Skip to main content
×
Home

A study of the effects of prenatal alcohol exposure on white matter microstructural integrity at birth

  • Kirsten Ann Donald (a1), Annerine Roos (a2), Jean-Paul Fouche (a3) (a4), Nastassja Koen (a4), Fleur M. Howells (a4), Roger P. Woods (a5), Heather J. Zar (a6), Katherine L. Narr (a5) and Dan J. Stein (a2) (a4)...
Abstract
Background

Neuroimaging studies have indicated that prenatal alcohol exposure is associated with alterations in the structure of specific brain regions in children. However, the temporal and regional specificity of such changes and their behavioural consequences are less known. Here we explore the integrity of regional white matter microstructure in infants with in utero exposure to alcohol, shortly after birth.

Methods

Twenty-eight alcohol-exposed and 28 healthy unexposed infants were imaged using diffusion tensor imaging sequences to evaluate white matter integrity using validated tract-based spatial statistics analysis methods. Second, diffusion values were extracted for group comparisons by regions of interest. Differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity were compared between groups and associations with measures from the Dubowitz neonatal neurobehavioural assessment were examined.

Results

Lower AD values (p<0.05) were observed in alcohol-exposed infants in the right superior longitudinal fasciculus compared with non-exposed infants. Altered FA and MD values in alcohol-exposed neonates in the right inferior cerebellar were associated with abnormal neonatal neurobehaviour.

Conclusion

These exploratory data suggest that prenatal alcohol exposure is associated with reduced white matter microstructural integrity even early in the neonatal period. The association with clinical measures reinforces the likely clinical significance of this finding. The location of the findings is remarkably consistent with previously reported studies of white matter structural deficits in older children with a diagnosis of foetal alcohol spectrum disorders.

