Werner Nikischin

The Influence of Mode of Delivery on Hematologic Values in the Umbilical Vein

A variable white blood cell count without clinical signs of sepsis or hematological disorders is often observed in newborns. The intention of this study was to investigate the effect of mode of delivery on hematologic measurements, especially white blood cell count in the umbilical vein. 121 term newborns were investigated prospectively. They were subdivided into three groups: spontaneous births (n = 83), vacuum extraction (n = 19) and cesarean sections (n = 19). The mode of delivery influenced the leukocyte count and the precursor cells. The mean leukocyte counts after spontaneous birth (14.6 +/- 4.0 leukocytes/nl) and after vacuum extraction (16.6 +/- 7.4 leukocytes/nl) were significantly higher than after cesarean section (12.1 +/- 4.4 leukocytes/nl; p < 0.05). The precursors of leukocytes were also significantly higher in infants with vacuum extraction (1.06 +/- 0.83 cells/nl) than in spontaneously delivered infants (0.54 +/- 0.47 cells/nl). An inverse relationship between the number of leukocytes and the arterial cord blood pH was observed (p < 0.05). No significant differences were observed in the effect of mode of delivery on erythrocyte and platelet counts.

Polymorphisms in the Renin-Angiotensin System and Outcome of Very-Low-Birthweight Infants

Background: The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE-ins/del) and the angiotensin II type 1 receptor 1166A/C polymorphism (ATR1166A/C) were reported to be associated with several unfavorable outcome parameters in preterm infants like bronchopulmonary dysplasia, persistent ductus arteriosus and impaired insulin sensitivity. Objective: To confirm the above-mentioned associations in a large cohort of very-low-birthweight (VLBW) infants. Method: Clinical data of VLBW infants were prospectively recorded. The ACE-ins/del polymorphism and the ATR1166A/C polymorphism were determined by polymerase chain reaction in 1,209 and 1,168 infants, respectively. Results: There was no significant association between ACE-ins/del or ATR1166A/C genotype and outcome parameters (death, intraventricular hemorrhage, sepsis, bronchopulmonary dysplasia, ventilation, supplemental oxygen at discharge, postnatal treatment with insulin, surgery for intestinal perforation/necrotizing enterocolitis/retinopathy of prematurity/persistent ductus arteriosus. Conclusion: Both known functional polymorphisms of the renin-angiotensin system do not seem to be associated with the outcome of VLBW infants.

Correction of compliance and resistance altered by endotracheal tube leaks.

Objective Measurements of lung compliance and resistance are influenced by endotracheal tube leaks. To keep compliance and resistance reliable, we developed an algorithm to correct inspiratory and expiratory volume and flow mathematically. Design Prospective, clinical study. Setting University research laboratory and neonatal intensive care unit. Model A ventilated lung model with a linear pressure-volume relationship and with adjustment of an increasing endotracheal tube leak was investigated. Patients A total of 21 ventilated premature neonates (median weight, 1220 g; range, 640–2160 g; median leak, 32%; range, 24–56%) were studied. Measurements and Main Results Compliance and resistance were calculated from the recordings of flow, volume, and airway pressure over time employing linear regression of the equation of motion to obtain compliance and resistance. Compliance and resistance altered by leaks were corrected and compared with measurements without leak. Compliance and resistance of the lung model could be corrected up to an endotracheal tube leak size of 86%. Compliance and resistance without leak and after leak correction did not differ significantly for all infants using the linear regression method (p > .05). For the correction of compliance in 15 and for the correction of resistance in 12 of the 21 infants, the coefficients of variation of ten measured breaths without leak were greater or equal to the differences of the values of compliance and resistance between conditions of no leak and corrected leak, respectively. Conclusion Pulmonary compliance and resistance can be reliably corrected even in the presence of a substantial endotracheal tube leak, which makes pulmonary function tests more reliable.

Tumor necrosis factor-α promoter -308 G/A polymorphism and susceptibility to sepsis in very-low-birth-weight infants.

