RESUMEN
High-frequency ventilation (HFV) has been used as a respiratory support mode for neonates for over 30 years. HFV is characterized by delivering tidal volumes close to or less than the anatomical dead space. Both animal and clinical studies have shown that HFV can effectively restore lung function, and potentially limit ventilator-induced lung injury, which is considered an important risk factor for developing bronchopulmonary dysplasia (BPD). Knowledge of how HFV works, how it influences cardiorespiratory physiology, and how to apply it in daily clinical practice has proven to be essential for its optimal and safe use. We will present important aspects of gas exchange, lung-protective concepts, clinical use, and possible adverse effects of HFV. We also discuss the study results on the use of HFV in respiratory distress syndrome in preterm infants and respiratory failure in term neonates. IMPACT: Knowledge of how HFV works, how it influences cardiorespiratory physiology, and how to apply it in daily clinical practice has proven to be essential for its optimal and safe use. Therefore, we present important aspects of gas exchange, lung-protective concepts, clinical use, and possible adverse effects of HFV. The use of HFV in daily clinical practice in lung recruitment, determination of the optimal continuous distending pressure and frequency, and typical side effects of HFV are discussed. We also present study results on the use of HFV in respiratory distress syndrome in preterm infants and respiratory failure in term neonates.
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Ventilación de Alta Frecuencia , Síndrome de Dificultad Respiratoria del Recién Nacido , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Recién Nacido , Humanos , Recien Nacido Prematuro , Ventilación de Alta Frecuencia/métodos , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Respiración Artificial/efectos adversos , Respiración Artificial/métodosRESUMEN
AIM: To determine the relationship between medical staff's response time (RT) to oxygen saturation (SpO2 ) below 80% and the associated time from tactile intervention until SpO2 normalisation (CT). METHODS: Time-lapse video and continuous SpO2 were recorded for six consecutive 24 h periods. Regression analyses of RT and SpO2 in association with postmenstrual age (PMA), weight, infant sex and frequency of intermittent hypoxemia (IH). RESULTS: Five hundred and twelve hypoxemia episodes received tactile intervention in 20 extremely preterm infants (gestational age ≤28 weeks, birthweight <1500 g). Median RT was 20.5 s (IQR 16.63-25.50). RT increased with increased IH frequency (p = 0.023) independently of PMA and weight. SpO2 decreased by 3.7% with every 10 s RT (p = 0.039). Time until SpO2 normalisation was strongly associated with RT (ß = 0.58, p = 0.042). The association was amplified by lower PMA (p = 0.043). Female preterm infants experienced longer RT than males (p = 0.027). Because the total length of an IH is the sum of RT and CT, preterm infants with low PMA can reach a critical hypoxemia duration of >60 s, even with short RT. CONCLUSION: The RT is a critical factor that affects the overall time of IH treatments and the depth of desaturation. The consequences of a prolonged RT are worse for more immature preterm infants.
