| Objective1.To describe the status of neonatal inherited metabolic diseases(IMD)on tandemmass spectrometry(MS/MS)in Gansu province,and to explore the effect of different detections on the positive rate of screening,which are good to provide a scientific basis study for making some economical,effective and feasible strategies to prevention and control of inherited metabolic diseases.2.The normal reference value of various amino acids and acyl carnitine analytes in MS / MS non-derivatized neonatal dry blood spot samples was proposed.The differences in the reference distribution of different conditions was discussed.To provide a theoretical basis for reducing the false positive rate of IMD screening in Gansu Province and determining the positive cut value.Methods1.The current study on IMD screening status of infants in Gansu provinceAccording to the proportion of the number of live births in municipalities in Gansu Province in 2015(According to the annual statistical standards for maternal and child information,the datas were collected from the October 1 in 2014 to September 30 in 2015).Using the cluster random sampling principle,31,600 newborns in Gansu Province were collected in 2016(October 1,2015 to September 30,2016),which were the birth of 2 to 7 days.After informed consent and signature by newborn parents,the sex,date of birth,date of birth,birth weight,gestational age,household registration,birth area and mother’s mode of delivery were recorded,using tandem mass spectrometry for screening,to recall,diagnose and follow up on positive infants.Through the statistics of inherited metabolic diseases screening positive rate,positive recall rate,diagnosis rate,confirmed disease spectrum and the prevalence of confirmed disease,comparison of sex,birth weight,gestational age,household registration,area,mode of delivery and birth season,infants inherited metabolic diseases screening results,to explore the inherited metabolic diseases screening results of the factors.Using SPSS19.0 and Excel2013 for data statistical analysis,using four tables,R * C contingency table chi-square test or Fisher exact test method for comparison between groups,α= 0.05 was used as the test level.2.To establish the normal reference value for non-derivatized analyte of tandem mass spectrometry in Gansu provinceAccording to the requirements of the American Association for Clinical Laboratory Standardization,this study included 31,553 samples from the Gansu Province by tandem mass spectrometry in 2015.The contents of 11 amino acids and 31 acyl carnitine in dry blood spot were detected by tandem mass spectrometry non-derivatization.Using SPSS19.0 and Excel 2013 for data processing and analysis.Using a single sample Kolmogorov-Smirnov test to determine the normality of the data,P>0.05 was the normal distribution;Levene’s test was used to check the variance homogeneity of each group.P>0.05 showed that the variance of the test data was uniform.Using T-test for the data consistent with the normal distribution and variance of the homogeneous;for the data do not meet the normality and variance of homogeneous,the two groups were compared using Mann-Whitney U test;multiple groups were compared using the Kruskal-Wallis H test,and α= 0.05 was used as the test level.Normal distribution of 95% and 99% of the reference range,bilateral use "?-1.96 s ~ ?+ 1.96s",unilateral upper limit "?+ 1.96s",unilateral lower limit "?-1.96s";99% of the reference range,bilateral use of "?-2.58 s ~ ?+2.58s",unilateral upper limit "?+2.58s",unilateral lower limit "?-2.58s";non-normal distribution of data using percentile method,95 % Of the reference range of bilateral “P2.5 ~ P97.5”,the upper limit of one side is “P95”,the lower limit of the single side is “P5”;99% of the reference range of both sides are “P0.5 ~ P99.5”,single-sided upper limit is “P99”,the lower limit of the single side is “P1”.Results1.Study on screening status of inherited metabolic diseases infants in Gansu province(1)In Gansu province,the positive rate of IMD was 3.97%,the positive recall rate was 83.17%,47 cases were diagnosed,the diagnosis rate was 0.15%,the overall prevalence rate was 158/million.8 species of inherited metabolic diseases were diagnosed,which contained 34 cases(114/million)of phenylketonuria,5 cases(17/million)of methylmalonal acidemia,2 cases(7/million)of Primary carnitine deficienc,2 cases(7/million)of fatty acid oxidative metabolic disorders,1 case(3/million)of isovaleric acidemia,1 case(3/million)0f urea nitrogen circulatory disturbance,1 case(3/Million)of β-ketothiolase deficiercy,and 1 case(3/million)of medium chain acyl-CoA dehydrogenase deficiency.