Claudia Roll

High-dose intravenous immune globulin therapy for hyperbilirubinemia caused by Rh hemolytic disease

We conducted a multicenter controlled trial to test the hypothesis that high-dose intravenous immune globulin (HDivIG) therapy can modulate bilirubin production and reduce the frequency of exchange transfusions in newborn infants with Rh hemolytic disease. Thirty-four patients with Rh incompatibility proved by positive direct antiglobulin test (Coombs test) results were randomly assigned to receive conventional treatment including phototherapy, with or without additional HDivIG therapy at 500 mg/kg given for a 2-hour period as soon as the diagnosis was established. Exchange transfusions were performed if serum bilirubin concentrations exceeded the modified curves of Polácek by more than 2 mg/dl. Two patients were excluded because of protocol violations. The results in 32 infants were analyzed. In the HDivIG group, 2 (12.5%) of 16 children required exchange transfusions, whereas it became necessary in 11 (69%) of 16 children in the control group (p less than 0.005). Bilirubin levels in the HDivIG group were lower despite reduced frequency of exchange transfusions. No side effects of HDivIG treatment were observed. We conclude that HDivIG therapy by a yet unknown mechanism reduces serum bilirubin levels and the need for blood exchange transfusions in children with Rh hemolytic disease.

The SafeBoosC Phase II Randomised Clinical Trial: A Treatment Guideline for Targeted Near-Infrared-Derived Cerebral Tissue Oxygenation versus Standard Treatment in Extremely Preterm Infants

Near-infrared spectroscopy-derived regional tissue oxygen saturation of haemoglobin (rStO2) reflects venous oxygen saturation. If cerebral metabolism is stable, rStO2 can be used as an estimate of cerebral oxygen delivery. The SafeBoosC phase II randomised clinical trial hypothesises that the burden of hypo- and hyperoxia can be reduced by the combined use of close monitoring of the cerebral rStO2 and a treatment guideline to correct deviations in rStO2 outside a predefined target range. Aims: To describe the rationale for and content of this treatment guideline. Methods: Review of the literature and assessment of the quality of evidence and the grade of recommendation for each of the interventions. Results and Conclusions: A clinical intervention algorithm based on the main determinants of cerebral perfusion-oxygenation changes during the first hours after birth was generated. The treatment guideline is presented to assist neonatologists in making decisions in relation to cerebral oximetry readings in preterm infants within the SafeBoosC phase II randomised clinical trial. The evidence grades were relatively low and the guideline cannot be recommended outside a research setting.

Less invasive surfactant administration is associated with improved pulmonary outcomes in spontaneously breathing preterm infants

Providing less invasive surfactant administration (LISA) to spontaneously breathing preterm infants has been reported to reduce mechanical ventilation and bronchopulmonary dysplasia (BPD) in randomised controlled trials. This large cohort study compared these outcome measures between LISA‐treated infants and controls.

Single‐centre vs. population‐based outcome data of extremely preterm infants at the limits of viability

Aim:  In response to the disappointing outcome data of the population‐based EPICure study published in 2000, we compared the outcome of infants 22 0/7 to 25 6/7 weeks of gestational age (GA) in a single tertiary care centre 2000–2004 with that of EPICure.

Ultrasound diagnosis of brain atrophy is related to neurodevelopmental outcome in preterm infants

BACKGROUND Intraventricular haemorrhage and periventricular leukomalacia are associated with poor outcome of very preterm infants, while the role of more subtle cerebral alterations, as detected by cranial ultrasound, is less clear. AIM In this study, we related periventricular echodensities and signs of brain atrophy to neurodevelopmental outcome at 3 y of age. PATIENTS AND METHODS All preterm infants born in 1997 in our institution with a gestational age <32 wk or birthweight <1500 g were subjected to repeated standardized cranial ultrasound examinations until discharge. Survivors were examined at 3 y of age employing the Bayley Scales of Infant Development II. RESULTS Eighty-seven infants were enrolled (birthweight 430-2500 g (median 1200 g), gestational age 24-34 wk (median 29 wk)). Periventricular echodensities were detected in 42 infants (48%); in 12 cases persisting <7 d, in 30 cases >7 d. At discharge, 18 infants (22%) had signs of brain atrophy. Neurodevelopmental outcome was assessed in 64 infants. Infants with signs of brain atrophy scored significantly lower on MDI (atrophy 91.8, no atrophy 101.9; p=0.02), PDI (atrophy 91.4, no atrophy 106.5; p=0.001) and Behaviour Rating Scale (atrophy 41.1, no atrophy 66.4; p=0.01) than infants without atrophy. Periventricular echodensities were not related to outcome. CONCLUSION Our data show that infants with sonographic signs of brain atrophy at discharge achieve lower scores in neurodevelopmental testing at 3 y.

Caffeine Increases Cerebral Cortical Activity in Preterm Infants

Caffeine improves the rate of survival without neurodevelopmental disability in preterm infants. The mechanisms underlying neuroprotection are incompletely understood. In 51 preterm infants studied by amplitude-integrated electroencephalography from 2 hours before to 2 hours after intravenous caffeine administration, we found that caffeine increases amplitudes and periods of continuity.

Risk for late-onset blood-culture proven sepsis in very-low-birth weight infants born small for gestational age: a large multicenter study from the German Neonatal Network.

