OBJECTIVE. Extremely preterm infants are at risk for poor growth and impaired neurodevelopment. The objective of this study was to determine whether intrauterine, early neonatal, or postdischarge growth is associated with neurocognitive and motor-developmental outcome in extremely preterm infants. METHODS. Surviving children who were born between July 1996 and June 1999 at <30 weeks' gestation and with a birth weight <1500 g were evaluated at the age of school entry by application of (1) a standardized neurologic evaluation, (2) the Kaufmann Assessment Battery for Children, and (3) the Gross Motor Function Classification Scale. Growth was assessed on the basis of SD scores of weight and head circumference measured at birth, at discharge, and at the time of the follow-up examination. All infants had received intensive early nutritional support. RESULTS. A total of 219 (83%) of 263 long-term survivors were evaluated at a median corrected age of 5.4 years. Increasing SD scores for weight and head circumference from birth to discharge were associated with a reduced risk for an abnormal neurologic examination. Catch-up growth of head circumference from birth to discharge was also associated with a reduced risk for impaired mobility. Weight SD score at birth, an increase of weight SD score from birth to discharge, and an increase of head circumference SD score from discharge to follow-up had an effect on the mental processing composite score. The effects of growth on neurodevelopment were by far exceeded by the consequences of intraventricular and periventricular hemorrhage. CONCLUSIONS. Growth from birth to discharge seemed to be associated with long-term motor development. Cognitive development was associated with intrauterine growth measured as weight at birth, early neonatal weight gain, and postdischarge head circumference growth. Improving particularly early neonatal growth may improve long-term outcome in extremely preterm infants, but the effects of improved growth may only be small.

Objective To determine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants monitored by cerebral near infrared spectroscopy (NIRS) oximetry. Design Phase II randomised, single blinded, parallel clinical trial. Setting Eight tertiary neonatal intensive care units in eight European countries. Participants 166 extremely preterm infants born before 28 weeks of gestation: 86 were randomised to cerebral NIRS monitoring and 80 to blinded NIRS monitoring. The only exclusion criterion was a decision not to provide life support. Interventions Monitoring of cerebral oxygenation using NIRS in combination with a dedicated treatment guideline during the first 72 hours of life (experimental) compared with blinded NIRS oxygenation monitoring with standard care (control). Main outcome measures The primary outcome measure was the time spent outside the target range of 55-85% for cerebral oxygenation multiplied by the mean absolute deviation, expressed in %hours (burden of hypoxia and hyperoxia). One hour with an oxygenation of 50% gives 5%hours of hypoxia. Secondary outcomes were all cause mortality at term equivalent age and a brain injury score assessed by cerebral ultrasonography. Randomisation Allocation sequence 1:1 with block sizes 4 and 6 in random order concealed for the investigators. The allocation was stratified for gestational age (<26 weeks or ≥26 weeks). Blinding Cerebral oxygenation measurements were blinded in the control group. All outcome assessors were blinded to group allocation. Results The 86 infants randomised to the NIRS group had a median burden of hypoxia and hyperoxia of 36.1%hours (interquartile range 9.2-79.5%hours) compared with 81.3 (38.5-181.3) %hours in the control group, a reduction of 58% (95% confidence interval 35% to 73%, P<0.001). In the experimental group the median burden of hypoxia was 16.6 (interquartile range 5.4-68.1) %hours, compared with 53.6 (17.4-171.3) %hours in the control group (P=0.0012). The median burden of hyperoxia was similar between the groups: 1.2 (interquartile range 0.3-9.6) %hours in the experimental group compared with 1.1 (0.1-23.4) %hours in the control group (P=0.98). We found no statistically significant differences between the two groups at term corrected age. No severe adverse reactions were associated with the device. Conclusions Cerebral oxygenation was stabilised in extremely preterm infants using a dedicated treatment guideline in combination with cerebral NIRS monitoring. Trial registration ClinicalTrial.gov NCT01590316.

It has been estimated that between 1990 and 2016, the overall burden from prematurity-related morbidity, including brain injury, measured as years lived with disability, had the largest increase among all common causes of disability.¹

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.

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. 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. 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 μg/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 ≥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. The combination of IL-8 and CRP is more reliable than PCT as a test for early diagnosis of BI in newborn infants.