A Multi-center Clinical Study Of Modified Atkins Diet In The Treatment Of Children With Global Developmental Delay

BackgroundGlobal developmental delay(GDD)is a common neurodevelopmental disorder.It is a transitional diagnosis and is suitable for infants under 5 years old.The incidence rate is high,about 1%~3%.Most children with GDD are currently unclear and lack effective treatment.Without timely intervention,most children may develop into intellectual disability(ID),which will affect their quality of life throughout their lives.The modified Atkins diet(MAD)is based on the ketogenic diet(KD)and is also a high-fat diet in nature.Our previous study confirmed that KD can improve the neurobehavioral development of children with GDD,but the sample size is small,the follow-up time is short,and the source is single.Therefore,in order to comprehensively evaluate the clinical efficacy,safety and compliance of MAD in the treatment of GDD,We expanded the sample size and extended the follow-up time to conduct a multi-center clinical controlled study of 121 children with GDD from multiple regions and different hospitals.Purpose1.To observe the effects of MAD therapy on neurobehavioral development,abnormal mood,social life ability and growth of children with GDD,and to monitor adverse reactions,thus providing new ideas for the clinical treatment of GDD.2.To compare the compliance of children with different degrees of developmental delay.MethodsA total of 154 children with GDD were enrolled in the Children's Rehabilitation Department of 9 hospitals in different regions of Henan Province.All the children were divided into the MAD treatment group(n=88)and the conventional treatment group(n=66)according to the random number table method.However,during the follow-up period,33 cases were detached due to various reasons.Finally,121 cases were included,including 62 cases in the MAD treatment group and 59 cases in the conventional treatment group.On the basis of comprehensive rehabilitation,the conventional treatment group was given a regular diet,and the other group was given MAD.The height and weight measurements,laboratory examination and scale assessment were performed before and every 3 months after treatment.Follow-up time was 15 months.To compare the neurobehavioral development,abnormal emotion,social living ability and growth of the two groups before and after treatment,to evaluate the compliance of children with different degrees of developmental delay,and to monitor the adverse reactions.Results1.Clinical efficacyIn the aspect of neurobehavioral development,the scores of adaptive,fine motor,language and personal socialization in the MAD treatment group were significantly improved compared with the conventional treatment group,the difference was statistically significant(P<0.05),and the longer the treatment time,the more obvious the improvement;there was no significant difference in the score of great movement between the two groups(P>0.05).In emotional and social behavior,at 6,9,12,15 months after treatment,the scores of ability dimension and problem dimension in MAD group were significantly improved than those in routine treatment group(P<0.05).In terms of social living ability,the improvement of Sam scale score in MAD group was better than that in routine treatment group at 9,12,15 months after treatment(P<0.05).2.Growth and developmentThere were no significant differences between the two groups in height for age Z score(HAZ)and weight for age Z score(WAZ)(P>0.05).3.Adverse reactionsIn the MAD treatment group,24 of the 62 patients developed various adverse reactions,mainly gastrointestinal dysfunction: 6 cases of diarrhea,5 cases of constipation,3 cases of nausea and vomiting.In addition,we also found refusal to eat(2 cases),lethargy(2 cases),dyslipidemia(2 cases),liver enzyme abnormalities(2 cases),transient hypoglycemia(1 cases)and urinary calculi(1cases).The adverse reactions were relieved gradually after symptomatic treatment and did not cause obvious damage to the body.No other serious adverse reactions such as hypoproteinemia,pancreatitis,and osteoporosis were observed during follow-up.4.Reservation rateAt the 15 th month of treatment,a total of 62 children with GDD remained,with a total retention rate of 70.45%.Compared with the 4 groups,the retention rate was 63.16% in the mild developmental delay group and 7 cases were withdrawn during the follow-up period.The retention rate was 79.31% in the moderate developmental delay group and 6 cases were withdrawn during the follow-up period.The retention rate was 75.00% in the severe developmental delay group and 8 cases were withdrawn during the follow-up.The retention rate was 37.50% in the extremely severe developmental delay group and 5 cases during the follow-up.Conclusions1.MAD can improve the neurobehavioral development,reduce abnormal mood,and improve social life in children with GDD,and the longer the treatment,the more obvious the effect.2.MAD has no significant effect on the growth and is a safe treatment with less adverse reactions for children with GDD.3.MAD has a better overall compliance in the treatment of children with GDD.Among them,the compliance of children with extremely severe developmental delay was the worst,that of mild developmental delay was the second,and that of moderate and severe developmental delay was the best.