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OBJECTIVES: This study aimed to compare plasma concentrations of anesthetic drugs administered during Cesarean section with low Apgar score in neonates deliveried under general anesthesia and analyze associated risk factors. METHODS: Data from 76 neonates undergoing Cesarean section under general anesthesia with blood concentrations of anesthetic drugs were analyzed. A low Apgar score was defined as ≤ 7. Perioperative maternal and neonatal data were collected and analyzed. Neonates were divided into a control group (Group CON, n = 65) and a low Apgar score group (Group LAS, n = 11) based on Apgar score. RESULTS: There were no significant differences in the plasma concentrations of anesthetic drugs in maternal artery, umbilical vein or umbilical artery blood between the two groups. Risk factors for neonatal low Apgar scores during Cesarean section under general anesthesia were premature delivery (aOR 10.2, 95% CI = 1.8-56.9) and preoperative fetal distress (aOR 9.6, 95% CI = 1.3-69.0). The prediction model was: probability = 1/(eY), Y= -4.607 + 2.318× (premature delivery) + 2.261× (fetal distress) (yes = 1, no = 0). The Hosmer-Lemeshow test showed χ²= 9.587, P = 0.213, and the area under the curve (AUC) was 0.850 (0.670 ~ 1.000). With a cutoff value of 0.695, sensitivity and specificity were 81.8% and 87.7%, respectively. CONCLUSIONS: There was no correlation between blood concentration of general anesthetic drugs and Apgar score or occurrence of neonatal low Apgar scores. Premature delivery and preoperative fetal distress were identified as independent risk factors for neonatal low Apgar scores after Cesarean section under general anesthesia.
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Anestesia Geral , Índice de Apgar , Cesárea , Humanos , Recém-Nascido , Anestesia Geral/efeitos adversos , Feminino , Gravidez , Fatores de Risco , Adulto , Anestesia Obstétrica/métodos , Anestesia Obstétrica/efeitos adversos , Masculino , Sofrimento Fetal/sangue , Estudos Retrospectivos , Anestésicos/sangue , Anestésicos/efeitos adversos , Nascimento PrematuroRESUMO
Background: Primary Carnitine Deficiency (PCD) is a potentially life-threatening autosomal recessive monogenic disorder arising from mutations in the organic cation transporter 2 (OCTN2) gene. Dilated cardiomyopathy (DCM) is a prevalent symptom associated with this condition, and episodes of metabolic disturbance may lead to sudden death. However, the pathogenic mechanism remains unclear. Here, we sought to investigate the response of cardiomyocytes and alterations in the intercellular communication in individuals with PCD DCM. Methods: The GSE211650 dataset was downloaded. Subsequently, modular analysis was performed using hdWGCNA. SCENIC was employed for transcription factor analysis. Monocle2 and SCP were applied to conduct trajectory inference and characterize dynamic features. CellChat was used to investigate intercellular interactions. Results: OCTN2-deficient cardiomyocytes displayed transcriptomic alterations indicative of reduced contractility, developmental abnormalities, and fibrosis. The reduced expression of genes encoding troponin, myosin, and calcium ion transporters may underlie the observed decrease in contractility. Suppressed Wnt signaling and downregulated transcription factors associated with myocardial development suggest potential developmental disturbances in cardiomyocytes. Growth arrest-specific 6 (GAS6) secreted by TNNC1 high cardiomyocytes is implicated in myocardial inflammation and fibrosis. Macrophages-derived secreted phosphoprotein 1 (SPP1) promotes the activation of fibroblasts. Furthermore, there was a reduction in neuronal genes in the OCTN2-deficient group. Conclusions: Our research has unveiled, for the first time, the responses of cardiomyocytes and alterations in the intercellular communication in PCD DCM, offering valuable insights for the precision treatment of this condition.
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BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.
