Sustained inflation improves initial lung aeration in newborn rabbits with a diaphragmatic hernia.

BACKGROUND: Infants with a congenital diaphragmatic hernia (DH) have underdeveloped lungs and require mechanical ventilation after birth, but the optimal approach is unknown. We hypothesised that sustained inflation (SI) increases lung aeration in newborn kittens with a DH. METHODS: In pregnant New Zealand white rabbits, a left-sided DH was induced in two fetal kittens per doe at 24-days gestation (term = 32 days); litter mates acted as controls. DH and control kittens were delivered by caesarean section at 30 days, intubated and mechanically ventilated (7-10 min) with either an SI followed by intermittent positive pressure ventilation (IPPV) or IPPV throughout. The rate and uniformity of lung aeration was measured using phase-contrast X-ray imaging. RESULTS: Lung weights in DH kittens were ~57% of controls. An SI increased the rate and uniformity of lung aeration in DH kittens, compared to IPPV, and increased dynamic lung compliance in both control and DH kittens. However, this effect of the SI was lost when ventilation changed to IPPV. CONCLUSION: While an SI improved the rate and uniformity of lung aeration in both DH and control kittens, greater consideration of the post-SI ventilation strategy is required to sustain this benefit. IMPACT: Compared to intermittent positive pressure ventilation (IPPV), an initial sustained inflation (SI) increased the rate and uniformity of lung aeration after birth. However, this initial benefit is rapidly lost following the switch to IPPV. The optimal approach for ventilating CDH infants at birth is unknown. While an SI improves lung aeration in immature lungs, its effect on the hypoplastic lung is unknown. This study has shown that an SI greatly improves lung aeration in the hypoplastic lung. This study will guide future studies examining whether an SI can improve lung aeration in infants with a CDH.

Practical approaches for supporting informed consent in neonatal clinical trials.

The survival and health of preterm and critically ill infants have markedly improved over the past 50 years, supported by well-conducted neonatal research. However, newborn research is difficult to undertake for many reasons, and obtaining informed consent for research in this population presents several unique ethical and logistical challenges. In this article, we explore methods to facilitate the consent process, including the role of checklists to support meaningful informed consent for neonatal clinical trials. CONCLUSION: The authors provide practical guidance on the design and implementation of an effective consent checklist tailored for use in neonatal clinical research.

Perinatal predictors of clinical instability at birth in late-preterm and term infants.

To identify characteristics associated with delivery room clinical instability in at-risk infants. Prospective cohort study. Two perinatal centres in Melbourne, Australia. Infants born at ≥ 35+0 weeks' gestation with a first-line paediatric doctor requested to attend. Clinical instability defined as any one of heart rate < 100 beats per minute for ≥ 20 s in the first 10 min after birth, maximum fraction of inspired oxygen of ≥ 0.70 in the first 10 min after birth, 5-min Apgar score of < 7, intubated in the delivery room or admitted to the neonatal unit for respiratory support. Four hundred and seventy-three infants were included. The median (IQR) gestational age at birth was 39+4 (38+4-40+4) weeks. Eighty (17%) infants met the criteria for clinical instability. Independent risk factors for clinical instability were labour without oxytocin administration, presence of a medical pregnancy complication, difficult extraction at birth and unplanned caesarean section in labour. Decision tree analysis determined that infants at highest risk were those whose mothers did not receive oxytocin during labour (25% risk). Infants at lowest risk were those whose mothers received oxytocin during labour and did not have a medical pregnancy complication (7% risk). CONCLUSIONS: We identified characteristics associated with clinical instability that may be useful in alerting less experienced clinicians to call for senior assistance early. The decision trees provide intuitive visual aids but require prospective validation. WHAT IS KNOWN: • First-line clinicians attending at-risk births may need to call senior colleagues for assistance depending on the infant's condition. • Delays in effectively supporting a compromised infant at birth is an important cause of neonatal morbidity and infant-mother separation. WHAT IS NEW: • This study identifies risk factors for delivery room clinical instability in at-risk infants born at ≥ 35+0 weeks' gestation. • The decision trees presented provide intuitive visual tools to aid in determining the need for senior paediatric presence.

Higher CPAP levels improve functional residual capacity at birth in preterm rabbits.

