Objective:To compare the effect of SMOF lipids composed of soybean oil, medium chain triglycerides, olive oil, and fish oil with medium-long chain mixed fat emulsions(Lipofundin) on parenteral nutrition-associated cholestasis(PNAC) in premature infants.Methods:Clinical data were collected from premature infants hospitalized in the neonatal intensive care unit of Shanghai Children′s Hospital from January 2018 to December 2019 with gestational age ≤34 weeks, birth weight ≤2 000 g, and duration of parenteral nutrition ≥14 days.They were devided into SMOF lipid group and Lipofundin group, and the incidence of PNAC, neonatal necrotizing enterocolitis(NEC), bronchopulmonary dysplasia(BPD), retinopathy of prematurity(ROP), periventricular-intraventricular hemorrhage(PVH-IVH), late-onset sepsis and liver function were compared between two groups.Results:The incidence of PNAC in the SMOF lipid group was significantly lower than that in Lipofundin group( P=0.042). The average level of ALT and AST in SMOF lipid group were markedly lower than those in Lipofundin group( P<0.05). The time to reach full enteral feeding of SMOF lipid group was shorter than that of Lipofundin group( P=0.005). There was no significant difference in the incidence of NEC, BPD, ROP, PVH-IVH, and late-onset sepsis between two groups( P>0.05). Conclusion:Compared with lipofundin, SMOF lipid can reduce the incidence of PNAC in premature infants, and has no significant effect on the incidence of NEC, BPD, ROP, PVH-IVH and late-onset sepsis.

Objective:To study the early predictive value of urine neutrophil gelatinase-associated lipoprotein (NGAL) and kidney injury molecule-1 (KIM-1) for acute kidney injury (AKI) in neonates with severe asphyxia.Method:From January 2019 to June 2020, neonates with severe asphyxia admitted to our hospital within 6 hours after birth were enrolled in the study. The dynamic changes of urine NGAL and KIM-1 at admission, 24 h, 48 h and 1 w after birth were examined. Neonates were assigned into AKI group and non-AKI group according to the clinical practice guidelines for AKI issued by KDIGO (Kidney Disease: Improving Global Outcome). The sensitivity and specificity of NGAL and KIM-1 predicting AKI at different time points were evaluated using ROC curve and area under curve (AUC).Result:According to the diagnostic criteria of neonatal AKI, 9 cases were in the AKI group and 42 cases in the non-AKI group, and the incidence of AKI was 17.6%. Urine NGAL was significantly increased in AKI group at admission and 24 h after birth compared with the non-AKI group [(115.6±75.5) ng/ml vs. (49.8±29.0) ng/ml, (90.7±35.6) ng/ml vs. (55.6±30.7) ng/ml] ( P<0.05). No significant differences existed at 48 h and 1 w after birth between the two groups. At 24 h after birth, urine KIM-1 in the AKI group was significantly higher than the non-AKI group [(808.3±555.3) pg/ml vs. (318.4±234.0) pg/ml, P<0.05] and no significant differences existed between the two groups at admission, 48 h and 1 w after birth. The AUC of NGAL predicting AKI at admission, 24 h, 48 h and 1w after birth were 0.804 (95% CI 0.573~1.000), 0.792 (95% CI 0.580~1.000), 0.732 (95% CI 0.517~0.947) and 0.551(95% CI 0.371~0.730), respectively. The AUC of KIM-1 predicted AKI at admission, 24 h, 48 h and 1 w after birth was 0.860 (95% CI 0.676~1.000), 0.824 (95% CI 0.655~0.993), 0.768 (95% CI 0.622~0.914), 0.622 (95% CI 0.392~0.852), respectively. Conclusion:At admission, 24 h and 48 h after birth, urine NGAL and KIM-1, as kidney injury markers, may predict the occurrence of AKI after severe neonatal asphyxia.