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Testes Genéticos , Atrofia Muscular Espinal , Triagem Neonatal , Humanos , Recém-Nascido , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Projetos Piloto , Testes Genéticos/normas , Testes Genéticos/métodos , Triagem Neonatal/normas , Triagem Neonatal/métodos , China , Teste em Amostras de Sangue Seco/normas , Teste em Amostras de Sangue Seco/métodos , Garantia da Qualidade dos Cuidados de Saúde , Laboratórios Clínicos/normas , Proteína 1 de Sobrevivência do Neurônio Motor/genéticaRESUMO
BACKGROUND: Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders. Research has highlighted a close association between the retinoic acid (RA) signaling pathway and ASD. This study investigates alterations in the vitamin A (VA, retinol) to RA metabolic pathway in children with ASD and speculates on the underlying reasons for these changes. We propose a subtype characterized by downregulated RA signaling in ASD, laying the groundwork for precise diagnosis and treatment research. METHODS: We included 489 children with ASD and 280 typically developing (TD) children. Those with ASD underwent evaluations of core symptoms and neuro-developmental levels, which were conducted by professional developmental behavior physicians using assessment scales. Serum VA and all-trans RA (atRA) levels were determined by high-performance liquid chromatography and ultra-high-performance liquid chromatography-tandem mass spectrometry. The expression levels and concentrations of enzyme molecules such as retinol dehydrogenase 10 were assessed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Children with ASD exhibited reduced serum atRA, accompanied by a downregulation of atRA synthesis enzymes. The reduction in serum atRA levels was linked not only to VA levels but also to the aberrant expression of metabolic enzymes responsible for atRA. Furthermore, the serum atRA levels in children with ASD were more strongly correlated with core symptoms and neurodevelopmental levels than VA levels. CONCLUSION: Children with ASD exhibited a dual regulation of reduced serum atRA levels, influenced by both VA levels and abnormal expression of atRA metabolic enzymes.
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BACKGROUND: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice. METHODS: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline. RESULTS: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory. CONCLUSIONS: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.
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Doenças Metabólicas , Fenilcetonúrias , Humanos , Controle de Qualidade , Laboratórios , Doenças Metabólicas/diagnóstico , China , Garantia da Qualidade dos Cuidados de SaúdeRESUMO
The aim of this study was to observe the outcomes of newborn screening (NBS) in a certain population by using next-generation sequencing (NGS) as a first-tier screening test combined with tandem mass spectrometry (MS/MS). We performed a multicenter study of 29,601 newborns from eight screening centers with NBS via NGS combined with MS/MS. A custom-designed panel targeting the coding region of the 142 genes of 128 inborn errors of metabolism (IEMs) was applied as a first-tier screening test, and expanded NBS using MS/MS was executed simultaneously. In total, 52 genes associated with the 38 IEMs screened by MS/MS were analyzed. The NBS performance of these two methods was analyzed and compared respectively. A total of 23 IEMs were diagnosed via NGS combined with MS/MS. The incidence of IEMs was approximately 1 in 1287. Within separate statistical analyses, the positive predictive value (PPV) for MS/MS was 5.29%, and the sensitivity was 91.3%. However, for genetic screening alone, the PPV for NGS was 70.83%, with 73.91% sensitivity. The three most common IEMs were methylmalonic academia (MMA), primary carnitine deficiency (PCD) and phenylketonuria (PKU). The five genes with the most common carrier frequencies were PAH (1:42), PRODH (1:51), MMACHC (1:52), SLC25A13 (1:55) and SLC22A5 (1:63). Our study showed that NBS combined with NGS and MS/MS improves the performance of screening methods, optimizes the process, and provides accurate diagnoses.