BACKGROUND: Preterm infants are commonly supported with 4-8 cm H2O continuous positive airway pressures (CPAP), although higher CPAP levels may improve functional residual capacity (FRC). METHODS: Preterm rabbits delivered at 29/32 days (~26-28 weeks human) gestation received 0, 5, 8, 12, 15 cm H2O of CPAP or variable CPAP of 15 to 5 or 15 to 8 cm H2O (decreasing ~2 cm H2O/min) for up to 10 min after birth. RESULTS: FRC was lower in the 0 (6.8 (1.0-11.2) mL/kg) and 5 (10.1 (1.1-16.8) mL/kg) compared to the 15 (18.8 (10.9-22.4) mL/kg) cm H2O groups (p = 0.003). Fewer kittens achieved FRC > 15 mL/kg in the 0 (20%), compared to 8 (36%), 12 (60%) and 15 (73%) cm H2O groups (p = 0.008). While breathing rates were not different (p = 0.096), apnoea tended to occur more often with CPAP < 8 cm H2O (p = 0.185). CPAP belly and lung bulging rates were similar whereas pneumothoraces were rare. Lowering CPAP from 15 to 5, but not 15 to 8 cm H2O, decreased FRC and breathing rates. CONCLUSION: In all, 15 cm H2O of CPAP improved lung aeration and reduced apnoea, but did not increase the risk of lung over-expansion, pneumothorax or CPAP belly immediately after birth. FRC and breathing rates were maintained when CPAP was decreased to 8 cm H2O. IMPACT: Although preterm infants are commonly supported with 4-8 cm H2O CPAP at birth, preclinical studies have shown that higher PEEP levels improve lung aeration. In this study, CPAP levels of 15 cm H2O improved lung aeration and reduced apnoea in preterm rabbit kittens immediately after birth. In all, 15 cm H2O CPAP did not increase the risk of lung over-expansion (indicated by bulging between the ribs), pneumothorax, or CPAP belly. These results can be used when designing future studies on CPAP strategies for preterm infants in the delivery room.

Sustained Inflation Versus Intermittent Positive Pressure Ventilation for Preterm Infants at Birth: Respiratory Function and Vital Sign Measurements.

OBJECTIVE: To characterize respiratory function monitor (RFM) measurements of sustained inflations and intermittent positive pressure ventilation (IPPV) delivered noninvasively to infants in the Sustained Aeration of Infant Lungs (SAIL) trial and to compare vital sign measurements between treatment arms. STUDY DESIGN: We analyzed RFM data from SAIL participants at 5 trial sites. We assessed tidal volumes, rates of airway obstruction, and mask leak among infants allocated to sustained inflations and IPPV, and we compared pulse rate and oxygen saturation measurements between treatment groups. RESULTS: Among 70 SAIL participants (36 sustained inflations, 34 IPPV) with RFM measurements, 40 (57%) were spontaneously breathing prior to the randomized intervention. The median expiratory tidal volume of sustained inflations administered was 5.3 mL/kg (IQR 1.1-9.2). Significant mask leak occurred in 15% and airway obstruction occurred during 17% of sustained inflations. Among 34 control infants, the median expiratory tidal volume of IPPV inflations was 4.3 mL/kg (IQR 1.3-6.6). Mask leak was present in 3%, and airway obstruction was present in 17% of IPPV inflations. There were no significant differences in pulse rate or oxygen saturation measurements between groups at any point during resuscitation. CONCLUSION: Expiratory tidal volumes of sustained inflations and IPPV inflations administered in the SAIL trial were highly variable in both treatment arms. Vital sign values were similar between groups throughout resuscitation. Sustained inflation as operationalized in the SAIL trial was not superior to IPPV to promote lung aeration after birth in this study subgroup. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02139800.

Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants.

BACKGROUND: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. METHODS: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. RESULTS: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06). CONCLUSIONS: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820 .).

A Randomized Trial of Conditioned or Unconditioned Gases for Stabilizing Preterm Infants at Birth.