Copyright
Corresponding author
Kirsten Ann Donald, Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital and University of Cape Town, Cape Town, South Africa. Tel: +27216585322; Fax: +27216585530; E-mail: kirsty.donald@uct.ac.za
References
Hide All
1.Jones KL, Smith DW, Ulleland CN, Streissguth AP. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet 1973;1:12671271.
2.Jones KL, Smith DW, Hansen JW. The fetal alcohol syndrome: clinical delineation. Ann N Y Acad Sci 1976;273:130139.
3.Riley EP, Alejandra Infante M, Warren K. Fetal alcohol spectrum disorders: an overview. Neuropsychol Rev 2011;21:7380.
4.Rodier PM. Vulnerable periods and processes during central nervous system development. Environ Health Perspective 1994;102(Suppl. 2):121124.
5.Rodier PM. Environmental causes of central nervous system maldevelopment. Pediatrics 2004;113:10761083.
6.O’Leary-Moore S, Parnell S, Lipinski R. Magnetic resonance-based imaging in animal models of fetal alcohol spectrum disorder. Neuropsychol Rev 2011;21:167185.
7.Lebel C, Roussotte F, Sowell ER. Imaging the impact of prenatal alcohol exposure on the structure of the developing human brain. Neuropsychol Rev 2011;21:102118.
8.Pannek K, Guzzetta A, Colditz P, Rose S. Diffusion MRI of the neonate brain: acquisition, processing and analysis techniques. Pediatr Radiol 2012;42:11691182.
9.Beaulieu C. The basis of anisotropic water diffusion in the nervous system – a technical review. NMR Biomed 2002;15:435455.
10.Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics 2007;4:316329.
11.Assaf Y, Pasternak O. Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review. J Mol Neurosci 2008;34:5161.
12.Song SK, Sun SW, Ramsbottom MJ, Chang C, Russell J, Cross AH. Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 2002;17:14291436.
13.Kinoshita Y, Ohnishi A, Kohshi K, Yokota A. Apparent diffusion coefficient on rat brain and nerves intoxicated with methylmercury. Environ Res 1999;80:348354.
14.Harsan LA, Poulet P, Guignard Bet al. Brain dysmyelination and recovery assessment by noninvasive in vivo diffusion tensor magnetic resonance imaging. J Neurosci Res 2006;83:392402.
15.Paus T, Pesaresi M, French L. White matter as a transport system. Neuroscience 2014;276:117125.
16.Dubois J, Dehaene-Lambertz G, Kulikova S, Poupon C, Hüppi PS, Hertz-Pannier L. The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants. Neuroscience 2014;276:4871.
17.Wozniak JR, Muetzel RL. What does diffusion tensor imaging reveal about the brain and cognition in fetal alcohol spectrum disorders. Neuropsychol Rev 2011;21:133147.
18.Wozniak JR, Mueller BA, Chang PN, Muetzel RL, Caros L, Lim KO. Diffusion tensor imaging in children with fetal alcohol spectrum disorders. Alcohol Clin Exp Res 2006;30:17991806.
19.Wozniak JR, Muetzel RL, Mueller BAet al. Microstructural corpus callosum anomalies in children with prenatal alcohol exposure: an extension of previous diffusion tensor imaging findings. Alcohol Clin Exp Res 2009;33:18251835.
20.Ma X, Coles CD, Lynch MEet al. Evaluation of corpus callosum anisotropy in young adults with fetal alcohol syndrome according to diffusion tensor imaging. Alcohol Clin Exp Res 2005;29:12141222.
21.Li L, Coles CD, Lynch ME, Hu X. Voxelwise and skeleton-based region of interest analysis of fetal alcohol syndrome and fetal alcohol spectrum disorders in young adults. Hum Brain Mapp 2009;30:32653274.
22.Treit S, Lebel C, Baugh L, Rasmussen C, Andrew G, Beaulieu C. Longitudinal MRI reveals altered trajectory of brain development during childhood and adolescence in fetal alcohol spectrum disorders. J Neurosci 2013;33:1009810109.
23.Fryer SL, Schweinsburg BC, Bjorkquist OA, Frank LR, Mattson SN, Spadoni AD, Riley EP. Characterisation of white matter microstructure in fetal alcohol spectrum disorders. Alcohol Clin Exp Res 2009;33:514521.
24.Lebel C, Rasmussen C, Wyper K, Walker L, Andrew G, Yager J. Brain diffusion abnormalities in children with fetal alcohol spectrum disorder. Alcohol Clin Exp Res 2008;32:17321740.
25.Sowell ER, Johnson A, Kan Eet al. Mapping white matter integrity and neurobehavioral correlates in children with fetal alcohol spectrum disorders. J Neurosci 2008;28:13131319.
26.Lebel C, Mattson SN, Riley EPet al. A longitudinal study of the long-term consequences of drinking during pregnancy: heavy in utero alcohol exposure disrupts the normal processes of brain development. J Neurosci 2012;32:1524315251.
