新生儿ABO溶血高胆红素血症血尿胱抑素C测定及临床价值探讨

目的 探讨新生儿ABO溶血高胆红素血症血、尿胱抑素C(Cys C)变化及其临床价值.方法 2008年1月至2010年1月本科确诊为ABO溶血症引起高胆红素血症(TBil≥220.6μmol/L)的新生儿为观察组,根据胆红素水平分为轻度组(TBil<256.5 μmol/L)和中重度组(TBil≥256.5 μmol/L).同期自然分娩、无黄疸的新生儿为对照组.测定观察组入院24 h内及黄疸消退期、对照组生后2～3 d血清胆红素、血尿Cys C、β2-微球蛋白(β2-MG)、BUN、Scr值,并对资料进行统计学分析.结果 轻度组18例,中重度组22例,对照组20例.中重度组血清Cys C、β2-MG值高于对照组(P<0.05);轻度组、中重度组尿Cys C、β2-MG值均高于对照组(P<0.05);中重度组血、尿Cys C、β2-MG值均高于轻度组(P<0.05);血清胆红素与血、尿Cys C水平呈正相关(r=0.627、0.538,P<0.01);血、尿Cys C水平分别与血、尿β2-MG水平呈正相关(r=0.385、0.368,P<0.05).观察组治疗后,血、尿Cys C值较治疗前明显下降(P<0.01).结论 高胆红素血症对新生儿肾功能有不同程度的损害,且对肾小管的损害早于肾小球,但肾损伤短暂、可逆;血、尿CysC测定时新生儿早期肾功能损害的诊断、治疗及疗效判断均具有十分重要的临床指导价值.     

血清γ-痕迹蛋白对新生儿ABO溶血症肾功能损害的诊断价值

目的 探讨ABO溶血症(ABO-HDN)新生儿血清γ-痕迹蛋白(cystatin-C,Cys-C)水平变化及其在判断新生儿肾功能损伤状况中的临床价值.方法 将入选新生儿分为2组:对照组20例,观察组40例.后者根据血清胆红素水平分为轻度组(18例)和中重度组(22例).测定血清BUN、SCr、β2-MG及Cys-C,并计算肌酐清除率(CCr),比较各组间各指标的差异及相关性,行ROC曲线分析.结果 轻度组血清Cys-C、β2-MG、CCr值与对照组比较,差异无统计学意义(P均＞ 0.05);中重度组血清Cys-C、β2-MG值较对照组及轻度组显著升高(P均＜ 0.05),CCr值较对照组及轻度组显著降低(P均＜ 0.05).各组BUN、SCr比较差异无统计学意义(P均＞ 0.05).血清1/Cys-C、1/β2-MG水平与CCr呈显著相关(r ＝ 0.524、0.463,P均＜ 0.05).血清Cys-C 最佳截断点为1.83 mg/L,敏感度为90.3%,特异度为89.5%;β2-MG 最佳截断点为4.87 mg/L,敏感度为85.2%,特异度为87.1%.血清Cys-C、β2-MG ROC曲线下面积分别为0.892、0.805,差异有统计学意义(P ＜ 0.05).结论 血清Cys-C比β2-MG更能反映新生儿肾小球滤过功能的损害,可作为ABO-HDN新生儿肾功能损害的敏感诊断指标.     

Prediction of significant hyperbilirubinemia in term neonates by early non-invasive bilirubin measurement

Background:Neonatal jaundice is a common problem.We evaluated the utility and best cut-off values of 24-and 48-hour transcutaneous bilirubin indices (TcBI) in predicting subsequent significant hyperbilirubinemia and evaluated various associated maternal and fetal risk factors.Methods:TcBI at 24 and 48 hours and serum bilirubin levels at 72 hours of age were obtained for healthy,term,appropriate for gestational age neonates.Neonates with prematurity,birth weight ＜2500 g,ABO or Rh incompatibility,onset of clinical jaundice ＜24 hours,clinical suspicion of septicemia,positive pressure ventilation at birth,admission in neonatal intensive care unit and contraindications for BiliChek were excluded.Twently-four and 48-hour TcB indices were assessed as predictors of subsequent hyperbilirubinemia,defined as serum bilirubin ＞17 mg/dL after 72 hours of life and various cut-offs,and were evaluated by calculating sensitivity,specificity and predictive values.Results:Of 500 newborns,4.6％ had significant hyperbilirubinemia,27％ had TcBI (mg/dL) ＜5 at 24 hours,and 27.4％ had TeBI ＜8 at 48 hours.None of them had subsequent hyperbilirubinemia (100％ negative predictive value).The percentage of newborns with subsequent hyperbilirubinemia increased from 3.4％ to 13.2％ as their 24-hour TcBI increased from 6 to above 9 mg/dL and from 4.2％ to 7.4％ as their 48-hour TcBI increased from 8 to above 11 mg/dL.The best cut-off value was TcBI (mg/dL) 7 (odd ratio=4.86,95％ confidence interval:1.66-15.22) at 24 hours and 10 (odd ratio=2.87,95％ confidence interval:1.04-8.29) at 48 hours.Area under the receiver operating characteristic curve for 24-and 48-hour measurements was 0.750 and 0.715,respectively.Maternal premature rupture of membranes,deep transverse arrest,post-date pregnancy,and fetal distress were significant risk factors for hyperbilirubinemia.Conclusions:Twenty-four and 48-hour TcB indices are good predictors of subsequent hyperbilirubinemia.Twenty-four-hour TcBI had better predictive ability than 48-hour TcBI.     

Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns

OBJECTIVE: To assess the predictive ability of a universal predischarge serum bilirubin measurement to screen for risk of subsequent significant hyperbilirubinemia in the direct Coombs negative healthy term and near-term newborn during the first postnatal week. METHODS: Total serum bilirubin (TSB) levels were obtained at the time of the routine metabolic screen in all term and near-term newborns cared for in the Pennsylvania Hospital Well Baby Nursery (n = 13 003). Postnatal age (in hours) at the time of TSB measurement was recorded. A percentile-based bilirubin nomogram for the first week was constructed from hour-specific predischarge and postdischarge TSB values of newborns (n = 2840; median BW = 3230 g and median gestational age = 39 weeks) who met classification criteria for healthy newborns (excluding those with a positive direct Coombs test or those requiring phototherapy before age 60 hours) and who were enrolled in a hospital supervised home or outpatient follow-up program. The accuracy of the predischarge TSB as a predictor of subsequent degree of hyperbilirubinemia was determined. RESULTS: The study patients in the nomogram were racially diverse. Nearly 60% were breastfed. Predischarge, 6.1% of the study population (172/2840) had TSB values in the high-risk zone (>/=95th percentile) at 18 to 72 hours; of these, 39.5% (68/172) remained in that zone (likelihood ratio [LR] = 14.08, sensitivity = 54%; specificity = 96.2%, probability = 39.5%). Predischarge, 32.1% of the population (912/2840) had TSB values in the intermediate-risk zone. In a clinically significant minority of these newborns (58/912 or 6.4%), the postdischarge TSB moved into the high-risk zone (LR of this move: 3.2 from the upper-intermediate zone and.48 from the lower-intermediate risk zone). The predischarge TSB in 61.8% of the newborns (1756/2840) was in the low-risk zone (<40th percentile) and there was no measurable risk for significant hyperbilirubinemia (LR = 0, sensitivity = 100%; specificity = 64.7%; probability = 0%). CONCLUSIONS: An hour-specific TSB before hospital discharge can predict which newborn is at high, intermediate or low risk for developing clinically significant hyperbilirubinemia (specifically defined as TSB levels >/=95th percentile for age in hours). Risk designation and subsequent increases or decreases of in TSB can be easily monitored on an hour-specific percentile based predictive bilirubin nomogram. A predischarge TSB measured as a universal policy would facilitate targeted intervention and follow-up in a safe, cost-effective manner. In conjunction with bilirubin practice parameter of the American Academy of Pediatrics, it could reduce the potential risk for bilirubin-induced neurologic dysfunction.     

ABO溶血病患儿应用丙种球蛋白的胆红素阈值探讨

目的 探讨选择应用丙种球蛋白治疗新生儿ABO溶血病的适宜胆红素阈值.方法 将我院新生儿科2011年7月至2012年9月收治的新生儿ABO溶血病患儿随机分为两组,试验1组患儿胆红素值达到Bhutani曲线第75百分位、试验2组达到第95百分位时,应用1次丙种球蛋白1 g/kg.比较两组患儿总光疗时间、治疗2天后胆红素下降幅度、住院时间、住院费用、血红蛋白值、应用丙种球蛋白的比例等资料.结果 试验1组(66例)和试验2组(63例)患儿总光疗时间、胆红素下降幅度、住院时间、住院费用、生后42天血红蛋白值差异均无统计学意义(P＞0.05),试验2组应用丙种球蛋白比例(34/63)小于试验1组(53/66),差异有统计学意义(P＜0.01),两组均没有需要换血或发生胆红素脑病的病例.结论 以Bhutani曲线第95百分位水平胆红素值作为应用丙种球蛋白治疗新生儿ABO溶血病的胆红素阈值更为合理.     

