Abstract
Preterm birth is a leading cause for impaired neurocognitive development with an increased risk for persistent cognitive deficits in adulthood. In newborns, preterm birth is associated with interrelated white matter (WM) alterations and deep gray matter (GM) loss; however, little is known about the persistence and relevance of these subcortical brain changes. We tested the hypothesis that the pattern of correspondent subcortical WM and GM changes is present in preterm-born adults and has a brain-injury-like nature, i.e., it predicts lowered general cognitive performance. Eighty-five preterm-born and 69 matched term-born adults were assessed by diffusion- and T1-weighted MRI and cognitive testing. Main outcome measures were fractional anisotropy of water diffusion for WM property, GM volume for GM property, and full-scale IQ for cognitive performance. In preterm-born adults, reduced fractional anisotropy was widely distributed ranging from cerebellum to brainstem to hemispheres. GM volume was reduced in the thalamus, striatum, temporal cortices, and increased in the cingulate cortices. Fractional anisotropy reductions were specifically associated with GM loss in thalamus and striatum, with correlation patterns for both regions extensively overlapping in the WM of brainstem and hemispheres. For overlap regions, fractional anisotropy was positively related with both gestational age and full-scale IQ. Results provide evidence for extensive, interrelated, and adverse WM and GM subcortical changes in preterm-born adults. Data suggest persistent brain-injury-like changes of subcortical–cortical connectivity after preterm delivery.
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References
Allin MP et al (2011) White matter and cognition in adults who were born preterm. PloS One 6:e24525. doi:10.1371/journal.pone.0024525
Anderson MJ, Robinson J (2001) Permutation tests for linear models. Aust N Z J Stat 43:75–88
Anjari M, Srinivasan L, Allsop JM, Hajnal JV, Rutherford MA, Edwards AD, Counsell SJ (2007) Diffusion tensor imaging with tract-based spatial statistics reveals local white matter abnormalities in preterm infants. NeuroImage 35:1021–1027. doi:10.1016/j.neuroimage.2007.01.035
Ball G et al (2012) The effect of preterm birth on thalamic and cortical development. Cereb Cortex (New York, NY: 1991) 22:1016–1024. doi:10.1093/cercor/bhr176
Ball G et al (2013a) The influence of preterm birth on the developing thalamocortical connectome. Cortex J Devot Study Nerv Syst Behav 49:1711–1721. doi:10.1016/j.cortex.2012.07.006
Ball G et al (2013b) Development of cortical microstructure in the preterm human brain. Proc Natl Acad Sci USA 110:9541–9546. doi:10.1073/pnas.1301652110
Ball G et al (2014) Rich-club organization of the newborn human brain. Proc Natl Acad Sci USA 111:7456–7461. doi:10.1073/pnas.1324118111
Bartos M, Vida I, Jonas P (2007) Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks Nature reviews. Neuroscience 8:45–56. doi:10.1038/nrn2044
Bäuml JG et al (2014) Correspondence between aberrant intrinsic network connectivity and gray-matter volume in the ventral brain of preterm born adults. Cereb Cortex (New York, NY: 1991). doi:10.1093/cercor/bhu133
Blencowe H et al (2012) National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 379:2162–2172. doi:10.1016/s0140-6736(12)60820-4
Boardman JP et al (2010) A common neonatal image phenotype predicts adverse neurodevelopmental outcome in children born preterm. NeuroImage 52:409–414. doi:10.1016/j.neuroimage.2010.04.261
Constable RT et al (2008) Prematurely born children demonstrate white matter microstructural differences at 12 years of age, relative to term control subjects: an investigation of group and gender effects. Pediatrics 121:306–316. doi:10.1542/peds.2007-0414
Counsell SJ et al (2008) Specific relations between neurodevelopmental abilities and white matter microstructure in children born preterm. Brain J Neurol 131:3201–3208. doi:10.1093/brain/awn268
Dean JM et al (2013) Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization. Sci Transl Med 5:168ra167. doi:10.1126/scitranslmed.3004669
Deary IJ, Bastin ME, Pattie A, Clayden JD, Whalley LJ, Starr JM, Wardlaw JM (2006) White matter integrity and cognition in childhood and old age. Neurology 66:505–512. doi:10.1212/01.wnl.0000199954.81900.e2
Deary IJ, Penke L, Johnson W (2010) The neuroscience of human intelligence differences Nature reviews. Neuroscience 11:201–211. doi:10.1038/nrn2793
