Abstract
The objective of the present study was to assess hair essential and toxic trace elements and minerals in children with cerebral palsy in relation to age of the examinees. A total of 70 children with cerebral palsy and 70 healthy controls aged 0–4 years old were enrolled in the present study. The examined children were also divided into two age groups of those younger and older than 2 years old. Hair trace element content was assessed using ICP-MS at NexION 300D (PerkinElmer, USA). The obtained data demonstrate that hair boron was more than 2-fold lower in CP children as compared with the control group. At the same time, hair Na, Se, and V levels were 21%, 12%, and 20% lower when compared with healthy controls, respectively. It is also notable that a 9% and 28% decrease in hair Fe and Li levels respectively were nearly significant. The observed alterations were more profound in a younger group of patients. No significant group difference in hair toxic metal and metalloid levels was observed between the general cohorts of children with and without CP. In regression models, only hair Al and Ca contents were significantly associated with the presence of cerebral palsy, whereas hair Mg, Na, Ni, and Se levels were characterized as significant negative predictors. The observed alteration in trace element metabolism may also provide an additional link between cerebral palsy, psychomotor delay, and certain diseases, including diabetes, epilepsy, and osteoporosis. However, further studies using other substrates (blood, urine) or biomarkers are required.
Similar content being viewed by others
References
Korzeniewski SJ, Slaughter J, Lenski M, Haak P, Paneth N (2018) The complex aetiology of cerebral palsy. Nat Rev Neurol 14:528–543. https://doi.org/10.1038/s41582-018-0043-6
Odding E, Roebroeck ME, Stam HJ (2006) The epidemiology of cerebral palsy: incidence, impairments and risk factors. Disabil Rehabil 28:183–191. https://doi.org/10.1080/09638280500158422
Surén P, Bakken IJ, Aase H, Chin R, Gunnes N, Lie KK, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Øyen A-S, Stoltenberg C (2012) Autism spectrum disorder, ADHD, epilepsy, and cerebral palsy in Norwegian children. Pediatrics 130:e152–e158. https://doi.org/10.1542/peds.2011-3217
Studenikin VM, Buksh VM, Kuzenkova LM, Kurenkov AL (2016) Cerebral palsy and epilepsy: epidemiology and etiology. Pract Doctor 3:68 [In Russian]
Sellier E, Platt MJ, Andersen GL, Krägeloh-Mann I, De La Cruz J, Cans C (2016) Decreasing prevalence in cerebral palsy: a multi-site European population-based study, 1980 to 2003. Dev Med Child Neurol 58:85–92. https://doi.org/10.1111/dmcn.12865
Sigurdardottir S (2018) Intellectual disability in cerebral palsy: a multifaceted epidemiology. Dev Med Child Neurol 60:640–640. https://doi.org/10.1111/dmcn.13902
Kruse M, Michelsen SI, Flachs EM, Brønnum-Hansen H, Madsen M, Uldall P (2009) Lifetime costs of cerebral palsy. Dev Med Child Neurol 51:622–628. https://doi.org/10.1111/j.1469-8749.2008.03190.x
Tonmukayakul U, Shih ST, Bourke-Taylor H, Imms C, Reddihough D, Cox L, Carter R (2018) Systematic review of the economic impact of cerebral palsy. Res Dev Disabil 80:93–101. https://doi.org/10.1016/j.ridd.2018.06.012
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
Pinto VV, Alves LAC, Mendes FM, Ciamponi AL (2016) The nutritional state of children and adolescents with cerebral palsy is associated with oral motor dysfunction and social conditions: a cross sectional study. BMC Neurol 16:55. https://doi.org/10.1186/s12883-016-0573-8