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Objective: This study aims to determine the drug concentration of etomidate, remifentanil, and rocuronium bromide for general anesthesia in fetus as well as the placental transport rate between term and preterm delivery, twins, and singleton. Study design: Sixty parturients with 72 fetuses undergoing cesarean section under general anesthesia were included. According to whether the fetus was a twin or premature, parturients were divided into Group I (term singleton), Group II (premature singleton), Group III (term twins), and Group IV (premature twins). The preoperative demographic characteristics and laboratory examination of parturients, hemodynamic indicators, the Apgar score of neonates at 1, 5, and 10 min after delivery and at specific assigned values, umbilical artery blood gas analysis results, neonatal weight, and resuscitative measures were recorded. Anesthetic drug concentrations in maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood were detected by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). Result: No significant differences were observed in the concentrations of etomidate, remifentanil, and rocuronium bromide in MA, UV, and UA blood, or in the UV/MA and UA/UV ratios between term and preterm infants, twins, and singletons. Moreover, there was no variation in the anesthetic drug concentration among each pair of twins. Additionally, no correlation was found between the neonatal weight and the plasma concentrations of anesthetic drugs in UV and UA blood, except for remifentanil in UA blood. Conclusion: Preterm or twin deliveries do not affect the neonatal concentration of etomidate, remifentanil, and rocuronium bromide used in general anesthesia for cesarean sections. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2100046547.
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Importance: Newborn screening via biochemical tests is in use worldwide. The availability of genetic sequencing has allowed rapid screening for a substantial number of monogenic disorders. However, the outcomes of this strategy have not been evaluated in a general newborn population. Objective: To evaluate the outcomes of applying gene panel sequencing as a first-tier newborn screening test. Design, Setting, and Participants: This cohort study included newborns who were prospectively recruited from 8 screening centers in China between February 21 and December 31, 2021. Neonates with positive results were followed up before July 5, 2022. Exposures: All participants were concurrently screened using dried blood spots. The screen consisted of biochemical screening tests and a targeted gene panel sequencing test for 128 conditions. The biochemical and genomic tests could both detect 43 of the conditions, whereas the other 85 conditions were screened solely by the gene panel. Main Outcomes and Measures: The primary outcomes were the number of patients detected by gene panel sequencing but undetected by the biochemical test. Results: This study prospectively recruited 29â¯601 newborns (15â¯357 [51.2%] male). The mean (SD) gestational age was 39.0 (1.5) weeks, and the mean (SD) birth weight was 3273 (457) g. The gene panel sequencing screened 813 infants (2.7%; 95% CI, 2.6%-2.9%) as positive. By the date of follow-up, 402 infants (1.4%; 95% CI, 1.2%-1.5%) had been diagnosed, indicating the positive predictive value was 50.4% (95% CI, 50.0%-53.9%). The gene panel sequencing identified 59 patients undetected by biochemical tests, including 20 patients affected by biochemically and genetically screened disorders and 39 patients affected by solely genetically screened disorders, which translates into 1 out of every 500 newborns (95% CI, 1/385-1/625) benefiting from the implementation of gene panels as a first-tier screening test. Conclusions and Relevance: In this cohort study, the use of gene panel sequencing in a general newborn population as a first-tier screening test improved the detection capability of traditional screening, providing an evidence-based suggestion that it could be considered as a crucial method for first-tier screening.
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Genômica , Triagem Neonatal , Recém-Nascido , Lactente , Humanos , Masculino , Feminino , Estudos de Coortes , Peso ao Nascer , ChinaRESUMO
Background: Congenital hypothyroidism (CH) is an neonatal endocrine disorder. Traditional newborn screening is the mainstream method of CH screening, so as to ensure the early detection and treatment of CH. This method is limited as it has high rates of false positives and negatives. Genetic screening can be used to address the shortcomings of traditional newborn Screening (NBS); however, the comprehensive clinical value of genetic screening is yet to be systematically studied. Methods: A total of 3,158 newborns who accepted the newborn screening and genetic screening were recruited for this study. Biochemical screening and genetic screening were performed at the same time. The level of TSH with the DBS was detected by time-resolved immunofluorescence assay. High-throughput sequencing technology based on targeted gene capture was used for genetic screening. The suspected neonatal was recalled and tested serum TSH, and FT4. Finally, the effectiveness of traditional NBS and combined screening was compared. Results: In this study, 16 cases were diagnosed by traditional NBS. 10 cases of DUOX2 mutation were found in newborn CH-related genetic screening, including 5 homozygous and 5 compound heterozygous variations. We found that the c.1588A > T mutations in DUOX2 constituting the predominant site in the present cohort.Compared with NBS and genetic screening, the sensitivity of combined screening increased by 11.1% and 55.6%, respectively. Compared with NBS and genetic screening, the negative predictive value of combined screening increased by 0.1% and 0.4%, respectively. Conclusions: Combined traditional NBS and genetic screening reduces the false negative rate of CH screening and improves the early and accurate identification of neonates with CH. Our research explains the mutation spectrum of CH in this region, and provisionally demonstrates the necessity, feasibility and significance of genetic screening in newborns and provides a solid basis for future clinical developments.
