Metyrapone as treatment in the neonatal McCune-Albright syndrome.

Objectives To present a case report of succesfully metyrapone treatment of a neonatal patient with McCune-Albrigth syndrome (MAS), a rare disease caused by a genetically mosaic disorder and is characterized by variable hyperfunctional endocrinopathies, bone dysplasia, and café-au-lait spots. Case presentation A preterm newborn was admitted to hospital and she presented difficulty controlling hypertension, café-au-lait spots, and failure to thrive. An abdominal ultrasound and a magnetic resonance showed a high volume of both suprarenal glands. Therefore, MAS was suspected. Laboratory data confirmed adrenocorticotropic hormone-independent Cushing's syndrome with hepatic dysfunction and metyrapone treatment was initiated. A progressive normalization of cortisol levels was achieved despite poor oral tolerance. Conclusion Our case shows that metyrapone is useful in the management of neonatal Cushing's syndrome due to McCune-Albright syndrome.

Survival and Neurodevelopmental Outcomes of Preterms Resuscitated With Different Oxygen Fractions.

BACKGROUND AND OBJECTIVES: Stabilization of preterm infants after birth frequently requires oxygen supplementation. At present the optimal initial oxygen inspiratory fraction (Fio2) for preterm stabilization after birth is still under debate. We aimed to compare neurodevelopmental outcomes of extremely preterm infants at 24 months corrected age randomly assigned to be stabilized after birth with an initial Fio2 of 0.3 versus 0.6 to 0.65 in 3 academic centers from Spain and the Netherlands. METHODS: Randomized, controlled, double-blinded, multicenter, international clinical trial enrolling preterm infants <32 weeks' gestation assigned to an initial Fio2 of 0.3 (Lowox group) or 0.6 to 0.65 (Hiox group). During stabilization, arterial pulse oxygen saturation and heart rate were continuously monitored and Fio2 was individually titrated to keep infants within recommended ranges. At 24 months, blinded researchers used the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) to assess visual acuity, neurosensory deafness, and language skills. RESULTS: A total of 253 infants were recruited and 206 (81.4%) completed follow-up. No differences in perinatal characteristics, oxidative stress, or morbidities during the neonatal period were assessed. Mortality at hospital discharge or when follow-up was completed didn't show differences between the groups. No differences regarding Bayley-III scale scores (motor, cognitive, and language composites), neurosensorial handicaps, cerebral palsy, or language skills between groups were found. CONCLUSIONS: The use of an initial lower (0.3) or higher (0.6-0.65) Fio2 during stabilization of extremely preterm infants in the delivery room does not influence survival or neurodevelopmental outcomes at 24 months.

Urinary Lipid Peroxidation Byproducts: Are They Relevant for Predicting Neonatal Morbidity in Preterm Infants?

Preterm infants have an immature antioxidant system; however, they frequently require supplemental oxygen. Oxygen-free radicals cause both pulmonary and systemic inflammation, and they are associated with increased morbidity and mortality. Consequently, screening of metabolite profiles representing the amount of lipid peroxidation is considered of great relevance for the evaluation of in vivo oxidative stress and derived inflammation and damage. Ranges for total relative contents of isoprostanes (IsoPs), isofurans (IsoFs), neuroprostanes (NeuroPs), and neurofurans (NeuroFs) within targeted SpO2 ranges were determined in urine samples of 254 preterm infants<32 weeks of gestation within the frame of two randomized, controlled, and blinded clinical trials employing ultra-performance liquid chromatography-tandem mass spectrometry. A total of 536 serial urine samples collected during the first 4 weeks after birth in recruited infants who did not develop free radical associated conditions were analyzed. A reference range for lipid peroxidation byproducts, including isoprostanes, isofurans, neuroprostanes, and neurofurans, was calculated and possible correlations with neonatal conditions were investigated. Urinary elimination of isofurans in the first 4 days after birth correlated with later development of bronchopulmonary dysplasia. Our observations lead to the hypothesis that early urinary determination of lipid peroxidation byproducts, especially isofurans, is relevant to predict development of chronic lung conditions.

