Early-life regional and temporal variation in filaggrin-derived natural moisturizing factor, filaggrin-processing enzyme activity, corneocyte phenotypes and plasmin activity: implications for atopic dermatitis.

BACKGROUND: Filaggrin is central to the pathogenesis of atopic dermatitis (AD). The cheeks are a common initiation site of infantile AD. Regional and temporal expression of levels of filaggrin degradation products [natural moisturizing factors (NMFs)], activities of filaggrin-processing enzymes [bleomycin hydrolase (BH) and calpain-1 (C-1)] and plasmin, and corneocyte envelope (CE) maturity in early life are largely unknown. OBJECTIVES: We conducted a cross-sectional, observational study investigating regional and age-dependent variations in NMF levels, activity of proteases and CE maturity in stratum corneum (SC) from infants to determine whether these factors could explain the observed predilection sites for AD in early life. METHODS: We measured NMF using a tape-stripping method at seven sites in the SC of 129 children (aged < 12 months to 72 months) and in three sites in 56 neonates and infants (< 48 h to 3 months). In 37 of these neonates and infants, corneocyte size, maturity, BH, C-1 and plasmin activities were determined. RESULTS: NMF levels are low at birth and increase with age. Cheek SC, compared with elbow flexure and nasal tip, has the lowest NMF in the first year of life and is the slowest to reach stable levels. Cheek corneocytes remain immature. Plasmin, BH and C-1 activities are all elevated by 1 month of age in exposed cheek skin, but not in elbow skin. CONCLUSIONS: Regional and temporal differences in NMF levels, CE maturity and protease activities may explain the predilection for AD to affect the cheeks initially and are supportive of this site as key for allergen priming in early childhood. These observations will help design early intervention and treatment strategies for AD.

Cross-colonization of infants with probiotic organisms in a neonatal unit.

This study aimed to assess probiotic cross-colonization between infants in a neonatal unit where probiotics were being administered to preterm infants during a clinical trial. We tested stool samples from all infants present in the unit at two time points; the first was during the trial and the second was after trial completion. Samples from 43 infants were tested during the trial; all five infants receiving probiotics and three of 38 not receiving probiotics were colonized. Only one of 44 infants tested after the trial was colonized. The rate of cross-colonization was lower than in previous probiotic studies.

Oxygen saturation and heart rate during delivery room resuscitation of infants <30 weeks' gestation with air or 100% oxygen.

BACKGROUND: Because of concerns about harmful effects of 100% oxygen on newborn infants, air has started to be used for resuscitation in the delivery room. OBJECTIVE: To describe changes in preductal oxygen saturation (Spo(2)) and heart rate (HR) in the first 10 min after birth in very preterm infants initially resuscitated with 100% oxygen (OX(100)) or air (OX(21)). PATIENTS AND METHODS: In July 2006, policy changed from using 100% oxygen to air. Observations of Spo(2) and HR before and after the change were recorded whenever a member of the research team was available to attend the birth. RESULTS: There were 20 infants in the OX(100) group and 106 in the OX(21) group. In the OX(100) group, Spo(2) had risen to a median of 84% after 2 min and 94% by 5 min. In the OX(21) group, median Spo(2) was 31% at 2 min and 54% at 5 min. In the OX(21) group, 92% received supplemental oxygen at a median of 5 min; the Spo(2) rose to a median of 81% by 6 min. In the first 10 min after birth, 80% and 55% of infants in the OX(100) and OX(21) groups, respectively, had an Spo(2) > or =95%. Increases in HR over the first 10 min were very similar in the two groups. CONCLUSIONS: Most very preterm infants received supplemental oxygen if air was used for the initial resuscitation. In these infants, the use of backup 100% oxygen and titration against Spo(2) resulted in a similar course to "normal" term and preterm infants. Of the infants resuscitated with 100% oxygen, 80% had Spo(2) > or =95% during the first 10 min. The HR changes in the two groups were very similar.

Pinching, electrocution, ravens' beaks, and positive pressure ventilation: a brief history of neonatal resuscitation.

Since ancient times many different methods have been used to revive newborns. Although subject to the vagaries of fashion for 2000 years, artificial respiration has been accepted as the mainstay of neonatal resuscitation for about the last 40. Formal teaching programmes have evolved over the last 20 years. The last 10 years have seen international collaboration, which has resulted in careful evaluation of the available evidence and publication of recommendations for clinical practice. There is, however, little evidence to support current recommendations, which are largely based on expert opinion. The challenge for neonatologists today is to gather robust evidence to support or refute these recommendations, thereby refining this common and important intervention.