Rempel G (2015) The importance of good nutrition in children with cerebral palsy. Phys Med Rehabil Clin N Clin 26:39–56. https://doi.org/10.1016/j.pmr.2014.09.001
Grammatikopoulou MG, Daskalou E, Tsigga M (2009) Diet, feeding practices, and anthropometry of children and adolescents with cerebral palsy and their siblings. Nutrition 25:620–626. https://doi.org/10.1016/j.nut.2008.11.025
Hillesund E, Skranes J, Trygg KU, Bøhmer T (2007) Micronutrient status in children with cerebral palsy. Acta Paediatr 96:1195–1198. https://doi.org/10.1111/j.1651-2227.2007.00354.x
Sullivan PB, Juszczak E, Lambert BR, Rose M, Ford-Adams ME, Johnson A (2002) Impact of feeding problems on nutritional intake and growth: Oxford Feeding Study II. Dev Med Child Neurol 44:461–467. https://doi.org/10.1017/S0012162201002365
Schoendorfer N, Boyd R, Davies PS (2010) Micronutrient adequacy and morbidity: paucity of information in children with cerebral palsy. Nutr Rev 68:739–748. https://doi.org/10.1111/j.1753-4887.2010.00342.x
Kalra S, Aggarwal A, Chillar N, Faridi MMA (2015) Comparison of micronutrient levels in children with cerebral palsy and neurologically normal controls. Indian J Pediatr 82:140–144. https://doi.org/10.1007/s12098-014-1543-z
Asmah RH, Anyele A, Asare-Anane H, Brown AC, Archampong TN, Amegatcher G, Badoe E, Adjei DN, Dzudzor B, Ayeh-Kumi PF (2015) Micronutrient levels and antioxidant status in pediatric cerebral palsy patients. Oxid Antioxid Med Sci 4:73–77. https://doi.org/10.5455/oams.260615.or.088
Jacobsson B, Hagberg G (2004) Antenatal risk factors for cerebral palsy. Best Pract Res Clin Obstet Gynaecol 18:425–436. https://doi.org/10.1016/j.bpobgyn.2004.02.011
Gilbertson M (2004) Male cerebral palsy hospitalization as a potential indicator of neurological effects of methylmercury exposure in Great Lakes communities. Environ Res 95:375–384. https://doi.org/10.1016/j.envres.2003.09.009
Bansal N, Aggarwal A, Faridi MMA, Sharma T, Baneerjee BD (2017) Association of lead levels and cerebral palsy. Glob Pediatr Health 4:2333794X17696681. https://doi.org/10.1177/2333794X17696681
Tanaka H, Tsukuma H, Oshima A (2010) Long-term prospective study of 6104 survivors of arsenic poisoning during infancy due to contaminated milk powder in 1955. J Epidemiol 20:439–445. https://doi.org/10.2188/jea.JE20090131
Kosanovic M, Jokanovic M (2011) Quantitative analysis of toxic and essential elements in human hair. Clinical validity of results. Environ Monit Assess 174:635–643. https://doi.org/10.1007/s10661-010-1484-6
Chojnacka K, Zielińska A, Górecka H, Dobrzański Z, Górecki H (2010) Reference values for hair minerals of Polish students. Environ Toxicol Pharmacol 29:314–319. https://doi.org/10.1016/j.etap.2010.03.010
Kempson IM, Lombi E (2011) Hair analysis as a biomonitor for toxicology, disease and health status. Chem Soc Rev 40:3915–3940. https://doi.org/10.1039/C1CS15021A
Khalique A, Shah MH, Jaffar M, Shaheen N, Tariq SR, Manzoor S (2006) Multivariate analysis of the selected metals in the hair of cerebral palsy patients versus controls. Biol Trace Elem Res 111:11–22. https://doi.org/10.1385/BTER:111:1:11
Józefczuk J, Wiktoria K, Czarnecki R, Graczyk A, Józefczuk P, Magda K, Lampart U, Mrozowska-Ząbek E, Surdy W, Kwiatkowska-Graczyk R (2017) Bioelements in hair of children with selected neurological disorders. Acta Biochim Pol 64:279–285. https://doi.org/10.18388/abp.2016_1380
Wojciak RW, Krejpcio Z (2002) Assessment of the content of selected bioelements in the hair of children with infantile cerebral palsy (paralysis cerebralis infantilis). Trace Elem Electrolytes 19:133–137