Minimally invasive surfactant therapy with a gastric tube is as effective as the intubation, surfactant, and extubation technique in preterm babies.

AIM: Preterm infants requiring surfactant replacement have been treated using the INSURE technique, which requires sedation and comprises tracheal intubation, surfactant instillation and extubation. However, minimally invasive surfactant therapy (MIST) does not require sedation, minimises airway injury and avoids placing positive pressure ventilation on an immature lung. This study compared the feasibility of the two techniques and the outcomes in preterm babies with respiratory distress syndrome (RDS). METHODS: Preterm infants with RDS prospectively received surfactant via a gastric tube placed in the trachea by direct laryngoscopy with no sedation. Technique-related complications and respiratory outcomes were analysed. RESULTS: We compared 44 patients who received MIST with a historic cohort of 31 patients who received INSURE. This showed no differences in the rate of intubation and mechanical ventilation in the first 72 h, or secondary respiratory outcomes and relevant morbidities, between the babies who received INSURE and those who received MIST. More babies in the MIST group (35%) needed a second dose of surfactant than the INSURE group (6.5%) (p < 0.0001). CONCLUSION: Surfactant administration using MIST, with no sedation, is feasible in preterm infants with RDS. No significant differences in secondary respiratory outcomes were found between the MIST and INSURE techniques.

Ventilator-associated pneumonia in neonatal patients: an update.

Ventilator-associated pneumonia (VAP) is a serious complication related to mechanical ventilation in the neonatal period. However, lack of a specific definition and difficulties obtaining noncontaminated samples of the lower respiratory airway render microbiological diagnosis and etiological treatment extremely difficult. Thus far, only few studies have approached VAP using accepted Centers for Disease Control and Prevention criteria and reliable sampling techniques. In recent years, however, the blind-protected bronchoalveolar lavage technique with protected specimen brush and the development of validated biomarkers have attempted to overcome the diagnostic difficulties and assess the response to therapy. This updated review on neonatal VAP aims to stimulate neonatologists' interest in this subtle but serious complication of mechanical ventilation.

Ventilator-associated pneumonia in newborn infants diagnosed with an invasive bronchoalveolar lavage technique: a prospective observational study.

OBJECTIVES: To establish the incidence, etiology, risk factors, and outcomes associated with ventilator-associated pneumonia using an invasive sampling technique to avoid contamination. PATIENTS: Eligible patients were intubated neonates treated with mechanical ventilation who followed the criteria of the Centers for Disease Control and Prevention/National Nosocomial Infection Surveillance. Bronchoalveolar lavage samples were collected using a blind-protected catheter to avoid contamination of upper respiratory microorganisms. Isolation of >10(3) colony-forming unit/mL was required for diagnosis. MEASUREMENTS AND MAIN RESULTS: In 198 neonates intubated for >48 hrs, a total of 18 episodes of ventilator-associated pneumonia in 16 infants representing a prevalence of 8.1 were diagnosed. The pooled mean ventilator-associated pneumonia rate was 10.9/1,000 ventilator days. The mean age at diagnosis of ventilator-associated pneumonia was 29 ± 15 days after a mean of 21 ± 16 days of mechanical ventilation. Gram-negative bacteria were the most commonly isolated pathogens and Pseudomonas aeruginosa was the most frequent causative agent. Hospital length of stay was significantly longer for ventilator-associated pneumonia patients; however, no significant differences in mortality were found. Univariate analysis comparing patients with and without ventilator-associated pneumonia showed that days of mechanical ventilation, days of oxygen, number of reintubations, number of transfusions, bloodstream infection, and enteral feeding were all significantly associated with ventilator-associated pneumonia. However, in multivariate analysis the unique independent risk factor was days of mechanical ventilation (odds ratio 1.12, confidence interval 95% 1.07-1.17). CONCLUSIONS: Ventilator-associated pneumonia is a frequent nosocomial infection in newborns. Only duration of mechanical ventilation has been identified as an independent risk factor for ventilator-associated pneumonia. The use of a blind invasive sampling technique seems to diminish sample contamination.

