Evaluation of ceruloplasmin in neonatal septicemia.

Serial serum ceruloplasmin (Cp) levels were estimated in healthy and septicemic neonates, using single radial immunodiffusion. In 25 healthy neonates mean Cp levels were 19.82 mg/dl at birth, 18.20 mg/dl at 12-24 hours, 17.26 mg/dl at 14 +/- 4 days and 17.68 mg/dl at 28 +/- 4 days of life. For the entire neonatal period the mean Cp levels were computed to be 18.24 mg/dl. In 20 culture positive, septicemic neonates, mean Cp levels were 27 mg/dl at onset of disease, 28.65 mg/dl 12-24 hours later and 36.2 mg/dl after 7 +/- 3 days of start of illness (p less than 0.001 for all sampling intervals as compared to healthy group values in first month of life). The mean Cp levels were unaffected by gestational age in both groups. In the septicemic neonates, the mean Cp levels in dying neonates did not differ significantly from recovering neonates for all sampling intervals. It is concluded that estimation of serum Cp levels may help in diagnosis of neonatal septicemia, but it is not useful as an early diagnostic aid or for prognostication.     

Serum leptin levels in neonatal bacterial septicemia

The principal aim of this study was to evaluate serum leptin concentrations and to analyze the interaction between serum leptin levels and C-reactive protein (CRP) levels, hematological parameters before and after antimicrobial therapy in neonates with bacterial septicemia. We studied 16 neonates with bacterial septicemia and 15 controls. Blood samples in neonates with septicemia were collected just before antimicrobial therapy and 2 weeks after treatment. The mean concentration of serum leptin, CRP levels, and immature/total neutrophil (IT) ratio in newborns with septicemia were significantly higher than those of controls at the start. Two weeks after treatment, serum leptin levels in newborns with septicemia had decreased and were similar to those of controls. Although there were positive correlations between serum leptin levels and serum CRP levels and IT ratio in the septicemic group at the start, there were no correlations between serum leptin levels and other hematological parameters. These results suggest that leptin is not only an adipostatic hormone but also a stress-related hormone.     

Rare alpha-1-antitrypsin phenotypes and liver-test abnormalities during infancy

Over 14 y of neonatal screening 71,675 dried blood samples were examined for the alpha-1-antitrypsin (alpha1-AT) alleles by isoelectric focusing in the Province of Bozen, Northern Italy. In infants carrying abnormal phenotypes the liver enzymes alanine aminotransferase and gamma-glutamyltransferase were determined at 2, 5 and 12 mo of age. In 17 neonates the PiMV phenotype was found, in 11 PiMF, in 11 PiMP, in 5 PiMN, in 3 PiMR, in 3 PiFZ, in 2 PiPZ and in 1 the PiMG phenotype was found. Two infants,1 carrying the PiMV and 1 the PiFZ phenotype showed at the age of 2 and 5 mo, respectively, elevated values of the liver enzyme S-ALAT[CE1]. Only the PiFZ and PiPZ carriers displayed low enough levels of alpha1-AT of 0.78 and 0.85 g l(-1) respectively, to be at moderately increased risk of pulmonary emphysema. Their early detection through the screening should discourage them from dangerous smoking habits. Conclusion: Only a neonatal screening based on phenotyping can detect these rare carriers early in life.     

Genetic regulation of alpha-1-antitrypsin levels in the neonatal period: The influence of the PiS allele and the PiM subtypes

Five groups of full-term newborn infants divided on the basis of the subtypes of M and one group of full-term newborn infants belonging to the phenotype M1S have been studied.A decrease in alpha-1-antitrypsin level in the M1S newborn infants was observed (P<0.001). A similar decrease was observed in a group of M1S preterm newborn infants in comparison with M1M1 and M2M2 newborn infants of the same gestational age.Moreover, full-term infants belonging to the subtype M1M2 also showed a decrease in the level of this inhibitor in comparison to the full-term infants belonging to other subtypes of M (P<0.01). Preterm newborn infants belonging to subtypes M1M2 and M1M1 showed identical circulating alpha-1-antitrypsin levels.When the phenotype is taken into account, data obtained from newborn infants free from perinatal pathology show that alpha-1-antitrypsin levels—but not alpha-2-macroglobulin levels—increase with fetal age.Moreover the specific compensatory response to the deficiency, consisting in an increase in alpha-2-macroglobulin levels, is absent in M1S and M1M2 neonates.The wide distribution of the M1M2 subtypes and, in some regions of the MS phenotype, suggests a need for genetic typing of the alpha-1-antitrypsin molecule in investigating the behaviour of this inhibitor in the perinatal period.Supported in part by a grant from Consiglio Nazionale delle Ricerche     