OBJECTIVE: To determine whether the use of heated-humidified gases for respiratory support during the stabilization of infants <30 weeks of gestational age (GA) in the delivery room reduces rates of hypothermia on admission to the neonatal intensive care unit (NICU). STUDY DESIGN: A multicenter, unblinded, randomized trial was conducted in Melbourne, Australia, between February 2013 and June 2015. Infants <30 weeks of GA were randomly assigned to receive either heated-humidified gases or unconditioned gases during stabilization in the delivery room and during transport to NICU. Infants born to mothers with pyrexia >38°C were excluded. Primary outcome was rate of hypothermia on NICU admission (rectal temperature <36.5°C). RESULTS: A total of 273 infants were enrolled. Fewer infants in the heated-humidified group were hypothermic on admission to NICU (36/132 [27%]) compared with controls (61/141 [43%], P < .01). There was no difference in rates of hyperthermia (>37.5°C); 20% (27/132) in the heated-humidified group compared with 16% (22/141) in the controls (P = .30). There were no differences in mortality or respiratory outcomes. CONCLUSIONS: The use of heated-humidified gases in the delivery room significantly reduces hypothermia on admission to NICU in preterm infants, without increased risk of hyperthermia. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Register (www.anzctr.org.au) ACTRN12613000093785.

Suction Mask vs Conventional Mask Ventilation in Term and Near-Term Infants in the Delivery Room: A Randomized Controlled Trial.

OBJECTIVE: To compare the suction mask, a new facemask that uses suction to create a seal between the mask and the infant's face, with a conventional soft, round silicone mask during positive pressure ventilation (PPV) in the delivery room in newborn infants >34 weeks of gestation. STUDY DESIGN: Single-center randomized controlled trial in the delivery room. The primary outcome was mask leak. RESULTS: Forty-five infants were studied at a median gestational age of 38.1 weeks (IQR, 36.4-39.0 weeks); 22 were randomized to the suction mask and 23 to the conventional mask. The suction mask did not reduce mask leak (49.9%; IQR, 11.0%-92.7%) compared with the conventional mask (30.5%; IQR, 10.6%-48.8%; P = .51). The suction mask delivered lower peak inspiratory pressure (27.2 cm H2O [IQR, 25.0-28.7 cm H2O] vs 30.4 cm H2O [IQR, 29.4-32.5 cm H2O]; P < .05) and lower positive end expiratory pressure (3.7 cm H2O [IQR, 3.1-4.5 cm H2O] vs 5.1 cm H2O [IQR, 4.2-5.7 cm H2O ]; P < .05). There was no difference in the duration of PPV or rates of intubation or admission to the neonatal intensive care unit. In 5 infants (23%), the clinician switched from the suction to the conventional mask, 2 owing to intermittently low peak inspiratory pressure, 2 owing to failure to respond to PPV, and 1 owing to marked facial bruising after 6 minutes of PPV. CONCLUSIONS: The use of the suction mask to provide PPV in newborn infants did not reduce facemask leak. Adverse effects such as the inability to achieve the set pressures and transient skin discoloration are concerning. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12616000768493.

Adherence to the neonatal resuscitation algorithm for preterm infants in a tertiary hospital in Spain.

BACKGROUND: There is evidence that delivery room resuscitation of very preterm infants often deviates from internationally recommended guidelines. There were no published data in Spain regarding the quality of neonatal resuscitation. Therefore, we decided to evaluate resuscitation team adherence to neonatal resuscitation guidelines after birth in very preterm infants. METHODS: We conducted an observational study. We video recorded resuscitations of preterm infants < 32 weeks' gestational age and evaluated every step during resuscitation according to a score-sheet specifically designed for this purpose, following Carbine's method, where higher scores indicated that more intense resuscitation maneuvers were required. We divided the score achieved by the total possible points per patient to obtain the percentage of adherence to the algorithm. We also compared resuscitations performed by staff neonatologists to those performed by pediatricians on-call. We compared percentages of adherence to the algorithm with the Chi-square test for large groups and Fisher's exact test for smaller groups. We compared assigned Apgar scores with those given after analyzing the recordings and described them by their median and interquartile range. We measured the interrater agreement between Apgar scores with Cohen's kappa coefficient. Linear and logarithmic regressions were drawn to characterize the pattern of algorithm adherence. Statistical analysis was performed using SPSS V.20. A p-value < 0.05 was considered significant. Our Hospital Ethics Committee approved this project, and we obtained parental written consent beforehand. RESULTS: Sixteen percent of our resuscitations followed the algorithm. The number of mistakes per resuscitation was low. Global adherence to the algorithm was 80.9%. Ventilation and surfactant administration were performed best, whereas preparation and initial steps were done with worse adherence to the algorithm. Intubation required, on average, 2.2 attempts; success on the first attempt happened in 33.3% of cases. Only 12.5% of intubations were achieved within the allotted 30 s. Many errors were attributable to timing. Resuscitations led by pediatricians on-call were performed as correctly as those by staff neonatologists. CONCLUSIONS: Resuscitation often deviates from the internationally recognized algorithm. Perfectly performed resuscitations are infrequent, although global adherence to the algorithm is high. Neonatologists and pediatricians need intubation training.