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Recien Nacido Extremadamente Prematuro , Oxígeno , Lactante , Masculino , Recién Nacido , Humanos , Femenino , Tiempo de Reacción , Oximetría , Hipoxia/complicaciones , Edad Gestacional , Recién Nacido de muy Bajo PesoRESUMEN
Developmentally regulated features of innate immunity are thought to place preterm and term infants at risk of infection and inflammation-related morbidity. Underlying mechanisms are incompletely understood. Differences in monocyte function including toll-like receptor (TLR) expression and signaling have been discussed. Some studies point to generally impaired TLR signaling, others to differences in individual pathways. In the present study, we assessed mRNA and protein expression of pro- and anti-inflammatory cytokines in preterm and term cord blood (CB) monocytes compared with adult controls stimulated ex vivo with Pam3CSK4, zymosan, polyinosinic:polycytidylic acid, lipopolysaccharide, flagellin, and CpG oligonucleotide, which activate the TLR1/2, TLR2/6, TLR3, TLR4, TLR5, and TLR9 pathways, respectively. In parallel, frequencies of monocyte subsets, stimulus-driven TLR expression, and phosphorylation of TLR-associated signaling molecules were analyzed. Independent of stimulus, pro-inflammatory responses of term CB monocytes equaled adult controls. The same held true for preterm CB monocytes-except for lower IL-1ß levels. In contrast, CB monocytes released lower amounts of anti-inflammatory IL-10 and IL-1ra, resulting in higher ratios of pro-inflammatory to anti-inflammatory cytokines. Phosphorylation of p65, p38, and ERK1/2 correlated with adult controls. However, stimulated CB samples stood out with higher frequencies of intermediate monocytes (CD14+CD16+). Both pro-inflammatory net effect and expansion of the intermediate subset were most pronounced upon stimulation with Pam3CSK4 (TLR1/2), zymosan (TR2/6), and lipopolysaccharide (TLR4). Our data demonstrate robust pro-inflammatory and yet attenuated anti-inflammatory responses in preterm and term CB monocytes, along with imbalanced cytokine ratios. Intermediate monocytes, a subset ascribed pro-inflammatory features, might participate in this inflammatory state.
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Monocitos , Receptor Toll-Like 4 , Adulto , Recién Nacido , Humanos , Monocitos/metabolismo , Receptor Toll-Like 4/metabolismo , Lipopolisacáridos , Receptor Toll-Like 1/metabolismo , Sangre Fetal/metabolismo , Zimosan , Receptores Toll-Like/metabolismo , Citocinas/metabolismo , Receptores de Lipopolisacáridos/metabolismoRESUMEN
BACKGROUND AND OBJECTIVE: Umbilical venous catheters (UVC) and peripherally inserted central catheters (PICC) are commonly used in preterm infants but have been associated with a number of serious complications. We performed a survey in Austria and Germany to assess the use of UVCs and PICCs in preterm infants with a birth weight <â¯1250â¯g and associated rates of catheter-related adverse events. METHODS: Electronic survey of participating centers of the NeoVitaA trial. Main outcome parameter was the reported rates of UVC- and PICC-associated complications (infection, thrombosis, emboli, organ injury, arrhythmia, dislocation, miscellaneous). RESULTS: In total, 20 neonatal intensive care units (NICU) providing maximal intensive care in Austria and Germany (level I) were contacted, with a senior neonatologist response rate of 12/20 (60%). The reported rates for UVC with a dwell time of 1-10 days were bacterial infection: 4.2⯱ 3.4% (range 0-10%); thrombosis: 7.3⯱ 7.1% (0-20%); emboli: 0.9⯱ 2.0% (0-5%); organ injury: 1.1⯱ 1.9% (0-5%); cardiac arrhythmia: 2.2⯱ 2.5% (0-5%); and dislocation: 5.4⯱ 8.7% (0-30%); and for PICCs with a dwell time of 1-14 days bacterial infection: 15.0⯱ 3.4% (range 2.5-30%); thrombosis; 4.3⯱ 3.5% (0-10%); emboli: 0.8⯱ 1.6% (0-5%); organ injury: 1.5⯱ 2.3% (0-5%); cardiac arrhythmia: 1.5⯱ 2.3% (0-5%), and dislocation: 8.5⯱ 4.6% (0-30%). CONCLUSION: The catheter-related complication rates reported in this survey differed between UVCs and PICCs and were higher than those reported in the literature. To generate more reliable data on this clinically important issue, we plan to perform a large prospective multicenter randomized controlled trial investigating the non-inferiority of a prolonged UVC dwell time (up to 10 days) against the early change (up to 5 days) to a PICC.