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Objective: Remifentanil, in combination with etomidate and sevoflurane, is commonly used in clinics for general anesthesia induction in cesarean section (CS). This study aimed to evaluate the correlation between the induction to delivery (I-D) time and neonatal plasma drug concentration and anesthesia, as well as its effects on neonates. Methods: Fifty-two parturients in whom general anesthesia was induced for CS were divided into group A (I-D<8 min) and group B (I-D≥8 min). Maternal arterial (MA), umbilical venous (UV), and umbilical arterial (UA) blood samples were collected at delivery to analyze the remifentanil and etomidate concentrations using liquid chromatography-tandem mass spectrometry. Results: There were no statistically significant differences between the two groups in terms of plasma concentrations of remifentanil in the MA, UA, and UV blood (P > 0.05). The plasma concentration of etomidate in MA and UV was higher in group A than that in group B (P<0.05), whereas the UA/UV ratio of etomidate was higher in group B than that in group A (P<0.05). The Spearman rank correlation test showed no correlation between the I-D time and plasma remifentanil concentration in the MA, UA, and UV plasma (P>0.05). The concentrations of etomidate in the MA and UV were negatively correlated with the I-D time (P < 0.05). Conclusion: Prolonged I-D time did not significantly influence the maternal or neonatal plasma concentration of remifentanil. It is safe to administer remifentanil target-controlled infusion in combination with etomidate and sevoflurane for general anesthesia induction during CS.
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Etomidato , Humanos , Recém-Nascido , Gravidez , Feminino , Remifentanil , Piperidinas , Cesárea , Sevoflurano , Anestesia Geral , Anestésicos IntravenososRESUMO
BACKGROUND: Newborn screening (NBS) is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases. The development of next-generation sequencing (NGS) technology provides new opportunities to expand current newborn screening methodologies. METHODS: We designed a a newborn genetic screening (NBGS) panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS. With this panel, a large-scale, multicenter, prospective multidisease analysis was conducted on dried blood spot (DBS) profiles from 21,442 neonates nationwide. RESULTS: We presented the positive detection rate and carrier frequency of diseases and related variants in different regions; and 168 (0.78%) positive cases were detected. Glucose-6-Phosphate Dehydrogenase deficiency (G6PDD) and phenylketonuria (PKU) had higher prevalence rates, which were significantly different in different regions. The positive detection of G6PD variants was quite common in south China, whereas PAH variants were most commonly identified in north China. In addition, NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants, which were normal in conventional NBS, but were confirmed later as abnormal in repeated biochemical testing after recall. Eighty percent of high-frequency gene carriers and 60% of high-frequency variant carriers had obvious regional differences. On the premise that there was no significant difference in birth weight and gestational age, the biochemical indicators of SLC22A5 c.1400C > G and ACADSB c.1165A > G carriers were significantly different from those of non-carriers. CONCLUSIONS: We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods. Our data also showed that the prevalence of diseases has significant regional characteristics, which provides a theoretical basis for screening diseases in different regions.