Background: It was the aim of this study to assess whether very-low-birth-weight (VLBW) infants born small for gestational age (SGA; birth weight less than 10th percentile) are at increased risk for late-onset sepsis. Methods: This was a prospective, multicenter study of the German Neonatal Network including VLBW infants from 23 to < 32 weeks post menstrual age born 2009–2011. Outcomes were compared between VLBW infants born SGA (birth weight less than tenth percentile according to gestational age and gender) and non-SGA infants. The main outcome measure was at least 1 episode of late-onset sepsis defined as blood-culture–confirmed clinical sepsis occurring at ≥72 hours of age. Results: 5886 VLBW infants were included. In SGA infants (n = 692), an increased incidence of late-onset sepsis was noted compared with non-SGA infants (20.1% vs. 14.3 %, P < 0.001). This difference was only observed among infants with a gestational age of 27 to < 32 weeks and attributed to sepsis episodes with coagulase-negative staphylococci (12.8% vs. 8.3%, P < 0.001). Different treatment modalities (eg more frequent use of central venous lines) and longer duration of invasive therapies (parenteral nutrition, mechanical ventilation, hospitalization) may account for the increased sepsis risk with coagulase-negative staphylococci in our SGA cohort. In a multivariate logistic regression analysis, higher gestational age [per week; odds ratio (OR): 0.75, 95% confidence interval (CI): 0.72–0.78, P< 0.0001], treatment with antenatal steroids (OR: 0.7, 95% CI: 0.53–0.92, P = 0.01), German descendance (OR: 0.76, 95% CI: 0.63–0.91, P = 0.003) and prophylaxis with glycopeptide antibiotics (OR: 0.64, 95% CI: 0.47–0.87, P = 0.005) were shown to be protective against late-onset sepsis. In contrast, longer duration of parenteral nutrition (per day; OR: 1.016, 95% CI: 1.011–1.021, P < 0.0001) and SGA were found to be risk factors (OR: 1.31, 95% CI: 1.02–1.68, P= 0.03). Conclusions: SGA contributes to the risk of late-onset sepsis in VLBW infants. Future studies are needed to investigate the underlying pathophysiology to guide individualized preventive measures in this vulnerable subgroup.

Short-term outcome of very-low-birthweight infants with arterial hypotension in the first 24 h of life

Objective To evaluate lowest mean arterial blood pressure during the first 24 h of life (minMAP24) in very-low-birthweight (VLBW) infants and to identify associations between hypotension and short-term outcome. Design Retrospective cohort analysis of the minMAP24 of 4907 VLBW infants with a gestational age <32 weeks in correlation with clinical data. Hypotension was defined as minMAP24 being lower than the median value of all patients of the same gestational age. Results MinMAP24 values correlated with gestational age. Median minMAP24 values of VLBW infants ≤29 weeks’ gestation were 1–2 mm Hg lower than gestational age in completed weeks. Hypotensive infants had a higher rate of intraventricular haemorrhage (IVH, 20.3% vs 15.9%, p<0.001), bronchopulmonary dysplasia (BPD, 19.2% vs 15.1%, p<0.001) and death (5.2% vs 3.0%, p<0.001). Multivariate logistic regression analyses, including potential confounders, confirmed these data. MinMAP24 was an independent risk factor for IVH (OR 0.97/mm Hg, 95% CI 0.96 to 0.99, p=0.003), BPD (OR 0.96/mm Hg, 95% CI 0.94 to 0.98, p<0.001) and mortality (OR 0.94/mm Hg, 95% CI 0.90 to 0.98, p=0.003). Conclusions Hypotension during the first 24 h of life is associated with adverse outcomes in VLBW infants. This underlines the need for randomised controlled trials on the use of vasoactive drugs in this vulnerable patient cohort.

Recommendations to Increase the Validity and Comparability of Peripheral Measurements by Near Infrared Spectroscopy in Neonates 'Round Table', Section of Haematology, Oxygen Transport and Microcirculation, 48th Annual Meeting of ESPR, Prague 2007

Several studies of peripheral measurements with near infrared spectroscopy (NIRS) and venous or arterial occlusion have been performed in neonates. Results have been variable. Reasons include differences in patient populations, technical aspects of the devices used or the way measurements were made. It is therefore important that there should be common elements for measurement protocols. This statement proposes a standardised approach to allow comparison between different study populations and devices.

Umbilical artery catheter blood sampling volume and velocity: Impact on cerebral blood volume and oxygenation in very-low-birthweight infants

AIM Blood sampling from umbilical artery catheters decreases cerebral blood volume and cerebral oxygenation. The aim of this study was to assess the impact of sampling volume and velocity. METHODS Forty-eight infants, median birthweight 965 g (480-1500 g), median gestational age 27 wk (23-34 wk), were studied during routine blood sampling from umbilical artery catheters. The sampling procedure was performed following a strict protocol for draw-up volume (1.6 ml), sampling volume (1.7 ml or 0.2 ml), re-injection volume (1.6 ml) and flushing volume (0.6 ml), time of aspiration (40 s or 80 s), re-injection (30 s) and flushing (6 s). In each infant, sampling volume and aspiration time were subject to sequential variation in a randomized fashion (1.7 ml/40 s, 1.7 ml/80 s, 0.2 ml/30 s). Using near-infrared spectroscopy, changes in concentrations of cerebral oxygenated and deoxygenated haemoglobin were measured, and changes in cerebral blood volume and cerebral oxygenation were calculated. RESULTS During all three sampling procedures, oxygenated haemoglobin decreased significantly from baseline, whereas deoxygenated haemoglobin did not change. Correspondingly, a decrease in cerebral blood volume and cerebral oxygenation occurred. This decrease was not affected significantly by extending the sampling time from 40 s to 80 s, whereas it was blunted by reducing the amount of blood withdrawn. CONCLUSION Blood sampling from umbilical artery catheters induces a decrease in cerebral blood volume and cerebral oxygenation. The magnitude of the decrease depends on the blood volume withdrawn but not on sampling velocity.