Morton J, Carolan VA, Gardiner PHE (2002) Removal of exogenously bound elements from human hair by various washing procedures and determination by inductively coupled plasma mass spectrometry. Anal Chim Acta 455:23–34. https://doi.org/10.1016/S0003-2670(01)01578-1
Skalny AV, Skalnaya MG, Grabeklis AR, Zhegalova IV, Serebryansky EP, Demidov VA, Uzhentseva MS, Lobanova YN, Skalny AA, Tinkov AA (2018) Interactive effects of age and gender on levels of toxic and potentially toxic metals in children hair in different urban environments. Int J Environ Anal Chem 98:520–535. https://doi.org/10.1080/03067319.2018.1480763
Penland JG (1998) The importance of boron nutrition for brain and psychological function. Biol Trace Elem Res 66:299–317. https://doi.org/10.1007/BF02783144
Penland JG (1994) Dietary boron, brain function, and cognitive performance. Environ Health Perspect 102:65–72. https://doi.org/10.1289/ehp.94102s765
Devirian TA, Volpe SL (2003) The physiological effects of dietary boron. Crit Rev Food Sci Nutr 43:219–231. https://doi.org/10.1080/10408690390826491
Uluisik I, Karakaya HC, Koc A (2018) The importance of boron in biological systems. J Trace Elem Med Biol 45:156–162. https://doi.org/10.1016/j.jtemb.2017.10.008
Bebars GM, Afifi MF, Mahrous DM, Okaily NE, Mounir SM, Mohammed EA (2019) Assessment of some micronutrients serum levels in children with severe acute malnutrition with and without cerebral palsy-a follow up case control study. Clin Nutr Exp 23:34–43. https://doi.org/10.1016/j.yclnex.2018.10.008
Munakata M, Onuma A, Kobayashi Y, Haginoya K, Yokoyama H, Fujiwara I, Yasuda H, Tsutsui T, Iinuma K (2006) A preliminary analysis of trace elements in the scalp hair of patients with severe motor disabilities receiving enteral nutrition. Brain Dev 28:521–525. https://doi.org/10.1016/j.braindev.2006.02.004
Schoendorfer N, Tinggi U, Sharp N, Boyd R, Vitetta L, Davies PS (2011) Micronutrient intakes in enterally and orally fed children with severe cerebral palsy. E Spen Eur E J Clin Nutr Metab 6:e259–e263
Schweizer U, Bräuer AU, Köhrle J, Nitsch R, Savaskan NE (2004) Selenium and brain function: a poorly recognized liaison. Brain Res Rev 45:164–178. https://doi.org/10.1016/j.brainresrev.2004.03.004
Steinbrenner H, Sies H (2013) Selenium homeostasis and antioxidant selenoproteins in brain: implications for disorders in the central nervous system. Arch Biochem Biophys 536:152–157. https://doi.org/10.1016/j.abb.2013.02.021
Nazıroğlu M (2009) Role of selenium on calcium signaling and oxidative stress-induced molecular pathways in epilepsy. Neurochem Res 34:2181–2191. https://doi.org/10.1007/s11064-009-0015-8
Zelnik N, Konopnicki M, Bennett-Back O, Castel-Deutsch T, Tirosh E (2010) Risk factors for epilepsy in children with cerebral palsy. Eur J Paediatr Neurol 14:67–72. https://doi.org/10.1016/j.ejpn.2009.06.002
Shahar A, Patel KV, Semba RD, Bandinelli S, Shahar DR, Ferrucci L, Guralnik JM (2010) Plasma selenium is positively related to performance in neurological tasks assessing coordination and motor speed. Mov Disord 25:1909–1915. https://doi.org/10.1002/mds.23218
Olopade JO, Connor JR (2011) Vanadium and neurotoxicity: a review. Curr Top Toxicol 7:33–39
Gruzewska K, Michno A, Pawelczyk T, Bielarczyk H (2014) Essentiality and toxicity of vanadium supplements in health and pathology. J Physiol Pharmacol 65:603–611
Liu Z, Li P, Zhao D, Tang H, Guo J (2012) Protection by vanadium, a contemporary treatment approach to both diabetes and focal cerebral ischemia in rats. Biol Trace Elem Res 145:66–70. https://doi.org/10.1007/s12011-011-9168-9
