Plasma levels of interleukin-6 and interleukin-10 in preterm neonates evaluated for sepsis

In a prospective study, plasma interleukin-6 (IL-6) and interleukin-10 (IL-10) levels were measured by enzyme-linked immunosorbent assay in 45 premature neonates (25–34 weeks gestational age) with signs and symptoms of suspected sepsis at 0, 12 and 24 h; C-reactive protein (CRP) was measured at 0–24 h after enrolment. Six subjects were excluded due to insufficient blood sampling. The remaining 39 neonates were assigned to one of three groups: 25 newborns with sepsis (blood culture positive), seven with pneumonia (positive results on broncho-alveolar lavage fluid culture and characteristic chest radiography) and seven with necrotising enterocolitis (NEC) (characteristic intestinal and radiological signs according to the criteria of Bell et al.). A group of 20 healthy preterm neonates represented control subjects. On admission, higher levels of IL-6, IL-10 and CRP were observed in neonates with sepsis: IL-6 (median 1500 pg/ml, range 487–10000 pg/ml), IL-10 (median 113 pg/ml, range 70–196 pg/ml), CRP (median 22 mg/l, range 4–80 mg/l); pneumonia: IL-6 (median 1500 pg/ml, range 747–8000 pg/ml, IL-10 (median 84 pg/ml, range 76–92 pg/ml), CRP (median 10 mg/l, range 8–33 mg/l) and NEC: IL-6 (median 6650 pg/ml, range 1595–7950 pg/ml), IL-10 (median 80 pg/ml, range 61–147 pg/ml), CRP (median 3 mg/l, range 2.8–8 mg/l) as compared to controls (IL-6 median 208 pg/ml, range 198–349 pg/ml; IL-10 median 36 pg/ml, range 19–50 pg/ml; CRP median <2 mg/l) (P < 0.05). In neonates with sepsis, IL-6 levels were significantly correlated with IL-10 levels (r=0.65; P=0.04) at the time of the second sample. The highest IL-6 levels were observed at onset, while IL-10 was predominant 12 h later. On admission, IL-10 and CRP levels were significantly higher in non-survivors (IL-10 median 507 pg/ml, range 422–753 pg/ml; CRP median 123 mg/l, range 20–219 mg/l) than in survivors (IL-10 median 76 pg/ml, range 61–143 pg/ml; CRP median 8 mg/l range 3–46 mg/l), while IL-10 levels were significantly higher (P < 0.05) also 12 h after admission (non-survivors: IL-10 median 600 pg/ml, range 538–800 pg/ml; survivors: IL-10 median 74 pg/ml, range 53–161 pg/ml). IL-6 and IL-10 levels were significantly correlated with CRP levels on admission (r=0.45; P=0.05). Conclusion Preterm neonates with sepsis, pneumonia or necrotising enterocolitis showed increased interleukin-6, interleukin-10 and C-reactive protein levels. High interleukin-10 concentration was associated with mortality and could be an early indicator of prognosis. Received: 21 November 2000 / Accepted: 23 January 2001     

Plasma RANTES increase during the first month of life independently of the feeding mode

The chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) plays a significant role in the innate immunity, which is particularly important in the neonatal period. In this study, we aimed to investigate the ability of the neonate to increase plasma levels of RANTES in the first month of life, and the possible impact of breast feeding on this ability. The study population consisted of 125 healthy term neonates that were exclusively breast-fed (n = 62) or formula-fed (n = 63) for at least 1 month after birth. Plasma RANTES concentrations (ELISA) as well as circulating leukocytes and platelets were measured on days 1 and 30 of life. Median RANTES concentrations of the total group showed a significant increase between day 1 [1000 (448–2100) pg/mL] and day 30 [3688 (1488–5400) pg/mL, p < 0.0001], as did median total lymphocyte, T-cell, B-cell, NK-cell and eosinophil counts (all p values <0.0001). Monocyte and platelet counts did not change significantly over the neonatal period. Further analysis according to the mode of feeding showed that RANTES levels as well as leukocyte populations and platelet counts did not differ significantly between breast-fed and formula-fed neonates on either day 1 or 30. Healthy term neonates are capable of increasing plasma RANTES levels during the 1st month after birth independently of the mode of feeding.     

Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease

We investigated serum vascular endothelial growth factor (SVEGF) levels in Kawasaki disease and determined whether these levels had any association with the development of coronary artery lesions. We measured SVEGF levels in 66 patients with Kawasaki disease, 18 patients with active infections and 18 afebrile controls. SVEGF levels of patients in the acute phase of Kawasaki disease (0.0–2003.6 pg/ml, median 59.87 pg/ml) were significantly higher than those of patients with active infections (0.0–45.2 pg/ml, median 8.10 pg/ml; P < 0.05) or afebrile controls (0.0–49.8 pg/ml, median 7.75 pg/ml; P < 0.05) and decreased to undetectable or low levels in the recovery phase (n=31, acute phase: 0.0–2003.6 pg/ml, median 62.50 pg/ml versus recovery phase: 0.0–146.5 pg/ml, median 26.90 pg/ml; P=0.0007) of the disease. There existed a positive correlation between SVEGF levels and serum C-reactive protein concentrations in the acute phase of Kawasaki disease (r _s =0.347, P=0.0051). In addition, SVEGF level and duration of fever were found to be major risk factors for the occurrence of coronary artery lesions by univariate (P=0.012 and P=0.003, respectively) and multivariate (P=0.037, OR 6.16 and P=0.0059, OR 7.59, respectively) analyses. Conclusion Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms. Received: 16 March 1999 / Accepted: 30 November 1999     

Prognostic Value of Pre- and Postoperative Cardiac Troponin I Measurement in Children Having Cardiac Surgery

The objective of this study was to determine if perioperative elevation of cardiac troponin I (cTnI) predicts mortality in infants and children after surgical correction of congenital heart defects. One hundred infants and children having open heart surgery were studied. Blood samples for cTnI analysis were collected before cardiopulmonary bypass (CPB) and at 4, 8, 12, and 24 h after initiation of CPB. Demographic information, cardiac defect, repair performed, duration of CPB, complications, and outcome were recorded. Cardiac defects were categorized as atrial septal defect (ASD), ventricular septal defect (VSD), hypoplastic left heart syndrome (HLHS), complex, and “other.” Baseline cTnI was significantly lower in survivors (mean 0.42 ng/ml, median 0.35 ng/ml) than in nonsurvivors (mean 1.89, median 1.30), p= 0.0001. Baseline cTnI was significantly higher in the HLHS group (mean 1.47, median 1.10) than in all other subgroups (mean 0.62, median 0.35), p≤ 0.009. There were no significant differences between survivors and nonsurvivors at the remaining sampling times. Children who died from cardiac failure (n = 2) were more likely to have 4 h cTnI >125 ng/ml compared to survivors (2 of 90). Within cardiac defect subgroups, 4 h cTnI was significantly higher in the complex group (mean = 53.51, median = 32.30) than in the ASD (mean = 23.84, median = 19.85) and other (mean = 21.59, median 21.50) subgroups. Perioperative measurement of cTnI identifies children within specific cardiac defect subgroups at risk of mortality after cardiac surgery. We speculate that detection of myocardial injury may decrease mortality and morbidity in children with complicated congenital cardiac lesions by leading to improvements in perioperative management. Received November 2, 1998; accepted April 7, 1999.     

Clinical significance of plasma endothelin levels in patients with biliary atresia

Biliary atresia (BA) is the end-result of a destructive inflammatory process that affects intra- and extrahepatic bile ducts, leading to fibrosis and obliteration of the biliary tracts with the development of biliary cirrhosis and portal hypertension (PH). Endothelins (ET) are 21-amino-acid peptides of endothelial origin with potent vasoconstrictor activity that bind to various cells of the liver. Nothing is presently known about plasma ET levels in BA. The aim of this study was to determine the clinical significance of plasma ET levels in patients with BA after hepatic portoenterostomy (Kasai's procedure) and to correlate these with liver function tests (LFT) and PH. We measured plasma concentrations of ET in 19 patients with BA (5 boys and 14 girls; mean age 11.6 ± 5.5 years) after portoenterostomy and 10 age-matched controls. Patients were grouped according to outcome based on LFT: group A consisted of 9 patients with an ‘‘unfavorable outcome” and Group B 10 patients with a “favorable outcome”. The plasma ET levels were measured using a highly sensitive and specific enzyme immunometeric assay (EIA). No patient had ascites or hepatorenal syndrome. Plasma ET levels were significantly higher in patients with BA than in controls (3.42 ± 0.42 vs 1.75 ± 0.39 pg/ml, respectively; P < 0.01) and in patients in group A than in group B. (3.75 ± 0.25 vs 3.06 ± 0.23 pg/ml, respectively; P < 0.01). In group A, plasma ET levels were higher in patients with PH (n = 4) than in those without PH (n = 5) (3.99 ± 0.06 vs 3.64 ± 0.22 pg/ml, respectively; P < 0.05). We conclude that plasma ET levels are high in patients with BA, especially those with severe biliary cirrhosis, and that ET may partially contribute to development of PH in BA. The results of the present study also suggest that plasma ET concentrations may be a useful marker in the follow-up of patients with BA. Accepted: 12 September 1997     

