title: Lower glial metabolite levels in brains of young children with prenatal nicotine exposure.
abstract: Many pregnant women smoke cigarettes during pregnancy, but the effect of nicotine on the developing human brain is not well understood, especially in young children. This study aims to determine the effects of prenatal nicotine exposure (PNE) on brain metabolite levels in young (3-4 years old) children, using proton magnetic resonance spectroscopy ((1)H MRS). Twenty-six children with PNE and 24 nicotine-unexposed children (controls) were evaluated with a structured examination, a battery of neuropsychological tests, and MRI/(1)H MRS (without sedation). Concentrations of N-acetyl compounds (NA), total creatine (tCR), choline-containing compounds (CHO), myo-inositol (MI), and glutamate+glutamine (GLX) were measured in four brain regions. Children with PNE had similar performance to controls on neuropsychological testing. However, compared to controls, the PNE group had lower MI (repeated measures ANOVA-p = 0.03) and tCr levels (repeated measures ANOVA-p = 0.003), especially in the basal ganglia of the girls (-19.3%, p = 0.01). In contrast, GLX was elevated in the anterior cingulate cortex of the PNE children (+9.4%, p = 0.03), and those with the highest GLX levels had the poorest performance on vocabulary (r = -0.67; p < 0.001) and visual motor integration (r = -0.53; p = 0.01). The amount of prenatal nicotine exposure did not correlate with metabolite concentrations. These findings suggest that PNE may lead to subclinical abnormalities in glial development, especially in the basal ganglia, and regionally specific changes in other neurometabolites. These alterations were not influenced by the amount of nicotine exposure prenatally. However, the effects of PNE on energy metabolism may be sex specific, with greater alterations in girls.
authors.affiliation: Division of Neurology, Department of Medicine, John A. Burns School of Medicine, University of Hawai'i at Manoa, 7th floor University Tower, Honolulu, HI 96813, USA. lchang@hawaii.edu
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.forename: Christine C
authors.initials: CC
authors.lastname: Cloak
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Jiang
authors.forename: Aaron
authors.initials: A
authors.lastname: Hoo
authors.forename: Antonette B
authors.initials: AB
authors.lastname: Hernandez
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Ernst
mesh_terms: D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009457:Neuroglia / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000009:adverse effects*; D018722:Nicotinic Agonists / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine