Angela Kribs

Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial.

BACKGROUND Surfactant is usually given to mechanically ventilated preterm infants via an endotracheal tube to treat respiratory distress syndrome. We tested a new method of surfactant application to spontaneously breathing preterm infants to avoid mechanical ventilation. METHOD In a parallel-group, randomised controlled trial, 220 preterm infants with a gestational age between 26 and 28 weeks and a birthweight less than 1·5 kg were enrolled in 12 German neonatal intensive care units. Infants were independently randomised in a 1:1 ratio with variable block sizes, to standard treatment or intervention, and randomisation was stratified according to centre and multiple birth status. Masking was not possible. Infants were stabilised with continuous positive airway pressure and received rescue intubation if necessary. In the intervention group, infants received surfactant treatment during spontaneous breathing via a thin catheter inserted into the trachea by laryngoscopy if they needed a fraction of inspired oxygen more than 0·30. The primary endpoint was need for any mechanical ventilation, or being not ventilated but having a partial pressure of carbon dioxide more than 65 mm Hg (8·6 kPa) or a fraction of inspired oxygen more than 0·60, or both, for more than 2 h between 25 h and 72 h of age. Analysis was by intention to treat. This study is registered, number ISRCTN05025922. FINDINGS 108 infants were assigned to the intervention group and 112 infants to the standard treatment group. All infants were analysed. On day 2 or 3 after birth, 30 (28%) infants in the intervention group were mechanically ventilated versus 51 (46%) in the standard treatment group (number needed to treat 6, 95% CI 3-20, absolute risk reduction 0·18, 95% CI 0·30-0·05, p=0·008). 36 (33%) infants in the intervention group were mechanically ventilated during their stay in the hospital compared with 82 (73%) in the standard treatment group (number needed to treat: 3, 95% CI 2-4, p<0·0001). The intervention group had significantly fewer median days on mechanical ventilation, (0 days. IQR 0-3 vs 2 days, 0-5) and a lower need for oxygen therapy at 28 days (30 infants [30%] vs 49 infants [45%], p=0·032) compared with the standard treatment group. We recorded no differences between groups for mortality (seven deaths in the intervention group vs five in the standard treatment group) and serious adverse events (21 vs 28). INTERPRETATION The application of surfactant via a thin catheter to spontaneously breathing preterm infants receiving continuous positive airway pressure reduces the need for mechanical ventilation. FUNDING German Ministry of Research and Technology, University of Lübeck, and Chiesi Pharmaceuticals.

Early administration of surfactant in spontaneous breathing with nCPAP: feasibility and outcome in extremely premature infants (postmenstrual age ≤27 weeks)

Background:  Spontaneous breathing supported by nasal continuous positive airway pressure (nCPAP) is thought to have some advantages compared with mechanical ventilation in extremely premature infants. In addition, early or prophylactic surfactant administration has been shown to be superior to delayed use. A strategy to combine these two principles was tested in our neonatal intensive care unit (NICU). The aim of this feasibility study was to describe the procedure and compare short‐term results with a historical control.

Factors Influencing Apnea and Bradycardia of Prematurity – Implications for Neurodevelopment

Background: Apnea and bradycardia of prematurity (ABP) are possible risks towards damage of the developing brain. Objectives: To characterize the influence of neonatal factors on ABP and to determine the relationship of ABP to neurodevelopmental outcome. Methods: ABP was described in very low birth weight infants (n = 83) using the frequency and severity of ABP episodes with a clinical score considering heart rate, oxygenation, duration and interventions performed during each episode. Neonatal factors were analyzed for their relationship to ABP using regression analysis. Neurodevelopment was investigated using the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development II at a corrected age of 13 months. Power of ABP parameters to predict outcome was assessed by logistic regression analysis. Results: ABP typically started within the first week after birth. Spontaneous resolution occurred at a postmenstrual age (PMA) of 36.0 ± 2.2 (31.1–44.1) weeks. A delayed resolution (>36 weeks PMA) and a higher average daily ABP score during a defined developmental period (31–37 weeks PMA) were associated with a higher incidence of unfavorable outcome (MDI or PDI <69 or death). Conclusion: ABP is an age-specific phenomenon. However, more severe courses than expected for PMA or the resolution at a later PMA indicated an increased risk of neurodevelopmental disturbances at a corrected age of 13 months.

Surfactant without intubation in preterm infants with respiratory distress: first multi-center data.

BACKGROUND Recently in a report of a single center a method has been described to apply surfactant via a thin endotracheal catheter to very low birth weight infants spontaneously breathing with nasal continuous positive airway pressure. We now analyzed available multicenter data. PATIENTS AND METHODS In a multicenter study investigating genetic risk factors, clinical and outcome data and data of antenatal and postnatal treatment of infants with a birth weight below 1,500 g were prospectively recorded. The measures of infants treated with the new method of surfactant application were compared to those of infants who received standard care. The analysis was restricted to infants with a gestational age below 31 weeks (n=1,541). RESULTS 319 infants were treated with the new method and 1,222 with standard care. The need for mechanical ventilation during the first 72 h (29% vs. 53%, p<0.001), the rate of bronchopulmonary dysplasia defined as oxygen at 36 weeks of postmenstrual age (10.9 % vs. 17.5%, p=0.004) and the rate of death or bronchopulmonary dysplasia were significantly lower in the treatment group than in the standard care group. Surfactant, theophyllin, caffeine and doxapram were significantly more often and analgetics, catecholamines and dexamethasone were significantly less frequently used in the treatment group. CONCLUSIONS A new method of surfactant application was associated with a lower prevalence of mechanical ventilation and better pulmonary outcome. A prospective controlled trial is required to determine whether this approach is superior to standard care.

Early surfactant in spontaneously breathing with nCPAP in ELBW infants--a single centre four year experience.

Objective: To evaluate whether the experience with a method to administer surfactant during spontaneous breathing with nasal continuous positive airway pressure (nCPAP) as primary respiratory support in infants with respiratory distress syndrome (RDS) influences the frequency of its use and affects the outcome of patients.

Propofol as an induction agent for endotracheal intubation can cause significant arterial hypotension in preterm infants.

Background:  Propofol is gaining increasing popularity as induction agent for pediatric endotracheal intubation. Recently, propofol has been described for the first time as induction agent for endotracheal intubation in preterm neonates. Propofol seemed to be efficient, safe and ideally suited for the INSURE (Intubation SURfactant Extubation) procedure in preterm neonates. The purpose of this study was to document intubating conditions, vital signs, extubation times and outcome in preterm neonates receiving propofol as induction agent for the INSURE procedure.

Outcome of extremely low gestational age newborns after introduction of a revised protocol to assist preterm infants in their transition to extrauterine life

Aim:  To evaluate the outcome of a cohort of extremely low gestational age newborn infants (ELGAN) below 26‐week gestation who were treated following a revised, gentle delivery room protocol to assist them in the transition and adaptation to extrauterine life.

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.

Mothers seeing their VLBW infants within 3 h after birth are more likely to establish a secure attachment behavior: evidence of a sensitive period with preterm infants?

Objective:Close contact of mother and child in the first hours after birth is essential for the establishment of a secure attachment behavior in term infants. To date, studies investigating whether a ‘sensitive period’ also exists for very low birth weight (VLBW) preterm infants are lacking.Study Design:Attachment patterns of 62 VLBW infants were assessed using the ‘strange situation’ setting and correlated with the time mothers saw their child for the first time. Furthermore, maternal and infant covariates possibly influencing the attachment behavior were analyzed. As maternal factors the mothers age, social status and pregnancy history were recorded and at three time points (time 1, 2 and 3 (t-1, t-2 and t-3)), a semi-structured interview, a depression and a social support questionnaire were performed. As infant factors neonatal basic data, ventilation time and length of hospital stay were recorded. Disease severity was scored using the clinical risk index for babies, score for neonatal acute physiology (SNAP), SNAP perinatal extension and nursery neurobiological risk score. At time points t-2 and t-3, the infants were examined using the second edition of Bayley scales of infant development.Results:In all, 53.2% of the children showed a secure, 33.9% an insecure-avoidant, 3.2% an insecure-ambivalent and 9.7% an insecure-disorganized attachment behavior. Preterm infants whose mothers had seen them within 3 h after birth had a higher rate of secure attachment than preterm infants with no early contact (76 versus 41%, P=0.009). Firstborns showed a significantly higher rate of insecure attachment behavior (93 versus 67%, P=0.01). No influence on attachment behavior was shown for any other maternal or infant factor.Conclusions:Our results support the hypothesis that the first hours after birth are a ‘sensitive period’ for the development of attachment behavior in VLBW infants. When a mother is enabled to see her infant shortly after birth, the ‘sensitive period’ right after birth may be used to help forming an important basis for the secure attachment of the preterm infant.

Remifentanil for INSURE in preterm infants: a pilot study for evaluation of efficacy and safety aspects.

Aim:  To evaluate intubating conditions, extubation times and outcome in preterm infants receiving remifentanil as induction agent for the INSURE procedure.