Objective To study efficacy and safety of continuous renal replacement therapy (CRRT) in the treatment of neonatal sepsis-related acute kidney injury (AKI).Method From June 2011 to June 2018,neonates with sepsis-related AKI hospitalized in the neonatal intensive care unit of our hospital and treated with CRRT were enrolled.Before CRRT,12 h,24 h,48 h after CRRT and by the end of CRRT,their clinical data including renal function,acid-base balance,electrolytes,blood pressure (BP)and the change of hemodynamic indexes were retrospectively analysed.The efficacy and safety of CRRT was evaluated.Kruskal-wallis H test was used for statistical analysis.Result A total of 9 cases of sepsis-related AKI neonates were enrolled in the study,all treated with continuous veno-venous hemofiltration dialysis.5 cases had oliguria,2 cases fluid overload and 2 cases shock.The duration of CRRT was 49 ～ 110 h (76.2 ±23.5) h.12 h after CRRT,BP were maintained at 40 ～60 mmHg and stable during the treatment,the blood pH value increased to 7.35 ～ 7.45 and the oxygenation index reached 200 mmHg.24 h after CRRT,the oxygenation index rose to more than 300 mmHg.Serum potassium,urea nitrogen and creatinine levels decreased significantly after 12 h of CRRT,and reached the normal range after 24 h of CRRT.After 24 h of CRRT,the urine volume significantly increased.Venous catheterization was performed successfully in 9 cases.2 cases had thrombocytopenia,1 case catheterization obstruction and 1 case hypotension during CRRT.No complications such as hypothermia,hemorrhage,thrombosis or infection occurred.All 9 patients were cured and discharged.Conclusion CRRT is safe and effective for the treatment of neonatal sepsis-related AKI.

Objective To study the clinical efficacy and safety of extracorporeal membrane oxygenation (ECMO) in critically ill neonates.Method From November 2016 to September 2018,the clinical data of 5 cases who received ECMO treatment in NICU of our hospital were retrospectively analyzed.The indication of ECMO was reversible respiratory failure irresponsive to conventional therapy.The treatment mode was V-A ECMO.Oxygenation index (OI),vasoactive-inotropic score,blood lactate before and 24 h after ECMO were recorded.Complications of ECMO were also studied.Paired t-test was used to compare the pre and post treatment parameters.Result Among the 5 cases,4 cases were male and 1 case was female.3 cases were diagnosed with meconium aspiration syndrome,2 cases pulmonary hypertension.OI[(9.5 ± 1.8) vs.(60.6 ± 19.4)],vasoactive-inotropic score[(19.5 ± 12.0) points vs.(204.0 ± 143.8) points]and blood lactate [(2.8 ± 1.5) mmol/L vs.(9.6 ± 3.6) mmol/L]) were all significantly decreased at 24 h after ECMO treatment (P ＜ 0.05).During follow-up,3 cases survived,2 cases died.All the 5 cases showed thrombocytopenia,3 cases developed renal failure and received continuous renal replacement therapy,1 case got intracranial hemorrhage.2 of the 3 survived cases developed neurological impairment and need long term follow-up and rehabilitation therapy.Conclusion ECMO treatment has remarkable effects on critically ill neonates and may actually save lives,but the risk of complications are quite high.