Oxygen saturation after birth in preterm infants treated with continuous positive airway pressure and air: assessment of gender differences and comparison with a published nomogram.

AIMS: The goal of the study was to compare preductal SpO2 in the first 10 min after birth in preterm infants treated with non-invasive continuous positive airway pressure (CPAP) and air with a published nomogram of preductal SpO2 in preterm infants who received no medical intervention, and to examine gender differences. DESIGN: Prospective observational study. PATIENTS AND METHODS: We enrolled infants of ≤32 weeks gestation who were spontaneously breathing with heart rate >100 bpm, and treated with face mask CPAP and air during postnatal stabilisation. SpO2 limits were targeted at ≥75% at 5 min and ≥85% at 10 min and heart rate at >100 bpm. FIO2 was titrated against SpO2. Preductal SpO2, airway pressure and FIO2 were recorded with a data acquisition system from birth until stabilisation. Babies receiving supplemental oxygen (>21%), positive pressure ventilation, were intubated and/or received chest compressions or drugs were excluded. RESULTS: Measurements were obtained in 102 babies with median gestational age of 29 (range: 24-31) weeks. Median SpO2 was significantly higher in the observational group than in the reference range at 3 min (82% (CI 71% to 85%) vs 76% (CI 67% to 83%); p<0.05), at 4 min (87% (CI 81% to 90%) vs 81% (CI 72% to 88%); p<0.05), at 5 min (92% (CI 88% to 95%) vs 86% (CI 80% to 92%); p<0.05), at 6 min (94% (CI 90% to 97%) vs 90% (CI 81% to 95%); p<0.05), at 7 min (95% (CI 92% to 97%) vs 92% (CI 85% to 95%); p<0.05), at 8 min (96% (CI 93% to 98%) vs 92% (CI 87% to 96%); p<0.05) and at 9 min (97% (CI 92% to 99%) vs 93% (CI 87% to 96%); p<0.05). Female babies achieved targeted SpO2 significantly earlier than male babies. CONCLUSIONS: Preterm babies receiving CPAP and air and especially female subjects achieve reference oxygen saturation more rapidly than spontaneously breathing preterm babies without respiratory aid.

Oxygen saturation targets for preterm infants in the delivery room.

Fetal life evolves in a low oxygen milieu as compared to the extra-uterine. In the fetal to neonatal transition rapid changes in the oxygen content of the newly born infant occur within a brief period of time. Delivery room care givers should be aware of the slow transition regarding oxygenation, and supply oxygen as needed trying to avoid damage caused by hyper-and-hypoxia. In this regard, titrating oxygen inspiratory fraction against oxygen saturation as measured by pulse oximetry following recent nomogram ranges is a valid method.

A survey of intravenous sodium bicarbonate in neonatal asphyxia among European neonatologists: gaps between scientific evidence and clinical practice.

BACKGROUND: Birth asphyxia is characterized by intermittent periods of hypoxia/ischemia leading to metabolic acidosis. The use of intravenous sodium bicarbonate (IVSB) is still a matter of controversy in clinical practice. OBJECTIVE: To assess the use of IVSB in birth asphyxia by attending neonatologists in European hospitals. DESIGN/METHODS: Survey using a questionnaire administered to neonatologists in Europe whose electronic addresses were provided by the national councils of neonatology of each participating country. The questionnaire consisted of a brief theoretical introduction followed by demographic questions related to the respondent's professional qualification. This was followed by a clinical case of an asphyxiated term neonate with severe combined metabolic and respiratory acidosis and case-specific questions related to the perceived indication for administration of IVSB and use of additional therapies to address the clinical situation. Descriptive statistics and χ² analysis were performed. RESULTS: The questionnaire was answered by 259 neonatologists from 17 countries. IVSB was believed to be indicated by 109 (42.2%) of the respondents in this clinical scenario. Results differed significantly between countries, with IVSB use varying from as high as 68% in Portugal and <5% in Scandinavian countries. However, there were no differences in the choice of other therapeutic measures. CONCLUSIONS: Although scientific evidence suggests that IVSB is not effective in asphyxiated newborns and current guidelines do not recommend its use, 42.2% of the consulted neonatologists in Europe would use it, with significant differences between but not within countries. There were no differences regarding additional measures to overcome asphyxia. Strategies to implement use of internationally accepted guidelines are needed.