Cord blood interleukin-10 levels are increased in preterm newborns

Cell-mediated immunosuppression due to interleukin (IL)-10 may contribute to normal pregnancy. By contrast, delivery is associated with a predominance of T-helper-1 (Th1) cytokines (IL-12, interferon-γ) and might be regarded as a graft rejection process. The aim of the study was to assess IL-10 and IL-12 levels in cord blood samples from newborns and their normal mothers in relation to the gestational age and type of delivery. Cord blood and serum samples were obtained from 31 term newborns (gestational age 38–42 weeks) and 40 preterm newborns (mean gestational age 32 weeks). Serum samples were obtained from 26 mothers of term newborns at birth. There were 18 term and preterm infants born by caesarean section. Measurements of IL-10 and IL-12 levels by ELISA were repeated in mothers 15 days after delivery and in 11 preterm infants (median 14 days of age). Cord blood IL-10 levels were significantly higher in preterm than in term newborns (median 17.0 versus 3.2 pg/ml, P = 0.0001), but were similar to term newborns and paired mothers (2.2 versus 1.0 pg/ml). Term and preterm newborns also showed similar cord blood IL-12 levels (median 349 versus 320 pg/ml), and these levels were significantly higher when compared to their paired mothers (median 14.5 pg/ml, P = 0.0003). Cord blood IL-10 levels showed a significant inverse correlation with gestational age (P = 0.0001). When preterm infants, at several weeks post-delivery, were compared to gestational age matched newborns, their IL-10 levels were similar (median 8.3 pg/ml) whereas IL-12 levels were clearly lower(147 pg/ml; P = 0.0007). The type of delivery (vaginal versus caesarean) did not influence cord blood IL-10 and IL-12 results. Conclusion Cord blood IL-10 levels are increased in preterm newborns and may be due to the immunosuppression occurring during pregnancy and to fetal immaturity because these levels are inversely correlated with gestational age. Received: 18 December 1998 and in revised form 12 October 1999 / Accepted: 25 October 1999     

Serum osteocalcin has limited usefulness as a diagnostic marker for rickets

Serum alkaline phosphatase (AP), the bone fraction of which is secreted by osteoblasts, is elevated in rickets. Both normal and elevated levels of serum osteocalcin (OC), a bone-specific marker secreted by osteoblasts, have been reported in rickets. Expression of the OC gene is enhanced by 1,25-dihydroxyvitamin D (1,25(OH)₂D) in experimental models. This study assessed serum OC levels in 14 controls and 41 patients with active rickets divided into a phosphopenic (n=20) and a calciopenic (n=21) group. Phosphopenic subjects were older (9.5 versus 5.7 years, P=0.03) with higher median serum calcium level (2.35 versus 2.16 mmol/l, P=0.0002) and serum 25-hydroxyvitamin D level (15.4 versus 10.4 ng/l, P=0.003); and lower serum phosphate (0.80 versus 1.51 mmol/l, P=0.0001), serum 1,25(OH)₂D (43.0 versus 95.6 pg/ml, P=0.0001) and intact serum parathyroid hormone level (45.0 versus 141.5 ng/l, P=0.01) than calciopenic subjects. There were no differences in median serum AP (774 versus 1430 IU/l, P=0.17) and OC (14.5 versus 13.4 ng/ml, P=0.6) between the two groups. The mean OC value for the 41 rickets subjects was 15.1 ± 6.2 ng/ml and 17.4 ± 7.8 ng/ml for the 14 control subjects. In the face of markedly elevated serum AP levels in the rickets subjects, all of the serum OC values in the study fell within two standard deviations of the mean for normals. There was no association between serum OC and 1,25-(OH)₂D in either the phosphopenic or the calciopenic group. Conclusion These results show that serum osteocalcin levels are not elevated in all forms of active rickets and that, unlike serum alkaline phosphatase, serum osteocalcin cannot be used in the diagnosis of rickets. Received: 24 September 1999 / Accepted: 23 March 2000     

