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BMC Pediatrics
Published in: BMC Pediatrics 1/2019

Open Access 01-12-2019 | Icterus | Research article

Improvement in gross motor function and muscle tone in children with cerebral palsy related to neonatal icterus: an open-label, uncontrolled clinical trial

Authors: Liem Nguyen Thanh, Kien Nguyen Trung, Chinh Vu Duy, Doan Ngo Van, Phuong Nguyen Hoang, Anh Nguyen Thi Phuong, Minh Duy Ngo, Thinh Nguyen Thi, Anh Bui Viet

Published in: BMC Pediatrics | Issue 1/2019

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Abstract

Background

Although stem cell transplantation has been successfully performed for cerebral palsy (CP) related to oxygen deprivation, clinical trials involving the use of stem cell transplantation for CP related to neonatal icterus have not been reported. The aim of this study was to evaluate the effectiveness of transplantation of autologous bone marrow mononuclear cell (BMMC) for improving gross motor function and muscle tone in children with CP related to neonatal icterus.

Methods

This open-label, uncontrolled clinical trial, which included 25 patients with CP related to neonatal icterus who had a Gross Motor Function Classification System (GMFCS) score between level II and level V, was conducted between July 2014 and July 2017 at Vinmec International Hospital (Vietnam). BMMC were harvested from the patients’ iliac crests. Two procedures involving BMMC transplantation via the intrathecal route were performed: the first transplantation was performed at baseline, and the second transplantation was performed 6 months after the first transplantation. Gross motor function and muscle tone were measured at three time points (baseline, 6 months, and 12 months) using the Gross Motor Function Measure (GMFM) and the Modified Ashworth Scale.

Results

In this trial, we observed significant improvement in gross motor function and a significant decrease in muscle tone values. Total score on the 88-item GMFM (GMFM-88), scores on each GMFM-88 domain, and the 66-item GMFM (GMFM-66) percentile were significantly enhanced at 6 months and 12 months after the first transplantation compared with the corresponding baseline measurements (p-values < 0.05). In addition, a significant reduction was observed in muscle tone score after the transplantations (p-value < 0.05).

Conclusion

Autologous BMMC transplantation can improve gross motor function and muscle tone in children with CP related to neonatal icterus.

