Frank Pohlandt

Delivery Room Management of Extremely Low Birth Weight Infants: Spontaneous Breathing or Intubation?

Objective. To study the effect of two different delivery room (DR) policies on the rate of endotracheal intubation and mechanical ventilation (EI/MV) and short term morbidity in extremely low birth weight infants (ELBWI; <1000 g, ≥24 weeks). Methods. Retrospective cohort study of 123 inborn ELBWIs born in 1994 and in 1996. DR policies have changed. Until 1994, ELBWIs were intubated immediately after delivery when presenting the slightest signs of respiratory distress or asphyxia after initial resuscitation using a face mask and a handbag. During 1995, the guidelines for respiratory support were changed. In 1996, continuous (15 to 20 seconds), pressure controlled (20 to 25 cm H2O) inflation of the lungs using a nasal pharyngeal tube, followed by continuous positive airway pressure (CPAP; 4 to 6 cm H2O) was applied to all ELBWIs immediately after delivery to establish a functional residual capacity and perhaps to avoid EI/MV. In addition to the changes in respiratory support, the prevention of conductive and evaporative heat loss was improved in 1996. For analysis of morbidity and mortality, infants were matched for gestational age and birth weight. Results. The rate of EI/MV in the DR decreased from 84% in 1994 to 40% in 1996. In 1996, 25% of the ELBWIs were never intubated (7% in 1994), but 35% of the ELBWIs needed secondary EI/MV, primarily because of respiratory distress syndrome (RDS). Initial ventilator settings, ventilator days, mortality, and morbidity were not different between ELBWIs with EI/MV in the DR and infants with secondary EI/MV attributable to RDS in the intensive care unit. ELBWIs with no EI/MV that was caused by RDS had a lower morbidity (ie, bronchopulmonary dysplasia, intraventricular hemorrhage >grade 2 and/or periventricular leukomalacia), mortality, and fewer hospital days (mean: 79 vs 105 days). The incidence of gastrointestinal adverse effects like feeding intolerance or necrotizing enterocolitis was not increased in 1996. Paco 2 was significantly higher at admission to the neonatal unit in ELBWIs with CPAP in 1996 (54 ± 15 mm Hg, 7.2 ± 2.0 kPa) compared with infants with EI/MV in 1994 (38 ± 11 mm Hg, 5.1 ± 1.5 kPa. A total of 26% of spontaneously breathing infants had hypercapnia (Paco 2 ≥60 mm Hg [8.0 kPa]), compared with 7% of infants with EI/MV in 1994. Within the first few hours of life, Paco 2decreased to 46 (32 to 57) mm Hg (6.1 [4.3 to 7.6] kPa) in never intubated ELBWIs (n = 17), but increased to 70 (57 to 81) mm Hg (9.3 [7.6 to 10.8] kPa) in ELBWIs (n= 14) with RDS and secondary EI/MV (age 5.5 [1 to 44] hours). Conclusions. In our setting, the individualized intubation strategy in the DR restricted EI/MV to those ELBWIs who ultimately needed it, without increasing morbidity or mortality in infants with secondary EI/MV attributable to RDS. We speculate that an individualized intubation strategy of the ELBWI is superior to immediate intubation of all ELBWIs with slight signs of respiratory distress after birth.

Diagnostic audit of C-reactive protein in neonatal infection.

A prospective study of 250 consecutive neonatal admissions to a regional perinatal referral centre and of 10 additional consecutive cases with culture-proven neonatal septicaemia was undertaken. Quantitative C-reactive protein (CRP) determination, white cell count and differential were performed on blood samples obtained from all babies on admission, as well as 10–14 h and 22–26 h later. Using clinical signs, chest X-rays, blood cultures, tracheal aspirates obtained within 4 h of delivery and an abnormal immature/total neutrophil ratio (I/T), infected babies were defined as belonging to one of the following groups: (1) Culture-proven septicaemia (n=19); (2) Clinical septicaemia (n=35); (3) Congenital pneumonia (n=28). The sensitivity, specificity, positive and negative predictive value of CRP were calculated for each sampling time and patient group. No baby had a rise in CRP (>6mg/l) before an abnormal I/T ratio was first detected. A delayed rise in CRP concentration in the majority of infected babies occurred approximately 12–24 h after the abnormal I/T ratio was first detected. The overall specificity of a CRP level of ≥10 mg/l remained approximately constant (97%–94%) while sensitivity increased from 22%–61% with increasing time after admission. The same pattern emerged if each patient group was considered separately. The positive predictive value for a CRP level of ≥10mg/l 22–26 h after admission was 83% and the negative predictive value 82%. CRP had no value in the early diagnosis of neonatal infection. Its main role lies rather in the exclusion or confirmation of infection 24 h after the first clinical suspicion.