Granulocyte colony-stimulating factor receptor expression on neutrophils of term and preterm neonates with and without signs of infection

Neutrophils are an essential component of the human host defence system against infection. Recombinant human granulocyte colony-stimulating factor induces neutrophilia and enhances effector functions of mature neutrophils. Since the biological effects of granulocyte colony-stimulating factor (G-CSF) are mediated by its receptor, we investigated the expression of G-CSF receptor on the surface of neutrophils of term and preterm neonates (n = 22) with and without signs of infection and of healthy adults (n = 13) by flow cytometry. In healthy adults, the percentage of neutrophils expressing G-CSF receptor was higher compared to cord blood of term and preterm neonates (87% vs 53%, P < 0.05). Between 2 and 32 h of life, neonates with signs of infection showed lower values of G-CSF receptor expression compared to neonates without signs of infection (32% vs 54%, P < 0.05). No correlation was detectable between expression of G-CSF receptor and gestational age. Conclusion Expression of granulocyte colony-stimulating factor receptor on neutrophils is lower than in adults. This may adversely affect granulopoiesis and neutrophil function during the neonatal period. Moreover, granulocyte colony-stimulating factor receptor expression seems to be down-regulated during neonatal infection. Received: 8 June 1998 / Accepted in revised form: 13 October 1998     

A detailed analysis of changes in serum C-reactive protein levels in neonates treated for bacterial infection

A prospective study was undertaken to characterize the rate of increase, time of peak values and rates of decrease in serum concentrations of C-reactive protein (CRP) in a group of infants treated for neonatal bacterial infection. A total of 176 consecutively admitted neonates with birth weight >1500 g and without mechanical ventilation or central lines in situ, who received antibiotic therapy for suspected bacterial infection, were enrolled. The changes in serum CRP concentration in 60 of 63 infants who had CRP values above 20 mg/l 24–48 h after the beginning of treatment were analysed in detail. Initial increase rates in serum CRP levels of up to 4.5 mg/l per h were documented peak were reached at a mean of 19.5 h after antibiotic therapy had been initiated, but in some patients an increase in serum CRP levels occurred up to 40–48 h after the beginning of treatment. The mean serum half-life of CRP in infected neonates was 21 h (range 11.2–38 h). Conclusion In neonates with bacterial infection (defined by a combination of clinical signs and increased C-reactive protein and immature-total quotient values) no differences in the overall pattern nor in any of the particular phases of the C-reactive protein response curves could be observed between neonates with positive (n = 13) or negative blood cultures (n = 47). Received: 18 July 1997 / Accepted in revised form: 5 May 1998     

Is Lower Vitamin D Level Associated with Increased Risk of Neonatal Sepsis? A Prospective Cohort Study

To evaluate the effect of maternal/ neonatal vitamin D levels on culture positive neonatal sepsis. This prospective cohort study was conducted in the NICU of a tertiary care teaching hospital in Odisha, Eastern India from January 2015 through December 2016. Forty (40) neonates with culture positive sepsis were included in the study group. Forty (40) healthy neonates admitted for evaluation of neonatal jaundice who are similar in gender, gestational age, postnatal age and without any clinical signs of sepsis were recruited as control group after informed consent. Vitamin D level (25 OH D) was assessed in the neonates and their mothers in both the groups. Neonatal 25 OH vitamin D level in the study group (12.71 ± 2.82 ng/ml) was significantly lower than in the control group (25.46 ± 7.02 ng/ml). The Odds ratio was 273 (95% CI 30.39–2451.6) for culture positive sepsis in neonates with vitamin D deficiency/insufficiency. Mothers of septic neonates had significantly lower 25 OH vitamin D level (20.92 ± 3.92 ng/ml) than the mothers of healthy neonates in control group (27.31 ± 6.83 ng/ml). The Odds ratio was 4.71 (95% CI 1.69–13.1) for culture positive sepsis in babies born to mothers with vitamin D deficiency/insufficiency. Neonates with vitamin D deficiency/insufficiency are at higher risk for developing sepsis than those with sufficient vitamin D levels. Lower vitamin D levels in mothers is also associated with increased risk of sepsis in the neonates.     