(2)Male and female screening positive rate were 3.97%,the diagnosis rate was 0.14%.The positive rate of screening for low birth weight was 5.26%,the diagnosis rate was 0.31%,the positive rate of normal weight was 3.90%,the diagnosis rate was 0.15%,the positive rate of giant screening was 4.53%,the diagnosis rate was 0.06%.The positive rate of natural childbirth screening was 4.03%,the diagnosis rate was 0.14%;the positive rate of cesarean section screening was 3.72%,the diagnosis rate was 0.20%.The positive rate of urban screening was 3.98% and the diagnosis rate was 0.15%.The positive rate of screening in rural areas was 3.96% and the diagnosis rate was 0.15%.There was no significant difference in the positive rate of chi-square test between the two groups,and the difference was not statistically significant(P>0.05).(3)The positive rate of screening was 6.02%,the diagnosis rate was 0.11%,the positive rate of normal children was 3.90%,the diagnosis rate was 0.15%,the positive rate of outpatient screening was 4.98%.The diagnosis rate was 0.33%.The difference was statistically significant(P <0.05),and the positive rate of screening was the highest among the two groups.There was no significant difference between the two groups(P> 0.05).(4)The first quarter screening rate was 6.32%,the diagnosis rate was 0.38%;the second quarter screening rate was 4.28%,the diagnosis rate was 0.24%;the third quarter screening rate was 4.40%,the diagnosis rate was 0.03%(P<0.05).The positive rate of screening was 0.14%,and the diagnosis rate was 0.02%.The positive rate of screening between the two groups was significantly different(P<0.05).The diagnostic rate was determined by chi-square test,which was significantly different(P<0.05).(5)In Gansu Province,the high positive rate of IMD screening were the Gannan region and the western region,and Zhangye City was the highest.The high rate of diagnosis was Gannan and Midwest,and the highest diagnosis rate was found in Gannan Prefecture(P <0.05).The difference between the two groups was significantly different(P<0.05).The difference between the two groups was statistically significant(P<0.05).2.To establish the normal reference value for non-derivatized analyte of tandem mass spectrometry in Gansu province.(1)The 95% reference values of 11 amino acids and 31 acyl carnitine are as followsBilateral range: ALA(222.85-713.20),ARG(1.90-31.99),CIT(6.06-31.60),GLY(193.93-866.46),LEU(84.93-288.00),MET(3.30-26.10),ORN(35.74-223.10),PHE(29.87-86.80),PRO(89.06-350.97),TYR(41.67-186.95),VAL(66.67-252.85),C0(10.87-48.96),C2(2.69-24.87),C3(0.51-3.29),C3DC_C4OH(0.05-0.32),C5: 1(0-0.01),C5DC_C6OH(0.05-0.23),C6(0.01-0.06),C8(0-0.32),C4(0.08-0.32)(0.02-0.08),C8: 1(0.06-0.32),C12(0.02-0.14),C12: 1(0.02-0.11),C14: 1(0.03-0.14),C16(0.67-5.14),C16:(0.03-0.32),C16: 1-OH(0.02-0.08),C18(0.31-1.32),C18: 1(0.60-2.38),C18: 2(0.09-0.52).Unilateral range: C10: 2(0-0.09),C14(0-0.28),C14: 2(0-0.03),C14OH(0-0.09),C10: 0-0.02),C16OH(0-0.03),C18: 1-OH(0-0.04),C18OH(0-0.02).(2)The distribution of 11 amino acids and 31 acyl carnitine analytes in the male and female groups were tested by nonparametric,except for C5: 1,C6 DC,C8: 1and C10: 2,the other indexes were significant different(P<0.05).(3)The distribution of 11 amino acids and 31 acyl carnitine analytes in different gestational weeks were tested by nonparametric test,except for C3DC_C4OH,C5: 1,C10: 1,C18: 2 s,the other indicators were significantly different(P<0.05).(4)The distribution of 11 amino acids and 31 acyl carnitine analytes from different birth weights was tested,CIT,PRO,C3,C4,C5: 1,C8,C8: 1 were significanty different(P<0.05).(5)The distribution of 11 amino acids and 31 acyl carnitine analytes in different delivery modes was tested by ALA test.CIT,GLY,LEU,ORN,PRO,TYR,VAL,C4,C5,C5DC_C6OH,C6,C8: 1,C10: C12: 1,C14: 1,C16: 1-OH,C18,C18: 1-OH and C18 OH were significantly different(P<0.05).(6)The distribution of 11 amino acids and 31 acyl carnitine analytes in different household registers was tested,PHE,TYR,C3DC_C4OH,C4DC_C5OH,C5,C5: 1,C14,C14 OH and C16 OH were not significantly different(P>0.05),and the other indexes were significantly different(P<0.05).(7)The distribution of 11 amino acids and 31 acyl carnitine analytes in different birth seasons and birth areas were significantly different(P<0.05).Conclusions1.In Gansu province,the positive rate of IMD screened by tandem mass spectrometry was higher,the positive recall rate was lower,the diagnosis spectrum was less,the coverage and techniques of IMD screening need to further strengthen and improve.2.In order to reduce the false positive rate of genetic test of IMD in Gansu Province,11 amino acids and 31 acyl carnitine were selected for the screening of infants in Gansu province.3.Pregnancy,seasonal andregional could affect the positive rate and the diagnostic rate.Through the preliminary exploration of the distribution of differences of 11 amino acids and 31 acyl carnitine under different conditions,it showed that some of the indicators will be different distribution under different conditions. |
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