探讨《第2期苯丙酮尿症(PKU)患儿特殊奶粉补助项目》(以下简称为"PKU项目")的临床实施效果。

选择2016年5月至2017年4月，PKU项目在11个省、自治区募集生后3个月内被确诊且符合PKU项目纳入与排除标准的190例PKU患儿为研究对象，纳入PKU组。选择与PKU组患儿同地区、同时期于生后3个月内被确诊为PKU，但是未参加PKU项目且愿意接受本调查随访的59例PKU患儿为对照，纳入对照组。PKU组患儿纳入PKU项目统一管理，对患儿监护人进行"线上+线下"PKU相关健康教育宣教，并免费提供PKU治疗所需无苯丙氨酸(Phe)配方奶粉，每个月约6罐(450 g/罐)，共计216罐。对于对照组PKU患儿治疗管理，主要参照2010年原国家卫生部颁布的《苯丙酮尿症和先天性甲状腺功能减低症诊治技术规范》相关原则和要求进行。对2组PKU患儿血Phe浓度、体格与智力发育情况定期监测。采用Mann-Whitney U检验、χ²检验、分层χ²检验或Fisher确切概率法，比较2组患儿治疗依从性，血Phe浓度、体格与智力发育监测次数达标率，血Phe浓度控制达标率≥80%者占比、体格与智力发育达到正常标准占比。本研究遵循的程序符合本院伦理委员会规定，通过该伦理委员会审查，并获得批准[审批文号：医学科研2021伦审批第(063)号]。本研究征得2组PKU患儿监护人知情同意，并签署临床研究知情同意书。2组患儿地区分布、性别构成比、城市与农村患儿构成比及入组月龄等一般临床资料比较，差异均无统计学意义(P>0.05)。

①PKU组患儿治疗完全依从、部分依从、完全不依从占比分别为72.1%(137/190)、25.3%(48/190)、2.6%(5/190)，对照组分别为39.0%(23/59)、35.6%(21/59)、25.4%(15/59)，PKU组患儿治疗依从性优于对照组患儿，并且差异有统计学意义(Z＝-5.303，P<0.001)。PKU组中来自城市、农村患儿治疗依从性，亦均优于对照组，并且差异均有统计学意义(Z＝-4.027、-3.574，P<0.001)。②PKU组患儿血Phe浓度控制达标率≥80%者占比为31.1%(59/190)，显著高于对照组的15.3%(9/59)，并且差异有统计学意义(χ²＝5.410，P＝0.020)。③PKU组患儿体格、智力发育达到正常标准占比分别为85.5%(163/190)与90.1%(146/190)，显著高于对照组的67.8%(40/59)与69.5%(41/59)，并且差异均有统计学意义(χ²＝9.830、12.582，P＝0.002、<0.001)。PKU组中来自农村患儿体格、智力发育达到正常标准占比，亦均显著高于对照组患儿，差异亦均有统计学意义(χ²＝6.186、9.506，P＝0.013、0.002)。

PKU项目通过对PKU患儿及其监护人进行一系列综合管理，可有效提高PKU患儿治疗依从性，有效治疗患儿生长发育迟缓状况。

To explore clinical implementation effects of Special Milk Powder Subsidizing Program for Children with Phenylketonuria (PKU) Phase 2 (referred to as " PKU project" ).

From May 2016 to April 2017, a total of 190 children with PKU diagnosed within 3 month after birth and meeting inclusion and exclusion criteria of PKU project were recruited into PKU project in 11 provinces and autonomous regions and were included into PKU group. Another 59 children with PKU who were diagnosed as PKU within 3 months after birth in the same region as children in PKU group, but did not participate in PKU project and were willing to be followed up in this survey were selected as controls and included into control group. Children in PKU group were included in unified management of PKU project, and guardians of children were provided with health education related with PKU online and offline, and children were provided with phenylalanine (Phe) free formula milk powder for free, about 6 cans (450 g/can) per month, a total of 216 cans. Treatment and management of PKU children in control group were mainly referred to relevant principles and requirements of Technical Specifications for Diagnosis and Treatment of Phenylketonuria and Congenital Hypothyroidism issued by the former National Ministry of Health in 2010. Blood Phe concentration, physical and intellectual development of children in two groups were monitored regularly. Mann-Whitney U test, chi-square test, Cochran-Mantel-Haenszel test and Fisher′s exact probability test were used to compare treatment compliance, compliance rate of monitoring times of blood Phe concentration, physical and intellectual development, proportion of children whose blood Phe concentration control compliance rate ≥80%, and proportion of physical and intellectual development reached normal standard. Procedures followed in this study met the standards formulated by the Ethics Review Committee of West China Second University Hospital, Sichuan University and has been approved by it [Approval No. 2021(063)]. The informed consent was obtained from the guardians of PKU children in two groups for this study and signed informed consent for clinical study. There were no significant differences in general clinical data such as regional distribution, gender composition ratio, urban and rural children composition ratio, and age at enrollment between two groups (P>0.05).

①Proportions of complete compliance, partial compliance, and total noncompliance of PKU children in PKU group were 72.1% (137/190), 25.3% (48/190), and 2.6% (5/190), respectively, and those in control group were 39.0% (23/59), 35.6% (21/59), and 25.4% (15/59), respectively. Treatment compliance of PKU children in PKU group was better than that of control group, and the difference was statistically significant (Z=-5.303, P<0.001). In both urban and rural areas, treatment compliance of children in PKU group was better than that in control group, and the differences were statistically significant (Z=-4.027, -3.574; P<0.001). ②Proportion of children in PKU group whose blood Phe concentration control compliance rate ≥80% was 31.1% (59/190), which was significantly higher than that in control group 15.3% (9/59), and the difference was statistically significant (χ²=5.410, P=0.020). ③Proportions of physical and intellectual development reached normal standard in PKU group were 85.5% (163/190) and 90.1% (146/190), respectively, which were significantly higher than those in control group 67.8% (40/59) and 69.5% (41/59), respectively, and the differences were statistically significant (χ²=9.830, 12.582; P=0.002, <0.001). In rural areas, proportions of physical and intellectual development reached normal standard in PKU group were significantly higher than those in control group, and the differences were statistically significant (χ²=6.186, 9.506; P=0.013, 0.002).

PKU project, through systematic and comprehensive management of children with PKU and their guardians, can effectively improve treatment compliance of children with PKU, and effectively treat growth and developmental retardation of children.