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Triagem Neonatal , Fenilcetonúrias , Humanos , Recém-Nascido , Triagem Neonatal/métodos , Estudos Prospectivos , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas de Transporte da Membrana Mitocondrial/genética , Membro 5 da Família 22 de Carreadores de Soluto/genéticaRESUMO
OBJECTIVE: To investigate the incidence, clinical characteristics, gene mutations and prognosis of fatty acid oxidation disorders (FAOD) in newborns in Chongqing. METHODS: Blood samples were collected from 35 374 newborns for screening of FAOD in the Neonatal Screening Center of Women and Children's Hospital of Chongqing Medical University from July 2020 to February 2022. The acylcarnitine spectrum was detected by tandem mass spectrometry, the positive children in primary screening were recalled within 2 weeks, and the diagnosis of FAOD was confirmed by urine organic acid measurement, blood biochemistry testing and genetic analysis. The confirmed children were given early intervention, treatment and followed-up. RESULTS: Among 35 374 newborns, there were 267 positive children in primary screening, with a positive rate of 0.75%. Five children with FAOD were diagnosed by gene detection, with an incidence rate of 1/7075. Among them, there were 3 cases of primary carnitine deficiency (PCD, 1/11 791), 1 case of short-chain acyl-CoA dehydrogenase deficiency (SCADD, 1/35 374) and 1 case of very long-chain acyl-CoA dehydrogenase deficiency (VLCADD, 1/35 374). The c.1400C>G and c.338G>A were the common mutations of SLC22A5 gene in 3 children with PCD, while c.621G>T was a novel mutation. There were no clinical manifestations during the follow-up period in 2 children with supplementation of L-carnitine. Another child with PCD did not follow the doctor's advice of L-carnitine treatment, and had acute attack at the age of 6â months. The child recovered after treatment, and developed normally during the follow-up. The detected ACADS gene mutations were c.417G>C and c.1054G>A in child with SCADD, who showed normal intelligence and physical development without any clinical symptoms. The mutations of ACADVL gene were c.1349G>A and c.1843C>T in child with VLCADD, who showed acute attack in the neonatal period and recovered after treatment; the child was fed with milk powder rich in medium-chain fatty acids and had normal development during the follow-up. CONCLUSIONS: The incidence of FAOD in Chongqing area is relatively high. PCD is the most common type, and the clinical phenotype of VLCADD is serious. After early diagnosis through neonatal screening, standardized treatment and management is followed, most of FAOD children can have good prognosis.
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Erros Inatos do Metabolismo Lipídico , Carnitina , Ácidos Graxos , Feminino , Seguimentos , Humanos , Recém-Nascido , Erros Inatos do Metabolismo Lipídico/diagnóstico , Erros Inatos do Metabolismo Lipídico/epidemiologia , Erros Inatos do Metabolismo Lipídico/genética , Mutação , Triagem Neonatal , Pós , Membro 5 da Família 22 de Carreadores de Soluto/genéticaRESUMO
Citrullinemia is a rare autosomal recessive disorder characterized by elevated concentrations of citrulline in the blood resulting from malfunction of the urea cycle. It is categorized into two types, types I and II, which are caused by argininosuccinate synthase 1 (ASS1), and citrin (SLC25A13) gene mutations, respectively. In this study, we performed genetic analysis on nine Chinese infants with citrullinemia using next-generation sequencing, which identified a novel mutation (p.Leu313Met) and a rare mutation (p.Thr323Ile, rs1250895424) of ASS1. We also found a novel splicing mutation of SLC25A13: c.1311 + 4_+7del. Functional analysis of the ASS1 missense mutations showed that both significantly impaired the enzyme activity of ASS1, with the p. Thr323Ile mutation clearly affecting the interaction between ASS1 and protein arginine methyltransferase 7 (PRMT7). These findings expand the mutational spectrum of ASS1 and SLC25A13, and further our understanding of the molecular genetic mechanism of citrullinemia in the Chinese population.