Peterson MD, Gordon PM, Hurvitz EA (2013) Chronic disease risk among adults with cerebral palsy: the role of premature sarcopoenia, obesity and sedentary behaviour. Obes Rev 14:171–182. https://doi.org/10.1111/j.1467-789X.2012.01052.x
Pessoa JC, Etcheverry S, Gambino D (2015) Vanadium compounds in medicine. Coord Chem Rev 301:24–48. https://doi.org/10.1016/j.ccr.2014.12.002
Elmufti H, Olney RC (2018) Endocrine dysfunction in children with cerebral palsy. In: Miller F, Bachrach S, Lennon N, O'Neil M (eds) Cerebral palsy. Springer, Cham, pp 1–9
Shrestha KP, Carrera AE (1988) Hair trace elements and mental retardation among children. Arch Environ Health 43:396–398. https://doi.org/10.1080/00039896.1988.9935857
Papadopoulos A, Ntaios G, Kaiafa G, Girtovitis F, Saouli Z, Kontoninas Z, Diamantidis MD, Savopoulos C, Hatzitolios A (2008) Increased incidence of iron deficiency anemia secondary to inadequate iron intake in institutionalized, young patients with cerebral palsy. Int J Hematol 88:495–497. https://doi.org/10.1007/s12185-008-0191-3
Madan N, Rusia U, Sikka M, Sharma S, Shankar N (2011) Developmental and neurophysiologic deficits in iron deficiency in children. Indian J Pediatr 78:58–64. https://doi.org/10.1007/s12098-010-0192-0
Petersen TG, Andersen AMN, Uldall P, Paneth N, Feldt-Rasmussen U, Tollånes MC, Strandberg-Larsen K (2018) Maternal thyroid disorder in pregnancy and risk of cerebral palsy in the child: a population-based cohort study. BMC Pediatr 18:181. https://doi.org/10.1186/s12887-018-1152-5
Hong T, Paneth N (2008) Maternal and infant thyroid disorders and cerebral palsy. Semin Perinatol 32:438–445. https://doi.org/10.1053/j.semperi.2008.09.011
Melse-Boonstra A, Jaiswal N (2010) Iodine deficiency in pregnancy, infancy and childhood and its consequences for brain development. Best Pract Res Clin Endocrinol Metab 24:29–38
Redman K, Ruffman T, Fitzgerald P, Skeaff S (2016) Iodine deficiency and the brain: effects and mechanisms. Crit Rev Food Sci Nutr 56:2695–2713. https://doi.org/10.1080/10408398.2014.922042
Gallicchio VS (2011) Lithium-still interesting after all these years. Trace Elem Electrolytes 28:56–69
Yuan J, Song J, Zhu D, Sun E, Xia L, Zhang X, Gao C, Agam G, Wang X, Blomgren K, Zhu C (2018) Lithium treatment is safe in children with intellectual disability. Front Mol Neurosci 11. https://doi.org/10.3389/fnmol.2018.00425
Yu F, Wang Z, Tchantchou F, Chiu CT, Zhang Y, Chuang DM (2012) Lithium ameliorates neurodegeneration, suppresses neuroinflammation, and improves behavioral performance in a mouse model of traumatic brain injury. J Neurotrauma 29:362–374. https://doi.org/10.1089/neu.2011.1942
Hashimoto R, Hough C, Nakazawa T, Yamamoto T, Chuang DM (2002) Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation. J Neurochem 80:589–597. https://doi.org/10.1046/j.0022-3042.2001.00728.x
Fukumoto T, Morinobu S, Okamoto Y, Kagaya A, Yamawaki S (2001) Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain. Psychopharmacology 158:100–106. https://doi.org/10.1007/s002130100871
Rouse DJ (2009) Magnesium sulfate for the prevention of cerebral palsy. Am J Obstet Gynecol 200:610–612. https://doi.org/10.1056/NEJMoa0801187
Rouse DJ, Hirtz DG, Thom E, Varner MW, Spong CY, Mercer BM, Iams JD, Wapner RJ, Sorokin Y, Alexander JM, Harper M, Thorp JM Jr, Ramin SM, Malone FD, Carpenter M, Miodovnik M, Moawad A, O'Sullivan MJ, Peaceman AM, Hankins GD, Langer O, Caritis SN, Roberts JM, Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network (2008) A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 359:895–905. https://doi.org/10.1056/NEJMoa0801187
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
