Abstract
Together, the multiple types of cerebral palsy (CP) represent the most common physical disability in childhood with the spastic type accounting for ~77% of cases. CP arises with a disturbance in the brain, which in most cases occurs between 24 weeks gestation and birth. Early intervention is desirable, but early diagnosis is very challenging, and diagnosis is often delayed for several months or even years. No current molecular biomarker platform readily identifies individuals with CP, but screening assays that could measure blood biomarkers, preferably collected at the time of birth, may allow for earlier diagnosis, intervention, and the development of novel therapeutics. Biomarkers that identify CP patients are needed, and multiple efforts to identify useful biomarkers in blood samples are underway. It is important to understand the nature of diagnostic biomarkers and the types of blood biomarkers being investigated in individuals with CP.
This is a preview of subscription content, log in via an institution to check access.
References
Adams Waldorf KM, McAdams RM (2013) Influence of infection during pregnancy on fetal development. Reproduction 146:R151–R162. https://doi.org/10.1530/REP-13-0232
Bahrami A et al (2018) The prognostic and therapeutic application of microRNAs in breast cancer: tissue and circulating microRNAs. J Cell Physiol 233:774–786. https://doi.org/10.1002/jcp.25813
Blaze J, Roth TL (2015) Evidence from clinical and animal model studies of the long-term and transgenerational impact of stress on DNA methylation. Semin Cell Dev Biol 43:76–84. https://doi.org/10.1016/j.semcdb.2015.04.004
Chapman S, Farina L, Kronforst K, Dizon M (2018) MicroRNA profile differences in neonates at risk for cerebral palsy. Phys Med Rehabil – Int 5:1148–1153
Costantine MM et al (2011) Umbilical cord blood biomarkers of neurologic injury and the risk of cerebral palsy or infant death. Int J Dev Neurosci 29:917–922. https://doi.org/10.1016/j.ijdevneu.2011.06.009
Crowgey EL, Marsh AG, Robinson KG, Yeager SK, Akins RE (2018) Epigenetic machine learning: utilizing DNA methylation patterns to predict spastic cerebral palsy. BMC Bioinf 19:225. https://doi.org/10.1186/s12859-018-2224-0
Data and Statistics | Cerebral Palsy | NCBDDD | CDC. (2017)
Epigenetics and Public Health: Why we should pay attention. (2014). https://blogs.cdc.gov/genomics/2014/10/09/epigenetics
FDA-NIH Biomarker Working Group: BEST (Biomarkers, EndpointS, and other Tools) Resource. (2016) https://www.ncbi.nlm.nih.gov/books/NBK326791/
Gebert LFR, MacRae IJ (2018) Regulation of microRNA function in animals. Nat Rev Mol Cell Biol. https://doi.org/10.1038/s41580-018-0045-7
Hadders-Algra M (2014) Early diagnosis and early intervention in cerebral palsy. Front Neurol 5:185. https://doi.org/10.3389/fneur.2014.00185
Hartley I et al (2013) Long-lasting changes in DNA methylation following short-term hypoxic exposure in primary hippocampal neuronal cultures. PLoS One 8:e77859. https://doi.org/10.1371/journal.pone.0077859
Houtepen LC et al (2016) Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans. Nat Commun 7:10967. https://doi.org/10.1038/ncomms10967
Hubermann L, Boychuck Z, Shevell M, Majnemer A (2016) Age at referral of children for initial diagnosis of cerebral palsy and rehabilitation: current practices. J Child Neurol 31:364–369. https://doi.org/10.1177/0883073815596610
Jiao Z et al (2017) Wholegenome scale identification of methylation markers specific for cerebral palsy in monozygotic discordant twins. Mol Med Rep 16:9423–9430. https://doi.org/10.3892/mmr.2017.7800
Jones MJ, Goodman SJ, Kobor MS (2015) DNA methylation and healthy human aging. Aging Cell 14:924–932. https://doi.org/10.1111/acel.12349
Joubert BR et al (2016) DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis. Am J Hum Genet 98:680–696. https://doi.org/10.1016/j.ajhg.2016.02.019
Key Findings: Birth Prevalence of Cerebral Palsy | Key Findings | Cerebral Palsy | NCBDDD | CDC. (2017)
