Effect of Leucovorin (Folinic Acid) on the Developmental Quotient of Children with Downs Syndrome (Trisomy 21) and Influence of Thyroid Status 英文参考文献.docVIP

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Effect of Leucovorin (Folinic Acid) on the Developmental Quotient of Children with Downs Syndrome (Trisomy 21) and Influence of Thyroid Status 英文参考文献.doc

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Effect of Leucovorin (Folinic Acid) on the Developmental Quotient of Children with Downs Syndrome (Trisomy 21) and Influence of Thyroid Status 英文参考文献

EffectofLeucovorin(FolinicAcid)ontheDevelopmental QuotientofChildrenwithDown’sSyndrome(Trisomy21) andInfluenceofThyroidStatus HenriBlehaut1,ClotildeMircher1,Aime′ Ravel1,MartineConte1,VeroniquedePortzamparc1 ,Gwendael Poret1,Franc?oise HuondeKermadec2,Marie-OdileRethore1,3,FranckG.Sturtz1,4 * 1InstitutJeromeLejeune,Paris,France,2LaboratoryofAppliedMathematics,Agrocampus,Rennes,France,3NationalAcademyofMedicine,Paris,France,4Department ofBiochemistryandMolecularGenetics,UniversityofLimoges,Limoges,France Abstract Background:Sevengenesinvolvedinfolatemetabolismarelocatedonchromosome21.Previousstudieshaveshownthat folatedeficiencymaycontributetomentalretardationinDown’ssyndrome(DS). Methodology: We investigated the effect of oral folate supplementation (daily dose of 1.060.3mg/kg) on cognitive functionsinDSchildren,agedfrom3to30months.Theyreceived1mg/kgleucovorinorplacebodaily,for12months,ina single-centre,randomised,double-blindstudy.Folinicacid(leucovorin,LV)waspreferredtofolicacidasitsbioavailabilityis higher.Thedevelopmentalage(DA)ofthepatientswasassessedontheBrunet-Lezinescale,frombaselinetotheendof treatment. Results: The intent-to-treat analysis (113 patients) did not show a positive effect of leucovorin treatment. However, it identifiedimportantfactorsinfluencingtreatmenteffect,suchasage,sex,andconcomitanttreatments,includingthyroid treatment in particular. A per protocol analysis was carried out on patients evaluated by the same examiner at the beginningandendofthetreatmentperiod.Thisanalysisof87patients(43LV-treatedvs.44patientsonplacebo)revealeda positiveeffectofleucovorinondevelopmentalage(DA).DAwas53.1%thenormalvaluewithleucovorinandonly44.1% withplacebo(p,0.05).Thispositiveeffectofleucovorinwasparticularlystronginpatientsreceivingconcomitantthyroxin treatment(59.5%vs.41.8%,p,0.05).Noadverseeventrelatedtoleucovorinwasobserved. Conclusion: These results suggest that leucovorin improves the psychomotor development of children with Down’s syndrome,atleast