Exploration of cut-off values of amino acid levels in premature infants in Sichuan / 中华实用儿科临床杂志

Objective:To detective the cut-off values of amino acid levels in premature infants in Sichuan.Methods:Data of newborns screening for inherited metabolic diseases (IMD) by tandem mass spectrometry in Sichuan Province from January 2018 to December 2019 were retrospectively analyzed.They were divided into premature infant group ( n=2 264, 1 312 males and 952 females) and full-term infant group ( n=53 275, 28 269 males and 25 006 females). The cut-off values of amino acids in dry blood spots were expressed as percentage ( P0.5 - P99.5), and rank sum test was used for comparison between preterm and full-term infants. Results:(1) The distribution of 11 amino acids [alanine (ALA), arginine (ARG), citrulline (CIT), glycine(GLY), leucine (LEU), methionine (MET), ornithine (ORN), phenylalanine (PHE), proline (PRO), tyrosine (TYR) and valine (VAL)] in premature infants were abnormal.(2) The cut-off values of amino acids in premature infants were as follows: ALA: 135.20-552.33 μmol/L, ARG: 1.34-47.04 μmol/L, CIT: 5.66-32.02 μmol/L, GLY: 181.48-909.93 μmol/L, LEU : 71.10-283.29 μmol/L, MET: 4.21-34.51 μmol/L, ORN: 40.58-293.76 μmol/L, PHE: 23.60-106.30 μmol/L, PRO: 77.76-358.24 μmol/L, TYR: 27.52-352.91 μmol/L, VAL: 53.74-228.37 μmol/L.(3) The cut-off values of amino acid in full-term infants were as follows: ALA: 135.20-552.33 μmol/L, ARG: 1.30-42.73 μmol/L, CIT: 5.92-30.35 μmol/L, GLY: 208.17-980.09 μmol/L, LEU: 72.91-287.49 μmol/L, MET: 4.27-33.90 μmol/L, ORN: 48.40-305.59 μmol/L, PHE: 27.63-92.27 μmol/L, PRO: 97.38-372.75 μmol/L, TYR: 40.19-276.54 μmol/L, VAL: 65.75-237.92 μmol/L.(4) Except for PHE ( Z=-0.58, P>0.05), the other indicators were significantly different between 2 groups [ALA ( Z=-15.32, P<0.05), ARG ( Z=-5.62, P<0.05), CIT ( Z=-5.86, P<0.05), GLY ( Z=-14.52, P<0.05), LEU ( Z=-5.62, P<0.05), MET ( Z=-5.22, P<0.05), ORN ( Z=-13.01, P<0.05), PRO ( Z=-22.09, P<0.05), TRY ( Z=-2.09, P<0.05), VAL ( Z=-17.82, P<0.05)]. Conclusions:The establishment of the cut-off values of amino acids in premature infants in Sichuan provides a theoretical basis for laboratory diagnosis of IMD screening, which enhances the accuracy of diagnosis and avoids excessive medical treatment.

Multivariate analyses of factors that affect neonatal screening amino acids / 中华实用儿科临床杂志

Objective:To explore the change characteristics of amino acid levels in neonates, so as to provide theoretical basis for accurate clinical interpretation.Methods:By preliminary screening and diagnosis from 32 855 newborns, 32 843 samples were collected using tandem mass spectrometry to inherited metabolic disease (IMD) scree-ning in Sichuan Province from January to December 2018.Afterwards, according to gestational age (1 363 premature infants, 31 468 full-term infants and 12 overdue infants), blood collection time (3-7 days old, 3 095 cases, 8-28 days old, 1 637 cases, and more than 28 days old, 248 cases) and season (7 737 cases in the first quarter, 11 428 cases in the second quarter, 5 482 cases in the third quarter, and 8 196 cases in the fourth quarter), neonates were divided into different study groups.The difference of amino acid level in each group was compared, and the correlation between various influencing factors and metabolic index was analyzed.Results:(1) The distribution of 11 amino acids [alanine(ALA), arginine(ARG), citrulline(CIT), glycine(GLY), leucine+ isoleucine+ hydroxyproline (LEU+ ILE+ PRO-OH), methionine(MET), ornithine(ORN), phenylalanine(PHE), proline(PRO), tyrosine(TYR), and valine(VAL)] in neonates showed non-normally distribution.(2)The distribution of 11 amino acids in different gestational age were tested by nonparametric test, except for PHE( H=0.61, P>0.05)and TYR( H=2.02, P>0.05), and other indicators were significantly different [ALA( H=187.11, P<0.05), ARG( H=23.60, P<0.05), CIT( H=22.90, P<0.05), GLY( H=85.18, P<0.05), LEU( H=56.42, P<0.05), MET( H=18.74, P<0.05), ORN( H=129.27, P<0.05), PRO( H=344.40, P<0.05), and VAL( H=272.92, P<0.05)]. (3) The distribution of 11 amino acids in different blood collection time were significantly different [ALA( H=65.19, P<0.05), ARG( H=404.48, P<0.05), CIT( H=502.13, P<0.05), GLY( H=1 719.44, P<0.05), LEU( H=396.41, P<0.05), MET( H=199.39, P<0.05), ORN( H=31.26, P<0.05), PHE( H=325.49, P<0.05), PRO( H=70.09, P<0.05), TYR( H=159.29, P<0.05), and VAL( H=102.52, P<0.05)]. (4) The distribution of 11 amino acids in different birth seasons were significantly different [ALA( H=401.37, P<0.05), ARG( H=3 229.03, P<0.05), CIT( H=65.45, P<0.05), GLY( H=597.82, P<0.05), LEU( H=1 120.42, P<0.05), MET( H=10 515.18, P<0.05), ORN( H=1 275.23, P<0.05), PHE( H=2 260.17, P<0.05), PRO( H=319.57, P<0.05), TYR( H=884.37, P<0.05), and VAL( H=1 824.49, P<0.05)]. Conclusion:According to different gestational age, season and blood collection time, the metabolism of amino acids in neonates was different.When using tandem mass spectrometry for detection, appropriate interpretation criteria should be selected based on different conditions.

Expert consensus on the follow-up of newborn screening for neonatal genetic and metabolic diseases / 中华医学遗传学杂志

Follow-up is a crucial step for the screening of neonatal genetic and metabolic diseases, which can directly influence the detection, diagnosis, efficacy of treatment, as well as the quality of neonatal screening. In view of the lack of follow-up, full understanding, and inconsistent requirement between various agencies and personnel in China, there is an urgent need for standardization. The Committee for Proficiency Testing of the Neonatal Genetic Metabolic Disease Screening Center of the National Health Committee of China has organized the writing of expert consensus for follow-up of neonatal genetic and metabolic disease screening after thorough discussion, so as to guide the follow-up work and improve its quality.