Eugen P Zilow

The effect of early and late cord‐clamping on blood viscosity and other hemorheological parameters in full‐term neonates

This study was done to compare postnatal alterations in blood viscosity (capillary viscometer) and its determinants: hematocrit, plasma viscosity (capillary viscometer), red cell aggregation (Myrenne aggregometer) and red cell deformability (rheoscope) in the first five days of postnatal life in full‐term neonates with early (< 10 s) and late (3 min) cord‐clamping. The fetal blood volume of the placenta (“residual placental blood volume”) decreased from 52±8 ml/kg of neonatal body weight after early cord‐clamping to 15±4 ml/kg after later cord‐clamping. Neonatal blood volume, calculated as the difference between an assumed total feto‐placental blood volume of 115 ml/kg and the measured fetal blood volume of the placenta, was 50% higher in the late cord‐clamped infants than in the early cord‐clamped infants. Both groups showed similar viscosity, hematocrit and other rheological parameters in cord blood. In the infants with early cord‐clamping, the hematocrit decreased from 0.48±0.04 1/1 at birth to 0.43±0.61/1 after 24 h (p < 0.05). Whole blood viscosity did not change significantly with age. After late cord‐clamping, the hematocrit rose from 0.50±0.04% at birth to 0.63±0.051/1 at 2 h of age (p < 0.005) and dropped to 0.59±0.51/1 (p < 0.05) at 24 h. Blood viscosity increased by 40% (p < 0.001) within the first 2 h, but did not change significantly during the following five days. In both groups, plasma viscosity and red cell aggregation increased significantly (p < 0.05) on day 5 due to significant increases in total plasma protein and fibrinogen concentrations (p < 0.01). Red cell deformation was not affected by the mode of cord‐clamping and did not change with age. We conclude that late cord‐clamping results in marked rise in blood viscosity due to increasing hematocrit. The postnatal rise in plasma viscosity and red cell aggregation may keep the blood viscosity at a high level despite falling hematocrit.

The effect of Leboyer delivery on blood viscosity and other hemorheologic parameters in term neonates

OBJECTIVE This study was done to compare postnatal alterations in blood viscosity, hematocrit value, plasma viscosity, red blood cell aggregation, and red blood cell deformability in term neonates undergoing both early umbilical cord clamping and delivery according to the Leboyer method. STUDY DESIGN The umbilical cords of 15 healthy, term infants were clamped within 10 seconds of birth (early cord clamping), and 15 infants delivered according to the Leboyer method were placed on the mothers abdomen, and the umbilical cords were clamped 3 minutes after birth. Hemorheologic parameters were studied in umbilical cord blood at 2 hours, 24 hours, and 5 days from the time of delivery. RESULTS The residual fetal placental blood volume decreased from 45 +/- 8 ml/kg (x +/- SD) after early cord clamping to 25 +/- 5 ml/kg after delivery by the Leboyer method. After Leboyer-method delivery, the hematocrit value rose from 48% +/- 5% at birth to 58% +/- 6% 2 hours after delivery, 56% +/- 7% at 24 hours, and 54% +/- 8% after 5 days. Blood viscosity in the Leboyer-method group increased by 32% within the first 2 hours but did not change significantly during the following 5 days. Plasma viscosity, red blood cell aggregation, and red blood cell deformability were not affected by the mode of cord clamping. CONCLUSIONS Delivery by the Leboyer method leads to a significant increase in blood viscosity as a result of increasing hematocrit value, whereas other hemorheologic parameters are similar to those of infants with early cord clamping.