Trial registration

ClinicalTrials.gov identifier: NCT03123562. Retrospectively registered on December 26, 2017.
Appendix
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Literature
1.
David K, Phyllis A, Susan R. Understanding newborn jaundice. J Perinatol. 2001;21(Suppl 1):S21–4 discussion S35–29.
2.
Le LT, Partridge JC, Tran BH, Le VT, Duong TK, Nguyen HT, et al. Care practices and traditional beliefs related to neonatal jaundice in northern Vietnam: a population-based, cross-sectional descriptive study. BMC Pediatr. 2014;14:264.PubMedPubMedCentralCrossRef
3.
4.
Johnson L, Bhutani VK, Karp K, Sivieri EM, Shapiro SM. Clinical report from the pilot USA kernicterus registry (1992 to 2004). J Perinatol: official journal of the California Perinatal Association. 2009;29(Suppl 1):S25–45.CrossRef
5.
Mukhopadhyay K, Chowdhary G, Singh P, Kumar P, Narang A. Neurodevelopmental outcome of acute bilirubin encephalopathy. J Trop Pediatr. 2010;56(5):333–6.PubMedCrossRef
6.
Okumura A, Kidokoro H, Shoji H, Nakazawa T, Mimaki M, Fujii K, et al. Kernicterus in preterm infants. Pediatrics. 2009;123(6):e1052–8.PubMedCrossRef
7.
Rasul CH, Hasan MA, Yasmin F. Outcome of neonatal hyperbilirubinemia in a tertiary care hospital in Bangladesh. Malays J Med Sci. 2010;17(2):40–4.PubMedPubMedCentral
8.
Maimburg RD, Bech BH, Bjerre JV, Olsen J, Moller-Madsen B. Obstetric outcome in Danish children with a validated diagnosis of kernicterus. Acta Obstet Gynecol Scand. 2009;88(9):1011–6.PubMedCrossRef
9.
Shapiro SM. Chronic bilirubin encephalopathy: diagnosis and outcome. Semin Fetal Neonatal Med. 2010;15(3):157–63.PubMedCrossRef
10.
Kaplan M, Bromiker R, Hammerman C. Severe neonatal hyperbilirubinemia and kernicterus: are these still problems in the third millennium? Neonatology. 2011;100(4):354–62.PubMedCrossRef
11.
Farouk ZL, Muhammed A, Gambo S, Mukhtar-Yola M, Umar Abdullahi S, Slusher TM. Follow-up of Children with Kernicterus in Kano, Nigeria. J Trop Pediatr. 2017;64(3):176–82.CrossRef
12.
13.
Shapiro SM. Bilirubin toxicity in the developing nervous system. Pediatr Neurol. 2003;29(5):410–21.PubMedCrossRef
14.
Wu YW, Kuzniewicz MW, Wickremasinghe AC, Walsh EM, Wi S, McCulloch CE, et al. Risk for cerebral palsy in infants with total serum bilirubin levels at or above the exchange transfusion threshold: a population-based study. JAMA Pediatr. 2015;169(3):239–46.PubMedCrossRef
15.
Kantake M, Hirano A, Sano M, Urushihata N, Tanemura H, Oki K, et al. Transplantation of allogeneic adipose-derived mesenchymal stem cells in a cerebral palsy patient (retracted). Regen Med. 2017;12(5):575.PubMedCrossRef
16.
Nguyen LT, Nguyen AT, Vu CD, Ngo DV, Bui AV. Outcomes of autologous bone marrow mononuclear cells for cerebral palsy: an open label uncontrolled clinical trial. BMC Pediatr. 2017;17(1):104.PubMedPubMedCentralCrossRef
17.
Park KI, Lee YH, Rah WJ, Jo SH, Park SB, Han SH, et al. Effect of intravenous infusion of G-CSF-mobilized peripheral blood mononuclear cells on upper extremity function in cerebral palsy children. Ann Rehabil Med. 2017;41(1):113–20.PubMedPubMedCentralCrossRef
18.
Liu X, Fu X, Dai G, Wang X, Zhang Z, Cheng H, et al. Comparative analysis of curative effect of bone marrow mesenchymal stem cell and bone marrow mononuclear cell transplantation for spastic cerebral palsy. J Transl Med. 2017;15(1):48.PubMedPubMedCentralCrossRef
19.
Abi Chahine NH, Wehbe TW, Hilal RA, Zoghbi VV, Melki AE, Habib EB. Treatment of cerebral palsy with stem cells: a report of 17 cases. Int J of Stem Cells. 2016;9(1):90–5.CrossRef
20.
Bansal H, Singh L, Verma P, Agrawal A, Leon J, Sundell IB, et al. Administration of Autologous Bone Marrow-Derived Stem Cells for treatment of cerebral palsy patients: a proof of concept. J Stem Cells. 2016;11(1):37–49.PubMed
21.
Feng M, Lu A, Gao H, Qian C, Zhang J, Lin T, et al. Safety of allogeneic umbilical cord blood stem cells therapy in patients with severe cerebral palsy: a retrospective study. Stem Cells Int. 2015;2015:325652.PubMedPubMedCentralCrossRef
22.
Sharma A, Sane H, Gokulchandran N, Kulkarni P, Gandhi S, Sundaram J, et al. A clinical study of autologous bone marrow mononuclear cells for cerebral palsy patients: a new frontier. Stem Cells Int. 2015;2015:905874.PubMedPubMedCentralCrossRef
