Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)
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 .).
BACKGROUND: Neonatal endotracheal intubation is a necessary skill. However, success rates among junior doctors have fallen to ,50%, largely owing to declining opportunities to intubate. Videolaryngoscopy allows instructor and trainee to share the view of the pharynx. We compared intubations guided by an instructor watching a videolaryngoscope screen with the traditional method where the instructor does not have this view.METHODS: A randomized, controlled trial at a tertiary neonatal center recruited newborns from February 2013 to May 2014. Eligible intubations were performed orally on infants without facial or airway anomalies, in the delivery room or neonatal intensive care, by doctors with ,6 months' tertiary neonatal experience. Intubations were randomized to having the videolaryngoscope screen visible to the instructor or covered (control). The primary outcome was first-attempt intubation success rate confirmed by colorimetric detection of expired carbon dioxide.RESULTS: Two hundred six first-attempt intubations were analyzed. Median (interquartile range) infant gestation was 29 (27 to 32) weeks, and weight was 1142 (816 to 1750) g. The success rate when the instructor was able to view the videolaryngoscope screen was 66% (69/104) compared with 41% (42/102) when the screen was covered (P , .001, OR 2.81, 95% CI 1.54 to 5.17). When premedication was used, the success rate in the intervention group was 72% (56/78) compared with 44% (35/79) in the control group (P , .001, OR 3.2, 95% CI 1.6 to 6.6).CONCLUSIONS: Intubation success rates of inexperienced neonatal trainees significantly improved when the instructor was able to share their view on a videolaryngoscope screen. WHAT'S KNOWN ON THIS SUBJECT:Endotracheal intubation is a mandatory skill for neonatal trainees. It is a difficult skill to acquire, and success rates of junior doctors are low and falling.WHAT THIS STUDY ADDS: Videolaryngoscopy allows the supervisor to share the intubator' s view of the airway and provide more informed guidance. Teaching intubation using a videolaryngoscope with the screen visible to the instructor results in significantly higher success rates for inexperienced doctors.
BackgroundNon-invasive ventilation is sometimes unable to provide the respiratory needs of very premature infants in the delivery room. While airway obstruction is thought to be the main problem, the site of obstruction is unknown. We investigated whether closure of the larynx and epiglottis is a major site of airway obstruction.MethodsWe used phase contrast X-ray imaging to visualise laryngeal function in spontaneously breathing premature rabbits immediately after birth and at approximately 1 hour after birth. Non-invasive respiratory support was applied via a facemask and images were analysed to determine the percentage of the time the glottis and the epiglottis were open.HypothesisImmediately after birth, the larynx is predominantly closed, only opening briefly during a breath, making non-invasive intermittent positive pressure ventilation (iPPV) ineffective, whereas after lung aeration, the larynx is predominantly open allowing non-invasive iPPV to ventilate the lung.ResultsThe larynx and epiglottis were predominantly closed (open 25.5%±1.1% and 17.1%±1.6% of the time, respectively) in pups with unaerated lungs and unstable breathing patterns immediately after birth. In contrast, the larynx and the epiglottis were mostly open (90.5%±1.9% and 72.3%±2.3% of the time, respectively) in pups with aerated lungs and stable breathing patterns irrespective of time after birth.ConclusionLaryngeal closure impedes non-invasive iPPV at birth and may reduce the effectiveness of non-invasive respiratory support in premature infants immediately after birth.
Excessive liquid in airways and/or distal lung tissue may underpin the respiratory morbidity associated with transient tachypnea of the newborn (TTN). However, its effects on lung aeration and respiratory function following birth are unknown. We investigated the effect of elevated airway liquid volumes on newborn respiratory function. Near-term rabbit kittens (30 days gestation; term ~32 days) were delivered, had their lung liquid-drained, and either had no liquid replaced (control; = 7) or 30 ml/kg of liquid re-added to the airways [liquid added (LA); = 7]. Kittens were mechanically ventilated in a plethysmograph. Measures of chest and lung parameters, uniformity of lung aeration, and airway size were analyzed using phase contrast X-ray imaging. The maximum peak inflation pressure required to recruit a tidal volume of 8 ml/kg was significantly greater in LA compared with control kittens (35.0 ± 0.7 vs. 26.8 ± 0.4 cmHO, < 0.001). LA kittens required greater time to achieve lung aeration (106 ± 14 vs. 60 ± 6 inflations, = 0.03) and had expanded chest walls, as evidenced by an increased total chest area (32 ± 9%, < 0.0001), lung height (17 ± 6%, = 0.02), and curvature of the diaphragm (19 ± 8%, = 0.04). LA kittens had lower functional residual capacity during stepwise changes in positive end-expiratory pressures (5, 3, 0, and 5 cmH0). Elevated lung liquid volumes had marked adverse effects on lung structure and function in the immediate neonatal period and reduced the ability of the lung to aerate efficiently. We speculate that elevated airway liquid volumes may underlie the initial morbidity in near-term babies with TTN after birth. Transient tachypnea of the newborn reduces respiratory function in newborns and is thought to result due to elevated airway liquid volumes following birth. However, the effect of elevated airway liquid volumes on neonatal respiratory function is unknown. Using phase contrast X-ray imaging, we show that elevated airway liquid volumes have adverse effects on lung structure and function in the immediate newborn period, which may underlie the pathology of TTN in near-term babies after birth.
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.
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