Clinical (video) findings and cerebrospinal fluid neurotransmitters in 2 children with severe chronic bilirubin encephalopathy, including a former preterm infant without marked hyperbilirubinemia VIDEO

Chronic bilirubin encephalopathy, characterized clinically by extrapyramidal movement abnormalities, vertical gaze abnormalities, and hearing loss, results from neuronal injury after marked hyperbilirubinemia in term and preterm infants. In premature infants, bilirubin staining of specific brain structures has been described at autopsy after only moderate hyperbilirubinemia, but classic chronic bilirubin encephalopathy without marked hyperbilirubinemia has been reported only rarely. We report a case of a 7-year-old, former 29-weeks' gestation, gravely ill premature infant with a peak bilirubin level of 13.3 mg/dL in the neonatal period. We compare this case with a 12-year-old, former term infant with a peak bilirubin level of 49.4 mg/dL on day 10 of life. Both children have dystonia, athetosis, upward gaze palsy, and sensorineural hearing loss, with MRIs showing characteristic abnormal signal in the globus pallidus. We add previously unreported cerebrospinal fluid neurotransmitter levels that show a mild decrease in the dopamine metabolite homovanillic acid in the former premature infant only.     

胎粪污染羊水新生儿发生重度胎粪吸入综合征的临床特征及预警因素分析北大核心CSCD

目的探讨胎粪污染羊水(meconium-stained amniotic fluid,MSAF)新生儿发生重度胎粪吸入综合征(meconium aspiration syndrome,MAS)的临床特征及预警因素。方法纳入2018年1月至2019年12月因Ⅲ°MSAF住院的新生儿295例为研究对象,按是否并发MAS分为无MAS组(n=199)、轻度/中度MAS组(n=77)和重度MAS组(n=19),回顾性收集3组患儿一般临床资料、血气分析结果、感染指标、母亲围生期临床资料等进行分析,并比较3组患儿出生后的呼吸支持方案。应用受试者工作特征曲线及多因素logistic回归分析MSAF新生儿发生重度MAS的预警因素。结果295例MSAF新生儿中32.5%(96/295)发生MAS,其中20%(19/96)为重度。重度MAS组出生5min Apgar评分低于轻度/中度MAS组及无MAS组(P<0.05),脐动脉血乳酸水平高于轻度/中度MAS组和无MAS组(P<0.05),生后1h外周血白细胞介素6(interleukin-6,IL-6)水平高于无MAS组(P<0.017)。重度MAS组患儿79%(15/19)出生无活力(其中13例行胎粪吸引术),100%在24h内开始机械通气。生后1 h外周血IL-6水平>39.02 pg/mL及生后1 h白细胞计数>30.345×10^(9)/L为MSAF新生儿发生重度MAS的预警指标(P<0.05)。结论胎粪吸引不能完全阻止MSAF新生儿严重MAS的发生;重度MAS患儿在出生早期即发生严重呼吸窘迫需要机械通气。监测脐动脉血乳酸及生后1 h外周血IL-6水平、白细胞计数有助于预警MAS的发生及严重程度。     

Determination of bilirubin in capillary plasma by a direct photometric method (DPM, bilirubinometer) and the chemical determination of bilirubin in the bilirubin determination (2,5-dichlorophenyldiazonium method) in serum of venous blood samples

The determination of bilirubin in serum was performed by the 2.5-dichlorphenyldiazonium method (DPD) and in capillary plasma by the direct photometric method (DPM). Both methods showed a good precision and accuracy. The investigation was carried out in 135 samples with a bilirubin concentration up to 25 mg/dl. The comparison of the two methods in 62 samples with a bilirubin concentration up to 10 mg/dl showed a correlation coefficient of r = 0.862 and in 73 samples with a bilirubin concentration between 10 and 25 mg/dl a correlation coefficient of r = 0.893. In 29 cases (21.5%) we found differences between the two methods of 1.5-4.0 mg/dl. Most of them were in the critical higher range. Discussion of the DPD and DPM methods.     