Impaired deformability of erythrocytes and neutrophils in children with newly diagnosed insulin-dependent diabetes mellitus

Aims/hypothesis. Abnormal rheological properties of erythrocytes, leucocytes and plasma may have a role in the development of diabetic microangiopathy. We hypothesized that changed haemorrheological variables may already be found in children with onset diabetes. Methods. Erythrocyte deformation (rheoscope), neutrophil deformation (micropipette), erythrocyte aggregation, blood and plasma viscosity were measured in 15 children with insulin-dependent diabetes mellitus before initiation of insulin treatment and 4 to 6 weeks later, 15 diabetic children treated with insulin for 5 to 8 years, 15 healthy children and 15 healthy adults. Results. At a low shear stress of 0.6 Pa, erythrocyte deformation was decreased in the diabetic children before (–28 %), after 4 to 6 weeks (–22 %) and after 5 to 8 years (–17 %) of insulin treatment compared with healthy children. More active neutrophils were counted in the untreated diabetic children (9 ± 6 %) than in healthy children (3 ± 2 %). Deformability of passive neutrophils was greatly decreased in the children with onset diabetes and moderately reduced in the diabetic children who were treated with insulin. Neutrophil deformation (r = –0.52) and erythrocyte deformation at 0.6 Pa (r = –0.62) were inversely related to haemoglobin A1 c. Haematocrit and blood viscosity were increased in the untreated children and in the children treated with insulin for 5 to 8 years. Plasma viscosity and erythrocyte aggregation were similar in the three groups of children. Conclusion/interpretation. Decreased erythrocyte deformation at low shear force, increased count of active neutrophils and impaired deformability of passive neutrophils may increase the risk for acute cerebro-vascular complications in children with uncontrolled insulin-dependent diabetes mellitus. [Diabetologia (1999) 42: 865–869]

Complement Activation in Newborn Infants with Early Onset Infection

ABSTRACT: The complement system is an important element in host defense. Quantitative deficiencies of total hemolytic complement activity and decreased C3 levels were reported in sera from normal neonates. However, little is known about complement activation products in the newborn. In a prospective study, complement activation products were determined in 32 healthy term neonates, in 41 neonates with colonization of their mothers, in 15 colonized neonates, and in 10 neonates with early onset infection. In all newborns, EDTA plasma was obtained within the first 6 h of life. The anaphylatoxin C3a-desArg was determined with a novel ELISA using an MAb reacting with a neoepitope of C3a-desArg. C3bBbP (alternative pathway convertase) and C1rsC1-inactivator (activation product of classical pathway) were measured with doublesandwich ELISA. C3 was determined by radial immunodiffusion. Plasma concentrations of C3a-desArg were similar in healthy term neonates and healthy adults, whereas diminished C3 levels were observed in the newborn infants. There were no significant differences between healthy neonates, neonates with colonized mothers, and colonized neonates. In neonates with infection, a significant elevation of C3a-desArg was found at the onset of the disease, resulting from alternative pathway activation. In contrast, the C1rsC1-inactivator complex showed no significant differences among healthy, colonized, and infected neonates. The anaphylatoxin C3a mediates inflammatory reactions such as vasodilatation and an increase in microvascular permeability and might therefore play an important role in severe neonatal infection.

The Spectrum of Renal Involvement in Epidermolysis Bullosa Dystrophica Hereditaria: Report of Two Cases

Epidermolysis bullosa dystrophica Hallopeau-Siemens (EBDH) is one of the most severe inherited epidermolyses, a group of mechanobullous dermatological disorders. We observed two patients presenting with a severely multilating type of EBDH who developed biopsy-proven renal disease, which substantially altered the evolution and pathogenesis of their disease. In a boy, chronic postinfectious glomerulonephritis developed, most probably due to recurring superinfections of bullous skin lesions. He also experienced acute oliguric renal failure due to severe diarrhea during exacerbation of EBDH. A female patient developed a nephrotic syndrome due to secondary amyloidosis. Hypoalbuminemia caused further fluid losses through bullous skin lesions, aggravating intravascular hypovolemia and leading to rapid renal failure secondary to bilateral renal vein thrombosis. The study shows that, although rare, renal complications may alter the natural course of EBDH.