23.
Zali A, Arab L, Ashrafi F, Mardpour S, Niknejhadi M, Hedayati-Asl AA, et al. Intrathecal injection of CD133-positive enriched bone marrow progenitor cells in children with cerebral palsy: feasibility and safety. Cytotherapy. 2015;17(2):232–41.PubMedCrossRef
24.
Wang X, Hu H, Hua R, Yang J, Zheng P, Niu X, et al. Effect of umbilical cord mesenchymal stromal cells on motor functions of identical twins with cerebral palsy: pilot study on the correlation of efficacy and hereditary factors. Cytotherapy. 2015;17(2):224–31.PubMedCrossRef
25.
Zhang C, Huang L, Gu J, Zhou X. Therapy for Cerebral Palsy by Human Umbilical Cord Blood Mesenchymal Stem Cells Transplantation Combined With Basic Rehabilitation Treatment: A Case Report. Glob Pediatr Health. 2015;2:2333794X15574091.PubMedPubMedCentral
26.
Shroff G, Gupta A, Barthakur JK. Therapeutic potential of human embryonic stem cell transplantation in patients with cerebral palsy. J Transl Med. 2014;12:318.PubMedPubMedCentralCrossRef
27.
Wang X, Cheng H, Hua R, Yang J, Dai G, Zhang Z, et al. Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study. Cytotherapy. 2013;15(12):1549–62.PubMedCrossRef
28.
Ren C, Geng RL, Ge W, Liu XY, Chen H, Wan MR, et al. An observational study of autologous bone marrow-derived stem cells transplantation in seven patients with nervous system diseases: a 2-year follow-up. Cell Biochem Biophys. 2014;69(1):179–87.PubMedCrossRef
29.
Moon JH, Kim MJ, Song SY, Lee YJ, Choi YY, Kim SH, et al. Safety and efficacy of G-CSF mobilization and collection of autologous peripheral blood stem cells in children with cerebral palsy. Transfus Apher Sci. 2013;49(3):516–21.PubMedCrossRef
30.
Jensen A, Hamelmann E. First autologous cell therapy of cerebral palsy caused by hypoxic-ischemic brain damage in a child after cardiac arrest-individual treatment with cord blood. Case Rep Transplant. 2013;2013:951827.PubMedPubMedCentral
31.
Wang L, Ji H, Zhou J, Xie J, Zhong Z, Li M, et al. Therapeutic potential of umbilical cord mesenchymal stromal cells transplantation for cerebral palsy: a case report. Case Rep Transplant. 2013;2013:146347.PubMedPubMedCentral
32.
Min K, Song J, Kang JY, Ko J, Ryu JS, Kang MS, et al. Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: a double-blind, randomized, placebo-controlled trial. Stem Cells. 2013;31(3):581–91.PubMedCrossRef
33.
Purandare C, Shitole DG, Belle V, Kedari A, Bora N, Joshi M. Therapeutic potential of autologous stem cell transplantation for cerebral palsy. Case Rep Transplant. 2012;2012:825289.PubMedPubMedCentral
34.
He S, Luan Z, Qu S, Qiu X, Xin D, Jia W, et al. Ultrasound guided neural stem cell transplantation through the lateral ventricle for treatment of cerebral palsy in children. Neural Regen Res. 2012;7(32):2529–35.PubMedPubMedCentral
35.
Li M, Yu A, Zhang F, Dai G, Cheng H, Wang X, et al. Treatment of one case of cerebral palsy combined with posterior visual pathway injury using autologous bone marrow mesenchymal stem cells. J Transl Med. 2012;10:100.PubMedPubMedCentralCrossRef
36.
Sharma A, Gokulchandran N, Chopra G, Kulkarni P, Lohia M, Badhe P, et al. Administration of autologous bone marrow-derived mononuclear cells in children with incurable neurological disorders and injury is safe and improves their quality of life. Cell Transplant. 2012;21(Suppl 1):S79–90.PubMedCrossRef
37.
Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol. 1997;39(4):214–23.PubMedCrossRef
38.
39.
40.
41.
42.
Kulak-Bejda A, Kulak P, Bejda G, Krajewska-Kulak E, Kulak W. Stem cells therapy in cerebral palsy: a systematic review. Brain and Development. 2016;38(8):699–705.PubMedCrossRef
Metadata
Title
Improvement in gross motor function and muscle tone in children with cerebral palsy related to neonatal icterus: an open-label, uncontrolled clinical trial
Authors
Liem Nguyen Thanh
Kien Nguyen Trung
Chinh Vu Duy
Doan Ngo Van
Phuong Nguyen Hoang
Anh Nguyen Thi Phuong
Minh Duy Ngo
Thinh Nguyen Thi
Anh Bui Viet
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2019
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-019-1669-2

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