CAJ | 학술논문

目的评价肠内营养粉剂(AA-PKU1)对0～1岁苯丙酮尿症(PKU)患儿治疗的有效性和安全性.方法采用前瞻、开放、自身前后对照、多中心临床研究方法,对2009年4月至2011年2月收治的39例0～4个月PKU患儿进行评估,评估基线、治疗8周及32周后患儿血苯丙氨酸(PHE)水平、发育商测定(Gesell法)、身高、体质量、头围、营养学指标以及血、尿常规、肝肾功能的变化情况和不良事件发生情况.结果治疗8周后脱落病例3例,36例进入符合方案集进行有效性统计分析,39例进入安全性统计分析;治疗32周后脱落病例5例,34例进入符合方案集进行有效性统计分析,39例进入安全性统计分析.治疗8周和32周时患儿血PHE平均水平分别为196.0 μmol/L、191.1 μmol/L,与基线水平(649.5μmol/L)比较,患儿血PHE水平显著下降,差异有统计学意义(P ＜0.000 1),血PHE水平控制在360 μmol/L以内的控制率分别为88.89％、88.24％;治疗8周和32周时发育商水平与基线比较,差异无统计学意义;治疗8周和32周时的身高、体质量、头围与基线比较,差异均有统计学意义(P均＜0.000 1);治疗32周时的血浆总蛋白、清蛋白、前清蛋白、总胆固醇、三酰甘油、低密度脂蛋白水平与基线比较,差异无统计学意义.安全性方面,不良反应发生例次14次,发生例数10例,均为轻中度胃肠道反应如腹泻、呕吐,可自行缓解或对症处理后缓解和消失.结论 AA-PKU1能有效控制0～1岁患儿的血PHE水平在360 μmol/L以内,通过有效控制患儿血PHE水平,可避免患儿发育商水平进一步下降;AA-PKU1能满足0～1岁患儿正常生长发育的需要并能满足患儿的营养需求及改善患儿的营养状况;临床应用安全、耐受性好.
목적 평개장내영양분제(AA-PKU1)대0～1세분병동뇨증(PKU)환인치료적유효성화안전성.방법 채용전첨、개방、자신전후대조、다중심림상연구방법,대2009년4월지2011년2월수치적39례0～4개월PKU환인진행평고,평고기선、치료8주급32주후환인혈분병안산(PHE)수평、발육상측정(Gesell법)、신고、체질량、두위、영양학지표이급혈、뇨상규、간신공능적변화정황화불량사건발생정황.결과 치료8주후탈락병례3례,36례진입부합방안집진행유효성통계분석,39례진입안전성통계분석;치료32주후탈락병례5례,34례진입부합방안집진행유효성통계분석,39례진입안전성통계분석.치료8주화32주시환인혈PHE평균수평분별위196.0 μmol/L、191.1 μmol/L,여기선수평(649.5μmol/L)비교,환인혈PHE수평현저하강,차이유통계학의의(P ＜0.000 1),혈PHE수평공제재360 μmol/L이내적공제솔분별위88.89％、88.24％;치료8주화32주시발육상수평여기선비교,차이무통계학의의;치료8주화32주시적신고、체질량、두위여기선비교,차이균유통계학의의(P균＜0.000 1);치료32주시적혈장총단백、청단백、전청단백、총담고순、삼선감유、저밀도지단백수평여기선비교,차이무통계학의의.안전성방면,불량반응발생례차14차,발생례수10례,균위경중도위장도반응여복사、구토,가자행완해혹대증처리후완해화소실.결론 AA-PKU1능유효공제0～1세환인적혈PHE수평재360 μmol/L이내,통과유효공제환인혈PHE수평,가피면환인발육상수평진일보하강;AA-PKU1능만족0～1세환인정상생장발육적수요병능만족환인적영양수구급개선환인적영양상황;림상응용안전、내수성호.
Objective To evaluate the efficacy and safety of phenylalanine-free amino acid-based formula (AA-PKU1) in the treatment of Chinese infants with phenylketonuria (PKU).Methods The prospective,open,selfcontrolled,multi-center trial was performed with a 32-week treatment period with recommended AA-PKU1 intake 20 g/(kg body weight · day).Each subject served as his/her own control and the values in treatment after 8 weeks and 32 weeks were compared to baseline.Total 39 PKU infants aged 0-4 months were enrolled in the study.The blood phenylalanine (PHE) level,developmental quotient (DQ),weight,height and head circumferences and nutritional biomarkers [total protein (TP),pre-albumin (Pre-Alb),albumin (Alb),total cholesterol (TC),total triglyceride (TG),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C)] were measured in baseline,after 8 weeks and 32 weeks,respectively.The routine blood & urine examination and the renal & hepatic function examinations were also conducted in baseline,after week 8 and week 32 with adverse events and adverse reactions observed during treatment.Results Three subjects dropped out,36 subjects entered the per protocol set with the statistical analysis of efficacy conducted and 39 subjects entered the safety set with the statistical analysis of safety conducted during treat ment after week 8.Five subjects dropped out,34 subjects entered the per protocol set with the statistical analysis of efficacy conducted and 39 subjects entered the safety set with the statistical analysis of safety conducted during treatment after week 32.The mean blood PHE level in the treatment of week 8 and week 32 were 196.0 μmol/L and 191.1μmol/L,respectively.Statistically significant differences were found between pre-treat PHE level(649.5 μmol/L) and post-treat PHE level(P ＜ 0.000 1).The PHE control rates in week 8 and week 32 were 88.89％ and 88.24％,respectively(the PHE control level ＜ 360 μmol/L).The DQ scores in 5 function areas (adaptive behavior,gross motor,fine motor,language and personal-social behavior) in week 8 and week 32 were similar to baseline.The height,weight and head circumferences in week 8 and week 32 increased significantly compared with baseline (all P ＜ O.000 1).The mean values of TP,Pre-Alb,Alb,TC,TG,LDL-C and HDL-C in week 8 and week 32 were close to baseline within the normal range.The drug-related adverse events(so-called:adverse drug reactions) occurred 14 times in 10 cases (8 cases of diarrhea,1 case of vomiting and 1 case of diarrhea with vomiting) with mild to moderate severity.All these symptoms could either relieve themselves or disappear with symptomatic treatment.Conclusions AA-PKU1 can effectively maintain the ideal blood PHE level and normal intelligence development,and can fulfill normal growth needs and improve the nutritional condition for PKU infants.AA-PKU1 feeding was also safe and well tolerated for PKU infants.