, and approved the final version as submitted.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Statement of consent
The study was approved by the Western Institutional Review Board, Puyallup, WA (HI) and the John F. Wolf Human Subjects Committee, Los Angeles, CA. All child participants in this study provided written informed assent in addition to the parental consent.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Oni-Orisan, O.O., Dansereau, L.M., Marsit, C.J. et al. DNA methylation in children with prenatal methamphetamine exposure and environmental adversity. Pediatr Res 89, 1152–1156 (2021). https://doi.org/10.1038/s41390-020-1058-4
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41390-020-1058-4
This article is cited by
-
Low reliability of DNA methylation across Illumina Infinium platforms in cord blood: implications for replication studies and meta-analyses of prenatal exposures
Clinical Epigenetics (2022)
-
Epigenetics as a Biomarker for Early-Life Environmental Exposure
Current Environmental Health Reports (2022)