Intracellular and plasma cytokine profile in neonates born to non-atopic parents: the impact of breast feeding

The aim of this study was to profile the changes in intracellular and plasma cytokines during the neonatal period and evaluate the impact of breast feeding on these parameters. For this purpose, we measured the interleukin (IL)-2 and IL-4 producing CD3+/CD69+ T-cells using flow cytometry and plasma concentrations of interferon (IFN)-gamma and IL-4 using ELISA, in 122 healthy term neonates, aged 6–12 h, born to non-atopic parents, and 25 healthy children aged 1–12 years. A total of 42/122 neonates exclusively breast-fed (BF) and 39/122 formula fed (FF) were studied again on the 30th day of life for the above parameters. Finally, a clinical evaluation for the presence of atopic disease was conducted at 2 years of age. We found that at birth, the percentage of CD3+/CD69+/IL-4+ T-cells (median = 15.8%, range = 4.4%–49%) and plasma concentrations of IL-4 (median = 0.22 pg/ml, range = 0.18–0.25 pg/ml) were significantly higher (P<0.0001) compared to those of children (median = 1.6%, range = 0.16%–2.7% for CD3+/CD69+/IL-4+ and median = 0.17 pg/ml, range = 0.13–0.26 pg/ml for IL-4), whereas plasma concentrations of IFN-gamma were significantly lower in neonates (median = 0.42 pg/ml, range = 0.3–1.5 pg/ml) than in children (median = 1.2 pg/ml, range = 0.3–2.6 pg/ml, P<0.0001). During the neonatal period, only the CD3+/CD69+/IL-4+ T-cells increased significantly in both BF and FF groups. Comparison between BF and FF groups revealed no significant difference in any of the parameters measured. Moreover, no difference in the development of atopy during the first 2 years of life was found between BF and FF infants. Conclusion: our findings demonstrate that during the entire neonatal period type 2 immunity dominates, regardless of the mode of feeding, whereas type 1 immunity dominates during childhood. Moreover, in the absence of family history of atopy, the mode of feeding per se does not play a crucial role in the development of atopy within the first 2 years of life.Abbreviations BF breast-fed - BFA brefeldin A - FITC fluorescein isothiocyanate - FF Formula-fed - IFN interferon - IL interleukin - MoAbs monoclonal antibodies - PBS-BSA phosphate buffered saline bovine serum albumin - PE-Cy 5 phycoerythrin-cyanin 5 - PMA phorbol 12-myristate 13-acetate - Tc T-cytotoxic - Th T-helper     

Circulating soluble adhesion molecule levels in children with acute lymphoblastic leukaemia

The aim of this study was to evaluate levels of serum soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) as parameters of disease activity and to monitor the response to treatment in children with acute lymphoblastic leukaemia (ALL). The above soluble adhesion molecules were determined in the serum of 35 children with ALL and 30 healthy children (control group) of the same age range. The samples were obtained before treatment, 6 months after the beginning of the treatment (remission of the disease), 6 months after the end of the treatment and during relapse of the disease. The mean levels of sICAM-1, sVCAM-1 and sE-selectin at the onset of the disease were 646.6 ± 80.9 ng/ml, 1786 ± 151.8 ng/ml and 140.5 ± 17.3 ng/ml, respectively. These values were significantly higher (P < 0.001) than those of the control group, which were, 245.8 ± 25.7 ng/ml, 798.6 ± 78.9 ng/ml and 44.7 ± 18.2 ng/ml respectively. During remission, the mean levels did not differ significantly from those of the control group. After the end of the treatment the mean levels again did not show any significant differences compared to the control group. During relapse the soluble adhesion molecule mean levels (923.9 ± 110.1 ng/ml, 2945.7 ± 349.9 ng/ml and 258.2 ± 5.1 ng/ml) were significantly higher (P < 0.001) than those of the control group and also than those obtained during remission and after the end of the treatment (P < 0.001). Pearson's correlation coefficient r was computed in order to detect possible linear correlations between: (1) sICAM-1 and sVCAM-1 (r = 0.632); (2) sICAM-1 and sE-selectin (r = 0.788) and (3) sVCAM-1 and sE-selectin (r = 0.752). All three cases correspond to P < 0.001, thus indicating strong linear correlations. Conclusion The levels of soluble circulating adhesion molecule levels can be utilized for monitoring disease activity of ALL and its response to treatment, as well as for early detection of relapse. Strong linear correlations between the three soluble adhesion molecules tested suggest that each of them may be sufficient as an indicator. Received: 5 August 1996 / Accepted: 13 February 1997     

