Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, 249203, India.
Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, 249203, India.
Eur J Pediatr. 2024 Nov;183(11):4827-4835. doi: 10.1007/s00431-024-05762-6. Epub 2024 Sep 7.
Oral folinic acid has shown potential to improve symptoms in children with autism spectrum disorder (ASD). However, randomized controlled trials (RCTs) are limited. This double-blind, placebo-controlled RCT aimed to compare changes in Childhood Autism Rating Scale (CARS) scores in children with ASD aged 2-10 years, among folinic acid (2 mg/kg/day, maximum of 50 mg/day) and placebo groups at 24 weeks, in comparison with baseline. Both the groups received standard care (ABA and sensory integration therapy). Secondary objectives included changes in behavioral problems measured by the Child Behavior Checklist (CBCL) and serum levels of anti-folate receptor autoantibodies and folic acid, correlated with changes in autism symptom severity. Out of the 40 participants recruited in each group, 39 and 38 participants completed the 24-week follow-up in the folinic acid and placebo groups, respectively. The change in CARS score was higher in the folinic acid group (3.6 ± 0.8) compared to the placebo group (2.4 ± 0.7, p < 0.001). Changes in CBCL total score and CBCL internalizing score were also better in the folinic acid group (19.7 ± 9.5 vs. 12.6 ± 8.4 and 15.4 ± 7.8 vs. 8.5 ± 5.7, p < 0.001 for both). High-titer anti-folate receptor autoantibodies were positive in 32/40 and 33/40 cases in the folinic acid and placebo groups, respectively (p = 0.78). In the placebo group, improvement in CARS score was comparable regardless of autoantibody status (p = 0.11), but in the folinic acid group, improvement was more pronounced in the high-titer autoantibody group (p = 0.03). No adverse reactions were reported in either group.
Oral folinic acid supplementation is effective and safe in improving ASD symptoms, with more pronounced benefits in children with high titers of folate receptor autoantibodies.
CTRI/2021/07/034901, dated 15-07-2021.
• Folate receptor autoantibodies are more prevalent in children with autism spectrum disorder (ASD) compared to typically developing children. • Folate receptor autoantibodies play a significant role in the neuropathogenesis of autism spectrum disorder.
• Add-on oral folinic acid supplementation is safe and effective in reducing the severity of symptoms in children with ASD. • The clinical benefits are more pronounced in children with high titers of folate receptor autoantibodies.
评估口服叶酸治疗儿童自闭症谱系障碍（ASD）的疗效和安全性。
采用双盲、安慰剂对照的 RCT 设计，纳入年龄 2-10 岁的 ASD 儿童，在标准治疗（ABA 和感觉统合疗法）的基础上，分别给予叶酸（2mg/kg/d，最大剂量 50mg/d）或安慰剂治疗 24 周，比较两组患儿在 ASD 严重程度（采用儿童自闭症评定量表，CARS）、行为问题（采用儿童行为检查表，CBCL）及叶酸和抗叶酸受体自身抗体血清水平的变化，并分析抗叶酸受体自身抗体与自闭症严重程度的相关性。
两组患儿分别有 40 例纳入研究，每组各有 39 例和 38 例患儿完成 24 周随访。与安慰剂组相比，叶酸组患儿的 CARS 评分改善更明显（3.6±0.8 比 2.4±0.7，p<0.001），CBCL 总分和 CBCL 内化评分的改善也更明显（19.7±9.5 比 12.6±8.4，15.4±7.8 比 8.5±5.7，均 p<0.001）。叶酸组和安慰剂组分别有 32/40 例和 33/40 例患儿血清抗叶酸受体自身抗体滴度较高（p=0.78）。在安慰剂组中，无论自身抗体状态如何，CARS 评分的改善情况无显著差异（p=0.11），但在叶酸组中，高滴度自身抗体组的改善更显著（p=0.03）。两组患儿均未出现不良反应。
口服叶酸补充剂可有效改善 ASD 患儿的症状，且在高滴度抗叶酸受体自身抗体患儿中获益更明显。