Objectives:To determine whether the tumor necrosis factor-&agr; −308 G/A polymorphism is associated with blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. Design:Genetic association studies. Setting:Prospective, population-based, multicentered cohort of 1944 very-low-birth-weight infants born in 14 German study centers between 2003 and 2008 and 976 mothers, and a second prospective cohort of 926 very-low-birth-weight infants born in 2009 (German Neonatal Network). Measurements and Main Results:In cohort I, 344 of 1944 (18.2%) very-low-birth-weight infants had at least one episode of blood culture-proven sepsis develop. The sepsis incidence stratified to genotype was 19.3% for G/G, 15.8% for G/A, 10.0% for A/A genotype (Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.32; 95% confidence interval, 1.03–1.71; G/G vs. A/A: odds ratio, 1.74; 95% confidence interval, 1.06–2.91; p = .03). There was a trend for association of tumor necrosis factor-&agr; −308 A/G genotype with late-onset sepsis episodes (incidence: 17.2% for G/G, 12.5% for G/A, 10.0% for A/A genotype; Cochrane-Armitage trend test: G/G vs. G/A: odds ratio, 1.43; 95% confidence interval, 1.09–1.9; G/G vs. A/A: odds ratio, 2.05; 95% confidence interval, 1.19–3.56; p = .009). However, after adjustment for multiple testing, no significant associations were found. Furthermore, the genotype of the investigated 976 mothers had no impact on sepsis risk for their very-low-birth-weight infants. We additionally studied a second prospective cohort of 926 very-low-birth-weight infants and found no associations with sepsis risk. Conclusions:No association was found between the tumor necrosis factor-&agr; −308 G/A polymorphism blood culture-proven sepsis in two large cohorts of very-low-birth-weight infants. A recent meta-analysis demonstrated that the tumor necrosis factor-&agr; −308 A allele is associated with higher sepsis risk in adult cohorts. Thus, potential differences between adults and infants need to be incorporated in future study designs evaluating risk profiles for sepsis.

Calculation of intratracheal airway pressure in ventilated neonatal piglets with endotracheal tube leaks.

Objective:In ventilated neonates, only the applied pressure of the ventilator is adjusted and monitored. When an endotracheal tube leaks, intratracheal pressure decreases depending on the size of the endotracheal tube and of the leak. Furthermore, an increase in resistance and/or compliance might delay the increase of intratracheal pressure during inspiration and its decline during expiration. Short inspiratory time can cause insufficient ventilation, because intratracheal pressure peak might not be reached. Short expiratory time may lead to air trapping, because intratracheal pressure could not return to baseline. The aim of this study was to develop a mathematical algorithm to calculate intratracheal pressure continuously during ventilation and to evaluate the accuracy of this method. Design:Prospective, animal study. Setting:University research laboratory. Subjects:To verify the mathematical algorithm, eight neonatal piglets (1600–2600 g) were studied under different endotracheal tube leak conditions (45% to 98%). The median compliance and resistance were 1.06 mL/cm H2O/kg and 123 cm H2O/L/sec, respectively. Interventions:Pressure decreases caused by the different endotracheal tubes were measured in a model while air flow was increased stepwise. Based on these results, a mathematical method was developed to calculate intratracheal pressure under leak conditions continuously in relation to the flow through the endotracheal tube as well as to calculate the values of resistance, compliance, and applied pressure of the ventilator. Measurements and Main Results:The intratracheal pressure calculated was compared with the measured intratracheal pressure over time. The differences between measured and calculated intratracheal pressure related to peak applied pressure of the ventilator did not exceed 10%. The medians of absolute amounts of differences between measured and calculated intratracheal pressure were <1 cm H2O. Conclusions:The accuracy of the calculation of intratracheal pressure ensures adequate monitoring of artificial ventilation, even in the presence of endotracheal tube leaks. This might decrease the risk of barotrauma and improve the effectiveness of ventilation.

Improvement in respiratory compliance after surfactant therapy evaluated by a new method

Descriptions of the effects of intratracheally applied surfactant on respiratory system compliance (Crs) have been somewhat controversial because the commonly used methods for assessing pulmonary function were designed for a linear pressure/volume (P/V) relation of the respiratory system. In infants with lung disease a linear P/V relation cannot be expected. Therefore, a new method (APVNL) was employed which enabled us to calculate respiratory system compliance (Crs) and resistance (Rrs) based on changes in volume (V). This method is independent of the P/V relation, and was used to assess the effects of intratracheal instillation of surfactant. Fourteen infants (gestational age, 24 to 30 weeks) with respiratory distress syndrome were treated with bovine surfactant intratracheally while the fractional inspired oxygen concentration (FiO2) exceeded 50%. Crs was evaluated for the infants using the APVNL method and the method of linear regression (LR) based on the equation of motion designed for linear P/V relationships.

Perinatal glucose metabolism as an indicator for stress and hypoxia during different forms of delivery

In 82 term newborns divided into three groups (spontaneous delivery, caesarean section and vacuum extraction) we investigated umbilical artery pH, artery and vein glucose levels and calculated the veno-arterial difference of glucose. The three groups showed significant differences of artery and vein glucose levels. The highest umbilical artery (UA) and umbilical vein (UV) glucose levels were found after vacuum extractions (n = 13, UA: 98 mg/dl, UV: 104 mg/dl), the lowest levels were present in the group of caesarean section (n = 16, UA: 52 mg/dl, UV: 65 mg/dl). After spontaneous deliveries the intermediate levels were observed (n = 55, UA: 70 mg/dl, UV: 84 mg/dl). The mean of UA-UV-glucose difference was low after vacuum extractions and statistically different from the values after caesarean section and spontaneous deliveries. The mean of UA-pH did not show statistically significant differences in the three groups. The regression analysis between UA-pH and UA-UV-glucose difference revealed a highly significant dependency in the group of caesarean section (p less than 0.01) but no dependency after vacuum extraction. Significant dependency was also found in the group of spontaneous delivery (p less than 0.05).