Deng W (2010) Neurobiology of injury to the developing brain Nature reviews. Neurology 6:328–336. doi:10.1038/nrneurol.2010.53
D’Onofrio BM, Class QA, Rickert ME, Larsson H, Langstrom N, Lichtenstein P (2013) Preterm birth and mortality and morbidity: a population-based quasi-experimental study. JAMA Psychiatry 70:1231–1240. doi:10.1001/jamapsychiatry.2013.2107
Douglas RJ, Martin KA (2004) Neuronal circuits of the neocortex. Annu Rev Neurosci 27:419–451. doi:10.1146/annurev.neuro.27.070203.144152
Dubowitz LM, Dubowitz V, Goldberg C (1970) Clinical assessment of gestational age in the newborn infant. J Pediatr 77:1–10
Eikenes L, Lohaugen GC, Brubakk AM, Skranes J, Haberg AK (2011) Young adults born preterm with very low birth weight demonstrate widespread white matter alterations on brain DTI. NeuroImage 54:1774–1785. doi:10.1016/j.neuroimage.2010.10.037
Fischi-Gomez E et al (2014) Structural brain connectivity in school-age preterm infants provides evidence for impaired networks relevant for higher order cognitive skills and social cognition. Cereb Cortex (New York, NY: 1991). doi:10.1093/cercor/bhu073
Gutbrod T, Wolke D, Soehne B, Ohrt B, Riegel K (2000) Effects of gestation and birth weight on the growth and development of very low birthweight small for gestational age infants: a matched group comparison. Arch Dis Child Fetal Neonatal Ed 82:F208–F214
Haynes RL, Billiards SS, Borenstein NS, Volpe JJ, Kinney HC (2008) Diffuse axonal injury in periventricular leukomalacia as determined by apoptotic marker fractin. Pediatr Res 63:656–661. doi:10.1203/PDR.0b013e31816c825c
Huang ZJ, Di Cristo G, Ango F (2007) Development of GABA innervation in the cerebral and cerebellar cortices. Nat Rev Neurosci 8:673–686. doi:10.1038/nrn2188
Inder TE, Warfield SK, Wang H, Huppi PS, Volpe JJ (2005) Abnormal cerebral structure is present at term in premature infants. Pediatrics 115:286–294. doi:10.1542/peds.2004-0326
Jaekel J, Baumann N, Wolke D (2013) Effects of gestational age at birth on cognitive performance: a function of cognitive workload demands. PloS One 8:e65219. doi:10.1371/journal.pone.0065219
Katz J et al (2013) Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis. Lancet 382:417–425. doi:10.1016/S0140-6736(13)60993-9
Kinney HC, Haynes RL, Xu G, Andiman SE, Folkerth RD, Sleeper LA, Volpe JJ (2012) Neuron deficit in the white matter and subplate in periventricular leukomalacia. Ann Neurol 71:397–406. doi:10.1002/ana.22612
Komitova M et al (2013) Hypoxia-induced developmental delays of inhibitory interneurons are reversed by environmental enrichment in the postnatal mouse forebrain. J Neurosci 33:13375–13387. doi:10.1523/jneurosci.5286-12.2013
Meng C et al (2013) Aberrant topology of striatum’s connectivity is associated with the number of episodes in depression. Brain J Neurol. doi:10.1093/brain/awt290
Milligan DW (2010) Outcomes of children born very preterm in Europe. Arch Dis Child Fetal Neonatal Ed 95:F234–F240. doi:10.1136/adc.2008.143685
Mullen KM et al (2011) Preterm birth results in alterations in neural connectivity at age 16 years. NeuroImage 54:2563–2570. doi:10.1016/j.neuroimage.2010.11.019
Nagy Z et al (2009) Structural correlates of preterm birth in the adolescent brain. Pediatrics 124:e964–e972. doi:10.1542/peds.2008-3801
Northam GB et al (2012) Interhemispheric temporal lobe connectivity predicts language impairment in adolescents born preterm. Brain J Neurol 135:3781–3798. doi:10.1093/brain/aws276
Nosarti C et al (2008) Grey and white matter distribution in very preterm adolescents mediates neurodevelopmental outcome. Brain J Neurol 131:205–217. doi:10.1093/brain/awm282
Nosarti C, Shergill SS, Allin MP, Walshe M, Rifkin L, Murray RM, McGuire PK (2009) Neural substrates of letter fluency processing in young adults who were born very preterm: alterations in frontal and striatal regions. NeuroImage 47:1904–1913. doi:10.1016/j.neuroimage.2009.04.041
Nosarti C et al (2012) Preterm birth and psychiatric disorders in young adult life. Arch Gen Psychiatry 69:E1–E8. doi:10.1001/archgenpsychiatry.2011.1374
Padilla N, Alexandrou G, Blennow M, Lagercrantz H, Aden U (2014) Brain growth gains and losses in extremely preterm infants at term. Cereb Cortex (New York, NY: 1991). doi:10.1093/cercor/bht431