Objective To explore the efficacy of continuous renal replacement therapy (CRRT) in the treatment of neonatal acute kidney injury (AKI).Methods Totally 17 critically ill neonates treated with CRRT were selected who were hospitalized at Department of Neonatology,Shanghai Children's Hospital,Children's Hospital Affiliated to Shanghai Jiaotong University,from June 2012 to June 2017,and among them there were 15 cases with AKI,and the clinical data of these 15 patients were retrospectively analyzed,while 15 AKI neonates were treated with CRRT combined with conventional treatment.The model for CRRT was continuous veno-venous hemofiltration dialysis (CVVH-DF) in 13 cases,plasma exchange (PE) in 2 cases.The changes of blood pressure(BP),renal function,electrolyte,acid-base balance index and hemodynamic indicators were analyzed respectively before CRRT treatment,12 h,24 h,48 h after treatment and by the end of CRRT treatment.The efficacy of CRRT treatment was evaluated in these 15 AKI neonates.Results Gestational age of 15 AKI newborns was 33 +4-40 +1 weeks,admission day age was 2-28 days,birth weight was 2.25-4.00 kg.Primary diseases were severe asphyxia in 6 cases,neonatal septicemia in 5 cases,congenital hereditary metabolic disease in 2 cases,traumatic asphyxia in 1 case,and liver failure in 1 case.CRRT treatment persisted for 49-190 hours.BP value [(50.8 ± 6.57) mmHg(1 mmHg =0.133 kPa)] could reach normal level after 12 h CRRT treatment,and blood pH value (7.31 ± 0.25) increased significantly after 12 h CRRT treatment,while blood K+[(5.51 ±1.86) mmoL/L],urea nitrogen (BUN) [(9.5 ±3.7) mmol/L],creatinine(Cr) [(93± 14)μmol/L] significantly decreased after 12 h CRRT treatment,and reached the normal range [K + (4.78 ± 2.95)mmol/L,BUN (7.5 ±2.1) mmol/L,Cr (54 ± 13) μmol/L] after 24 h treatment,but urine volume[(0.8 ±0.2)mL/(kg· h)] significantly increased after 24 h treatment.Partial pressure of oxygen/fraction of inspired oxygen reached 200 mmHg after 12 h treatment and more than 300 mmHg after 24 h treatment.CRRT treatment of 15 AKI neonates turned out to be effective.Conclusions CRRT can effectively improve the internal environment of AKI neonates and reduce the death rate of neonatal AKI,which can provide an effective adjuvant treatment measures for the treatment of AKI neonates.

ObjectiveTo investigate the timing and efficacy of continuous renal replacement therapy (CRRT) in neonatal acute kidney injury (AKI).MethodsNineteen AKI neonates treated with CRRT were enrolled during hospitalization in the Department of Neonatology of the Children's Hospital of Shanghai from June 2011 to June 2018. Their clinical data were retrospectively analyzed. According to their baseline renal function, these neonates were divided into two groups using an improved RIFLE (Risk, Injury, Failure, Loss and End-stage renal disease) standard: AKI stage 1-2 group and AKI stage 3 group. CRRT included continuous veno-venous hemodiafiltration (CVVHDF) and plasma exchange (PE). Several parameters included blood pressure (BP), renal function, electrolyte, blood gas and hemodynamic indicators were analyzed before, 12 h, 24 h, and 48 h after the initiation of CRRT and at the end of CRRT. Changes in neonatal renal function before, 24 h after the initiation of CRRT and at the end of CRRT were compared between the two groups. Efficacy of CRRT was evaluated, and clinical outcomes were analyzed. Kruskal-WallisH-test ort-test was applied for statistic analysis.Results(1) Among the 19 neonates with AKI, there were 12 in stage 1-2 and seven in stage 3. Seventeen cases were treated with CVVHDF, and the other two underwent plasma exchange. The duration of CRRT was 49-190 h with an average of (89.2±33.9) h. (2) After 12 h of CRRT, the blood pressure of all 19 AKI neonates returned to normal (40-60 mmHg, 1 mmHg=0.133 kPa) and was maintained at that level during the treatment. The blood pH value also increased to a normal range (7.35-7.45) at the same time. The oxygenation index reached 200 mmHg after 12 h of CRRT and rose to over 300 mmHg after 24 h. The levels of serum potassium, urea nitrogen, and creatinine decreased significantly after 12 h of CRRT and reached the normal range after 24 h of CRRT. After 24 h of CRRT, the urine volume significantly increased. (3) Serum levels of urea nitrogen and creatinine in neonates with AKI stage 1-2 decreased significantly after 24 h of CRRT. At any time points before and after CRRT (24 h before, 24 h after and at the end of CRRT), serum levels of urea nitrogen and creatinine in AKI stage 3 neonates were higher than those in AKI stage 1-2 neonates [urea nitrogen: (15.8± 4.1) mmol/L vs (10.2±5.1) mmol/L, (11.5±2.4) mmol/L vs (6.3±2.3) mmol/L, (9.8±2.1) mmol/L vs (5.1± 2.2) mmol/L,t=2.468, 2.226 and 2.171, respectively; creatinine: (184±32) μmol/L vs (152±26) μmol/L, (110±35) μmol/L vs (87±25) μmol/L, (63±12) μmol/L vs (44±9) μmol/L,t= 2.404, 2.423 and 3.972, respectively; allP<0.05]. (4) Venous catheterization was successful in the 19 AKI neonates. Three cases were complicated with thrombocytopenia, two with obstruction and two with hypotension during CRRT. Complications such as hypothermia, hemorrhage, thrombosis, and infection were not reported. (5) Among the 19 AKI neonates, 12 (including five of severe asphyxia, five of septic sepsis and two of inherited metabolic disorders and in metabolic crisis) were cured and discharged. The other seven cases (two in stage 1-2 and five in stage 3) lived through the oliguria stage but died after their family members gave up the treatment.ConclusionsCRRT is a safe and effective management for neonatal AKI. The optimal opportunity for CRRT treatment in AKI neonates should be at stage 1-2.