Antenatal Medical Therapies to Improve Lung Development in Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) is a birth defect characterized by failed closure of the diaphragm, allowing abdominal viscera to herniate into the thoracic cavity and subsequently impair pulmonary and vascular development. Despite improving standardized postnatal management, there remains a population of severe CDH for whom postnatal care falls short. In these severe cases, antenatal surgical intervention (fetoscopic endoluminal tracheal occlusion [FETO]) may improve survival; however, FETO increases the risk of preterm delivery, is not widely offered, and still fails in half of cases. Antenatal medical therapies that stimulate antenatal pulmonary development are therefore interesting alternatives. By presenting the animal research underpinning novel antenatal medical therapies for CDH, and considering the applications of these therapies to clinical practice, this review will explore the future of antenatal CDH management with a focus on the phosphodiesterase-5 inhibitor sildenafil.

Lung hypoplasia in newborn rabbits with a diaphragmatic hernia affects pulmonary ventilation but not perfusion.

BackgroundA congenital diaphragmatic hernia (DH) can result in severe lung hypoplasia that increases the risk of morbidity and mortality after birth; however, little is known about the cardiorespiratory transition at birth.MethodsUsing phase-contrast X-ray imaging and angiography, we examined the cardiorespiratory transition at birth in rabbit kittens with DHs. Surgery was performed on pregnant New Zealand white rabbits (n=18) at 25 days' gestation to induce a left-sided DH. Kittens were delivered at 30 days' gestation, intubated, and ventilated to achieve a tidal volume (Vt) of 8 ml/kg in control and 4 ml/kg in DH kittens while they were imaged.ResultsFunctional residual capacity (FRC) recruitment and Vt in the hypoplastic left lung were markedly reduced, resulting in a disproportionate distribution of FRC into the right lung. Following lung aeration, relative pulmonary blood flow (PBF) increased equally in both lungs, and the increase in pulmonary venous return was similar in both control and DH kittens.ConclusionThese findings indicate that nonuniform lung hypoplasia caused by DH alters the distribution of ventilation away from hypoplastic and into normally grown lung regions. During transition, the increase in PBF and pulmonary venous return, which is vital for maintaining cardiac output, is not affected by lung hypoplasia.

Survey of neonatal resuscitation practices showed post-training improvements but need to reinforce preterm management, monitoring and adrenaline use.

AIM: Neonatal resuscitation surveys have showed practice variations between countries, centres and levels of care. We evaluated delivery room practices after a nationwide neonatal resuscitation training programme focused on nontertiary centres. METHODS: A 2012 survey sent to all Spanish hospitals handling deliveries covered staff availability and training, equipment and practices in the delivery room and during transfers to neonatal intensive care units. The results from 98 centres that had completed a previous survey in 2007 were analysed by levels of care. Pearson's chi-square test was used to compare the proportions. RESULTS: The following had significantly improved in 2012 compared to 2007: the availability of T-piece resuscitators (71.4% vs. 41.8%), plastic wraps (69.4% vs. 31.6%), gas blenders (79.6% vs. 40.8%), pulse oximetry (92.9% vs. 61.2%), use of continuous positive airway pressure (82.7% vs. 43.9%) (all p < 0.01), the availability of instructors (55.6% vs. 83.3%, p < 0.05) and neonatal resuscitation courses (40.8% vs. 79.6%, p < 0.05) in nontertiary centres. In 2012, the use of exhaled carbon dioxide detectors was <7% and endotracheal administration of adrenaline was >90%. CONCLUSION: Neonatal resuscitation equipment and practices improved over time, but several aspects needed to be reinforced in training programmes, namely preterm infants' management, monitoring and adrenaline administration.

Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes.

Cofactor disorders of mitochondrial energy metabolism are a heterogeneous group of diseases with a wide variety of clinical symptoms, particular metabolic profiles and variable enzymatic defects. Mutations in NFU1, BOLA3, LIAS and IBA57 have been identified in patients with deficient lipoic acid-dependent enzymatic activities and defects in the assembly and activity of the mitochondrial respiratory chain complexes. Here, we report a patient with an early onset fatal lactic acidosis presenting a biochemical phenotype compatible with a combined defect of pyruvate dehydrogenase (PDHC) and 2-ketoglutarate dehydrogenase (2-KGDH) activities, which suggested a deficiency in lipoic acid metabolism. Immunostaining analysis showed that lipoylated E2-PDH and E2-KGDH were extremely reduced in this patient. However, the absence of glycine elevation, the normal activity of the glycine cleavage system and the normal lipoylation of the H protein suggested a defect of lipoic acid transfer to particular proteins rather than a general impairment of lipoic acid biosynthesis as the potential cause of the disease. By analogy with yeast metabolism, we postulated LIPT1 as the altered candidate gene causing the disease. Sequence analysis of the human LIPT1 identified two heterozygous missense mutations (c.212C>T and c.292C>G), segregating in different alleles. Functional complementation experiments in patient's fibroblasts demonstrated that these mutations are disease-causing and that LIPT1 protein is required for lipoylation and activation of 2-ketoacid dehydrogenases in humans. These findings expand the spectrum of genetic defects associated with lipoic acid metabolism and provide the first evidence of a lipoic acid transfer defect in humans.

The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks' gestation.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and long-term respiratory and neurological morbidity in very preterm infants. While survival rates of very preterm infants have increased over the past two decades there has been no decrease in the rate of BPD in surviving infants. Evidence from animal and human studies has suggested potential benefits of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, in the prevention of chronic lung disease. This randomised controlled trial aims to determine the effectiveness of supplementary DHA in reducing the rate of BPD in infants less than 29 weeks' gestation. METHODS/DESIGN: This is a multicentre, parallel group, randomised, blinded and controlled trial. Infants born less than 29 weeks' gestation, within 3 days of first enteral feed and with parent informed consent are eligible to participate. Infants will be randomised to receive an enteral emulsion containing DHA or a control emulsion without DHA. The DHA emulsion will provide 60 mg/kg/day of DHA. The study emulsions will continue to 36 weeks' postmenstrual age (PMA). The primary outcome is BPD as assessed by the requirement for supplemental oxygen and/or assisted ventilation at 36 weeks' PMA. Secondary outcomes include the composite of death or BPD; duration of respiratory support and hospitalisation, major neonatal morbidities. The target sample size is 1244 infants (622 per group), which will provide 90 % power to detect a clinically meaningful absolute reduction of 10 % in the incidence of BPD between the DHA and control emulsion (two tailed α =0.05). DISCUSSION: DHA supplementation has the potential to reduce respiratory morbidity in very preterm infants. This multicentre trial will provide evidence on whether an enteral DHA supplement reduces BPD in very preterm infants. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry: ACTRN12612000503820 . Registered 09 May 2012.

The accuracy of delivery of target pressures using self-inflating bag manometers in a benchtop study.

AIM: We tested whether operators using manometers attached to self-inflating bags could accurately deliver set targeted peak inspiratory pressures (PIPs) compared to the Neopuff(™) T-piece resuscitator (TPR). METHODS: Participants provided positive pressure ventilation to a leak-free neonatal test lung at a rate of 60 inflations/min and a flow of 8 L/min. Participants used three manometers attached to self-inflating bags and a Neopuff(™) TPR to target PIPs of 20, 30 and 40 cmH2 O on each device. Mean PIPs delivered with each manometer were compared to the 'gold standard' Neopuff(™) TPR. RESULTS: In total, 13 991 inflations delivered by 20 participants were analysed. At all target PIPs, the mean PIP delivered using the Mercury Medical manometer attached to a Laerdal self-inflating bag was significantly higher by 5 cmH2 O (p < 0.01) than the Neopuff(™) TPR. The PIP delivered using both the Ambu(™) and Parker Healthcare manometers attached to their respective devices was similar to that delivered by the Neopuff(™) TPR at all targeted PIPs. CONCLUSION: Accurately targeted PIPs can be achieved when a manometer specifically designed for use on a self-inflating bag is used during manual ventilation. This may be useful in settings where access to a Neopuff(™) TPR or a gas flow source is limited.