Comparison of umbilical arterial versus umbilical venous blood PH correlated with arterio-venous glucose difference and cardiotocographic score

The value of clinical parameters and umbilical arterial blood pH as indicator of prenatal hypoxia is disputed. In a prospective study of 86 vaginally delivered full-term infants, cardiotocographic (CTG) findings obtained 0–30 min and 30–60 min before birth were compared to pH values, O2 and CO2 partial pressures and glucose difference in umbilical arterial and venous blood. CTG findings were expressed as a score, higher values indicating fetal hypoxia. The venous but not the arterial blood pH was significantly related to the later (0–30 min) CTG score. The arterio-venous glucose difference was significantly related to both CTG scores. There was a significant statistical relationship between glucose difference and venous but not arterial blood pH. The later CTG score (0–30 min) also correlated significantly with O2 and CO2 partial pressures and base excess in the umbilical vein of all vaginally born infants. If CTG is accepted as an objective indicator of fetal hypoxia before birth, the arterio-venous glucose difference, and in the investigated range of pH-values, umbilical venous blood pH are more suitable than the arterial blood pH to ascertain the peripartal situation of the newborn.

Effect on work of breathing of different continuous positive airway pressure devices evaluated in a premature neonatal lung model.

Objective: A device for the application of continuous positive airway pressure to switch injected breathing gas to the outlet during expiration, known as Infant Flow, claims to reduce work of breathing and peak pressure change. So far the Infant Flow system has been investigated in lung models with tidal volumes of not <12 mL. However, premature neonates below 1000 g of weight generate a tidal volume of approximately 4 mL only. The aim of this study was to compare work of breathing and peak pressure change of the Infant Flow and another system that uses nasal prongs, Baby Flow, with conventional continuous positive airway pressure delivered by a pharyngeal tube. Design: Laboratory investigation, basic research. Setting: University research laboratory. Model: A piston pump simulating the spontaneous breathing of premature neonates was connected without leak to three different continuous positive airway pressure devices (pharyngeal tube, Baby Flow, and Infant Flow) and with a produced leak to the systems using nasal prongs (Baby Flow and Infant Flow). Intervention: The pressures of the airway and continuous positive airway pressure systems and airway flow were recorded. Peak pressure change and work of breathing were determined for all systems and settings. Percentages of reduction of peak pressure change and work of breathing in relation to the continuous positive airway pressure delivered by pharyngeal tube were calculated. Measurements and Main Results: The switching of injected breathing gas to the outlet during expiration of Infant Flow systems require a tidal volume of at least 5 mL. It was possible to decrease peak pressure change and work of breathing: Baby Flow system at a tidal volume of 4 mL (Inspiration: peak pressure change 82%, work of breathing 80%; Expiration: peak pressure change: 68%, work of breathing: 61%) and at a tidal volume of 8 mL (Inspiration: peak pressure change 75%, work of breathing 73%; Expiration: peak pressure change: 67%, work of breathing: 57%). Infant Flow system at tidal volume of 4 mL (Inspiration: peak pressure change 50%, work of breathing 55%; Expiration: peak pressure change: 46%, work of breathing: 43%) and at a tidal volume of 8 mL (Inspiration: peak pressure change 47%, work of breathing 46%; Expiration: peak pressure change: 24%, work of breathing: 23%), related to the continuous positive airway pressure delivered by pharyngeal tube without leak. Even under conditions of leak peak pressure change and work of breathing could be reduced: Baby Flow system at a tidal volume of 4 mL (Inspiration: peak pressure change 59%, work of breathing 64%; Expiration: peak pressure change: 68%, work of breathing: 59%) and at a tidal volume of 8 mL (Inspiration: peak pressure change 45%, work of breathing 43%; Expiration: peak pressure change: 54%, work of breathing: 53%). Infant Flow system at a tidal volume of 4 mL (Inspiration: peak pressure change 49%, work of breathing 53%; Expiration: peak pressure change: 44%, work of breathing: 40%) and at a tidal volume of 8 mL (Inspiration: peak pressure change 48%, work of breathing 43%; Expiration: peak pressure change: 36%, work of breathing: 40%), related to the continuous positive airway pressure delivered by pharyngeal tube without leak. Conclusion: Peak pressure change and work of breathing were decreased by Baby Flow and Infant Flow systems, even under conditions of leak.

Correction of Pulmonary Compliance for Presence of ET-Tube Leaks † 1711

Introduction: To evaluate pulmonary mechanics of premature newborns pulmonary function tests (PFTs) are necessary. The measurement of lung compliance (C) in the presence of ET-tube leaks leads to erroneous results. To keep the PFT reliable we developed an algorithm to correct the inspiratory and expiratory volume (V) mathematically when it was altered by a leak. We hypothesize that the leak correction delivers reliable results of C.