OBJECTIVETo carry out rapid genetic diagnosis for a child affected with citrullinemia type Ⅰ.

METHODSPeripheral venous blood samples were obtained from the two-day-old child and his parents as well as 100 healthy controls. Serum ammonia and citrulline was determined by biochemical test and tandem mass spectrometry. Sixteen pairs of primers were designed for high-resolution melting (HRM) analysis of all exons and adjacent intronic sequences of the ASS1 gene in the proband, parents and healthy controls. Suspected mutations were confirmed by DNA sequencing, while the mRNA transcripts of the ASS1 gene were determined by reverse transcription (RT)-PCR. Functional impact of the mutation sites was predicted with PolyPhen-2 and SIFT Blink software.

RESULTSBlood ammonia and citrulline of the proband have respectively reached 286 μmol/L and 487.69 μmol/L, which far superseded the normal values. HRM analysis and DNA sequencing have identified in the child a homozygous c.380G>A (p.R127Q) mutation in exon 6 of the ASS1 gene, in addition with a homozygous IVS8+60G>A substitution in intron 8, while his parents were heterozygous carriers for both mutations. RT-PCR assay indicated that the IVS8+60G>A mutation did not result in abnormal splicing of the ASS1 gene transcripts. Bioinformatic analysis suggested that the site for p.R127Q was conserved among 45 species of vertebrates and may play a crucial role in citrulline metabolism.

CONCLUSIONThe severe urea cycle disorder in the proband was probably due to the compound homozygous R127Q and IVS8+60G>A mutations of the ASS1 gene.

Objective To explore the clinical features, diagnosis, and treatment of non-immunologic hydrops fetalis (NIHF). Methods The clinical data of 10 cases of NIHF in neonatal intensive case unit during January 2011 to December 2016 were analyzed retrospectively. The related literatures were reviewed. Results In 10 cases of NIHF (6 males and 4 females). the gestational age were 32-42 weeks, and the birth weight was 2.25-3.95 kg. Among them, there were 3 cases of infectious diseases (cytomegalovirus, Streptococcus agalactiae, and parvovirus infection, one case each), 2 cases of fetal cardiovascular abnormalities, 2 cases of chromosomal abnormalities, 1 case of abnormal thoracic structures, 1 case of twin transfusion syndrome, and 1 case of etiology unknown of fetal hydrops. The clinical manifestations showed that there were 8 cases with 2 or more areas of edema (or hydrops), and only 2 cases with skin edema. Finally, 6 cases were cured and discharged, 2 cases were discharged by themself, and 2 cases died. Conclusions Prenatal ultrasound is a reliable method for the diagnosis of NIHF. Fetal edema in early pregnancy, especially with congenital malformations, is recommended for termination of pregnancy. After birth, NIHF should be diagnosed promptly so as to avoid or reduce severe complications.