Neonatal resuscitation in resource-limited settings: titrating oxygen delivery without an oxygen blender.

OBJECTIVE: To test whether 4 commonly used self-inflating bags with a reservoir in situ can reliably deliver different oxygen concentrations (21%-100%) using a portable oxygen cylinder with flows of ≤5 L/min. STUDY DESIGN: Four self-inflating bags (from Laerdal, Ambu, Parker Healthcare, and Mayo Healthcare) were tested to provide positive pressure ventilation to a manikin at 60 inflations/min by 4 operators. Oxygen delivery was measured for 2 minutes, combining oxygen flows (0.25, 0.5, 1, 5 L/min) and peak inspiratory pressures (PIPs 20-25, 35-40 cmH2O). RESULTS: Combinations (n=128) were performed twice. Oxygen delivery depended upon device, oxygen flow, and PIP. All self-inflating bags delivered mean oxygen concentrations of <40% with 0.25 L/min, regardless of PIP. Three self-inflating bags delivered ≤40% with flow 0.5 L/min at PIP 35-40 cmH2O, whereas all delivered >40% at PIP 20-25 cmH2O. With 1 L/min, 3 self-inflating bags delivered 40%-60% at PIP 35-40 cmH2O and all delivered >60% at PIP 20-25 cmH2O. With 5 L/min, all self-inflating bags delivered close to or 100%, regardless of PIP. Differences in oxygen delivery between self-inflating bags were statistically significant (P<.001) even when differences were not clinically important. CONCLUSION: Self-inflating bags with a reservoir in situ can deliver a variety of oxygen concentrations without a blender, from <40% with 0.25 L/min oxygen flow to 100% with 5 L/min. The adjustment of oxygen flow may be a useful method of titrating oxygen in settings where air-oxygen blenders are unavailable.

Relationship between insulin-like growth factor I levels, early insulin treatment, and clinical outcomes of very low birth weight infants.

OBJECTIVES: Insulin regulates the secretion of insulin-like growth factor I (IGF-I) in the newborn, and low levels of IGF-I have been linked to neonatal morbidity. As part of the Neonatal Insulin Replacement Therapy in Europe Trial, we investigated the impact of early insulin treatment on IGF-I levels and their relationship with morbidity and growth. STUDY DESIGN: Prospective cohort analyses of data collected as part of an international randomized controlled trial. Blood samples (days 1, 3, 7, and 28), were taken for IGF-I bioassay from 283 very low birth weight infants (<1500 g). RESULTS: Early insulin treatment led to a late increase in IGF-I levels between day 7 and 28 (P = .028). In the first week of life IGF-I levels were lower in infants with early hyperglycemia; mean difference -0.10 µg/L (95% CI -0.19, -0.02, P = .02). Lower levels of IGF-I at day 28 were independently associated with an increased risk of chronic lung disease, OR 3.23 (95% CI, 1.09-9.10), and greater IGF-I levels were independently associated with better weight gain, 0.10 kg (95% CI, 0.03-0.33, P = .02). CONCLUSIONS: Early intervention with insulin is related to increased IGF-I levels at 28 days. Low IGF-I levels are associated with hyperglycemia, increased morbidity, and reduced growth. Increasing IGF-I levels may improve outcomes of very low birth weight infants.

How ABBA may help improve neonatal resuscitation training: auditory prompts to enable coordination of manual inflations and chest compressions.