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Background: Neonatal seizures are a common neurological emergency in newborns. Phenobarbital (PB) is the first-line antiepileptic drug (AED). However, PB has some side effects, such as hypotension and respiratory depression, and it can accelerate neuronal apoptosis in the immature brain. Levetiracetam (LEV), a new antiepileptic drug, has been used as a second-line drug for the treatment of neonatal seizures. Compared with PB, LEV has many advantages, including a low incidence of side effects and better neurodevelopmental outcomes. However, there are only a few systematic reviews of LEV for the treatment of neonatal seizures. Objective: To evaluate the efficacy and safety of LEV for neonatal seizures and to compare the efficacy, side effects, and neurological outcomes between LEV and PB in the treatment of neonatal seizures. Methods: The keywords LEV, PB, and neonatal seizure were searched in the MEDLINE, Cochrane Library, Web of Science, EMBASE, clinicaltrials.gov, and China National Knowledge Internet (CNKI) databases with a last update in July 2021 to collect high-quality studies. We collected studies studying the efficacy or safety of LEV and PB in the treatment of neonatal seizures applying strict inclusion and exclusion criteria. The data were extracted and outcome measures, including efficacy, side effect rate, neurological score, and mortality rate, were analyzed with RevMan 5.3 software. Results: Ten articles were finally included in the meta-analysis. The meta-analysis showed that there was no difference in efficacy between LEV and PB in the treatment of neonatal seizures. Compared with PB, the incidence of side effects of LEV was lower. The incidence of hypotension and respiratory depression in the LEV group was significantly lower than that in the PB group. In terms of long-term neurodevelopmental outcomes, there was no significant difference in the Bayley Scales of Infant Development (BSID) scores between LEV and PB. Conclusion: PB is still the first-line AED recommended by the WHO for the treatment of neonatal seizures. The new AEDs LEV may not have better efficacy than PB. At the same time, LEV is associated with better neurodevelopment outcomes and a lower risk of adverse effects. In addition, continuous EEG monitoring should be used to diagnose neonatal seizures to evaluate the severity of the seizures, remission, and drug efficacy. Systematic Review Registration: PROSPERO, identifier: CRD42021279029.
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To compare the clinical and genetic characteristics of patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and idiopathic neonatal cholestasis (INC). The clinical data of 30 patients with NICCD and 30 patients with INC admitted in Children's Hospital of Chongqing Medical University during September 2012 and December 2017 were retrospectively analyzed. The clinical manifestations, biochemical indicators and genetic characteristics were compared between two groups. Patients in both groups presented similar clinical manifestations, however the chubby face and clay-colored stool were more common in NICCD patients (both <0.01). Comparing with INC group, NICCD group showed significantly decreased blood levels of glucose, prealbumin, albumin, total protein, fibrinogen, and aminotransferases (<0.05 or <0.01), while significantly increased blood levels of indirect bilirubin, total bile acid, alkaline phosphatase, lactic dehydrogenase, ammonium, alpha fetoprotein, and markers of coagulation function (<0.05 or <0.01). In addition, NICCD patients showed remarkably increased blood levels of citrulline, methionine, tyrosine, arginine, and threonine; as well as significantly increased urine levels of 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvic acid and phenyllactic acid, while those indicators in INC patients were normal (all <0.01). All the patients with NICCD had mutation including 8 homozygotes, 9 compound heterozygotes, and 13 single heterozygotes. Among all mutations, c.851_854del was most common (53.19%), c.1196T>A and c.919G>T were two novel mutations. The manifestations of chubby face and clay-colored stool may provide clue for early diagnosis of NICCD along with the elevated biochemical parameters, such as ammonium, alpha-fetal protein, citrulline in blood and 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvic acid, phenyllactic acid in urine. Target gene trapping and high-throughput sequencing have the key values in diagnosis and differential diagnosis of NICCD.
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Colestase Intra-Hepática , Colestase , Citrulinemia , Transportadores de Ânions Orgânicos , Criança , Colestase Intra-Hepática/etiologia , Colestase Intra-Hepática/genética , Citrulinemia/genética , Humanos , Lactente , Recém-Nascido , Proteínas de Transporte da Membrana Mitocondrial/genética , Mutação , Transportadores de Ânions Orgânicos/genética , Estudos RetrospectivosRESUMO
Metabolomics has become an important tool for clinical research, especially for analyzing inherited metabolic disorders (IMDs). The purpose of this study was to explore the performance of metabolomics in diagnosing IMDs using an untargeted metabolomic approach. A total of 40 urine samples were collected: 20 samples from healthy children and 20 from pediatric patients, of whom 13 had confirmed IMDs and seven had suspected IMDs. Samples were analyzed by Orbitrap mass spectrometry in positive and negative mode alternately, coupled with ultra-high liquid chromatography. Raw data were processed using Compound Discovery 2.0 ™ and then exported for partial least squares discriminant analysis (PLS-DA) by SIMCA-P 14.1. After comparing with m/zCloud and chemSpider libraries, compounds with similarity above 80% were selected and normalized for subsequent relative quantification analysis. The uncommon compounds discovered were analyzed based on the Kyoto Encyclopedia of Genes and Genomes to explore their possible metabolic pathways. All IMDs patients were successfully distinguished from controls in the PLS-DA. Untargeted metabolomics revealed a broader metabolic spectrum in patients than what is observed using routine chromatographic methods for detecting IMDs. Higher levels of certain compounds were found in all 13 confirmed IMD patients and 5 of 7 suspected IMD patients. Several potential novel markers emerged after relative quantification. Untargeted metabolomics may be able to diagnose IMDs from urine and may deepen insights into the disease by revealing changes in various compounds such as amino acids, acylcarnitines, organic acids, and nucleosides. Such analyses may identify biomarkers to improve the study and treatment of IMDs.