Comparison of procalcitonin with interleukin 8, C-reactive protein and differential white blood cell count for the early diagnosis of bacterial infections in newborn infants

OBJECTIVE To evaluate procalcitonin (PCT) as a test for early diagnosis of bacterial infections (BI) in newborn infants and to compare the results of PCT with those of interleukin 8 (IL-8), C-reactive protein (CRP) and differential white blood cell count. STUDY DESIGN PCT was prospectively measured along with IL-8, CRP and differential white blood cell counts and blood cultures in 197 newborn infants at the first suspicion of bacterial infection. PCT, IL-8, CRP and differential white blood cell counts were analyzed for sensitivity, specificity and positive and negative predictive values after receiver operating characteristic curve analysis for best thresholds. The kinetics of PCT was determined in infants with and without BI. RESULTS Forty-six infants were diagnosed clinically as having BI, of whom 9 had BI with positive blood cultures. At a cutoff value of 0.50 microg/l, PCT detected combined culture-proved and clinical BI with a sensitivity of 57% (95% confidence interval, 41%, 71%) and a specificity of 66% (95% confidence interval, 57%, 74%). The combination of IL-8 > or =70 ng/l and/or CRP >10 mg/l achieved a sensitivity of 91% (95% confidence interval, 79%, 98%) and a specificity of 73% (95% confidence interval, 64%, 81%). PCT values of infected and not infected infants tended to rise for 24 h after initial evaluation and then decreased. CONCLUSION The combination of IL-8 and CRP is more reliable than PCT as a test for early diagnosis of BI in newborn infants.

Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections.

Objective. To examine whether the determination of interleukin 8 (IL-8) and C-reactive protein (CRP) in neonates with suspected nosocomial bacterial infection (NBI) is feasible and cost-effective in reducing antibiotic therapy. Methods. Between April 1996 and May 1997, IL-8 was measured 260 times along with blood cultures, CRP, and immature-to-total-neutrophil (IT) ratio for suspected NBI in term and preterm neonates. All infants were retrospectively analyzed for NBI. Sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals were calculated for IL-8, CRP, and IT ratio. Receiver-operating characteristic curves were analyzed to determine optimal thresholds. Between June 1997 and June 1998, IL-8 was measured 215 times in newborn infants with suspected NBI and the decision to start antibiotic therapy was based on increased IL-8 and/or CRP values. A cost-effectiveness analysis was performed and sensitivity, specificity, and receiver-operating characteristic curves were reevaluated. Results. At the first suspicion of NBI, the combination of IL-8 ≥ 53 pg/mL and/or CRP >10 mg/L detected culture-proven NBI with 96% sensitivity. The combined culture-proven and clinical NBI were detected with 93% sensitivity and 80% specificity. The use of IL-8 reduced unnecessary antibiotic therapy for suspected NBI by 73% and was cost-effective when compared with initiating antibiotic therapy based on clinical signs alone or based on clinical signs and an increased IT ratio and/or CRP. Conclusions. The combination of IL-8 and/or CRP is a reliable and early test for the diagnosis of NBI in newborn infants. Using the combination of IL-8 and/or CRP to restrict antibiotic therapy to truly infected infants reduces unnecessary antibiotic therapy and is cost-effective.