Hemostatic changes in idiopathic venous thrombosis in childhood and adolescence]

The prevalence of inherited thrombotic syndrome in the general population appears to be higher than that of inherited bleeding disorders. The most important candidates for screening are patients with unexplained venous thromboembolism at ages of less than 40 years: In 18 children and adolescents suffering from "idiopathic" vein thrombosis laboratory screening has been performed: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-2-antiplasmin and alpha-2-macroglobulin. Compared to an age matched healthy control group in children with idiopathic vein thrombosis we could demonstrate in vitro platelet activation with significant enhanced platelet aggregation and elevated levels of von Willebrand factor in the onset of the disease. Antithrombin III, protein C, alpha-2-antiplasmin and alpha-2-macroglobulin were significantly decreased. These changes turned to be normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, alpha-1-antichymotrypsin and c1-inactivator showed no alterations compared to the control. Platelet activation and alteration of platelet function in vivo and in vitro is established to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The decreased inhibitors of the hemostatic system antithrombin III and protein C in the onset period of thrombotic diseases are discussed to be an increased turnover, whereas the decreased levels of alpha-2-antiplasmin and alpha-2-macroglobulin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system.     

Concentration of C-reactive protein,procalcitonin and alpha-1-antitrypsin in blood of neonates and infants with signs of inflammation

We determined the concentration of C-reactive protein (CRP), procalcilonin (PCT) and alpha-1-antitrypsin (AAT) in blood of neonates and infants with suspected infection. Investigations were carried out in 88 children. Increased concentrations of CRP (>5mg/L). procalcitonin (>0.5ng/ml) and AAT (> 200mg/dl) were observed in: CRP - 24%. PCT- 46%, AAT - 49% of neonates in 70, 60 and 70% of infants. We concluded, that the examined parameters are good and sensitive markers of inflammation in neonates and infants.     

Physiologic blood coagulation studies in idiopathic arterial thrombosis]

QUESTIONING: The prevalence of inherited thrombotic syndromes in the general population appears to be higher than that of inherited bleeding disorders. However, the most important candidates for screening are patients with unexplained thromboembolism at ages of less than 40 years: In 19 children suffering from "idiopathic" arterial thrombosis laboratory screening has been performed. METHODS: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand-factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-2-antiplasmin and alpha-2-macroglobulin have been investigated. RESULTS: Compared to an age matched healthy control group we could demonstrate in children with arterial thrombosis in vitro platelet activation with significant enhanced platelet aggregation, elevated levels of von Willebrand-factor and alpha-1-antichymotrypsin at the onset of disease. Protein C and alpha-2-antiplasmin were significantly decreased. These changes turned back to normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, c1-inactivator and alpha-2-macroglobulin showed no alterations compared to controls. CONCLUSIONS: Platelet activation and alteration of platelet function have been shown in vivo and in vitro to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The lowering of protein C levels at the onset of thrombotic diseases is discussed to be due to an increased turnover, whereas the decreased levels of alpha-2-antiplasmin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system.     