Elevated Lp(a) with a small apo(a) isoform in children: risk factor for the development of premature coronary artery disease

Background: levels of Lp(a) and low‐molecular‐weight apolipoprotein(a) isoform are strongly associated with the development of early cardiovascular disease. Certain types of apo(a) isoforms in combination with elevated levels of Lp(a) may be important in the determining of premature coronary artery disease. Therefore, we investigated the association of familial history of premature coronary artery disease and apo(a) size and Lp(a) levels in children and adolescents with hypercholesterolemia using a novel method determining apo(a) isoforms. Methods and results: Isoforms were classified in six phenotype patterns: S1–S4, B, F and according to their K‐IV repeats. Apo(a) isoforms were divided into two groups: low‐molecular‐ and high‐molecular apo(a) isoforms. In subjects with double‐banded apo(a) isoforms containing a small‐ and a large‐isoform Lp(a) each contribution was based on the intensity of staining of the two bands. The percentage of patients with elevated levels of Lp(a) and a small apo(a) isoform (i.e. elevated small‐isoform Lp(a)) was 46% in the risk group and 20% in the control group, p < 0.05. The percentage number of children and adolescents with elevated Lp(a) levels was higher in the risk group, reaching statistical significance (p < 0.05). Conclusion: Elevated levels of small‐isoform Lp(a) might be a strong and independent risk factor for the development of premature coronary artery disease in children and adolescents with hypercholesterolemia.     

Minimal residual disease (MRD) measurement as a tool to compare the efficacy of chemotherapeutic drug regimens using Escherichia Coli-asparaginase or Erwinia-asparaginase in childhood acute lymphoblastic leukemia (ALL)

BACKGROUND: L-asparaginase is a crucial drug in childhood acute lymphoblastic leukemia (ALL) induction therapy, but much debate remains regarding the optimal formulation and dosage. As minimal residual disease (MRD) can accurately measure extremely low levels of lymphoblasts, it is a sensitive reflection of leukemia cell kill. We utilized MRD to compare the efficacy of Erwinia-asparaginase (Erwinia-asp) and E. coli-asparaginase (E. coli-asp) during induction therapy for childhood ALL. PROCEDURE: Of 116 precursor-B ALL patients, 22 were treated with Erwinia-asp, 90 with E. coli-asp, and 4 were switched from E. coli-asp to Erwinia-asp. MRD levels at the end of induction were analyzed for 90 patients (Erwinia-asp = 16; E. coli-asp = 74). Patients were stratified into MRD > or =10(-2), between 10(-2)-10(-4) and < or =10(-4). Toxicity information during induction was available for 110 patients. RESULTS: MRD was the only significant prognosticator compared to conventional criteria. Patients treated with Erwinia-asp were 6.7 times more likely to have MRD levels > or =10(-2) (P = 0.031), reflecting slower lymphoblast clearance. While non-asparaginase related toxicities were similar in both groups, more E. coli-asp patients experienced severe asparaginase-related toxicity. CONCLUSION: E. coli-asp is superior to Erwinia-asp in childhood ALL induction. Although E. coli-asp is more toxic, this is balanced by better response to therapy. Early response to treatment as measured by MRD is a direct reflection of leukemic cell kill and is a significant prognosticator of eventual outcome, making it a good surrogate marker to evaluate the efficacy of induction drugs in childhood ALL.     

Metabolic risk in contemporary children is unrelated to socio‐economic status: longitudinal study of a UK urban population (EarlyBird 42)

Lifestyle interventions to improve health in young children tend to target areas of relative deprivation, but the evidence for so doing is largely historical. Accordingly, we have re‐examined the link between deprivation, obesity and metabolic risk in contemporary UK children. Using a postcode‐based index of multiple deprivation (IMD), we assessed 269 children from the community‐based EarlyBird Study, attending 53 schools representing a wide socio‐economic range. Annual measures of fatness from 5 to 8 yr included body mass index (BMI), waist circumference (WC), and sum of five skinfolds (SSF). A metabolic risk score, based on blood pressure, lipids and insulin resistance, was derived from annual fasting blood samples. There were no significant associations between deprivation and any measure of adiposity in girls (all p > 0.37). In boys, there was a weak but consistently inverse relationship between deprivation and WC (r = ?0.19, p = 0.03) and BMI (r = ?0.14, p = 0.09) at 8 yr. Changes in adiposity over 3 yr were unrelated to deprivation in boys. In girls there was a slight but significant increase in SSF only (1 mm/yr per 20 IMD units, p = 0.001). Importantly, in both genders, metabolic risk score was unrelated to deprivation throughout (r values ?0.05 to ?0.13, all p > 0.12), as was change in metabolic risk (all p > 0.30). Our data do not support the assumption that obesity, metabolic disturbance and thus risk of type 2 diabetes are more prevalent among poorer children. In today's increasingly obesogenic environment, youngsters from all backgrounds appear to be vulnerable, with population‐wide implications for public health spending, and the prevention of diabetes in contemporary youth.