Neonatal resuscitation 3: manometer use in a model of face mask ventilation.

BACKGROUND: Adequate ventilation is the key to successful neonatal resuscitation. Positive pressure ventilation (PPV) is initiated with manual ventilation devices via face masks. These devices may be used with a manometer to measure airway pressures delivered. The expiratory tidal volume measured at the mask (V(TE(mask))) is a good estimate of the tidal volume delivered during simulated neonatal resuscitation. AIM: To assess the effect of viewing a manometer on the peak inspiratory pressures used, the volume delivered, and leakage from the face mask during PPV with two manual ventilation devices in a model of neonatal resuscitation. METHODS: Participants gave PPV to a modified resuscitation mannequin using a Laerdal infant resuscitator and a Neopuff infant resuscitator at specified pressures ensuring adequate chest wall excursion. Each participant gave PPV to the mannequin with each device twice, viewing the manometer on one occasion and unable to see the manometer on the other. Data from participants were averaged for each device used with the manometer and without the manometer separately. RESULTS: A total of 7767 inflations delivered by the 18 participants were recorded and analysed. Peak inspiratory pressures delivered were lower with the Laerdal device. There were no differences in leakage from the face mask or volumes delivered. Whether or not the manometer was visible made no difference to any measured variable. CONCLUSIONS: Viewing a manometer during PPV in this model of neonatal resuscitation does not affect the airway pressure or tidal volumes delivered or the degree of leakage from the face mask.

Neonatal resuscitation 2: an evaluation of manual ventilation devices and face masks.

BACKGROUND: The key to successful neonatal resuscitation is effective ventilation. Little evidence exists to guide clinicians in their choice of manual ventilation device or face mask. The expiratory tidal volume measured at the mask (V(TE(mask))) is a good estimate of the tidal volume delivered during simulated neonatal resuscitation. AIM: To compare the efficacy of (a) the Laerdal infant resuscitator and the Neopuff infant resuscitator, used with (b) round and anatomically shaped masks in a model of neonatal resuscitation. METHODS: Thirty four participants gave positive pressure ventilation to a mannequin at specified pressures with each of the four device-mask combinations. Flow, inspiratory tidal volume at the face mask (V(TI(mask))), V(TE(mask)), and airway pressure were recorded. Leakage from the mask was calculated from V(TI(mask)) and V(TE(mask)). RESULTS: A total of 10,780 inflations were recorded and analysed. Peak inspiratory pressure targets were achieved equally with the Laerdal and Neopuff resuscitators. Positive end expiratory pressure was delivered with the Neopuff but not the Laerdal device. Despite similar peak pressures, V(TE(mask)) varied widely. Mask leakage was large for each combination of device and mask. There were no differences between the masks. CONCLUSION: During face mask ventilation of a neonatal resuscitation mannequin, there are large leaks around the face mask. Airway pressure is a poor proxy for volume delivered during positive pressure ventilation through a mask.

Neonatal resuscitation 1: a model to measure inspired and expired tidal volumes and assess leakage at the face mask.

BACKGROUND: Neonatal resuscitation is a common and important intervention, and adequate ventilation is the key to success. In the delivery room, positive pressure ventilation is given with manual ventilation devices using face masks. Mannequins are widely used to teach and practise this technique. During both simulated and real neonatal resuscitation, chest excursion is used to assess tidal volume delivery, and leakage from the mask is not measured. OBJECTIVE: To describe a system that allows measurement of mask leakage and estimation of tidal volume delivery. METHODS: Respiratory function monitors, a modified resuscitation mannequin, and a computer were used to measure leakage from the mask and to assess tidal volume delivery in a model of neonatal resuscitation. RESULTS: The volume of gas passing through a flow sensor was measured at the face mask. This was a good estimate of the tidal volume entering and leaving the lung in this model. Gas leakage between the mask and mannequin was also measured. This occurred principally during inflation, although gas leakage during deflation was seen when the total leakage was large. A volume of gas that distended the mask but did not enter the lung was also measured. CONCLUSION: This system can be used to assess the effectiveness of positive pressure ventilation given using a face mask during simulated neonatal resuscitation. It could be useful for teaching neonatal resuscitation and assessing ventilation through a face mask.

Air versus oxygen for resuscitation of infants at birth.