Blood Viscosity and Optimal Hematocrit in Preterm and Full-Term Neonates in 50– to 500–μm Tubes

ABSTRACT: Blood viscosity is an important determinant of blood flow resistance. Because a substantial part of flow resistance arises in small arteries and arterioles with diameters of 100 μm and less, rheologic properties of blood from preterm infants (24 to 36 wk of gestation), full-term neonates, and adults were measured in glass tubes with diameters of 50, 100, and 500 μm for a wide range of adjusted feed hematocrits (0.15–0.70). At each of the feed hematocrits, blood viscosity decreased when going from a 500–μm tube to a 50–μm tube. The viscosity reduction increased with increasing hematocrit. Moreover, the viscosity reduction was more pronounced in the neonates than in the adults. At a hematocrit of 0.70, the viscosity reduction averaged 56% in preterm infants, 50% in full-term neonates, and 39% in adults (p < 0.005). However, the viscosity reductions at a hematocrit of 0.30 were only 35, 29, and 19%, respectively (p < 0.05). In all four groups, blood viscosity increased exponentially with increasing hematocrit. The steepness of the hematocrit-viscosity curves decreased with decreasing tube diameter and with decreasing maturity of the infants. Erythrocyte transport efficiency (hematocrit/blood viscosity) was calculated to estimate the optimal hematocrit (i.e. hematocrit with maximum erythrocyte transport). In 500-Ann tubes, the optimal hematocrit was about 0.40 in all of the groups. In 100–μm tubes, the optimal hematocrit was 0.44 ± 0.05 in the adults and 0.52 ± 0.04 in the neonates (p < 0.05). In 50–μm tubes, the optimal hematocrit was 0.51 ± 0.04 in adults and 0.60 ± 0.05 in the neonates. There was no significant difference in the optimal hematocrit among preterm and full-term infants. Our results suggest that the strong viscosity reduction at high hematocrits may help to maintain oxygen transport in polycythemic neonates.

Blood viscosity and optimal hematocrit in narrow tubes

Blood viscosity in normal adults was measured in glass tubes with diameters of 50, 100 and 500 microns for a wide range of adjusted feed hematocrits (15-70%). Blood viscosity decreased at each of the adjusted feed hematocrits when going from a 500-micron tube to a 50-micron tube. The viscosity reduction increased with increasing hematocrit. The steepness in the hematocrit-viscosity curves decreased with decreasing tube diameter. Erythrocyte transport efficiency (hematocrit/blood viscosity) was calculated to estimate the optimal hematocrit for oxygen transport. Optimal hematocrit averaged 38% in 500-micron tubes, 44% in 100-micron tubes and 51% in 50-micron tubes. Our results suggest that the strong Fåhraeus-Lindqvist effect at high hematocrits may help to maintain oxygen transport in polycythemic patients as long as the driving pressure is sufficient.

Effects of high-frequency oscillatory ventilation on circulation in neonates with pulmonary interstitial emphysema or RDS

