I. Reiss

Disinfectant contaminated with Klebsiella oxytoca as a source of sepsis in babies

We report an outbreak of sepsis from contaminated disinfectant in a neonatal and paediatric intensive-care unit. 28 infants were infected with Klebsiella oxytoca and basic measures to control the outbreak failed. The resistance of K. oxytoca against the disinfectant was probably mediated by capsule formation, visible as mucoid colonies.

Hypoxia-induced intrauterine growth retardation: effects on pulmonary development and surfactant protein transcription.

Background and Objectives: Preterm infants with intrauterine growth retardation (IUGR) reveal an increased risk for the development of acute and chronic pulmonary disorders, i.e. bronchopulmonary dysplasia (BPD). In order to investigate the effect of IUGR on pulmonary development, an easily reproducible animal model for fetal growth restriction has been established using hypoxia as a sole intervention in the last third of pregnancy. Methods: Date-mated mice were randomly assigned to either being kept at a fraction of inspired oxygen (FiO2) of 0.10 (hypoxic group) starting at day 14 or under normoxic conditions until day 17.5 of gestation (control group). Variables of somatic growth were assessed and standardized histomorphometric analyses of pulmonary tissue were performed. Expression of surfactant proteins (SP)-A, -B, -C and -D was determined by quantitative rt-PCR as biochemical indicators for lung development and maturation. Results: Fetuses were delivered preterm at 0.87 of gestation. Those grown under hypoxic conditions revealed significantly lower birth weights (median: 0.69 vs. 0.97 g in controls; p < 0.001), body lengths (median: 17.5 vs. 20.2 mm in controls; p < 0.001) and fronto-occipital diameters (median: 9.4 vs. 10.1 mm in controls; p < 0.001) compared to controls. Histomorphometric analyses were found to be without significant differences between both groups. On the transcriptional level, however, mRNA expression of SP-A, -B and -C but not SP-D could be shown to be significantly reduced in hypoxic fetuses compared to normoxic controls. Conclusions: In conclusion, hypoxic conditions from day 14 to 17.5 led to IUGR in preterm mice and to significant alterations of the developing surfactant system. We speculate restricted development of SP gene expression to be a causal factor for the increased risk of acute and chronic pulmonary disorders in preterm infants with IUGR.

Value of Myocardial Hypoxia Markers (Creatinine Kinase and Its MB-Fraction, Troponin-T, QT-Intervals) and Serum Creatinine for the Retrospective Diagnosis of Perinatal Asphyxia

Neonatal asphyxia is a major topic of neonatal research. However, no clear-cut physiologic parameters exist which enable an early identification of neonatal infants who are either at risk to develop brain damage or posthypoxic heart failure. Parameters indicating dysfunction of the heart and kidneys as creatinine and creatinine kinase have been evaluated. In our study, 47 asphyxiated infants (umbilical artery pH <7.18 and either a 1-min Apgar score <4 or a 5-min Apgar score <7) were compared to 27 nonasphyxiated controls regarding significant differences in creatinine, creatinine kinase, its MB fraction, and a newly introduced myocardial hypoxia indicator – troponin T – to establish the value of these parameters in the retrospective diagnosis of asphyxia. Further we evaluated two subsets of these 47 asphyxiated infants with either subsequent signs of encephalopathy (seizures) or heart failure. Creatinine, creatinine kinase and troponin T were significantly elevated in asphyxiated infants compared with controls; no differences were found in creatinine kinase and its MB fraction. In asphyxiated infants with heart failure, troponin T was significantly higher than in the other asphyxiated infants. However, none of the parameters studied was significantly different in patients with brain damage compared with asphyxiated infants without neurological sequelae. Troponin T has a high positive predictive value in the postnatal diagnosis of asphyxia. The diagnostic power of troponin T equals that of creatinine. However, troponin T is more sensitive in the identification of infants with asphyxia and cardiocirculatory failure than creatinine. Creatinine kinase and its MB fraction have no diagnostic value.