Reference values of cord blood transferrin, ceruloplasmin, alpha-1 antitrypsin, prealbumin, and alpha-2 macroglobulin concentrations in healthy term newborns

Acute phase proteins are sensitive markers of tissue necrosis and inflammatory process. These markers may be especially useful in the neonatal period, in which mortality and morbidity rates are high, because fetus and baby are subjected to numerous metabolic, genetic, physiologic and environmental injuries such as neonatal asphyxia and septicemia. The purpose of the present study was to establish normal cord blood levels of some acute phase proteins in healthy term neonates. Umbilical cord blood was obtained at the time of vaginal delivery in 60 newborn infants (30 girls, 30 boys). Specific protein concentrations were measured by nephelometric assay. Transferrin, ceruloplasmin, alpha-1 antitrypsin, prealbumin, and alpha-2 macroglobulin concentrations [arithmetic mean (+/- SD)] were found to be 199.7 (+/- 34.6) mg/dl, 14.6 (+/- 4.0) mg/dl, 160.2 (+/- 23.6) mg/dl, 11.9 (+/- 2.2) mg/dl, and 284.6 (+/- 44.4) mg/dl, respectively. Prealbumin levels for girls [12.9 (+/- 2.2)] were found to be significantly higher than those of boys [10.9 (+/- 1.8)] (p < 0.001), while there were no significant differences between the other proteins. We conclude that these results may be used as reference values for the diagnosis of pathological conditions in newborns.     

Increased intestinal clearance of alpha 1-antitrypsin in patients with alpha 1-antitrypsin deficiency

To evaluate the possible contribution of enteric losses of alpha 1-antitrypsin (alpha 1-AT) to the low serum levels of alpha 1-AT seen in patients with alpha 1-AT deficiency, we investigated intestinal clearance of alpha 1-AT (C-alpha 1-AT) in five of these patients (mean age 3.4 years) and compared it to that of 10 patients (mean age 3.7 years) with gastrointestinal disorders and normal serum albumin values who served as controls. C-alpha 1-AT was also determined in four patients (mean age 9 months) with noncirrhotic liver disease. The percent of daily alpha 1-AT turnover which could be attributed to stool losses was calculated in these groups of patients. alpha 1-AT was measured in stool and serum by radial immunodiffusion and the clearance calculated. The mean C-alpha 1-AT in the patients with alpha 1-AT deficiency was significantly (p less than 0.05) higher than that of the controls. The liver disease patients had values for C-alpha 1-AT in the range of the controls. Three of the alpha 1-AT deficiency patients had values for C-alpha 1-AT greater than the mean plus 3 SD of the control, but these were not in the range seen in patients with protein losing enteropathy. Mean percent contribution of stool losses to total daily alpha 1-AT turnover was similar in all three groups. We conclude that patients with alpha 1-AT deficiency have increased fecal clearance of alpha 1-AT seemingly unrelated to the liver disease, but that this is not a major cause of the low serum levels.     

Fecal alpha-1-antitrypsin excretion in acute diarrhea: relationship with causative pathogens

Concentrations of alpha-1-antitrypsin (AT) in random fecal samples from 68 infants (92.7% outpatients) with acute diarrhea and 32 healthy controls were determined. The mean +/- s.d. for AT in infants with diarrhea was 2.07 +/- 1.88 mg/g dry stool (mg/g d.s.) compared with 1.29 +/- 0.72 mg/g d.s. (p less than 0.05) in controls. Fecal AT was significantly greater than that of the controls only for diarrhea caused by Rotavirus or Salmonella. Salmonella patients also had significantly higher fecal levels of AT than patients with diarrhea caused by Campylobacter. Fifty percent of the infants with Salmonella infections excreted more than 2.73 mg/g d.s. AT, which is above the control mean + 2 s.d. Fecal excretion of AT was highest in patients with macroscopic intestinal bleeding, but it still depended more on the causative agent than on bleeding per se. This finding of increased intestinal protein loss during acute diarrhea, even in the less severe diseases, emphasizes the necessity to rapidly restart adequate nutritional intake.     

C-reactive protein (CRP) in early diagnosis of neonatal septicemia.