Objective: Mechanical ventilation may impair cardiovascular function if the transpulmonary pressure rises. Studies on the effects of high-frequency oscillatory ventilation (HFOV) on cardiovascular functions have yielded conflicting results. This study was done to compare alterations in left ventricular output and blood flow velocities in the anterior cerebral artery, internal carotid artery, and celiac artery using a Doppler ultrasound divice before and 2 h after initiating HFOV in neonates with respiratory distress syndrome (RDS) or pulmonary interstitial emphysema (PIE). Design: Prospective clinical study. Setting: Neonatal intensive care unit in a perinatal center. Patients: 18 critically ill infants (postnatal age 47 ± 12 h; mean ± SD) were studied before and during HFOV (piston oscillator). Indications for HFOV were severe respiratory failure due to PIE (n = 10) and severe surfactant deficiency (RDS, n = 8). In the RDS group, gestational age was 27 ± 6 weeks (range 26–31 weeks) and birthweight 1620 ± 380 g (range 850–1970 g). In the PIE group, gestational age was 28 ± 2 weeks (range 26–36 weeks) and birthweight 1740 ± 470 g (range 890–2760 g). Measurements and main results: During HFOV, mean airway pressure was maintained at the same level as during intermittent mandatory ventilation in both groups (RDS, 12 ± 2 cmH2O; PIE, 10 ± 2 cmH2O). Compared to intermittent mandatory ventilation, several of the 12 parameters studied changed significantly (p < 0.004) during HFOV. In the RDS group, the partial pressure of oxygen in arterial blood/fractional inspired oxygen (PaO2/FIO2) ratio increased from 56 ± 9 to 86 ± 7 and partial pressure of carbon dioxide in arterial blood (PaCO2) decreased from 49 ± 4 to 35 ± 3 mmHg. In the PIE group, PaO2/FIO2 ratio increased from 63 ± 8 to 72 ± 7 and PaCO2 decreased from 63 ± 7 to 40 ± 5 mmHg. In the PIE group, heart rate decreased (135 ± 15 before HFOV vs 115 ± 14 min− 1 during HFOV) and mean systolic blood pressure increased (before 43 ± 4 vs 51 ± 4 mmHg during HFOV) significantly, whereas these parameters did not change in the RDS group. Left ventricular output increased significantly in the PIE group (210 ± 34 before vs 245 ± 36 ml/kg per min during HFOV; p < 0.004), but not in the RDS group (225 ± 46 before vs 248 ± 47 ml/kg per min during HFOV; k < 0.05). Shortening fraction and systemic resistance did not change in either group. In the PIE group, mean blood flow velocities in the internal carotid artery (+ 59 %), anterior cerebral artery (+ 65 %) and celiac artery (+ 45 %) increased significantly but did not change in the RDS group. Conclusions: The results show that HFOV as used in this study, improves oxygenation, CO2 elimination, and circulation in infants with RDS and PIE. However, systemic, cerebral, and intestinal circulation improved more in neonates with PIE than in those with RDS. This may be due to higher pulmonary compliance in infants with PIE when compared to those with RDS.

Drotrecogin alpha (activated) in neonatal septic shock

A 12-d-old neonate suffering from group B streptococcal septic shock was treated with 24 μg/kg/h recombinant human activated protein C [rhAPC, drotrecogin alpha (activated)] for 96 h. The protein C activity increased from 5% to 53% after rhAPC infusion. The patient recovered within 14 d without any adverse effects.

Hepatic failure with neonatal tissue siderosis of hemochromatotic type in an infant presenting with meconium ileus. Case report and differential diagnosis of the perinatal iron storage disorders.

We report on a female preterm infant with hepatic failure and neonatal tissue siderosis of hemochromatotic type diagnosed by using both histochemistry and atomic absorption spectroscopy. The infant presented with meconium ileus, signs of rapidly progressive hepatic failure, and hyperferritinemia (7132 ng/ml). Despite surgery and intensive care the infant died 32 days after birth. Postmortem examination showed a wrinkled liver with extensive collapse of the hepatic architecture and regenerating nodules as well as hepatic and extrahepatic iron accumulation of hemochromatotic type, sparing the reticuloendothelial system. Atomic absorption spectroscopy confirmed an increase in the iron content of various organs: liver, heart, pancreas, oral salivary gland, kidney, and adrenal gland. The increase in the iron content of various organs was determined by comparing the analysis of the propositus with those of 5 gestationally age-related preterm infants who had died in the intensive care unit: 2 died of meconium aspiration syndrome, the other 3 of hyaline membrane disease, bronchopulmonary dysplasia, and immaturity, respectively. We also compared the analysis of 15 fetuses having a a condition predisposing to iron accumulation (trisomy 21, trisomy 18, cytomegalovirus, amnion infection syndrome, Rhesus- and ABO-incompatibility, congenital hemolysis, anti-phospholipid syndrome, congenital heart disease). Delta F508, the most frequent mutation seen in cystic fibrosis patients, was excluded by gene sequencing. Different noxae causing iron accumulation in the neonatal period have led to the statement that neonatal hemochromatosis may collect different etiologies, such as metabolic disorders, infections, chromosomal aberrations, and immunological disorders. In this study, we report the singular evidence of neonatal iron accumulation of hemochromatotic type in an infant presenting with meconium ileus and propose a classification of the neonatal disorders associated with iron accumulation.