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Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI.
Neuroimage Clin. 2018; 17:596-606.NC

Abstract

Background

Preterm infants are at high risk of diffuse white matter injury and adverse neurodevelopmental outcome. The multiple hit hypothesis suggests that the risk of white matter injury increases with cumulative exposure to multiple perinatal risk factors. Our aim was to test this hypothesis in a large cohort of preterm infants using diffusion weighted magnetic resonance imaging (dMRI).

Methods

We studied 491 infants (52% male) without focal destructive brain lesions born at < 34 weeks, who underwent structural and dMRI at a specialist Neonatal Imaging Centre. The median (range) gestational age (GA) at birth was 30+ 1 (23+ 2-33+ 5) weeks and median postmenstrual age at scan was 42+ 1 (38-45) weeks. dMRI data were analyzed using tract based spatial statistics and the relationship between dMRI measures in white matter and individual perinatal risk factors was assessed. We tested the hypothesis that increased exposure to perinatal risk factors was associated with lower fractional anisotropy (FA), and higher radial, axial and mean diffusivity (RD, AD, MD) in white matter. Neurodevelopmental performance was investigated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III) in a subset of 381 infants at 20 months corrected age. We tested the hypothesis that lower FA and higher RD, AD and MD in white matter were associated with poorer neurodevelopmental performance.

Results

Identified risk factors for diffuse white matter injury were lower GA at birth, fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition, necrotizing enterocolitis and male sex. Clinical chorioamnionitis and patent ductus arteriosus were not associated with white matter injury. Multivariate analysis demonstrated that fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition were independently associated with lower FA values. Exposure to cumulative risk factors was associated with reduced white matter FA and FA values at term equivalent age were associated with subsequent neurodevelopmental performance.

Conclusion

This study suggests multiple perinatal risk factors have an independent association with diffuse white matter injury at term equivalent age and exposure to multiple perinatal risk factors exacerbates dMRI defined, clinically significant white matter injury. Our findings support the multiple hit hypothesis for preterm white matter injury.

Authors+Show Affiliations

Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London SE1 7EH, UK.Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London SE1 7EH, UK.Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London SE1 7EH, UK.Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London SE1 7EH, UK.Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London SE1 7EH, UK.Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London SE1 7EH, UK.Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London SE1 7EH, UK.St George's Hospital NHS Trust, Blackshaw Road, London SW17 0QT, UK.Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London SE1 7EH, UK.Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London SE1 7EH, UK.Centre for the Developing Brain, Division of Imaging Sciences & Biomedical Engineering, King's College London, London SE1 7EH, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29234596

Citation

Barnett, Madeleine L., et al. "Exploring the Multiple-hit Hypothesis of Preterm White Matter Damage Using Diffusion MRI." NeuroImage. Clinical, vol. 17, 2018, pp. 596-606.
Barnett ML, Tusor N, Ball G, et al. Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI. Neuroimage Clin. 2018;17:596-606.
Barnett, M. L., Tusor, N., Ball, G., Chew, A., Falconer, S., Aljabar, P., Kimpton, J. A., Kennea, N., Rutherford, M., David Edwards, A., & Counsell, S. J. (2018). Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI. NeuroImage. Clinical, 17, 596-606. https://doi.org/10.1016/j.nicl.2017.11.017
Barnett ML, et al. Exploring the Multiple-hit Hypothesis of Preterm White Matter Damage Using Diffusion MRI. Neuroimage Clin. 2018;17:596-606. PubMed PMID: 29234596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI. AU - Barnett,Madeleine L, AU - Tusor,Nora, AU - Ball,Gareth, AU - Chew,Andrew, AU - Falconer,Shona, AU - Aljabar,Paul, AU - Kimpton,Jessica A, AU - Kennea,Nigel, AU - Rutherford,Mary, AU - David Edwards,A, AU - Counsell,Serena J, Y1 - 2017/11/21/ PY - 2017/01/15/received PY - 2017/10/25/revised PY - 2017/11/18/accepted PY - 2017/12/14/entrez PY - 2017/12/14/pubmed PY - 2018/7/26/medline KW - ALIC, anterior limb of the internal capsule KW - BSITD-III, Bayley Scales of Infant and Toddler Development Third Edition KW - Brain KW - Development KW - Diffusion MRI KW - GA, gestational age KW - IMD, index of multiple deprivation KW - Multiple hit hypothesis KW - PLIC, posterior limb of the internal capsule KW - PMA, postmenstrual age KW - Prematurity KW - SLF, superior longitudinal fasciculus KW - dMRI, diffusion magnetic resonance imaging SP - 596 EP - 606 JF - NeuroImage. Clinical JO - Neuroimage Clin VL - 17 N2 - Background: Preterm infants are at high risk of diffuse white matter injury and adverse neurodevelopmental outcome. The multiple hit hypothesis suggests that the risk of white matter injury increases with cumulative exposure to multiple perinatal risk factors. Our aim was to test this hypothesis in a large cohort of preterm infants using diffusion weighted magnetic resonance imaging (dMRI). Methods: We studied 491 infants (52% male) without focal destructive brain lesions born at < 34 weeks, who underwent structural and dMRI at a specialist Neonatal Imaging Centre. The median (range) gestational age (GA) at birth was 30+ 1 (23+ 2-33+ 5) weeks and median postmenstrual age at scan was 42+ 1 (38-45) weeks. dMRI data were analyzed using tract based spatial statistics and the relationship between dMRI measures in white matter and individual perinatal risk factors was assessed. We tested the hypothesis that increased exposure to perinatal risk factors was associated with lower fractional anisotropy (FA), and higher radial, axial and mean diffusivity (RD, AD, MD) in white matter. Neurodevelopmental performance was investigated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III) in a subset of 381 infants at 20 months corrected age. We tested the hypothesis that lower FA and higher RD, AD and MD in white matter were associated with poorer neurodevelopmental performance. Results: Identified risk factors for diffuse white matter injury were lower GA at birth, fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition, necrotizing enterocolitis and male sex. Clinical chorioamnionitis and patent ductus arteriosus were not associated with white matter injury. Multivariate analysis demonstrated that fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition were independently associated with lower FA values. Exposure to cumulative risk factors was associated with reduced white matter FA and FA values at term equivalent age were associated with subsequent neurodevelopmental performance. Conclusion: This study suggests multiple perinatal risk factors have an independent association with diffuse white matter injury at term equivalent age and exposure to multiple perinatal risk factors exacerbates dMRI defined, clinically significant white matter injury. Our findings support the multiple hit hypothesis for preterm white matter injury. SN - 2213-1582 UR - https://www.unboundmedicine.com/medline/citation/29234596/Exploring_the_multiple_hit_hypothesis_of_preterm_white_matter_damage_using_diffusion_MRI_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-1582(17)30297-8 DB - PRIME DP - Unbound Medicine ER -