BACKGROUND: 100% oxygen is the commonly recommended gas for the resuscitation of infants at birth. There is growing evidence from both animal and human studies that room air is as effective as 100% oxygen and that 100% oxygen may have adverse effects on breathing physiology and cerebral circulation. There is also the theoretical risk of tissue damage due to free oxygen radicals when 100% oxygen is given. The use of room air has, therefore, been suggested as a safer and possibly more effective alternative. OBJECTIVES: In newborn infants requiring resuscitation, does the use of room air reduce the incidence of death, neurological disability and short term morbidity when compared with the use of 100% oxygen? SEARCH STRATEGY: This included searches of the Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004) and MEDLINE PubMed 1966 to December 2003, and handsearches of reference lists of relevant articles and conference proceedings. SELECTION CRITERIA: All randomised and quasi-randomised studies comparing the use of room air or any other concentration of oxygen versus 100% oxygen in the resuscitation of infants at birth. DATA COLLECTION AND ANALYSIS: Three authors assessed the methodological quality of eligible trials and extracted data independently. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. For categorical data the relative risk (RR), risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals (CI) were calculated. Continuous data were analysed using weighted mean difference (WMD). MAIN RESULTS: Five studies were identified which enrolled a total of 1302 infants. In two studies allocation was randomised and the caregivers were blinded to intervention group. In the other three studies, allocation was quasi-randomised and the caregivers were not blinded. Pooled analysis of the four trials reporting effect on death showed a significant reduction in the rate of death in the group resuscitated with room air [typical RR 0.71 (0.54, 0.94), typical RD -0.05 (-0.08, -0.01), NNT 20 (12, 100)]. There were no significant differences between the groups with respect to rates of grade 2 or 3 hypoxic ischaemic encephalopathy. One of the four trials reported a statistically significant difference in median 5 minute Apgar scores, favouring the group allocated to room air. However, the absolute difference between the medians was small and there were no significant differences in the median 10 minute Apgar scores in the three trials reporting this outcome. One trial followed up a selected subgroup of survivors to 18-24 months. There were no significant differences in rates of adverse neurodevelopmental outcomes including cerebral palsy and failure to achieve various milestones; however, the proportion of eligible patients seen was less than 70%. Analyses that were planned for this review, but not able to be carried out because of lack of published data, included a sub-analysis stratified by gestational age and assessments of the effect on bronchopulmonary dysplasia and retinopathy of prematurity. AUTHORS' CONCLUSIONS: There is insufficient evidence at present on which to recommend a policy of using room air over 100% oxygen, or vice versa, for newborn resuscitation. A reduction in mortality has been seen in infants resuscitated with room air, and no evidence of harm has been demonstrated. However, the small number of identified studies and their methodologic limitations dictate caution in interpreting and applying these results. We note the use of back-up 100% oxygen in more than a quarter of infants randomised to room air. Therefore, on the basis of currently available evidence, if one chooses room air as the initial gas for resuscitation, supplementary oxygen should continue to be made available.

Obtaining pulse oximetry data in neonates: a randomised crossover study of sensor application techniques.

Pulse oximetry may be useful during neonatal resuscitation. A randomised crossover study was performed to determine the most efficient method of applying the sensor. Applying it to the infant before connecting to the oximeter resulted in quickest acquisition of accurate heart rate. This technique should be preferred during resuscitation.

Air versus oxygen for resuscitation of infants at birth.