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Infecciones Bacterianas , Cateterismo Venoso Central , Trombosis , Lactante , Recién Nacido , Humanos , Recien Nacido Prematuro , Peso al Nacer , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Estudios Prospectivos , Austria , Estudios Retrospectivos , Catéteres , Infecciones Bacterianas/etiología , Trombosis/epidemiología , Trombosis/etiología , Recién Nacido de muy Bajo PesoRESUMEN
BACKGROUND: Medical management of neonates is often established upon safe and reliable vascular access, frequently utilized to provide physiological monitoring, parenteral and supportive treatments, and diagnostic and/or procedural purposes. For this, peripherally inserted central catheters (PICCs) are often used to provide safe vascular access and infusion-related therapies in the neonatal intensive care (NICU) setting. PURPOSE: Difficult PICC guidewire removal is understood to cause catheter damage, causing luminal rupture or possible breakage of the catheter or guidewire itself. The aim of this study was to assess and compare the incidence of therapy failures with use of a preflush fluid using normal saline (NSS) versus a diluted lipid solution (DLS) prior to device insertion, to assist with guidewire removal and prevent unnecessary catheter damage. METHOD AND SETTING: A retrospective, observational study was performed in the Neonatal Intensive Care Unit (NICU) of the Women's Wellness and Research Centre, Hamad Medical Corporation, Qatar. This single site study included 507 neonates who required intravenous therapy administered via a PICC during the study period. RESULTS: Results demonstrated the use of a diluted lipid solution preflush (DLS) resulted in significantly lesser failures, when compared with the control group (NSS). This highlights a clinical significance after adjusting for day of insertion, gestational age, birth weight and catheter type. CONCLUSION: DLS preflush demonstrated a benefit over the use of a NSS preflush to enhance PICC guidewire removal in neonatal patients in the NICU. The risk for development of maintenance-related complications leading to premature device removal decreased significantly if the DLS preflush was used. During the study period, no complications related to the use of a lipid preflush solution were identified. IMPLICATIONS FOR PRACTICE AND RESEARCH: This may be the first study published investigating and supporting guidewire removal enhancement by using a diluted lipid/saline preflush solution. When the requirement for vascular access is most pertinent in the neonate, using a diluted lipid preflush may provide an effective method to assist in guidewire removal to prevent malposition and vascular device complications in the neonatal population.
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Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Cateterismo Periférico , Infecciones Relacionadas con Catéteres/epidemiología , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Catéteres , Emulsiones , Femenino , Humanos , Recién Nacido , Lípidos , Lubricantes , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Albumin is a major serum protein and is frequently used as a cell culture supplement. It is crucially involved in the regulation of osmotic pressure and distribution of fluid between different compartments. Alveolar epithelial Na+ transport drives alveolar fluid clearance (AFC), enabling air breathing. Whether or not albumin affects AFC and Na+ transport is yet unknown. We therefore determined the acute and chronic effects of albumin on Na+ transport in fetal distal lung epithelial (FDLE) cells and the involved kinase pathways. Chronic BSA treatment strongly increased epithelial Na+ transport and barrier integrity in Ussing chambers. BSA did not elevate mRNA expression of Na+ transporters in FDLE cells after 24 h. Moreover, acute BSA treatment for 45 min mimicked the chronic effects. The elevated Na+ transport was caused by an increased maximal ENaC activity, while Na,K-ATPase activity remained unchanged. Acute and chronic BSA treatment lowered membrane permeability, confirming the increased barrier integrity observed in Ussing chambers. Western blots demonstrated an increased phosphorylation of AKT and SGK1, and PI3K inhibition abolished the stimulating effect of BSA. BSA therefore enhanced epithelial Na+ transport and barrier integrity by activating the PI3K/AKT/SGK1 pathway.