27.Lebel C, Rasmussen C, Wyper K, Andrew G, Beaulieu C. Brain microstructure is related to math ability in children with fetal alcohol spectrum disorder. Alcohol Clin Exp Res 2010;34:354363.
28.Fan J, Meintjes EM, Molteno CDet al. White matter integrity of the cerebellar peduncles as a mediator of effects of prenatal alcohol exposure on eyeblink conditioning. Hum Brain Mapp 2015; doi:10.1002/hbm.22785 [Epub ahead of print].
29.Green CR, Lebel C, Rasmussen C, Beaulieu C, Reynolds JN. Diffusion tensor imaging correlates of saccadic reaction time in children with fetal alcohol spectrum disorder. Alcohol Clin Exp Res 2013;37:14991507.
30.Taylor PA, Jacobson SW, van der Kouwe Aet al. A DTI-based tractography study of effects on brain structure associated with prenatal alcohol exposure in newborns. Hum Brain Mapp 2015;36:170186.
31.May PA, Gossage JP, Kalberg K, Robinson L, Buckley D, Manning M. Prevalence and epidemiologic characteristics of FASD from various research methods with an emphasis on recent in-school studies. Dev Disabil Res Rev 2009;15:176192.
32.May PA, Blankenship J, Marais Aet al. Approaching the prevalence of the full spectrum of fetal alcohol spectrum disorders in a south african population-based study. Alcohol Clin Exp Res 2013;37:818830.
33.Donald KA, Eastman E, Howells FMet al. Neuroimaging effects of prenatal alcohol-exposure on the developing human brain: a magnetic resonance imaging review. Acta Neuropsychiatrica 2015;119 [Epub ahead of print].
34.Stein DJ, Koen N, Donald KAet al. Investigating the psychosocial determinants of child health in Africa: The Drakenstein Child Health Study. J Neurosci Methods 2015; pii: S0165-0270(15)00099-0. doi: 10.1016/j.jneumeth.2015.03.016 [Epub ahead of print].
35.Humeniuk R, Ali R, Babor TFet al. Validation of the alcohol, smoking and substance involvement screening test (ASSIST). Addiction 2008;103:10391047.
36.Jackson PB, Williams DR, Stein DJ, Herman A, Williams SL, Redmond DL. Race and psychological distress: The South African Stress and Health Study. J Health Soc Behav 2010;51:458477.
37.Lozarno J, Garcia-Algar O, Vall O, de la Torre R, Scaravelli G, Pichini S. Biological matrices for the evaluation of in utero exposure to drugs of abuse. Ther Drug Monit 2007;29:711734.
38.Noble Y, Boyd R. Neonatal assessments for the preterm infant up to 4 months corrected age: a systematic review. Dev Med Child Neurol 2012;54:129139.
39.Dubowitz L, Mercurio E, Dubowitz V. An optimality score for the neurological examination of the term newborn. J Pediatr 1998;133:406416.
40.Smith SM, Jenkinson M, Johansen-Berg Het al. Tract-based spatial statistics: voxel-wise analysis of multi-subject diffusion data. Neuroimage 2006;31:14871505.
41.Dubois J, Hertz-Pannier L, Dehaene-Lambertz G, Cointepas Y, Le Bihan D. Assessment of the early organization and maturation of infants' cerebral white matter fiber bundles: a feasibility study using quantitative diffusion tensor imaging and tractography. Neuroimage 2006;30:11211132.
42.Andersson JLR, Jenkinson M, Smith S. Non-linear registration, aka spatial normalisation. FMRIB technical report TR07JA2. www.fmrib.ox.ac.uk/analysis/techrep. 2007, accessed 20 December 2014.
43.Mori S, Wakana S, van Zijl PCM, Nagae-Poetscher LM. MRI atlas of human white matter. Amsterdam: Elsevier, 2005.
44.Mattson S, Crocker N, Nguyen T. Fetal alcohol spectrum disorders: neuropsychological and behavioral features. Neuropsychol Rev 2011;21:81101.
45.Mattson SN, Roesch SC, Fagerlund Ået al. Toward a neurobehavioral profile of fetal alcohol spectrum disorders. Alcohol Clin Exp Res 2010;34:16401650.
46.Mattson SN, Riley EP, Jernigan TLet al. A decrease in the size of the basal ganglia following prenatal alcohol exposure: a preliminary report. Neurotoxicol Teratol 1994;16:283289.
47.O'Hare ED, Kan E, Yoshii Jet al. Mapping cerebellar vermal morphology and cognitive correlates in prenatal alcohol exposure. Neuroreport 2005;16:12851290.
48.Provenzale JM, Liang L, DeLong D, White LE. Diffusion tensor imaging assessment of brain white matter maturation in the first postnatal year. Am J Radiol 2007;189:476486.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Acta Neuropsychiatrica
  • ISSN: 0924-2708
  • EISSN: 1601-5215
  • URL: /core/journals/acta-neuropsychiatrica
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 15
Total number of PDF views: 84 *
Loading metrics...

Abstract views

Total abstract views: 404 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 20th November 2017. This data will be updated every 24 hours.