Pandit AS et al (2013) Whole-brain mapping of structural connectivity in infants reveals altered connection strength associated with growth and preterm birth. Cereb Cortex (New York, NY: 1991). doi:10.1093/cercor/bht086
Peterson BS et al (2000) Regional brain volume abnormalities and long-term cognitive outcome in preterm infants. JAMA 284:1939–1947
Pierson CR, Folkerth RD, Billiards SS, Trachtenberg FL, Drinkwater ME, Volpe JJ, Kinney HC (2007) Gray matter injury associated with periventricular leukomalacia in the premature infant. Acta Neuropathol 114:619–631. doi:10.1007/s00401-007-0295-5
Poulsen G, Wolke D, Kurinczuk JJ, Boyle EM, Field D, Alfirevic Z, Quigley MA (2013) Gestational age and cognitive ability in early childhood: a population-based cohort study. Paediatr Perinat Epidemiol 27:371–379. doi:10.1111/ppe.12058
Prechtl HF (1967) Neurological sequelae of prenatal and perinatal complications. Br Med J 4:763–767
Riegel K, Orth B, Wolke D, Osterlund K (1995) Die Entwicklung gefährdet geborener Kinder bis zum 5 Lebensjahr. Thieme, Stuttgart (Germany)
Ritter J, Schmitz T, Chew LJ, Buhrer C, Mobius W, Zonouzi M, Gallo V (2013) Neonatal hyperoxia exposure disrupts axon-oligodendrocyte integrity in the subcortical white matter. J Neurosci 33:8990–9002. doi:10.1523/jneurosci.5528-12.2013
Robinson S, Li Q, Dechant A, Cohen ML (2006) Neonatal loss of gamma-aminobutyric acid pathway expression after human perinatal brain injury. J Neurosurg 104:396–408. doi:10.3171/ped.2006.104.6.396
Salmaso N, Jablonska B, Scafidi J, Vaccarino FM, Gallo V (2014) Neurobiology of premature brain injury. Nat Neurosci 17:341–346. doi:10.1038/nn.3604
Serenius F et al (2013) Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in Sweden. JAMA 309:1810–1820. doi:10.1001/jama.2013.3786
Skranes J et al (2007) Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight. Brain J Neurol 130:654–666. doi:10.1093/brain/awm001
Smith SM, Nichols TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. NeuroImage 44:83–98. doi:10.1016/j.neuroimage.2008.03.061
Smith SM et al (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage 31:1487–1505. doi:10.1016/j.neuroimage.2006.02.024
Srinivasan L, Dutta R, Counsell SJ, Allsop JM, Boardman JP, Rutherford MA, Edwards AD (2007) Quantification of deep gray matter in preterm infants at term-equivalent age using manual volumetry of 3-tesla magnetic resonance images. Pediatrics 119:759–765. doi:10.1542/peds.2006-2508
Swanson LW (2000) Cerebral hemisphere regulation of motivated behavior. Brain Res 886:113–164
Von Aster M, Neubauer A, Horn R (2006) Wechsler Intelligenztest für Erwachsene (WIE). Deutschsprachige Bearbeitung und Adaptation des WAIS-III von David Wechsler. Harcourt Test Services, Frankfurt/Main (Germany)
Wolke D, Meyer R (1999) Cognitive status, language attainment, and prereading skills of 6-year-old very preterm children and their peers: the Bavarian Longitudinal Study. Dev Med Child Neurol 41:94–109
Zubiaurre-Elorza L et al (2011) Gray matter volume decrements in preterm children with periventricular leukomalacia. Pediatr Res 69:554–560. doi:10.1203/PDR.0b013e3182182366
Acknowledgments
We thank all current and former members of the Bavarian Longitudinal Study Group who contributed to general study organization, recruitment, and data collection, management and subsequent analyses, including (in alphabetical order): Stephan Czeschka, Claudia Grünzinger, Christian Koch, Diana Kurze, Sonja Perk, Andrea Schreier, Antje Strasser, Julia Trummer, and Eva van Rossum. We are grateful to the staff of the Department of Neuroradiology in Munich and the Department of Radiology in Bonn for their help in data collection. Most importantly, we thank all our study participants and their families for their efforts to take part in this study. This study was supported by Chinese Scholar Council (CSC, File No: 2010604026 to C.M.), German Federal Ministry of Education and Science (BMBF 01ER0801 to P.B. and D.W., BMBF 01EV0710 to A.M.W., BMBF 01ER0803 to C.S.) and the Kommission für Klinische Forschung, Technische Universität München (KKF 8765162 to C.S).
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Meng, C., Bäuml, J.G., Daamen, M. et al. Extensive and interrelated subcortical white and gray matter alterations in preterm-born adults. Brain Struct Funct 221, 2109–2121 (2016). https://doi.org/10.1007/s00429-015-1032-9
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DOI: https://doi.org/10.1007/s00429-015-1032-9