Objective To observe the expression levels of kidney injury molecule-1(KIM-1) in renal tissues of ischemia-reperfusion rats,and to explore the value in the diagnosis of acute kidney injury.Methods Rats were randomly divided into two groups,control(CON) group (n=64) and acute kidney ischemia reperfusion injury (AIKI) group (n=64).Rats were sacrificed following reperfusion 2h,6h,24h,48h,72h,1 week (w),2 w,and 4 w.The changes of morphology were checked on HE staining sections under light microscope.The extent of tubulointerstitial injury was determined by Sayhan classification.The distribution and expression of KIM-1 in renal tissue were observed by immunohistochemistry and Western blotting.Serum samples were collected and serum creatinine measurement was performed at different reperfusion time points.Results (1) Compared with the CON group,the renal tubulointerstitial injury scores of AIKI group were significantly higher at all times after reperfusion (P<0.01).(2) The expression of KIM-1 was consistent with the tubulointerstitial injury.The positive correlation between KIM-1 and the tubulointerstitial injury scores was significant(r=0.887,P=0.003).(3) Compared with the CON group,serum creatinine in AIKI group was significant higher at 2h,6h,24h,48h,72h after reperfusion (P<0.05).Serum creatinine had no correlation with the damage of renal tubulointerstitial.Conclusion The expression of KIM-1 increases significantly in renal ischemia reperfusion injury,and it is consistent with the tubulointerstitial injury.Compared with serum creatinine,KIM-1 may be a more accurate biomarker of renal damage.

OBJECTIVEMaple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder that is caused by mutations in the subunits of the branched chain α-ketoacid dehydrogenase (BCKD) complex. This report presents a Han ethnic Chinese newborn infant with the severe classic form of MSUD caused by two novel missense mutations in the BCKDHB gene.

METHODThe clinical and biochemical data of a Chinese neonate with classic form of MSUD were analyzed, and the DNA sequences of BCKDHA, BCKDHB, DBT and DLD genes were investigated for mutations. Then the DNA samples of the proband and the patient's parents were tested with Sanger sequencing.

RESULTThe manifestations of this patient were poor feeding, low reaction, and compensatory metabolic acidosis. Tandem mass spectrometry (MS/MS) showed that leucine and valine were significantly higher than normal. Urine gas chromatography-mass spectrometry (GC/MS) showed significant abnormality. Brain CT scan showed white matter changes. We identified two previously unreported mutations in the BCKDHB gene, p.Leu194Phe (c.580 C>T) and p.Ser199Arg (c.597 T>G) in exon 5. Segregation analysis showed that the novel mutation p.Ser199Arg was maternally inherited and the novel mutation p.Leu194Phe was paternally inherited. Neither mutation was found in the 186 alleles of 93 normal Han ethnic Chinese individuals. In human BCKDHB protein crystal structure, the 194th and 199th amino acids changes are likely to affect the spatial structure of the protein. The 194th and 199th amino acid of human BCKDHB protein was conserved among species. PolyPhen protein function prediction indicated that the 194th and 199th amino acid changes were likely to affect protein function.

CONCLUSIONTwo novel missense mutations were identified in the BCKDHB gene in the Chinese patient with MSUD.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) ; genetics ; Alleles ; Asian Continental Ancestry Group ; Base Sequence ; DNA ; Exons ; Gas Chromatography-Mass Spectrometry ; Humans ; Infant ; Infant, Newborn ; Maple Syrup Urine Disease ; genetics ; Mutation, Missense ; Tandem Mass Spectrometry