Abstract
In utero exposure to alcohol leads to a spectrum of fetal alcohol related disorders (FASD). However, few studies used have used proton magnetic resonance spectroscopy (1H-MRS) to understand how neurochemical disturbances relate to the pathophysiology of FASD. Further, no studies to date have assessed brain metabolites in infants exposed to alcohol in utero. We hypothesize that neonates exposed to alcohol in utero will show decreased glutamatergic activity, pre-emptive of their clinical diagnosis or behavioural phenotype. Single voxel 1H-MRS data, sampled in parietal white and gray matter, were acquired from 36 neonates exposed to alcohol in utero, and 31 control unexposed healthy neonates, in their 2nd-4th week of life. Metabolites relative to creatine with phosophocreatine and metabolites absolute concentrations using a water reference are reported. Male infants exposed to alcohol in utero were found to have reduced concentration of glutamate with glutamine (Glx) in their parietal white matter (PWM), compared to healthy male infants (p = 0.02). Further, male infants exposed to alcohol in utero had reduced concentration and ratio for glutamate (Glu) in their PWM (p = 0.02), compared to healthy male infants and female infants exposed to alcohol in utero. Female infants showed higher relative Glx and Glu ratios for parietal gray matter (PGM, p < 0.01), compared to male infants. We speculate that the decreased Glx and Glu concentrations in PWM are a result of delayed oligodendrocyte maturation, which may be a result of dysfunctional thyroid hormone activity in males exposed to alcohol in utero. Further study is required to elucidate the relationship between Glx and Glu, thyroid hormone activity, and oligodendrocyte maturation in infants exposure to alcohol in utero.
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Abbreviations
- 1H-MRS:
-
Proton magnetic resonance spectroscopy
- FASD:
-
fetal alcohol spectrum disorders
- Glx:
-
glutamate with glutamine concentration
- Glu:
-
glutamate concentration
- PWM:
-
parietal white matter
- PGM:
-
parietal gray matter
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Acknowledgments
We thank two MRI experts who assisted during the development of the MRI protocol – Dr André van der Kouwe, MGH Harvard University, USA, and Dr Stefan Blüml, University of Southern California, USA. Mrs Robyn Kalan, our study’s neonatal nurse, who cared for the infants during scan preparation and during the MRI scan. We thank the study staff and the staff at Paarl Hospital, Mbekweni and TC Newman clinics for their support of the study. We also wish to thank the Drakenstein child lung and health research team and staff, led by PI Dr Heather Zar, who without, this study would not have been possible. Lastly, we thank the families and infants who participated in this study.
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The study was supported by a Foundation of Alcohol Research grant as well as the Bill and Melinda Gates Foundation [OPP 1017641]. FMH also acknowledges her funding source, administered by the Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, a Hasso Plattner mid-career development programme award.
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Howells, F.M., Donald, K.A., Roos, A. et al. Reduced glutamate in white matter of male neonates exposed to alcohol in utero: a 1H-magnetic resonance spectroscopy study. Metab Brain Dis 31, 1105–1112 (2016). https://doi.org/10.1007/s11011-016-9850-x
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DOI: https://doi.org/10.1007/s11011-016-9850-x