The usefulness of CRP in early detection of neonatal septicemia/meningitis and urinary tract infection was studied in a neonatal unit using a semiquantitative latex-agglutination as a rapid screening method, and electroimmuno assay as reference method for CRP determination. In 94% of non-infected infants CRP was less than or equal to 15 mg/l and 82% had CRP less than 10 mg/l up to 3 days of age. After 3 days of age 96% had CRP less than 10 mg/l. The initial CRP level was increased in 16 out of 18 patients (89%) with bacterial septicemia. Low CRP was seen in one patient with total agranulocytosis and septicemia from Streptococcus type B and in one patient with Staphylococcus albus sepsis. A rise in CRP was also seen in very pre-term infants with septicemia. Increased initial CRP was uncommon in neonatal urinary tract infection (2 of 9), but a rise was seen in 3 additional patients. A comparison between CRP, total neutrophil blood cell count and band neutrophil count as diagnostic parameters was in favour of CRP at this early stage of infection. CRP is of definite value as an aid in early diagnosis of neonatal septicemia and bacterial meningitis.     

13 parameters of coagulation and fibrinolysis--univariate pediatric normal values of hemostasis

In order to establish age related univariate nonparametric tolerance regions in 74 healthy children and adolescents (age 2-18 years) undergoing elective surgery the following haemostatic parameters have been investigated: platelet count, von Willebrand factor, factor VIIIC, ristocetin-cofactor, antithrombin III, protein C fibrinogen, plasminogen, alpha-2-antiplasmin, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin and alpha-macroglobulin. Compared to adult normal values medians of von Willebrand factor and protein C were lowered, alpha-2-antiplasmin, C1-inactivator and alpha-2-macroglobulin were elevated, whereas the medians of alpha-1-antitrypsin and alpha-1-antichymotrypsin reached the lower adult borderline. The other investigated parameters showed no difference to those of adults.     

Plasma and urine elastase alpha-1-proteinase inhibitor levels in neonatal urinary tract infection

OBJECTIVE: To examine whether plasma or urine elastase alpha(1)-proteinase inhibitor (E-alpha(1)-PI) levels could be used as a diagnostic marker of urinary tract infection (UTI) in neonates. SUBJECTS AND METHODS: Plasma and urine E-alpha(1)-PI levels were measured by immunoassay in 23 neonates with UTI at the time of admission and 72 h after the onset of treatment and in 10 'normal' neonates (i.e. with trivial problems). Additionally E-alpha(1)-PI plasma levels were measured in 15 neonates with septicemia. RESULTS: E-alpha(1)-PI plasma levels did not differ between normal neonates and those with UTI. Urine E-alpha(1)-PI levels were significantly higher in neonates with UTI on admission compared to normal neonates. A significant decrease in urine E-alpha(1)-PI levels was noticed 72 h after the onset of treatment in all but 2 neonates in whom infection persisted. In this study, we have found that the urine E-alpha(1)-PI concentration at a cutoff level of 48 microg/l had a sensitivity of 83%, a specificity of 90%, a positive predictive value of 95% and a negative predictive value of 69% for the diagnosis of neonatal UTI. CONCLUSION: Elevated levels of E-alpha(1)-PI in urine seem to be a useful tool for the diagnosis of UTI in neonates (even in those that have already been started on antibiotics) and possibly a valuable marker for early recognition of treatment failure.     

Lipid peroxidation and antioxidants in neonatal septicemia

Free radicals have been implicated in the pathogenesis of neonatal septicemia. The present study was planned to estimate the lipid peroxidation and antioxidant status in neonatal septicemia. The study was done to evaluate the lipid peroxidation and antioxidant status, both enzymatic and non-enzymatic in neonates with septicemia. This prospective study included 44 septicemic babies as cases and a group of 84 matched healthy babies formed the control. Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione peroxidase (GTPx), Catalase, Uric acid (UA) and Albumin (Alb) were estimated in the serum and compared between the groups. The statistical analysis was done by using SPSS-10 software. Neonates with septicemia had significantly higher levels of MDA, SOD, GTPx, and Catalase, while the levels of UA and Alb were significantly lower as compared to controls (p<0.001). Significantly elevated levels of MDA (p<0.05) and depressed levels of UA (p<0.001) were found in babies with late onset sepsis. Neonates who ultimately succumbed had significantly elevated levels of MDA, SOD, GTPx and Catalase, whereas levels of UA and Alb were significantly depressed (p<0.001). Neonates with sepsis are handicapped in terms of their defense mechanism against free radicals. The utility of supplementation of antioxidant enzymes in neonates with septicemia needs further evaluation.     