BACKGROUND: 100% oxygen is the commonly recommended gas for the resuscitation of infants at birth. There is growing evidence from both animal and human studies that room air is as effective as 100% oxygen and that 100% oxygen may have adverse effects on breathing physiology and cerebral circulation. There is also the theoretical risk of tissue damage due to free oxygen radicals when 100% oxygen is given. The use of room air has, therefore, been suggested as a safer and possibly more effective alternative. OBJECTIVES: In newborn infants requiring resuscitation, does the use of room air reduce the incidence of death, neurological disability and short term morbidity when compared with the use of 100% oxygen? SEARCH STRATEGY: This included searches of the Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004) and MEDLINE PubMed 1966 to December 2003, and handsearches of reference lists of relevant articles and conference proceedings. SELECTION CRITERIA: All randomised and quasi-randomised studies comparing the use of room air or any other concentration of oxygen versus 100% oxygen in the resuscitation of infants at birth. DATA COLLECTION AND ANALYSIS: Three authors assessed the methodological quality of eligible trials and extracted data independently. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. For categorical data the relative risk (RR), risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals (CI) were calculated. Continuous data were analysed using weighted mean difference (WMD). MAIN RESULTS: Five studies were identified which enrolled a total of 1302 infants. In two studies allocation was randomised and the caregivers were blinded to intervention group. In the other three studies, allocation was quasi-randomised and the caregivers were not blinded. Pooled analysis of the four trials reporting effect on death showed a significant reduction in the rate of death in the group resuscitated with room air [typical RR 0.71 (0.54, 0.94), typical RD -0.05 (-0.08, -0.01), NNT 20 (12, 100)]. There were no significant differences between the groups with respect to rates of grade 2 or 3 hypoxic ischaemic encephalopathy. One of the four trials reported a statistically significant difference in median 5 minute Apgar scores, favouring the group allocated to room air. However, the absolute difference between the medians was small and there were no significant differences in the median 10 minute Apgar scores in the three trials reporting this outcome. One trial followed up a selected subgroup of survivors to 18-24 months. There were no significant differences in rates of adverse neurodevelopmental outcomes including cerebral palsy and failure to achieve various milestones; however, the proportion of eligible patients seen was less than 70%. Analyses that were planned for this review, but not able to be carried out because of lack of published data, included a sub-analysis stratified by gestational age and assessments of the effect on bronchopulmonary dysplasia and retinopathy of prematurity. REVIEWERS' CONCLUSIONS: There is insufficient evidence at present on which to recommend a policy of using room air over 100% oxygen, or vice versa, for newborn resuscitation. A reduction in mortality has been seen in infants resuscitated with room air, and no evidence of harm has been demonstrated. However, the small number of identified studies and their methodologic limitations dictate caution in interpreting and applying these results. We note the use of back-up 100% oxygen in more than a quarter of infants randomised to room air. Therefore, on the basis of currently available evidence, if one chooses room air as the initial gas for resuscitation, supplementary oxygen should continue to be made available.

Positive pressure ventilation at neonatal resuscitation: review of equipment and international survey of practice.

BACKGROUND: The equipment used to provide positive pressure ventilation to newborns needing resuscitation at delivery varies between institutions. Devices were reviewed and their use surveyed in a sample of neonatal centres worldwide. AIM: To determine which equipment is used to resuscitate newborns at delivery in a sample of teaching hospitals around the world. METHODS: A questionnaire was sent via e-mail to a neonatologist at each of 46 NICUs in 23 countries on five continents, asking which resuscitation equipment they used. If it was not returned, follow-up was by e-mail. RESULTS: Data were obtained from 40 (87%) centres representing 19 countries. Round face masks are used at 34 (85%) centres, anatomically shaped masks are used exclusively at six (15%) and a mixture of types are used at 11 (28%). Straight endotracheal tubes are used exclusively at 36 (90%) centres: shouldered tubes are used infrequently at three of the four centres that have them. The self-inflating bag is the most commonly used manual ventilation device (used at 33 (83%) centres), the Laerdal Infant Resuscitator the most popular model. Flow-inflating bags are used at 10 (25%) centres. The Neopuff Infant Resuscitator is used at 12 (30%) centres. Varying oxygen concentrations are provided during neonatal resuscitation at half of the centres, while 100% oxygen is routinely used at the other half. CONCLUSIONS: This survey shows considerable variation in practice, reflecting this lack of evidence and consequent uncertainty among clinicians. Comparison of the two most popular manual ventilation devices, the Laerdal Infant Resuscitator and the Neopuff Infant Resuscitator, is urgently required.

Neonatal resuscitation: review of ventilation equipment and survey of practice in Australia and New Zealand.

OBJECTIVE: The equipment used to provide positive pressure ventilation at neonatal resuscitation varies between institutions. Available devices were reviewed and their use surveyed in a geographically defined region. The aim of this study was to establish which resuscitation equipment is used at neonatal intensive care units in Australia and New Zealand. METHODS: A questionnaire was sent to a neonatologist at each of the 29 neonatal intensive care units in Australia and New Zealand, asking which resuscitation equipment they used. If it was not returned, follow up was by email and telephone. RESULTS: Data was obtained from all units. Round face masks are used at all centres. Anatomically shaped masks are infrequently used at two of the three centres (10%) that have them. Straight endotracheal tubes are used exclusively at 23 (79%) centres. Shouldered tubes are used infrequently at three of the six centres that have them. The Laerdal Infant Resuscitator self-inflating bag is used at 22 (76%) centres. Flow-inflating bags are used at 12 (41%) centres. The Neopuff Infant Resuscitator is used at 14 (48%) centres. Varying oxygen concentrations are provided at delivery at 6/25 (24%) centres. CONCLUSIONS: There is a paucity of evidence for the efficacy of the equipment used currently to resuscitate newborn infants. This complete survey of the tertiary centres in a geographical region shows considerable variation in practice, reflecting this lack of evidence and consequent uncertainty among clinicians. Further research is necessary to determine which devices are preferable for this most important and common intervention.