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Original Investigation
December 2016

Sex-Specific Alterations of White Matter Developmental Trajectories in Infants With Prenatal Exposure to Methamphetamine and Tobacco

Author Affiliations
  • 1Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu
  • 2Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 3Department of Pediatrics, Sørlandet Hospital, Arendal, Norway
  • 4Department of Laboratory Medicine, Children's and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway
  • 5Department of Psychiatry, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu
  • 6Department of Obstetrics, Gynecology and Women’s Health, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu
JAMA Psychiatry. 2016;73(12):1217-1227. doi:10.1001/jamapsychiatry.2016.2794
Key Points

Question  Do infants with prenatal methamphetamine and/or tobacco exposure show brain abnormalities?

Findings  In this case-control study of 139 neonates, methamphetamine- and tobacco-exposed infants showed delayed developmental trajectories on active muscle tone, and the exposed boys also had significantly delayed trajectories in superior and posterior corona radiatae that normalized by ages 3 to 4 months. However, persistently lower fractional anisotropy was found in anterior corona radiata of methamphetamine/tobacco- and tobacco-exposed girls as well as lower diffusion in the thalamus and internal capsule of all tobacco-exposed infants.

Meaning  Prenatal methamphetamine/tobacco or tobacco exposure may lead to delayed motor development and white matter maturation in sex- and regional-specific manners.

Abstract

Importance  Methamphetamine is a common illicit drug used worldwide. Methamphetamine and/or tobacco use by pregnant women remains prevalent. However, little is known about the effect of comorbid methamphetamine and tobacco use on human fetal brain development.

Objective  To investigate whether microstructural brain abnormalities reported in children with prenatal methamphetamine and/or tobacco exposure are present at birth before childhood environmental influences.

Design, Setting, and Participants  A prospective, longitudinal study was conducted between September 17, 2008, and February 28, 2015, at an ambulatory academic medical center. A total of 752 infant-mother dyads were screened and 139 of 195 qualified neonates were evaluated (36 methamphetamine/tobacco exposed, 32 tobacco exposed, and 71 unexposed controls). They were recruited consecutively from the community.

Exposures  Prenatal methamphetamine and/or tobacco exposure.

Main Outcomes and Measures  Quantitative neurologic examination and diffusion tensor imaging performed 1 to 3 times through age 4 months; diffusivities and fractional anisotropy (FA) assessed in 7 white matter tracts and 4 subcortical brain regions using an automated atlas-based method.

Results  Of the 139 infants evaluated, 72 were female (51.8%); the mean (SE) postmenstrual age at baseline was 41.5 (0.27) weeks. Methamphetamine/tobacco-exposed infants showed delayed developmental trajectories on active muscle tone (group × age, P < .001) and total neurologic scores (group × age, P = .01) that normalized by ages 3 to 4 months. Only methamphetamine/tobacco-exposed boys had lower FA (group × age, P = .02) and higher diffusivities in superior (SCR) and posterior corona radiatae (PCR) (group × age × sex, P = .002; group × age × sex, P = .01) at baseline that normalized by age 3 months. Only methamphetamine/tobacco- and tobacco-exposed girls showed persistently lower FA in anterior corona radiata (ACR) (group, P = .04; group × age × sex, P = .01). Tobacco-exposed infants showed persistently lower axial diffusion in the thalamus and internal capsule across groups (P = .02).

Conclusions and Relevance  Prenatal methamphetamine/tobacco exposure may lead to delays in motor development, with less coherent fibers and less myelination in SCR and PCR only in male infants, but these abnormalities may normalize by ages 3 to 4 months after cessation of stimulant exposure. In contrast, persistently less coherent ACR fibers were observed in methamphetamine/tobacco- and tobacco-exposed girls, possibly from increased dendritic branching or spine density due to epigenetic influences. Persistently lower diffusivity in the thalamus and internal capsule of all tobacco-exposed infants suggests aberrant axonal development. Collectively, prenatal methamphetamine and/or tobacco exposure may lead to delayed motor development and white matter maturation in sex- and regional-specific manners.

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