Altered local cerebellar and brainstem development in preterm infants
Open accessAbstract
BACKGROUND: Premature birth is associated with high prevalence of neurodevelopmental impairments in surviving infants. The putative role of cerebellar and brainstem dysfunction remains poorly understood, particularly in the absence of overt structural injury. METHOD: We compared in-utero versus ex-utero global, regional and local cerebellar and brainstem development in healthy fetuses (n = 38) and prematurely born infants without evidence of structural brain injury on conventional MRI studies (n = 74) that were performed at two time points: the first corresponding to the third trimester, either in utero or ex utero in the early postnatal period following preterm birth (30-40 weeks of gestation; 38 control fetuses; 52 premature infants) and the second at term equivalent age (37-46 weeks; 38 control infants; 58 premature infants). We compared 1) volumetric growth of 7 regions in the cerebellum (left and right hemispheres, left and right dentate nuclei, and the anterior, neo, and posterior vermis); 2) volumetric growth of 3 brainstem regions (midbrain, pons, and medulla); and 3) shape development in the cerebellum and brainstem using spherical harmonic description between the two groups. RESULTS: Both premature and control groups showed regional cerebellar differences in growth rates, with the left and right cerebellar hemispheres showing faster growth compared to the vermis. In the brainstem, the pons grew faster than the midbrain and medulla in both prematurely born infants and controls. Using shape analyses, premature infants had smaller left and right cerebellar hemispheres but larger regional vermis and paravermis compared to in-utero control fetuses. For the brainstem, premature infants showed impaired growth of the superior surface of the midbrain, anterior surface of the pons, and inferior aspects of the medulla compared to the control fetuses. At term-equivalent age, premature infants had smaller cerebellar hemispheres bilaterally, extending to the superior aspect of the left cerebellar hemisphere, and larger anterior vermis and posteroinferior cerebellar lobes than healthy newborns. For the brainstem, large differences between premature infants and healthy newborns were found in the anterior surface of the pons. CONCLUSION: This study analyzed both volumetric growth and shape development of the cerebellum and brainstem in premature infants compared to healthy fetuses using longitudinal MRI measurements. The findings in the present study suggested that preterm birth may alter global, regional and local development of the cerebellum and brainstem even in the absence of structural brain injury evident on conventional MRI.
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In healthy fetuses between 30-40 GW and age-matched ex-utero premature infants, the left and right cerebellar hemispheres grow faster compared to the vermis, and the pons grows faster than the midbrain and medulla in both groups.
“Another study on shape analysis of the brainstem and cerebellum compares healthy fetuses between 30–40 GW with age-matched ex-utero premature infants [52] and suggests that the left and right cerebellar hemispheres grow faster compared to the vermis, and the pons grows faster than the midbrain and medulla in both groups [52].”
From Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy (2024) · cites this paper as [52]
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Relation between predischarge auditory brainstem responses and clinical factors in high‐risk infants
Suzuki, N., & Suzumura, H. (2004) · Pediatrics International · doi:10.1111/j.1442-200x.2004.01897.x · Cited by 18 · see citing works
Early extra-uterine exposure alters regional cerebellar growth in infants born preterm
Brossard‐Racine, M., McCarter, R., Murnick, J. G., Tinkleman, L., Vézina, G., & Limperopoulos, C. (2018) · NeuroImage Clinical · doi:10.1016/j.nicl.2018.101646 · Cited by 18 · see citing works
Self-citationGupta, A. K., Anand, N. K., & Raj, H. (1991) · The Indian Journal of Pediatrics · doi:10.1007/bf02825449 · Cited by 15 · see citing works
Building a surface atlas of hippocampal subfields from MRI scans using FreeSurfer, FIRST and SPHARM
Cong, S., Rizkalla, M., Du, E. Y., et al. (2014) · Conference proceedings · doi:10.1109/mwscas.2014.6908539 · Cited by 12 · see citing works
Sato, K., Ishigame, K., Ying, S., Oishi, K., Miller, M. I., & Mori, S. (2014) · American Journal of Neuroradiology · doi:10.3174/ajnr.a4085 · Cited by 9 · see citing works
Mild maturational delay of the brainstem at term in late preterm small-for-gestation age babies
Jiang, Z. D., & Li, Z. H. (2015) · Early Human Development · doi:10.1016/j.earlhumdev.2015.02.006 · Cited by 9 · see citing works
Jiang, Z. D., & Ping, L. L. (2015) · Clinical Neurophysiology · doi:10.1016/j.clinph.2015.09.132 · Cited by 9 · see citing works
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Wu, Y., De Asis-Cruz, J., & Limperopoulos, C. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02449-0 · Cited by 124 · see citing works
“…of the brainstem and cerebellum compares healthy fetuses between 30 – 40 GW with age-matched ex-utero premature infants [52] and suggests that the left and right cerebellar hemispheres grow faster compared to the vermis, and the pons grows faster than the midbrain and medulla in both groups [52].”
BackgroundSelf-citation
- Authors
- Wu, Y., Stoodley, C., Brossard-Racine, M., Kapse, K., Vezina, G., Murnick, J., du Plessis, A. J., & Limperopoulos, C.
- Affiliations
- Children's National (US)
- American University (US)
- Corresponding author
- Limperopoulos, Catherine
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 213
- Pages
- 116702
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC7165064
- OpenAlex
- W3010623341
- Cited by
- 57
- References
- 94
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 12 · 2023: 10 · 2022: 4 · 2021: 11 · 2020: 2 · 2018: 1
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- American University Research Archive
- Funders
- Thrasher Research Fund
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- cerebellar development, brainstem development, cerebellar vermis, passive optical networks, midbrain, medulla, neurodevelopmental impairment, fetal brain MRI, longitudinal MRI, cerebellar hemispheres, cerebellar lobes, neuroprognostic biomarkers
- MeSH terms
- Brain Stem, Cerebellum, Female, Fetus, Gestational Age, Humans, Infant, Newborn, Infant, Premature, Magnetic Resonance Imaging, Male, Pregnancy
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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