AIM: Resuscitation guidelines recommend 90 chest compressions (CCs) and 30 inflations (INFs) per minute for neonatal cardiopulmonary resuscitation (nCPR). We hypothesised that auditory prompts would help coordinate these actions. Our aim was to investigate the effect of musical prompts during nCPR training on adherence to recommended CC and INF rates and on the quality of delivered INFs. METHODS: A simulation study was conducted employing 30 experienced neonatal staff, a respiratory function monitor and a neonatal manikin. The effects of five different auditory prompts on adherence to recommended rates of CC and INF were tested against baseline (no music). The five auditory prompts (popular musical tunes) were investigated in random order. Quality of INFs was assessed by comparing the peak inflation pressures (PIP), positive end-expiratory pressures (PEEP), percentage mask leak and tidal volumes (VT). RESULTS: Mean baseline rates at which CCs and INFs were delivered were 80 (SD 6) per minute and 28 (SD 2) per minute, respectively. Listening to auditory prompts had varying effects on CC and INF delivery rates. For CCs, a significant difference to baseline was found only when participants listened to ABBA's 'SOS', with 86 (SD 7) per minute (P = 0.04). For INFs, we found a statistically significant improvement to baseline rate only for 'SOS', with 29 (SD 2) per minute (P = 0.04), and there was no significant difference in INF quality among the auditory prompts. CONCLUSIONS: Musical prompts can help with adherence to recommended CC and INF rates but do not improve the quality of INFs during nCPR training. The lasting effect of auditory prompts as musical mnemonics on nCPR performance in vivo needs to be established.

Time to adjust to changes in ventilation settings varies significantly between different T-piece resuscitators, self-inflating bags, and manometer equipped self-inflating bags.

OBJECTIVE: Resuscitation guidelines give no preference over use of self-inflating bags (SIBs) or T-piece resuscitators (TPR) for manual neonatal ventilation. We speculated that devices would differ significantly regarding time required to adjust to changed ventilation settings. STUDY DESIGN: This was a laboratory study. Time to adjust from baseline peak inflation pressure (PIP) (20 cmH2O) to target PIP (25 and 40 cmH2O), ability to adhere to predefined ventilation settings (PIP, PEEP, and inflation rate [IR]), and the variability within and between operators were assessed for a SIB without manometer, SIB with manometer (SIBM), and two TPRs. RESULTS: Adjustment time was significantly longer with TPRs, compared with SIB and SIBM. The SIBM and TPRs were < 5% (median) off target PIP, and the SIB was 14% off target PIP. Significant variability between operators (interquartile range [IQR]: 71%) was seen with SIBs. CONCLUSION: PIP adjustment takes longer with TPRs, compared with SIB/SIBM. TPRs and SIBM allow satisfactory adherence to ventilation parameters. SIBs should only be used with manometer attached.

The cardiopulmonary benefits of physiologically based cord clamping persist for at least 8 hours in lambs with a diaphragmatic hernia.

Introduction: Infants with congenital diaphragmatic hernia can suffer severe respiratory insufficiency and pulmonary hypertension after birth. Aerating the lungs before removing placental support (physiologically based cord clamping, PBCC) increases pulmonary blood flow (PBF) and reduces pulmonary vascular resistance (PVR) in lambs with a diaphragmatic hernia (DH). We hypothesized that these benefits of PBCC persist for at least 8 h after birth. Methods: At ∼138 days of gestation age (dGA), 21 lambs with a surgically induced left-sided DH (∼86 dGA) were delivered via cesarean section. The umbilical cord was clamped either before ventilation onset (immediate cord clamping, ICC, n = 9) or after achieving a tidal volume of 4 ml/kg, with a maximum delay of 10 min (PBCC, n = 12). The lambs were ventilated for 8 h, initially with conventional mechanical ventilation, but were switched to high-frequency oscillatory ventilation after 30 min if required. Ventilatory parameters, cardiopulmonary physiology, and arterial blood gases were measured throughout the study. Results: PBF increased after ventilation onset in both groups and was higher in the PBCC DH lambs than the ICC DH lambs at 8 h (5.2 ± 1.2 vs. 1.9 ± 0.3 ml/min/g; p < 0.05). Measured over the entire 8-h ventilation period, PBF was significantly greater (p = 0.003) and PVR was significantly lower (p = 0.0002) in the PBCC DH lambs compared to the ICC DH lambs. A high incidence of pneumothoraces in both the PBCC (58%) and ICC (55%) lambs contributed to a reduced sample size at 8 h (ICC n = 4 and PBCC n = 4). Conclusion: Compared with ICC, PBCC increased PBF and reduced PVR in DH lambs and the effects were sustained for at least 8 h after ventilation onset.