血清脂肪酸结合蛋白4与3岁及以下儿童自闭症谱系障碍诊断及神经发育的相关性

Correlation between serum FABP4 levels and diagnosis and neurodevelopment of autism spectrum disorders in children under 3 years of age

目的探讨血清脂肪酸结合蛋白4(FABP4)水平与3岁以下儿童自闭症谱系障碍(ASD)诊断及神经发育的相关性。方法选取2019-05至2022-04空军军医大学第一附属医院儿科和儿童心理科共招募60例≤3岁ASD儿童为研究对象(ASD组),另外纳入同时期正常发育儿童共68例作为对照组。使用酶联免疫吸附试验法测定血清FABP4浓度。ASD的症状用Kaufman儿童成套评价测验(K-ABC)、自闭症诊断观察量表第2版(ADOS-2)进行评估。采用中国儿童神经心理行为检查量表2016版(CNBS-R2016)评估ASD患儿的神经发育水平,计算发育商(DQ),DQ<70分定义为发育障碍。结果ASD组血清FABP4[14.83(9.83,17.93)ng/ml]、血清游离脂肪酸[354.88(282.86,407.76)μmol/L]、血清脂联素[17.04(15.12,21.39)μg/ml]水平显著低于对照组的血清FABP4[17.89(14.05,21.85)ng/ml]、血清游离脂肪酸[410.75(377.51,460.90)μmol/L]、血清脂联素[19.45(18.23,22.20)μg/ml],差异有统计学意义(P<0.05)。经多因素logistic回归分析显示,血清FABP4是ASD发病的独立预测因子(OR=0.914,95%CI:0.857~0.975,P=0.006)。经Spearman秩相关分析,血清FABP4与瘦素、游离脂肪酸呈正相关(P<0.05)。ASD患儿血清FABP4水平与K-ABC智力评分、成就评分及ADOS-2重复刻板行为、社交影响、总分、标准化的严重程度评分均呈负相关(P<0.05)。ASD患儿血清FABP4水平与DQ、CNBS-R2016粗大运动、精细运动、语言评分均呈正相关(P<0.05)。血清FABP4水平是影响ASD患儿神经发育障碍的独立保护因素(OR=0.677,95%CI:0.495~0.925,P=0.014)。结论对于3岁以下的儿童,血清FABP4可能是用于ASD诊断和预测神经发育不良风险的候选生物标志物。

Objective To investigate the correlation between serum fatty acid binding protein 4(FABP4)levels and the diagnosis and neurodevelopment of autism spectrum disorder(ASD)in children≤3 years of age.Methods A total of 60 children with ASD aged 1 to 3 years old were recruited from the Department of Pediatrics and Child Psychology of the First Affiliated Hospital of Military Medical University of Chinese PLA Air Force from May 2019 to April 2022,and a total of 68 children with normal development during the same period were included as the control group.The serum FABP4 concentration was determined by enzyme-linked immunosorbent assay.Symptoms of ASD were assessed using the Kaufman Assossment Battery for Children(K-ABC)and the Autism Diagnostic Observation Scale version 2(ADOS-2).The neurodevelopmental level of children with ASD was evaluated using the Children Neuropsychological and Behavioral Scale-Revision 2016(CNBS-R2016),and the developmental quotient(DQ)was calculated.The score of DQ<70 was defined as developmental disorder(DD).Results The levels of serum FABP4[14.83(9.83,17.93)ng/ml],serum free fatty acid[354.88(282.86,407.76)μmol/l]and serum adiponectin[17.04(15.12,21.39)μg/ml]in ASD group were significantly lower than those in control group respectively[17.89(14.05,21.85)ng/ml,410.75(377.51,460.90)μmol/l,19.45(18.23,22.20)μg/ml],with statistical significance(P<0.05).Multivariate Logistic regression analysis showed that serum FABP4 was an independent factor affecting ASD(OR=0.914,95%CI:0.857-0.975,P=0.006).By Spearman rank correlation analysis,serum FABP4 was positively correlated with leptin and free fatty acid(P<0.05).Serum FABP4 level in children with ASD was negatively correlated with K-ABC mental processing index,achievement score,ADOS-2 restricted repetitive behavior,social affect,total score and calibrated severity score(P<0.05).Serum FABP4 level was positively correlated with DQ,CNBS-R2016 gross motor,fine motor and language scores in ASD children(P<0.05).Serum FABP4 level was an independent protective factor for neurodevelopmental disorders in children with ASD(OR=0.677,95%CI:0.495-0.925,P=0.014).Conclusions In children≤3 years old,serum FABP4 may be a candidate biomarker for ASD diagnosis and prediction of the risk of neurodysplasia.