Critical systematic review of the level of evidence for routine use of probiotics for reduction of mortality and prevention of necrotizing enterocolitis and sepsis in preterm infants

BACKGROUND & AIMS Probiotics have been suggested to prevent severe necrotizing enterocolitis (NEC) and decrease mortality in preterm infants. The aim of this paper was to systematically analyze the level of evidence (LoE) of published controlled randomized trials (RCTs) on probiotics in preterm infants. METHODS Literature searches were made up to November 2010. LoE of recommendations based on single trials or meta-analyses were scored following the Oxford Center for Evidence based Medicine approach (1a - meta-analyses of 1b LoE studies; 1b - well designed RCT; 2a - meta-analyses which include 2b LoE studies; 2b - lesser quality RCT). RESULTS Fifteen trials were included (Two 1b LoE trials and thirteen 2b LoE trials). Methodological assessment revealed considerable heterogeneity. Some probiotics may be beneficial in relation to reduction of severe NEC (2b LoE) and reduction of mortality (2b LoE). Probiotics do not accelerate feeding advancement (1b and 2b LoE). There was no convincing benefit with regard to prevention of sepsis (1b and 2b LoE). CONCLUSION There is insufficient evidence to recommend routine probiotics. However, there is encouraging data (2b LoE) which justifies the further investigation regarding the efficacy and safety of specific probiotics in circumstances of high local incidence of severe NEC.

Randomized comparison of high-frequency ventilation with high-rate intermittent positive pressure ventilation in preterm infants with respiratory failure

OBJECTIVE In a randomized, controlled, multicenter trial, we tested the hypothesis that high-frequency ventilation (HFV) with a high lung volume strategy results in fewer treatment failures than intermittent positive pressure ventilation (IPPV) with high rates and low peak inspiratory pressures. STUDY DESIGN Infants with a gestational age between >/=24 weeks and <30 weeks, requiring mechanical ventilation within 6 hours of birth, were randomly assigned to receive either IPPV or HFV until 240 hours after randomization, extubation, or meeting treatment failure criteria. Treatment failure, the primary end point, was determined when air leaks, an oxygenation index >35 to 45 (depending on gestational age), death, or chronic lung disease occurred. Chronic lung disease was defined as persistent requirement of mechanical ventilation, continuous positive airway pressure, or supplemental oxygen at a postmenstrual age of 36 weeks. Secondary end points included the incidence of intracranial hemorrhage. RESULTS The third scheduled interim analysis led to termination of the trial after recruitment of 284 infants. Treatment failure criteria were met by 46% of infants receiving IPPV and 54% of infants receiving HFV (1-tailed primary hypothesis, P =.92; 2-tailed chi2 test, P =.15). Air leaks occurred in 31% and 42% (P =.042), CLD in 23% and 25%, and grade 3-4 intracranial hemorrhage in 13% and 14% of IPPV-treated and HFV-treated patients, respectively. The mortality rate before discharge was 10% in both groups. CONCLUSION HFV with a high lung volume strategy did not cause less lung injury in preterm infants than IPPV with a high rate and low peak inspiratory pressures.

Single-dose dexamethasone treatment of hypotension in preterm infants

OBJECTIVE To test the efficacy of single-dose dexamethasone (DXM) in the management of severe arterial hypotension of newborn infants. Our hypothesis was that epinephrine infusions could be discontinued in 70% of patients within 12 hours after DXM administration compared with 10% in the placebo group. STUDY DESIGN Twenty preterm infants (median birth weight 690 g, gestational age 28 weeks, age at intervention 2 days) who did not respond to a standardized treatment protocol (blood/colloid followed by dopamine infusion stepwise increased to 15 micrograms/kg and minute) were started on an epinephrine infusion and were randomly allocated to receive either DXM (0.25 mg/kg) or placebo intravenously. The primary outcome criterion was the need for an epinephrine infusion 12 hours after treatment. RESULTS Three infants were excluded. Epinephrine infusion was discontinued in 5 of 8 infants with DXM but in only 1 of 9 infants in the control group. The duration of epinephrine infusion was significantly shorter in the DXM group (exact log-rank test, P =. 023). CONCLUSIONS DXM was effective for the management of severe arterial hypotension in preterm infants not responding to standardized treatment.

