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OBJECTIVES: To determine role of folinic acid in improving the adaptive skills and language impairment in autism spectrum disorder (ASD) among children aged 3-14 years.
METHODS: This open label randomized controlled trial was conducted at the Out-patient Department of Pediatric Neurology, The Children Hospital & The Institute of Child Health Multan, Pakistan from October-2020 to March-2021. A total of 44 (22 in each group) children of both genders, aged 3-14 years with diagnosis of ASD were included. Children receiving folinic acid (dose of 2mg/kg/day in two divide doses) and behavioral therapy were assigned to Group-A while Group-B received only behavioral therapy. Primary outcome measures were improvement of language and adaptive skills while secondary outcome measures were stereotype movements, verbal communication, hyperactivity, peer relationship and inattention were these parameters measured at baseline, 6-weeks and 12-weeks (final outcome) intervals.
RESULTS: Of 44 children, 34 (77.3%) were male and 10 (22.7%) female. Mean age was 4.28±1.57 years. At baseline, outcome measures scores in between both study groups had no statistically significant difference (p>0.05). Regarding final outcome, among children in Group-A, primary outcome measures as gross motor development age (51.41±16.29 months vs. 39.23±51.41 months, p=0.002), self-help (48.64±13.68 months vs. 37.45±6.82 months, p=0.001) and language (18.68±6.34 months vs. 15.15±5.22 months, p=0.050) scores improved significantly when compared to Group-B. Regarding secondary outcome, stereotype movements (p=0.028) improved significantly in Group-A in comparison to Group-B.
CONCLUSION: Folinic acid along with behavioral therapy helped improving language and adaptive skills in children with ASD when compared to behavioral therapy alone.
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Hodges H, Fealko C, Soares N. Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation. Transl Pediatr 2020;9(Suppl 1):S55-S65. https://doi.org/10.21037/tp.2019.09.09
Baxter AJ, Brugha TS, Erskine HE, Scheurer RW,Vos T, Scott JG. The epidemiology and global burdenof autism spectrum disorders. Psychol Med 2015;45(3):601-13. https://doi.org/10.1017/S003329171400172X
Akhter M, Ashraf M, Ali A, Rizwan I, Rehman R. Integration of therapies in Autistic children; A survey based in Karachi, Pakistan. J Pak Med Assoc 2018;68:1508.
Furrukh J, Anjum G. Coping with Autism spectrum disorder (ASD) in Pakistan: A phenomenology of mothers who have children with ASD. Cogent Psychol 2020;7:1728108. https://doi.org/10.1080/23311908.2020.1728108
Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA. Cerebral folate receptor autoantibodies in autism spectrum disorder. Mol Psychiatry 2013;18(3):369-81. https://doi.org/10.1038/mp.2011.175
Frye RE, Rossignol DA, Scahill L, McDougle CJ, Huberman H, Quadros EV. Treatment of Folate Metabolism Abnormalities in Autism Spectrum Disorder. Semin Pediatr Neurol 2020;35:100835. https://doi.org/10.1016/j.spen.2020.100835
Frye RE, Slattery J, Delhey L, Furgerson B, Strickland T, Tippett M, et al. Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. Mol Psychiatry 2016;23(2):1-10. https://doi.org/10.1038/mp.2016.168
McBain RK, Kareddy V, Cantor JH, Stein BD, Yu H. Systematic Review: United States Workforce for Autism-Related Child Healthcare Services. J Am Acad Child Adolesc Psychiatry 2020;59(1):113-39. https://doi.10.1016/j.jaac.2019.04.027
Ramaekers VT, Hausler M, Opladen T, Heimann G, Blau N. Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: a novel neurometabolic condition responding to folinic acid substitution. Neuropediatrics 2002;33:301-8. https://doi.org/10.1055/s-2002-37082
Moretti P, Peters SU, Del Gaudio D, Sahoo T, Hyland K, Bottiglieri T et al. Brief report: autistic symptoms, developmental regression, mental retardation, epilepsy, and dyskinesias in CNS folate deficiency. J Autism Dev Disord 2008;38:1170-7. https://doi.org/10.1007/s10803-007-0492-z
Ramaekers VT, Sequeira JM, Artuch R, Blau N, Temudo T, Ormazabal A, et al. Folate receptor autoantibodies and spinal fluid 5-methyltetrahydrofolate deficiency in Rett syndrome. Neuropediatrics 2007;38:179-83. https://doi.org/10.1055/s-2007-991148
Vargason T, Kruger U, Roth E, Delhey LM, Tippett M, Rose S, et al. Comparison of three clinical trial treatments for Autism Spectrum Disorder through multivariate analysis of changes in metabolic profiles and adaptive behavior. Front Cell Neurosci 2018;12:503. https://doi.org/doi:10.3389/fncel.2018.00503
Schreibman L, Stahmer AC. A randomized trial comparison of the effects of verbal and pictorial naturalistic communication strategies on spoken language for young children with autism. J Autism Dev Disord 2014;44:1244-51. https://doi.org/10.1007/s10803-013-1972-y
Wetherby AM, Guthrie W, Woods J, Schatschneider C, Holland RD, Morgan L, et al. Parent-implemented social intervention for toddlers with autism: an RCT. Pediatrics 2014;134:1084-93. https://doi.org/10.1542/peds.2014-0757
Boarman DM, Baram J, Allegra CJ. Mechanism of leucovorin reversal of methotrexate cytotoxicity in human MCF-7 breast cancer cells. Biochem Pharmacol 1990;40:2651-60. https://doi.org/10.1016/0006-2952(90)90583-7
Frye RE, James SJ. Metabolic pathology of autism in relation to redox metabolism. Biomark Med 2014;8:321-30. https://doi.org/10.2217/bmm.13.158
Desai A, Sequeira JM, Quadros EV. The metabolic basis for developmental disorders due to defective folate transport. Biochimie 2016;126:31-42. https://doi.org/10.1016/j.biochi.2016.02.012
Correll CU, Manu P, Olshanskiy V, Napolitano B, Kane JM, Malhotra AK. Cardiometabolic risk of second-generation antipsychotic medications during first time use in children and adolescents. JAMA 2009;302:1765-73. https://doi.org/10.1001/jama.2009.1549
Bobo WV, Cooper WO, Stein CM, Olfson M, Graham D, Daugherty J, et al. Antipsychotics and the risk of type 2 diabetes mellitus in children and youth. JAMA Psychiatry 2013;70:1067-75. https://doi.org/10.1001/jamapsychiatry.2013.2053