Labonte B et al (2012) Genome-wide epigenetic regulation by early-life trauma. Arch Gen Psychiatry 69:722–731. https://doi.org/10.1001/archgenpsychiatry.2011.2287
MacLennan AH, Thompson SC, Gecz J (2015) Cerebral palsy: causes, pathways, and the role of genetic variants. Am J Obstet Gynecol 213:779–788. https://doi.org/10.1016/j.ajog.2015.05.034
Maitre NL, Slaughter JC, Aschner JL (2013) Early prediction of cerebral palsy after neonatal intensive care using motor development trajectories in infancy. Early Hum Dev 89:781–786. https://doi.org/10.1016/j.earlhumdev.2013.06.004
McIntyre S, Blair E, Badawi N, Keogh J, Nelson KB (2013) Antecedents of cerebral palsy and perinatal death in term and late preterm singletons. Obstet Gynecol 122:869–877. https://doi.org/10.1097/AOG.0b013e3182a265ab
Mohandas N et al (2018) Epigenome-wide analysis in newborn blood spots from monozygotic twins discordant for cerebral palsy reveals consistent regional differences in DNA methylation. Clin Epigenetics 10:25. https://doi.org/10.1186/s13148-018-0457-4
Nelson KB, Ellenberg JH (1986) Antecedents of cerebral palsy. Multivariate analysis of risk. N Engl J Med 315:81–86. https://doi.org/10.1056/NEJM198607103150202
Pacis A et al (2015) Bacterial infection remodels the DNA methylation landscape of human dendritic cells. Genome Res 25:1801–1811. https://doi.org/10.1101/gr.192005.115
Palatnik A, Rouse DJ, Stamilio DM, McPherson JA, Grobman WA (2015) Association between cerebral palsy or death and umbilical cord blood magnesium concentration. Am J Perinatol 32:1263–1267. https://doi.org/10.1055/s-0035-1554798
Rask-Andersen M et al (2016) Epigenome-wide association study reveals differential DNA methylation in individuals with a history of myocardial infarction. Hum Mol Genet. https://doi.org/10.1093/hmg/ddw302
Smith ZD, Meissner A (2013) DNA methylation: roles in mammalian development. Nat Rev Genet 14:204–220. https://doi.org/10.1038/nrg3354
Sorokin Y et al (2014) Umbilical cord serum interleukin-6, C-reactive protein, and myeloperoxidase concentrations at birth and association with neonatal morbidities and long-term neurodevelopmental outcomes. Am J Perinatol 31:717–726. https://doi.org/10.1055/s-0033-1359723
Spittle A, Orton J, Anderson PJ, Boyd R, Doyle LW (2015) Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants. Cochrane Database Syst Rev 11:CD005495. https://doi.org/10.1002/14651858.CD005495.pub4
Stirzaker C et al (2015) Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value. Nat Commun 6:5899. https://doi.org/10.1038/ncomms6899
Toffolo K et al (2018) Circulating microRNAs as biomarkers in traumatic brain injury. Neuropharmacology. https://doi.org/10.1016/j.neuropharm.2018.08.028
Treiber T, Treiber N, Meister G (2018) Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat Rev Mol Cell Biol. https://doi.org/10.1038/s41580-018-0059-1
Varner MW et al (2015) The association of cord serum cytokines with neurodevelopmental outcomes. Am J Perinatol 30:115–122. https://doi.org/10.1055/s-0034-1376185
Xiao X et al (2016) Fetal growth restriction and methylation of growth-related genes in the placenta. Epigenomics 8:33–42. https://doi.org/10.2217/epi.15.101
Yuan Y (2017) Study of global DNA methylation in monozygotic twins with cerebral palsy. Pak J Pharm Sci 30:1467–1473
Ziller MJ et al (2013) Charting a dynamic DNA methylation landscape of the human genome. Nature 500:477–481. https://doi.org/10.1038/nature12433
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this entry
Cite this entry
Akins, R.E., Robinson, K.G. (2019). Biomarker Blood Tests for Cerebral Palsy. In: Miller, F., Bachrach, S., Lennon, N., O'Neil, M. (eds) Cerebral Palsy. Springer, Cham. https://doi.org/10.1007/978-3-319-50592-3_211-1
Download citation
DOI: https://doi.org/10.1007/978-3-319-50592-3_211-1
Received:
Accepted:
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-50592-3
Online ISBN: 978-3-319-50592-3
eBook Packages: Springer Reference MedicineReference Module Medicine