Antenatal steroids and antioxidant enzyme activity in preterm infants: influence of gender and timing.

Antenatal steroids have improved the survival of preterm infants; however, the mechanism of action is not fully understood. We aimed to establish an association between antenatal steroids and antioxidant activity and postnatal oxidative stress. In a prospective cohort study, extremely preterm neonates receiving antenatal steroids (CORT) or not (NOCORT) were enrolled. An association between antenatal steroids and activities of antioxidant enzymes and glutathione cycle enzymes in cord blood was found. In addition, reduced oxidative stress (GSH/GSSG ratio, CORT vs. NOCORT, 35.68 + or - 12.20 vs. 28.38 + or - 9.92; p < 0.01) and, decreased oxidation of proteins (ortho-tyrosine/phenylalanine ratio, CORT vs. NOCORT, 8.66 + or - 2.45 vs. 12.55 + or - 4.41; p < 0.01) and DNA (8oxodG/2dG ratio, CORT vs. NOCORT, 6.73 + or - 2.18 vs. 9.53 + or - 3.83; p < 0.01) also was found. Antenatal steroids were associated with reduced oxygen supplementation, mechanical ventilation, and conditions such as bronchopulmonary dysplasia, intra-periventricular hemorrhage, or retinopathy of prematurity. The maximal effectiveness was when steroids were administered 2-4 days before delivery. Female preterm infants had less oxidative stress and increased antioxidant activity and better clinical outcomes than did male infants, independent of receiving or not antenatal steroids. Antenatal steroids are accompanied by a reduction in postnatal oxidative-stress-derived conditions and increased antioxidant enzyme activity. Both these effects seem to be influenced by specific timing and female gender.

Human milk enhances antioxidant defenses against hydroxyl radical aggression in preterm infants.

BACKGROUND: Preterm infants endowed with an immature antioxidant defense system are prone to oxidative stress. Hydroxyl radicals are very aggressive reactive oxygen species that lack specific antioxidants. These radicals cannot be measured directly, but oxidation byproducts of DNA or phenylalanine in urine are reliable markers of their activity. Human milk has a higher antioxidant capacity than formula. OBJECTIVE: We hypothesized that oxidative stress associated with prematurity could be diminished by feeding human milk. DESIGN: We recruited a cohort of stable preterm infants who lacked perinatal conditions associated with oxidative stress; were not receiving prooxidant or antioxidant drugs, vitamins, or minerals before recruitment; and were fed exclusively human milk (HM group) or preterm formula (PTF group). Collected urine was analyzed for oxidative bases of DNA [8-hydroxy-2'-deoxyguanosine (8-oxodG)/2'-deoxyguanosine (2dG) ratio] and oxidative derivatives of phenylalanine [ortho-tyrosine (o-Tyr)/Phe ratio] by HPLC coupled to tandem mass spectrometry. Healthy term newborn infants served as control subjects. RESULTS: Both preterm groups eliminated greater amounts of metabolites than did the control group. However, the PTF group eliminated significantly (P < 0.02) higher amounts of 8-oxodG (8-oxodG/2dG ratio: 10.46 +/- 3.26) than did the HM group (8-oxodG/2dG ratio: 9.05 +/- 2.19) and significantly (P < 0.01) higher amounts of o-Tyr (o-Tyr/Phe ratio: 14.90 +/- 3.75) than did the HM group (o-Tyr/Phe ratio: 12.53 +/- 3.49). When data were lumped together independently of the type of feeding received, a significant correlation was established between the 8-oxodG/2dG and o-Tyr/Phe ratios in urine, dependent on gestational age and birth weight. CONCLUSION: Prematurity is associated with protracted oxidative stress, and human milk is partially protective.