Prebiotic oligosaccharides reduce stool viscosity and accelerate gastrointestinal transport in preterm infants

AIM To investigate whether a mixture of prebiotic non-digestible oligosaccharides (GosFos; referring to galacto- and fructo-oligosaccharides) would improve feeding tolerance in preterm infants on full enteral formula feeding. We hypothesized that GosFos would: (1) reduce stool viscosity and (2) accelerate gastrointestinal transport. METHODS In a placebo-controlled double-blind trial 20 preterm infants on full enteral nutrition (gestational age 27 (24-31) weeks, postnatal age 42 (11-84) days, and weight at study entry 1570 (1080-2300) g were randomly allocated to have their feedings supplemented with either GosFos (1 g/100 mL) or placebo for 14 days. Stool viscosity was measured by high-pressure capillary rheometry. Gastrointestinal transport time was assessed as the time from feeding carmine red to its appearance in the diaper. The hypotheses were tested as a priori ordered hypotheses. Data are shown as median (range). RESULTS Birth weight, gestational age, postnatal age, and weight at study entry did not differ between groups. GosFos significantly reduced both stool viscosity, as measured by extrusion force (32 (2-67) versus 158 (24-314) N), and gastrointestinal transit time (12 (4-33) versus 26 (5-52) h). No adverse effects were observed. CONCLUSION Formula supplementation with GosFos reduced stool viscosity and accelerated gastrointestinal transport. Further trials are required to investigate whether GosFos facilitates enteral feeding advancement and early enteral nutrition thereby eventually reducing the incidence of catheter-related nosocomial infections and improving long-term outcome.

Sustained pressure-controlled inflation or intermittent mandatory ventilation in preterm infants in the delivery room? A randomized, controlled trial on initial respiratory support via nasopharyngeal tube.

Aim: To prove the hypothesis that sustained pressure‐controlled inflation compared to intermittent mandatory ventilation for lung recruitment via nasopharyngeal tube after delivery is more effective in reducing the rate of endotracheal intubation and mechanical ventilation in very preterm infants. Methods: The study was designed as a randomized, controlled trial. The setting was the delivery room and neonatal intensive care unit of a university hospital in Germany. Subjects were 61 infants (25.0–28.9 wk of gestation) with signs of respiratory distress immediately after birth. The infants were randomized in the delivery room to two different respiratory interventions: either to sustained pressure‐controlled inflation (15 s) or to intermittent mandatory ventilation (rate 60 min−1). This respiratory support was given by a nasopharyngeal tube. The inflation pressure or peak inspiratory pressure was increased stepwise (20–25‐30 cm H2O) according to the response of heart rate and oxygenation. Results: The main outcome measure was treatment failure, i.e., endotracheal intubation and mechanical ventilation according to given intubation criteria. Treatment failure occurred in 61 % (95% CI, sustained pressure‐controlled inflation: 42–78) and 70% (95% CI, intermittent mandatory ventilation: 51–85) (p= 0.59). The rates of mortality (3/61), severe intraventricular haemorrhage (5/61) and chronic lung disease (10/58) were not different between groups.

Prospective Randomized Trial of Early Versus Late Enteral Iron Supplementation in Infants With a Birth Weight of Less Than 1301 Grams

Objectives. To examine whether early enteral iron supplementation (EI) would improve serum ferritin as a measure of nutritional iron status at 2 months of age and would prevent definite iron deficiency (ID) in infants with a birth weight of <1301 g. Methods. Infants were randomly assigned to receive enteral iron supplementation of 2 to 6 mg/kg/day as soon as enteral feedings of >100 mL/kg/day were tolerated (EI) or at 61 days of life (late enteral iron supplementation [LI]). Nutritional iron status was assessed: 1) at birth, 2) at 61 days of life, 3) when the infants reached a weight of 1.6 times birth weight, and 4) before blood was transfused at a hematocrit of <.25. ID was defined by any one of the following criteria: ferritin, <12 μg/L; transferrin saturation, <17%; or increase of absolute reticulocyte counts by >50% one week after the onset of enteral iron supplementation. Restrictive red cell transfusion guidelines were followed and all transfusions were documented. Erythropoietin was not administered. The primary outcome variables were: 1) ferritin at 61 days and 2) the number of infants with ID. Results. Ferritin at 61 days was not different between the groups. Infants in the LI group were more often iron-deficient (26/65 vs 10/68) and received more blood transfusions after day 14 of life. No adverse effects of EI were noted. Conclusions. EI is feasible and probably safe in infants with birth weight <1301 g. EI may reduce the incidence of ID and the number of late blood transfusions. ID may occur in very low birth weight infants despite early supplementation with iron and should be considered in the case of progressive anemia. preterm infant, iron supplementation, iron deficiency, blood transfusion.