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Doenças Metabólicas/diagnóstico , Doenças Metabólicas/urina , Metabolômica , Aminoácidos/metabolismo , Aminoácidos/urina , Biomarcadores/metabolismo , Biomarcadores/urina , Carnitina/análogos & derivados , Carnitina/metabolismo , Carnitina/urina , Criança , Humanos , Espectrometria de Massas , Doenças Metabólicas/metabolismo , Nucleosídeos/metabolismo , Nucleosídeos/urinaRESUMO
BACKGROUND: Anti-epileptic drugs have different effects on neonatal seizures, and new agents have been widely used in recent years. Meanwhile, significant differences still exist in the treatment for neonatal seizures, whether in choice of drug or in duration of treatment. And with the increase in options for treatment, the best choice of second-line treatment has not been recommended. METHODS: The MEDLINE, the Cochrane Library, Web of Science, Embase and clinicaltrials.gov databases were searched (January 1, 1960 to October 20, 2020). Randomized controlled trials (RCTs) or observational investigations studying anti-epileptic drugs for neonatal seizures were selected. And then we conducted a network meta-analysis and examined comparative efficacy of the first-line and second-line anti-epileptic drugs for neonatal seizures. RESULTS: Data were extracted from 11 included studies by 2 independent investigators. Random effects models were used to estimate odds ratios (ORs). We performed direct meta-analyses with a random effects model and network meta-analyses for first-line and second-line drugs. Five published RCTs and 6 observational investigations with 1333 patients and 6 interventions contributed to the analysis. CONCLUSION: We recommend phenobarbital as the first-line drug for neonatal seizures. In addition, there is a tendency for levetiracetam to be an effective second-line treatment for neonatal seizures after failure of first-line drugs.
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Anticonvulsivantes , Preparações Farmacêuticas , Anticonvulsivantes/uso terapêutico , Carbamazepina , Humanos , Recém-Nascido , Metanálise em Rede , Convulsões/tratamento farmacológicoRESUMO
BACKGROUND: Pneumonia is a serious global health problem. In traditional Chinese medicine, acupuncture or moxibustion is used to directly stimulate select acupoints on the surface of the human body and produce physical stimulation to further stimulate regulatory functions in the body, strengthening bodily resistance, eliminating disease, and adjusting the viscera. However, this Chinese medicine knowledge does not include the specific mechanisms of action or targets of acupoints. Therefore, an in-depth research is needed. METHODS: An acupoint-element database was constructed, and the target elements of the Feishu point were screened. The UniProt-Swiss-Prot sublibrary was used to obtain correct gene name information. The National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database and GEO2R were used to analyze differentially expressed genes in pneumonia. The STRING database was used to analyze interactions, construct a network of the Feishu point efficacy system in pneumonia, and elucidate the mechanisms of action. RESULTS: The Feishu point comprises 34 elements in total. The protein interaction analysis has 38 nodes and 115 edges. The Feishu point efficacy system-pneumonia system network shows that cytokine signaling in the immune system, signaling by interleukins (ILs), IL-4 and IL-13 signaling, and the immune system may be related to immunity and inflammation. The Feishu point efficacy system regulating pneumonia showed that FCER2, IL4R, FASLG, TGFB1, IL6R, STAT6, IL1B, CASP3, IL5RA, IL2RB, MYD88, SQSTM1, IL12RB1, IFNGR1, ADAM17, and CDH1 are the main targets. CONCLUSION: From the perspective of systematic acupuncture and moxibustion, the Feishu point regulates cytokine signaling in the immune system, signaling by ILs, IL-4 and IL-13 signaling, and the immune system by targeting FCER2, IL4R, FASLG, TGFB1, IL6R, STAT6, IL1B, CASP3, IL5RA, IL2RB, MYD88, SQSTM1, IL12RB1, IFNGR1, ADAM17, and CDH1, thereby regulating pneumonia.