组织因子途径抑制物及前降钙素在新生儿败血症诊断中的价值

目的 了解组织因子途径抑制物(TFPI)、前降钙素(PCT)在新生儿败血症诊断中的价值.方法 通过检测48例败血症新生儿及30例健康新生儿血TFPI、PCT、C-反应蛋白(CRP)浓度,比较各炎症指标对诊断败血症的灵敏度、特异度、阳性预测值、阴性预测值和约登指数,评价它们对该病的早期诊断价值.结果 (1)以TFPI≥30μg/L、CRP≥8 mg/L、PCT≥2 ng/ml为阳性标准,三指标对诊断败血症的灵敏度分别为86.92%、89.83%、87.50%,差异无显著性(P＞0.05),其中PCT的特异度96.67%、阳性预测值97.50%、阴性预测值83.32%、约登指数0.84;(2)在败血症组中,20例血培养阳性患儿的TFPI值为(35.5±4.5)μg/L,28例血培养阴性患儿的TFPI值为(34.3±3.2)μg/L,差异无显著性(P＞0.05);但是相对于正常对照组(26.9±5.24)μg/L,败血症组的TFPI值明显升高(P＜0.05).结论 TFP≥30μg/L对诊断新生儿败血症是一个具有较高灵敏度(86.92%)、中度特异度(59.3%)的指标;TFPI对新生儿败血症早期诊断有一定的价值,但均不及PCT及CRP,所有检测指标中PCT特异度、阳性预测值、阴性预测值、约登指数均最高.     

Increased serum concentrations of soluble tumor necrosis factor receptors p55 and p75 in early onset neonatal sepsis

Sepsis and pneumonia are major causes of morbidity and mortality in the neonatal period. The symptoms are variable and unspecific. So far, no reliable diagnostic test for neonatal infection has been found. In this study we measured serum levels of soluble tumor necrosis factor receptors (sTNFR) p55 and p75 in non-infected and infected neonates, and evaluated the diagnostic value of these mediators as tests for early detection of neonates with sepsis or pneumonia. Blood was collected on admission and after 3–4 days from 161 neonates consecutively admitted to the Neonatal Intensive Care Unit (NICU) during the first week of life. Twenty two neonates suffered from infection and 127 were classified as non-infected (controls). Samples were analyzed for p55 and p75, C-reactive protein (CRP) and white blood cell count with differential. Both preterm and term infected neonates had initially higher concentrations of p55 (both p<0.01) and p75 (p=0.01 and p=0.05, respectively) than controls. In non-infected neonates p55 levels decreased in the perinatal period, whereas p75 levels remained stable. Levels of both p55 and p75 decreased in neonates with infection during the perinatal period. CRP was a more specific parameter than p55 and p75 (CRP: 97%, p55: 65% and p75: 75%) whereas the sensitivity of all three parameters was at similar levels (CRP: 59%, p55: 70% and p75: 67%). We conclude that assessment of sTNFR may not improve accuracy in the diagnosis of early onset neonatal sepsis compared to the use of CRP.     

Selected trace elements and proteins in serum of apparently healthy newborn infants of mothers who smoked during pregnancy

The serum concentrations of selected trace elements and proteins in cord blood from 17 newborn infants whose mothers were habitual smokers were compared with values from 22 infants of non-smoking mothers. All the mothers were healthy with normal pregnancies and deliveries. Cigarette smoke exposure was verified by determinations of nicotine, cotinine and thiocyanate concentrations in cord blood. Infants of smoking mothers had a slightly lower mean birth weight (3490 +/- 430 g) than control infants (3780 +/- 460 g). Infants of smokers had lower serum iron (p = 0.05) and prealbumin (p less than 0.05), but higher serum copper (p less than 0.05) and ceruloplasmin (p less than 0.01) levels than the controls. Infants of smoking mothers tended to have higher levels of the acute-phase reactants alpha-2-macroglobulin and orosomucoid, but lower levels of albumin, transferrin and retinol-binding-protein, although differences were not statistically significant.     