Fragale N, Navarre N, Rogers J (2019) General nutrition for children with cerebral palsy. In: Miller F, Bachrach S, Lennon N, O'Neil M (eds) Cerebral palsy. Springer, Cham, pp 1–10. https://doi.org/10.1007/978-3-319-50592-3_23-1
Sen AP, Gulati A (2010) Use of magnesium in traumatic brain injury. Neurotherapeutics 7:91–99. https://doi.org/10.1016/j.nurt.2009.10.014
Westermaier T, Stetter C, Kunze E, Willner N, Raslan F, Vince GH, Ernestus RI (2013) Magnesium treatment for neuroprotection in ischemic diseases of the brain. Exp Transl Stroke Med 5:6. https://doi.org/10.1186/2040-7378-5-6
Lingam I, Robertson NJ (2018) Magnesium as a neuroprotective agent: a review of its use in the fetus, term infant with neonatal encephalopathy, and the adult stroke patient. Dev Neurosci 40:1–12. https://doi.org/10.1159/000484891
Lecuyer M, Rubio M, Chollat C, Lecointre M, Jégou S, Leroux P, Cleren C, Leroux-Nicollet I, Marpeau L, Vivien D, Marret S, Gonzalez BJ (2017) Experimental and clinical evidence of differential effects of magnesium sulfate on neuroprotection and angiogenesis in the fetal brain. Pharmacol Res Perspect 5:e00315. https://doi.org/10.1002/prp2.315
Kim HJ, Choi HN, Yim JE (2018) Food habits, dietary intake, and body composition in children with cerebral palsy. Clin Nutr Res 7:266–275. https://doi.org/10.7762/cnr.2018.7.4.266
Omotosho IO, Akinade AO, Lagunju IA (2018) Calcium and magnesium levels are down regulated in Nigerian children with autism spectrum disorder and cerebral palsy. Neurosci Med 9:159–170. https://doi.org/10.4236/nm.2018.93016
Miekeley N, de Carvalho Fortes LM, da Silveira CP, Lima MB (2001) Elemental anomalies in hair as indicators of endocrinologic pathologies and deficiencies in calcium and bone metabolism. J Trace Elem Med Biol 15:46–55. https://doi.org/10.1016/S0946-672X(01)80026-2
Houlihan CM, Stevenson RD (2009) Bone density in cerebral palsy. Phys Med Rehabil Clin N Am 20:493–508. https://doi.org/10.1016/j.pmr.2009.04.004
Zhukovskaya ED, Orlova NS, Skalny AV, Kamenschikov AE, Schwarz IA (1992) Contents of some trace elements in hair and red blood cells at cerebral palsy. Pediatria 71:76–77 [in Russian]
Mold M, Umar D, King A, Exley C (2018) Aluminium in brain tissue in autism. J Trace Elem Med Biol 46:76–82. https://doi.org/10.1016/j.jtemb.2017.11.012
Andrew MJ, Sullivan PB (2010) Growth in cerebral palsy. Nutr Clin Pract 25:357–361. https://doi.org/10.1177/0884533610374061
Herskind A, Ritterband-Rosenbaum A, Willerslev-Olsen M, Lorentzen J, Hanson L, Lichtwark G, Nielsen JB (2016) Muscle growth is reduced in 15-month-old children with cerebral palsy. Dev Med Child Neurol 58:485–491. https://doi.org/10.1111/dmcn.12950
Funding
The project was financially supported by the grant of the President of the Russian Federation (No. 075-15-2019-393, MK-1348.2019.7).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
All procedures within the study (examination, sampling) were performed in accordance with the principles of the Declaration of Helsinki and later amendments (2013). The protocol of the present study was approved by the Local Institutional Ethics Committee at Yaroslavl State University (Yaroslavl, Russia). Informed consent was obtained from children’s parents or legal representatives.
Conflict of Interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Tinkov, A.A., Ajsuvakova, O.P. & Skalny, A.V. A Case-Control Study of Essential and Toxic Trace Elements and Minerals in Hair of 0–4-Year-Old Children with Cerebral Palsy. Biol Trace Elem Res 195, 399–408 (2020). https://doi.org/10.1007/s12011-019-01876-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-019-01876-3