Comparison of plasma atrial natriuretic peptide levels in healthy children from birth to adolescence and in children with cardiac diseases

An age-related dependence of plasma ANP levels was studied in 163 healthy children (94 boys, 69 girls) between the ages of day 1 and 16 yr. In neonates during the first 2-4 days of life, significantly higher plasma ANP plasma levels (range 129-356 pg/ml, mean 227) were found compared with older infants and children (p less than 0.001). Beyond the neonatal period through adolescence no significant difference in ANP concentrations could be found between the various age groups. Plasma ANP levels ranged between 2 and 109 pg/ml (mean 47) for all age groups after the newborn period. ANP levels were also determined in 15 adult volunteers and in arterial and venous cord blood of 16 healthy newborns, and concentrations were similar to those found in children. In addition, plasma ANP levels were measured in 40 children with various cardiac diseases; 22 of 40 patients exhibited ANP levels above the upper normal range seen in control children. Of these 22 patients all except two children revealed clinical signs of heart failure. In contrast 15 of 17 children without heart failure showed plasma ANP levels within the range of control children. ANP plasma levels ranged between 93 and 967 pg/ml (mean 284) in patients with heart failure and between 15 and 118 pg/ml (mean 57) in patients without heart failure, respectively. Increased ANP levels in neonates and cardiac patients may result from increased atrial distention and reflect a compensatory mechanism to improve cardiac function by reducing pre- and afterload.     

Suppression of elevated plasma interleukin-8 levels due to total ischemia and reperfusion of the small intestine by luminal perfusion with fetal bovine serum

 A previous study demonstrated that continuous enteric luminal perfusion of fetal bovine serum (FBS) protects the small intestine from total ischemia/reperfusion injury (IRI) and increases the intestinal mass. In this study, we further investigated the changes in plasma interleukin-8 (IL-8) level caused by total ischemia/reperfusion of the small intestine and the effect of FBS on plasma IL-8 levels. A 3-h total ischemia was induced in a 15-cm segment of terminal ileum and then reperfusion was instituted. Luminal perfusion of FBS was conducted via an osmotic minipump connected to the stomach through a fine polyethylene tube, starting 3 days prior to total ischemia. The rats were killed after 10 and 30 min and 1 and 3 h of total ischemia, and 1, 6, and 12 h or 1, 2, and 3 days after initiation of reperfusion. Plasma IL-8 was measured by enzyme-linked immunosorbent assay. The results were compared among the FBS-treated and untreated groups. The plasma IL-8 level was elevated from 1 h of total ischemia to 6 h after initiation of reperfusion (P < 0.05) with a peak of 641.5 ± 36.9 pg/ml in the untreated group and 471.6 ± 42.2 pg/ml in the treated group. Luminal perfusion of FBS significantly suppressed plasma IL-8 levels after 1 h of total ischemia and 1 h after initiation of reperfusion (P < 0.05). The results suggest that FBS might play a role in the treatment of total IRI of the small intestine. Accepted: 21 March 2001     

Soluble Intercellular adhesion molecule-1 in newborn infants

The aim of this study was to evaluate the effect of increasing postnatal age on soluble intercellular adhesion molecule-1 (sICAM-1), a very early and sensitive marker of immune activation and response in the serum of newborn infants. Serum sICAM-1 was measured by EIA (T Cell Diagnostics) in 20 healthy adults (controls) and in 43 (24 females/19 males) healthy neonates, of whom 28 were full term, and 15 were born at a gestational age between 35 and 38 weeks of pregnancy, on the 1st, 5th and 30th day of life. Neonatal serum sICAM-1 values showed a very significant increase (P<0.01) from the 1st day (137.3 ± 62.0 ng/ml) to the 5th day (259.3 ± 124.0 ng/ml) and then to the 30th day of life (415.0 ± 114.0 ng/ml), being significantly lower on the 1st day (P<0.01), whereas significantly higher on the 30th day of life (P<0.05), than those in healthy adults (305 ± 195 ng/ml). Serum sICAM-1 values on the 1st day of life depended on both the mode of delivery (significantly higher in neonates born vaginally) and the gestational age at birth (significantly lower in those born at a gestational age over 38 weeks). A significant strong correlation was found in sICAM-1 values between the 1st and the 5th day following delivery (r _P =0.77, P<0.009). Conclusion The results of this study demonstrate a significant rise of serum sICAM-1 during the 1st month of life in healthy neonates suggesting a progressively increased activation of the neonatal immune system. Received: 20 June 1996 and in revised form: 24 March 1997 / Accepted: 24 April 1997     

