Helmut Küster

Bilirubin Measurement for Neonates: Comparison of 9 Frequently Used Methods

OBJECTIVE. High blood concentrations of bilirubin are toxic to the brain and may cause kernicterus. Therefore, determination of bilirubin levels is performed for many newborns, and several different methods are available. We compared 9 frequently used methods for bilirubin determination among newborns under routine conditions, to define their sequence of use. METHODS. In a prospective study, bilirubin concentrations were determined with 9 different methods, ie, 3 skin test devices, 3 nonchemical photometric devices (including 2 blood gas analyzers), and 3 laboratory analyzers. RESULTS. A total of 124 samples were obtained. All 3 laboratory methods showed very strong correlations with each other, and their means were used as comparison values. To these comparison values, the skin test devices had correlation coefficients between 0.961 and 0.966, and the nonchemical photometric devices between 0.980 and 0.994. Bland-Altman plots demonstrated good agreement with the comparison values for all nonchemical photometric devices. All skin test devices and 1 nonchemical photometric device underestimated bilirubin levels, particularly at high concentrations. CONCLUSIONS. In the routine care of newborns, the first method for bilirubin testing should be a skin test. If the skin test result exceeds 200 μmol/L and other analytes are to be determined with a nonchemical photometric device, then bilirubin can be included in this analysis and the result trusted up to 250 μmol/L. If the skin test result exceeds 200 μmol/L and only bilirubin concentrations are needed, then a standard laboratory method is the first choice, to avoid repeated blood sampling. Bilirubin concentrations from nonchemical photometric devices that exceed 250 μmol/L should be confirmed with standard laboratory methods.

Genetic Polymorphisms of Hemostasis Genes and Primary Outcome of Very Low Birth Weight Infants

BACKGROUND. Recent investigations have reported an influence of thrombophilic mutations and antithrombotic risk factors with development of intraventricular hemorrhage. It was our objective for this study to investigate the impact of genetic polymorphisms of hemostasis genes on the primary outcome measures of sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, and periventricular leukomalacia in a large cohort of very low birth weight infants. METHODS. There were 586 very low birth weight infants enrolled prospectively in a multicenter trial between September 2003 and July 2005, and an additional 595 very low birth weight infants, who had been recruited in a previous prospective trial, were studied. DNA samples were taken by buccal swab, and genotypes of factor V Leiden mutation, prothrombin G20210A mutation, the factor VII-323 del/ins polymorphism, and the factor XIII-Val34Leu polymorphisms were determined by polymerase chain reaction and restriction enzyme digestion. RESULTS. In contrast to data published previously, the frequency of intraventricular hemorrhage or periventricular leukomalacia was not significantly influenced by any of the genetic variants tested. Carriers of the factor XIII-Val34Leu polymorphism, however, had a higher sepsis rate and a longer period of hospital care compared with noncarriers. The factor VII-323 del/ins polymorphism was found to be a potential protective factor against bronchopulmonary dysplasia. CONCLUSIONS. We could not confirm previously reported associations of hemostasis gene variants and development of intraventricular hemorrhage in very low birth weight infants. To better understand gene-disease associations in very low birth weight infants, the prospective development of large-scale cohorts with well-defined phenotypes and corresponding DNA samples is essential.

Variations of Apgar score of very low birth weight infants in different neonatal intensive care units

Objective:u2002 The Apgar score should be an objective method to assess the state of newborns; however, its applicability in preterm infants is hampered by large variations among different observers. The study tested whether physicians that give low scores to written case descriptions also apply lower scores to preterm infants.