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Objectives: This study aimed to explore the changes in infant vitamin A (VA) status and the effect of early VA supplementation on VA level throughout the first 6 months of life. Methods: A prospective cohort study was conducted in Chongqing, China. A total of 1,016 healthy infants were enrolled at birth. Then, 930, 882, 854 and 822 healthy infants were followed up at postnatal day 7 and postnatal months 1, 3, and 6, respectively. Blood samples and dietary survey and physical development data were collected. Serum VA was measured by chromatography tandem-mass spectrometry and was classified according to the VA deficiency (VAD) criteria for older children aged 6-70 months (<0.70, 0.70-1.05, ≥1.05 µmol/L). Normally distributed continuous variables are presented as the mean ± standard deviation. The categorical variables are described by the frequency and percentage (%). The reference interval for the VA level was the 2.5th-97.5th percentile. Changes in VA status with age and the relationship of VA supplementation with VA level were investigated by generalized estimating equations followed by Bonferroni post hoc test, controlling for the effects of feeding pattern and sex. Results: Infant VA levels increased significantly from 0.499 ± 0.146 to 1.061 ± 0.414 µmol/L with age at 6 months, even without VA supplementation (P < 0.05). From birth to 6 months, the percentage of infants with a VA level <0.70 µmol/L decreased from 88.6 to 19.5%. During follow-up, no infant demonstrated clinical VAD conditions, such as night blindness, conjunctival xerosis or Bitot's spots. Less than 7.0% of infants were underdeveloped in terms of weight, length and head circumference. The VA status of infants with VA≥0.588 µmol/L at birth gradually increased to adequate VA (VA ≥ 1.05 µmol/L) at 6 months. For these infants, there was no significant difference in VA level between the VA supplementation and non-supplementation groups (P > 0.05). Infants with VA <0.430 µmol/L at birth still had VA <0.70 µmol/L at 6 months; in this group, VA levels increased by 0.08 µmol/L more among supplemented infants than among non-supplemented infants (P < 0.05). Conclusions: A low VA level among neonates at birth may be a normal physiological state and may increase with age; thus, not all neonates may need early VA supplementation. More multicenter studies are needed to determine a new cutoff point for the diagnosis of neonatal VAD and the administration of nutritional intervention.
Assuntos
Deficiência de Vitamina A , Vitamina A , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Suplementos Nutricionais , Humanos , Lactente , Recém-Nascido , Estudos Prospectivos , Deficiência de Vitamina A/tratamento farmacológicoRESUMO
Importance: COVID-19 has become a worldwide pandemic. Many countries have reported cases of infection in children and newborns, and there is a trend of significantly increasing infections among these populations. Therefore, it is important to provide advice and guidance for the prevention and control of COVID-19 in children. Observations: Children are as susceptible to SARS-CoV-2 infection as adults. The manifestations in children are atypical, and children are much less likely to have critical cases. If children are infected, they may play an important role in the spread of SARS-CoV-2 because their symptoms are less obvious and less likely to be detected. To prevent COVID-19 from spreading among children, efforts to prevent, and control the infection should be increased by controlling the source of infection, blocking the route of transmission and protecting the susceptible population. Conclusions and Relevance: The early identification of the COVID-19 in children and the protection of families are important measures to prevent the continued spread of SARS-CoV-2.