Cerebral blood flow and neurological outcome in the preterm infant

Cerebral blood flow (CBF) studies have provided some insight into pathophysiological mechanisms of cerebral damage in newborn children; their value in predicting brain damage, however, remains elusive. The purpose of our study was to evaluate the role of CBF measurements in predicting developmental outcome in preterm neonates at 18 months. Preterm babies with a gestational age of less than 34 weeks and a birth weight of less than 1500 g (n = 71) were enrolled in the study. CBF was measured by the nonivasive intravenous ¹³³Xe method on three different occasions. We classified our measurements into three groups: depending on the time when performed group 1: between 2 and 36 h (n = 52); group 2: between 36 and 108 h (n = 44); group 3: between 108 and 240 h (n = 41). At the age of 18 months neurodevelopment testing was performed according to the Bayley mental and motor scales. Surviving infants had a higher mean CBF over the three groups than non surviving children (15.2 ± 3.5 ml/100 g brain tissue/min vs 13.0 ± 2.1 ml/100 g brain tissue/min, P < 0.05). There was no correlation of CBF with mental or motor development in our study population in either of the three groups. Conclusion In preterm infants basal CBF is higher in surviving than in non surviving infants, but there is no correlation of resting CBF and later neurological outcome. Received: 7 November 1997 / Accepted in revised form: 30 March 1998     

Contribution of the blood glucose level in perinatal asphyxia

This is a comparative study between 60 asphyxiated newborns (cases) and 60 normal neonates (controls) in respect of their plasma glucose and uric acid levels and also their clinical and neurological status. The mean plasma glucose level was significantly lower (35.1 ± 11.4 mg/dl vs. 56.9 ± 5.5 mg/dl; P < 0.001) and the mean serum uric acid level was higher (8.0 ± 1.2 mg/dl vs. 4.5 ± 0.83 mg/dl; P < 0.001) in the asphyxiated group when compared to the controls. Within the perinatal asphyxia group, the plasma glucose level and Apgar scores showed a significant positive linear correlation (r = 0.740, P < 0.001), whereas a significant negative linear correlation was observed between the glucose level and different stages of hypoxic ischemic encephalopathy (HIE) (r = −0.875, P < 0.001). Although a strong positive linear correlation was found between uric acid and HIE stages (r = 0.734, P ≤ 0.001), the linear correlation between uric acid and Apgar scores (r = −0.885, P < 0.001) and uric acid and the plasma glucose level (r = −0.725, P < 0.001) were found to be significantly negative among the cases. Conclusion: The severity of encephalopathy and cellular damage varies with the severity of hypoglycemia.     

Correlation of Plasma Adrenomedullin to Myocardial Preservation During Open-Heart Surgery

Adrenomedullin (ADM) is a vasoactive peptide with potent dilatory effects. We studied whether perioperative myocardial injury could be altered by the presence of ADM. Blood samples from 19 children with congenital heart disease undergoing surgical repair were collected at six time points: preoperative, on cardiopulmonary bypass (CPB), and 0, 3, 6, and 12 hours after CPB. Blood levels of ADM (pg/ml) and troponin-I (Tn-I; ng/ml), a specific marker of myocardial injury, were measured. Patients were divided into three groups based on their 12-hour Tn-I levels (I, < 10, n= 6; II, 10–25, n= 6; III, >25, n= 7). Preoperative Tn-I levels were within the normal range for all patients. Preoperative ADM levels in group I (with little or no evidence of myocardial injury) were significantly greater than those of either group II or III (242.7 ± 15.4 vs 83.8 ± 18 and 85.2 ± 5.5, respectively; p≤ 0.0001 for each). The 12-hour ADM levels in group I remained significantly lower than preoperative levels (242.7 ± 15.4 vs 197.4 ± 11.6, p≤ 0.03) but higher than in the other groups. In group III, ADM increased at the 12-hour time point (159.2 ± 6.5, p≤ 0.0001 vs baseline). Higher preoperative ADM levels are associated with lower levels of myocardial injury (as assessed by troponin-I release) during congenital heart surgery.     