The Apgar Score

To the Editor .—nnThe Apgar score is a simple and rapid method to evaluate the condition of a newborn infant.1 As shown recently by Lopriore et al,2 its value is hampered because of nonuniform definitions used by individual caregivers, causing great variations when scoring ventilated infants.nnThe American Academy of Pediatrics and the American College of Obstetricians and Gynecologists recently suggested an expanded version of the Apgar score reporting form3 for infants on resuscitation. This form allows a more detailed description of resuscitation efforts, but the problem of inconsistencies in definitions is not solved. Even with the expanded version, …

Evaluation of the Glucometer Elite XL device for screening for neonatal hypoglycaemia

To prevent persistent neurodevelopment and physical growth deficits in neonatal care, it is mandatory to determine blood glucose levels as quickly and precisely as possible, preferably using micro-methods. However, most commercially available instruments have not been validated and approved for this purpose. The aim of this study was to validate the Glucometer Elite XL, a newly developed device for point-of-care testing (POCT). In samples from 869 newborn infants, glucose levels were simultaneously measured by the Glucometer Elite XL in whole blood and by an accepted clinical laboratory method in haemolysed blood using the ECA 2000 device. An acceptable method agreement was found between the POCT and the ECA 2000 method (mean difference 0.013xa0mmol/l, SD 0.69). As determined by regression analysis (Passing-Bablok), the slope was 1.086 with a y-intercept of −0.4xa0mmol/l ( r =0.959, P <0.05). The differences between measurement pairs of both assays versus the haematocrit were negligible. With a cut-off for hypoglycaemia at 2.6xa0mmol/l glucose in haemolysed blood, the sensitivity of the POCT device was 0.63 and specificity was 0.98. Raising the cut-off of the Glucometer Elite XL to 3.2xa0mmol/l, the sensitivity and specificity incremented to 1.0 and 0.89, respectively. Conclusion:The Glucometer Elite XL instrument can be recommended for point-of-care blood glucose measurement in newborn infants if its character as a screening method is taken into account. To compensate deviating results, we advise to shift its cut-off for hypoglycaemia recognition to a safe threshold of 3.2xa0mmol/l. However, hypoglycaemia has to be confirmed by a valid glucose measurement in the clinical laboratory.

Increase of Caffeine and Decrease of Corticosteroids for Extremely Low Birthweight Infants with Respiratory Failure from 1997 to 2011

To compare treatment strategies for respiratory failure in extremely low‐birthweight (ELBW) infants in Germany in 1997 to Germany, Austria and Switzerland in 2011.

Case 1: Unexpected muscular hypotonia and need for mechanical ventilation in a preterm infant (Case Presentation)

Figure 1 tal and succinylcholine were used for induction of anaesthesia. A male preterm was born with a birth weight of 1680 g (10th percentile), length of 42 cm (25th percentile) and head circumference of 29 cm (3rd percentile). Amniotic fluid was clear, umbilical cord pH was 7.43 and APGAR score was 6/5/7/7 (at 1/2/5/10 min, respectively). As respiration was insufficient, intermittent mask ventilation was necessary. At 60 min after birth, endotracheal

Less invasive ventilation in extremely low birth weight infants from 1997 to 2011: survey versus evidence