Alpha-1-antitrypsin concentration in human milk

Alpha-1-antitrypsin concentration was analyzed by immunoelectrophoresis in samples of human colostrum (n = 3) and of mature milk from mothers between 2 to 52 wk postpartum (n = 39), one of whom was known to be PiMZ with a PiZZ infant. All milk samples tested contained alpha-1-antitrypsin. The three colostrum samples contained 140, 520, and 250 mg/liter. The mature milk of women who had been lactating less than 6 months had a higher concentration (7.2 +/- 3.6 mg/liter) (mean +/- SD) than in the women who had been lactating 6-12 months (4.8 +/- 1.8 mg/liter) (p less than 0.03). The milk of the woman of Pi type MZ had an alpha-1-antitrypsin concentration of 7.0 mg/liter at 7 wk postpartum and 4.1 mg/liter at 52 wk. It has been previously demonstrated that enhanced absorption of intact proteins occurs in early infancy. The presence of antiproteases in human milk provided during early infancy may serve to inhibit the absorption of intact proteases, limiting their entry into the portal circulation.     

可溶性细胞间黏附分子-1、降钙素原在新生儿败血症诊断中的价值

目的　了解可溶性细胞间黏附分子 1(sICAM 1)、降钙素原 (PCT)在新生儿败血症诊断中的价值。方法　通过检测 5 0例败血症的新生儿及 35例健康新生儿血sICAM 1、PCT、CRP浓度及WBC计数 ,比较各炎症指标对诊断败血症的灵敏度、特异度、阳性预测值、阴性预测值和准确性、约登指数 ,评价它们对诊断该病的价值。结果　 (1)以sICAM 1≥ 30 0ng/ml、CRP≥ 8mg/l、PCT≥ 2ng/ml为阳性标准 ,三指标对诊断败血症的灵敏度分别为 85 %、87 5 %、86 % ,P >0 0 5 ,差异无显著意义 ,但均高于WBC计数 (仅 30 % ,P <0 0 5 ) ,其中PCT的特异度 94 3%、阳性预测值 95 6 %、阴性预测值82 5 %、准确性 89 4 %、约登指数 80 3% ;(2 )sICAM 1浓度在治疗前后差异无显著意义 ,P >0 0 5 ;CRP浓度在两组差异有显著意义 ,P <0 0 5 ;PCT在恢复期全部转阴 ;(3)sICAM 1与CRP呈正相关 ,r =0 339,P <0 0 1;PCT与sICAM 1、CRP浓度的等级相关系数分别为 0 5 6 9、0 4 82 (P <0 0 1)。结论　sICAM 1≥ 30 0ng/ml对于诊断新生儿败血症是一个具有较高灵敏度 (85 % )、中度特异度 (5 4 3% )的指标 ;所有检测指标中PCT特异度、阳性预测值、阴性预测值、准确性、约登指数最高     

C-REACTIVE PROTEIN (CRP) IN EARLY DIAGNOSIS OF NEONATAL SEPTICEMIA

Abstract. The usefulness of CRP in early detection of neonatal septicemia/meningitis and urinary tract infection was studied in a neonatal unit using a semiquantitative latex-agglutination as a rapid screening method, and electroimmuno assay as reference method for CRP determination. In 94% of non-infected infants CRP was 15 mg/l and 82 % had CRP <10 mg/l up to 3 days of age. After 3 days of age 96% had CRP < 10 mg/l. The initial CRP level was increased in 16 out of 18 patients (89%) with bacterial septicemia. Low CRP was seen in one patient with total agranulocytosis and septicemia from Streptococcus type B and in one patient with Staphylococcus albus sepsis. A rise in CRP was also seen in very pre-term infants with septicemia. Increased initial CRP was uncommon in neonatal urinary tract infection (2 of 9), but a rise was seen in 3 additional patients. A comparison between CRP, total neutrophil blood cell count and band neutrophil count as diagnostic parameters was in favour of CRP at this early stage of infection. CRP is of definite value as an aid in early diagnosis of neonatal septicemia and bacterial meningitis.