Ponderal index for discrimination between symmetric and asymmetric growth restriction: Percentiles for neonates from 30 weeks to 43 weeks of gestation

Aims. The ponderal index describes body proportionality at birth thus distinguishing symmetric from asymmetric growth restriction. We aimed to develop ponderal index percentiles for preterm and term neonates born in a European population. Methods. Auxologic data were obtained from neonates born from January 1990 to December 1998 from the datasets reported to the perinatal quality assurance system of the Federal State of Hesse, Germany. We excluded data from neonates with lethal malformations, with chromosomal aberrations, from multiple births, from neonates with uncertain gestational age, and from neonates of a gestational age of less than 30 completed weeks. We calculated the weekly 5th, 10th, 25th, 50th, 75th, 90th, and 95th ponderal index percentile values. Results. A total of 480 841 neonates (233 662 females and 247 179 males) were included. Charts and tables of ponderal index values show percentiles for males, females, and for the total group. There were no significant differences between boys and girls. Conclusion. Our data offer the ability to refer a neonates body proportionality to updated percentiles. The percentiles allow the discrimination between symmetric and asymmetric growth restriction in preterm and term infants.

Maturational Changes of Lymphocyte Surface Antigens in Human Blood: Comparison between Fetuses, Neonates and Adults

The objective of this study was to investigate the maturational changes of lymphocyte surface antigens during ontogeny from fetuses to adults using the proven whole blood lysis technique. Two-color flow cytometric analysis of lymphocyte surface markers was performed on 20 fetal blood samples obtained by cordocentesis, 70 cord blood and 30 adult blood samples. The leukocyte count and all T-cell subsets were highest in neonates compared to fetuses and declined into adulthood. In contrast, the percentage of CD2+ T cells (fetal blood 57% versus adult blood 82%; p ≤ 0.001), CD3+ T cells (fetal blood 52% versus adult blood 77%; p ≤ 0.001), CD4+ T cells (fetal blood 39% versus adult blood 50%; p ≤ 0.05) and CD8+ T cells (fetal blood 15% versus adult blood 24%; p ≤ 0.001) showed a significant increase from fetuses to adults. The absolute and relative amounts of B cells were highest in fetuses (fetal blood 547 × 106/l, 18%) followed by a steady decline to adulthood (adult blood 243 × 106/l, 13%; p ≤ 0.001). The discordance between the absolute and relative size of lymphocyte subpopulations emphasizes the consideration of both variables in the assessment of lymphocyte maturation. The presented data may contribute to a better knowledge of the maturation of the immune system.

Prolonged mechanical ventilation induces pulmonary inflammation in preterm infants.

Lung inflammation plays an important role in the pathogenesis of chronic lung disease in preterm infants. To test the hypothesis that prolonged mechanical ventilation induces pulmonary inflammation, we analyzed pro- and anti-inflammatory mediators in bronchoalveolar lavage fluid obtained from ventilated preterm infants having respiratory distress syndrome. Our results show a strong correlation between the duration of mechanical ventilation and the amount of proinflammatory mediators. However, the anti-inflammatory cytokine interleukin 10 remained stable during the whole period of mechanical ventilation. These data support the hypothesis that prolonged mechanical ventilation contributes to the development of chronic lung disease by the induction of lung inflammation without adequate stimulation of the counterregulatory cytokine interleukin 10 in preterm infants with respiratory distress syndrome.

Synthetic and natural surfactant differentially modulate inflammation after meconium aspiration.

ObjectiveMeconium aspiration syndrome remains a relevant cause of neonatal respiratory failure and is associated with severe pulmonary changes including surfactant inactivation and pronounced inflammatory changes. The present study investigated the effect of two different surfactant preparations—recombinant surfactant protein C surfactant (rSP-C Surf) and natural bovine surfactant—on pulmonary gas exchange and inflammatory response.Design and subjectsTwenty-three newborn piglets were intubated, mechanically ventilated, received 5 ml/kg 20% sterile meconium for induction of lung injury, and were randomized thereafter for controls (n=7), rSP-C Surf (n=8), or natural surfactant (n=8). Surfactants were given as an intratracheal bolus (75 mg/kg) and animals were further ventilated.Measurements and resultsLung function variables, arterial blood gas samples and lung tissues were obtained. Histological evaluation was performed in right lung tissue using an established score. Cytokine mRNA expression (left lung tissue) was quantified using TaqMan real-time PCR (ΔΔCT method, normalized to controls). In addition to significant improvement in gas exchange and lung function, histological evaluation showed significantly lower sum scores in the rSP-C Surf group than in controls). Cytokine mRNA expression of IL-1β in whole lung tissue was significantly lower after administration of rSP-C Surf than in natural surfactant and controls whereas IL-10 mRNA expression was significantly induced in both surfactant groups.ConclusionsSurfactant administration improved both gas exchange and pulmonary inflammatory cytokine transcription. Mechanisms underlying the differential inflammatory response in both surfactant preparations need to be further addressed.