AbstractEvidence for target values of arterial oxygen saturation (SaO2), CO2, and pH has changed substantially over the last 20xa0years. A representative survey concerning treatment strategies in extremely low-birth-weight infants (ELBW) was sent to all German neonatal intensive care units (NICUs) treating ELBW infants in 1997. A follow-up survey was conducted in 2011 and sent to all NICUs in Germany, Austria, and Switzerland. During the observation period, NICUs targeting SaO2 of 80, 85, and 90xa0% have increased, while units aiming for 94 and 96xa0% decreased (all pu2009<u20090.001). Similarly, NICUs aiming for pHxa07.25 or lower increased, while 7.35 or higher decreased (both pu2009<u20090.001). Furthermore, more units targeted a CO2 of 50xa0mmHg (7.3 kPa) or higher (pu2009<u20090.001), while fewer targeted 40 or 35xa0mmHg (pu2009<u20090.001). Non-invasive ventilation (NIV) was used in 80.2xa0% of NICUs in 2011. The most frequently used ventilation modes were synchronized intermittent mandatory ventilation (SIMV) (67.5xa0%) and intermittent positive pressure ventilation (IPPV) (59.7xa0%) in 1997 and SIMV (77.2xa0%) and synchronized intermittent positive pressure ventilation (SIPPV) (26.8xa0%) in 2011. NICUs reporting frequent or always use of IPPV decreased to 11.0xa0% (pu2009<u20090.001). SIMV (77.2xa0%) and SIPPV (26.8xa0%) did not change from 1997 to 2011, while high-frequency oscillation (HFO) increased from 9.1 to 19.7xa0% (pu2009=u20090.018). Differences between countries, level of care, and size of the NICU were minimal.n Conclusions: Target values for SaO2 decreased, while CO2 and pH increased significantly during the observation period. Current values largely reflect available evidence at time of the surveys.What is Known:• Evidence concerning target values of oxygen saturation, CO2, and pH in extremely low-birth-weight infants has grown substantially.• It is not known to which extent this knowledge is transferred into clinical practice and if treatment strategies have changed.What is New:• Target values for oxygen saturation in ELBW infants decreased between 1997 and 2011 while target values for CO2and pH increased.• Similar treatment strategies existed in different countries, hospitals of different size, or university versus nonuniversity hospitals in 2011.

1631 Change of Habits after Years of Evidence: A Questionnaire on Neonatal Care

Background and Aims Evidence based knowledge in neonatal care has substantially increased during the last years. We tried to evaluate how well guidelines and evidence from studies have been implemented into clinical practice during the last 15 years. Methods Detailed questionnaires were sent 15 years apart to all neonatal units potentially treating VLBW infants in Germany (1995) and all German speaking countries (2010). Results The response rate was 66% both times. Whereas in 1995 2/3 of the units used 100% oxygen and ¼ 50% to start respiratory support in the delivery room, in 2010 only 3% and 5% of the units used 100% and 50% oxygen, respectively. Caffeine and Theophylline were used to treat apnoea of prematurity by 50% and 87% of the units in 1995 compared to 96% and 10% in 2010, respectively. Pasteurization of breast milk was done in 24% of the units in 1995 compared to 53% in 2010. In 1995, 37% of the units routinely used erythropoietin in ELBW infants compared to 27% in 2010. Conclusions Treatment of VLBW infants changed significantly within the last 15 years and some of the existing guidelines and evidence seem to be transferred into clinical practice in most units.

Case 1: Unexpected muscular hypotonia and need for mechanical ventilation in a preterm infant (Discussion and Diagnosis)

DISCUSSION This premature infant presented with an unexpected and prolonged need for ventilation that was not due to respiratory distress. The infant’s progress seemed rather to indicate an underlying neuromuscular disorder. However, we suspected an adverse effect of the 1.5 mg dose of diazepam, which corresponds to 10-fold of the recommended dose (0.1 mg/kg/day). After injection, diazepam is distributed throughout the body. Due to its high lipid solubility and octanol/water partition coefficient (log P 2.68) (2), it is found at higher concentrations in the storage pool consisting of adipose tissue, muscles and brain (3). Diazepam is metabolized through demethylation and oxidation, leading to the active metabolites N1desmethyldiazepam, temazepam and oxazepam. Subsequent conjugation with glucuronic acid enables urinary excretion. The apparent plasma elimination rate of diazepam is prolonged in premature infants. Due to the immaturity of metabolic pathways, the preferred pathway is via N1-desmethyldiazepam to oxazepam (4). However, little data existed regarding benzodiazepine pharmacokinetics in preterm infants with birth weights <2000 g. The half-life of diazepam was estimated to be 60–100 h (5–9), which agreed with the clinical course of this case. To test this hypothesis, we analysed diazepam levels in all blood samples obtained during clinical routine. Using low sample volumes, benzodiazepine concentrations (sum of diazepam and its metabolites) in plasma were determined (80 μL plasma samples, single measurements) using fluorescence polarization immunoassay (FPIA) technology with the TDxFLx R