Elevated platelet activating factor in the tracheal aspirate at birth and signs of intra-uterine inflammation in infants with neonatal pulmonary emphysema

To investigate the pathophysiology of the neonatal pulmonary emphysema, we assayed platelet activating factor (PAF) in the tracheal aspirates of the low birth weight infants. A total of 29 neonates (birth weight <1750 g) who required mechanical ventilation were enrolled. Tracheal aspirates were obtained within 48 h and blood samples collected within 24 h of life. PAF was assayed on the basis of its ability to cause aggregation of washed rabbit platelets. PAF was significantly elevated in four infants who showed pulmonary emphysema within the 1st week of life (median 24 pg/g lipid phosphorus, range 9.9–200) compared with those detected in the other three groups of infants; infants with respiratory distress syndrome (RDS) in whom chronic lung disease (CLD) did not develop (median 1.8 pg/g lipid phosphorus, range 0–30; P < 0.05), infants without RDS nor CLD (median 0.64 pg/g lipid phosphorus, range 0–14; P < 0.05) and infants with other types of CLD (median 1.1 pg/g lipid phosphorus, range 0–1.8; P < 0.01). The four infants who developed pulmonary emphysema within the 1st week of life, had significantly elevated serum IgM and neutrophilia at birth. The increased amount of PAF in the tracheal aspirates shows the presence of inflammation in the lung at birth. The elevated serum IgM level and neutrophilia indicate that the inflammation begins in utero. Conclusion Our data suggest that neonatal pulmonary emphysema is caused by intra-uterine inflammation increasing platelet activating factor in the lungs. Platelet activating factor may play a role in aggravating the process of pulmonary emphysema. Received: 20 July 1998 / Accepted: 14 February 1999     

Insulin resistance is associated with at least threefold increased risk for prothrombotic state in severely obese youngsters

Obesity in childhood increases the risk for early adult cardiovascular disease. However, the underlying mechanism is not fully known. The aims of this study were to measure levels of prothrombotic factors and examine their possible association with obesity and insulin resistance in obese children and adolescents. A total of 313 obese children and adolescents were recruited. In a cross-sectional design, we measured anthropometric parameters, plasminogen activator inhibitor-1-antigen (PAI-1-Ag), von Willebrand factor-antigen (vWF-Ag), fibrinogen (FB), lipids, fasting glucose, and insulin (FI) levels. Insulin resistance was estimated using the homeostasis model assessment for insulin resistance (HOMA-IR) index. Boys presented significantly higher PAI-1-Ag levels than girls (82.6 vs. 71.3 ng/ml, p = 0.01). Higher levels of PAI-1-Ag (96.8 vs. 69 ng/ml, p < 0.001), vWF-Ag (123.5 vs. 107.6%, p = 0.004) but not FB (353.1 vs. 337.6 mg/dl, p = 0.137) were found in insulin-resistant (IR) participants after adjusted for age, gender, and pubertal stage. IR patients were at 2.98 (CI: 1.084–8.193) and 4.86 (CI: 1.119–15.606) times greater risk for high PAI-1-Ag and vWF-Ag levels, respectively. All three prothrombotic factors were positively correlated with body mass index (BMI) and FI levels (p < 0.05), but only PAI-1-Ag and vWF-Ag were significantly correlated with HOMA-IR index (p ≤ 0.001). After adjustment for confounding factors, both BMI and HOMA-IR indices remained significantly associated with PAI-1-Ag (r ² = 0.225, p < 0.001) and vWF-Ag levels (r ² = 0.077, p = 0.003). Conclusion: This study shows that obesity in youngsters, when accompanied with insulin resistance, is associated with at least threefold increased risk for elevated levels of prothrombotic factors, contributing to the early development of atherothrombosis. This impaired prothrombotic state may partially explain the increased risk for developing cardiovascular disease later in adulthood.