Endoscopic surgical anatomy of the paediatric third ventricle studied using virtual neuroendoscopy based on 3-D ultrasonography

IntroductionEndoscopic treatment for occlusive hydrocephalus requires knowledge of individual ventricular and vascular anatomies of the ventricular system.MethodsWe studied the feasibility of virtual neuroendoscopy (VNE) based on 3-D ultrasonography (3-D US) for the identification of parenchymal and vascular anatomical landmarks of the third ventricle and its impact on the surgical planning of endoscopic third ventriculostomy (ETV) in paediatric patients. 3-D US was performed through the anterior fontanel in four infants with hydrocephalus.ResultsVirtual neuroendoscopy revealed the size of the foramen of Monro, anatomical landmarks of the floor of the third ventricle crucial for correct fenestration during ETV, but not the premesencephalic cistern. The basilar bifurcation was identified in relation to the floor of the third ventricle by VNE (power-Doppler ultrasonography) and confirmed intraoperatively after ETV.Conclusion3-D US-based VNE reveals detailed anatomical information on the ventricular system including the foramen of Monro and the floor of the third ventricle. Within the premesencephalic cistern vascular anatomy can be visualized, but not non-vascular structures.

Randomized Controlled Trial Comparing Different Single Doses of Intravenous Paracetamol for Placement of Peripherally Inserted Central Catheters in Preterm Infants

Background: The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different paracetamol doses in preterm infants are lacking. Objectives: To determine the analgesic effects of different single intravenous paracetamol doses on pain from peripherally inserted central catheter (PICC) placement in preterm infants. Methods: In a blinded randomized controlled trial, the analgesic effects of 10-, 15-, and 20-mg/kg single-dose intravenous paracetamol before PICC placement were compared in neonates with a gestational age <32 weeks. Secondly, a separate age-matched nonrandomized control group receiving oral sucrose was included. Pain was assessed with the Premature Infant Pain Profile (PIPP) and the COMFORTneo score. Peak plasma concentrations of paracetamol were determined. Results: A total of 60 patients were included in the paracetamol dose groups (median gestational age = 27.8, IQR: 25.7-29.2 weeks). PIPP scores were comparable: median = 8 (IQR: 6-10.5), 7 (IQR: 6-9), and 8 (IQR: 6-10) for the 10-, 15-, and 20-mg/kg paracetamol groups, respectively (p = 0.94). COMFORTneo scores were not statistically different between the different paracetamol dose groups (p = 0.35). All randomized subjects, except for 3 who received 10 mg/kg of paracetamol, had peak paracetamol concentrations >9 mg/L. PIPP (p = 0.78) and COMFORTneo (p = 0.08) scores were also comparable between paracetamol- and sucrose-treated patients. Conclusions: We found no analgesic benefit from intravenous paracetamol studied in different single doses over sucrose for PICC placement in preterm infants. Paracetamol is not a suitable analgesic for this procedure in preterm infants.

Evaluation of an Intubation Readiness Score to Assess Neonatal Sedation before Intubation

Background: Premedication for neonatal intubation facilitates the procedure and reduces stress and physiological disturbances. However, no validated scoring system to assess the effect of premedication prior to intubation is available. Objective: To evaluate the usefulness of an Intubation Readiness Score (IRS) to assess the effect of premedication prior to intubation in newborn infants. Methods: Two-center prospective study in neonates who needed endotracheal intubation. Intubation was performed using a standardized procedure with propofol 1–2 mg/kg as premedication. The level of sedation was assessed with the IRS by evaluating the motor response to a firm stimulus (1 = spontaneous movement; 2 = movement on slight touch; 3 = movement on firm stimulus; 4 = no movement). Intubation was proceeded if an adequate effect, defined as an IRS of 3 or 4, was reached. IRS was compared to the quality of intubation measured with the Viby-Mogensen intubation score. Results: A total of 115 patients, with a median gestational age of 27.7 weeks (interquartile range 5.3) and a median birth weight of 1,005 g (interquartile range 940), were included. An adequate IRS was achieved in 105 patients, 89 (85%) of whom also had a good Viby-Mogensen intubation score and 16 (15%) had an inadequate Viby-Mogensen intubation score. The positive predictive value of the IRS was 85%. Conclusions: Preintubation sedation assessment using the IRS can adequately predict optimal conditions during intubation in the majority of neonates. We suggest using the IRS in routine clinical care. Further research combining the IRS with other parameters could further improve the predictability of adequate sedation during intubation.