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Canales Epiteliales de Sodio , Fosfatidilinositol 3-Quinasas , Células Epiteliales/metabolismo , Canales Epiteliales de Sodio/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sodio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
AIMS: The study investigated a putative association between early-onset-sepsis (EOS) and poor neurodevelopmental outcomes at 2 years corrected age in very low birth weight infants. METHODS: This was a single-center cohort study on infants weighing less than 1500 g with a gestational age below 35 weeks at birth born between 2008 and 2011. Neurodevelopmental outcomes were assessed at follow-up with the Bayley Scales of Infant Development-II. EOS was defined as either culture-proven EOS or clinical EOS using blood culture, CrP levels, and clinical symptoms and treatment. Neurodevelopmental impairment (NDI) was defined as one or more of the following: Mental Developmental Index (MDI) and/or Psychomotor Developmental Index (PDI) scores lower than 70; presence of cerebral palsy. RESULTS: Of 405 eligible newborns in the study period 166 were included. Two had culture-proven and 29 clinical EOS. Median MDI scores in patients with EOS were 96 (IQR: 86-106) and in the control group 94 (84-106, p = 0.77). PDI scores in patients with EOS were 96 (86-106) and in the control group 99,5 (92-103, p = 0.03). Of infected patients 7/31 (24%) showed NDI as defined, whereas only 11/135 (8%) showed NDI in the control group (OR 3.3, p = 0.03). Multiple regression analyses identified chorioamnionitis and poor CRIB-Scores as individual risk factors for MDI or PDI values < 70. CONCLUSION: In our study, EOS among VLBW-infants significantly impaired the neurodevelopment at 2 years corrected age. As shown in previous reports infection continues to be a problem and strategies for a reduction need further improvement.
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Corioamnionitis , Sepsis , Niño , Corioamnionitis/diagnóstico , Corioamnionitis/epidemiología , Estudios de Cohortes , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/etiología , Femenino , Humanos , Lactante , Recién Nacido , Recién Nacido de muy Bajo Peso , Embarazo , Sepsis/diagnósticoRESUMEN
Importance: Red blood cell transfusions are commonly administered to infants weighing less than 1000 g at birth. Evidence-based transfusion thresholds have not been established. Previous studies have suggested higher rates of cognitive impairment with restrictive transfusion thresholds. Objective: To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability. Design, Setting, and Participants: Randomized clinical trial conducted in 36 level III/IV neonatal intensive care units in Europe among 1013 infants with birth weights of 400 g to 999 g at less than 72 hours after birth; enrollment took place between July 14, 2011, and November 14, 2014, and follow-up was completed by January 15, 2018. Interventions: Infants were randomly assigned to liberal (n = 492) or restrictive (n = 521) red blood cell transfusion thresholds based on infants' postnatal age and current health state. Main Outcome and Measures: The primary outcome, measured at 24 months of corrected age, was death or disability, defined as any of cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Secondary outcome measures included individual components of the primary outcome, complications of prematurity, and growth. Results: Among 1013 patients randomized (median gestational age at birth, 26.3 [interquartile range {IQR}, 24.9-27.6] weeks; 509 [50.2%] females), 928 (91.6%) completed the trial. Among infants in the liberal vs restrictive transfusion thresholds groups, respectively, incidence of any transfusion was 400/492 (81.3%) vs 315/521 (60.5%); median volume transfused was 40 mL (IQR, 16-73 mL) vs 19 mL (IQR, 0-46 mL); and weekly mean hematocrit was 3 percentage points higher with liberal thresholds. Among infants in the liberal vs restrictive thresholds groups, the primary outcome occurred in 200/450 (44.4%) vs 205/478 (42.9%), respectively, for a difference of 1.6% (95% CI, -4.8% to 7.9%; P = .72). Death by 24 months occurred in 38/460 (8.3%) vs 44/491 (9.0%), for a difference of -0.7% (95% CI, -4.3% to 2.9%; P = .70), cognitive deficit was observed in 154/410 (37.6%) vs 148/430 (34.4%), for a difference of 3.2% (95% CI, -3.3% to 9.6%; P = .47), and cerebral palsy occurred in 18/419 (4.3%) vs 25/443 (5.6%), for a difference of -1.3% (95% CI, -4.2% to 1.5%; P = .37), in the liberal vs the restrictive thresholds groups, respectively. In the liberal vs restrictive thresholds groups, necrotizing enterocolitis requiring surgical intervention occurred in 20/492 (4.1%) vs 28/518 (5.4%); bronchopulmonary dysplasia occurred in 130/458 (28.4%) vs 126/485 (26.0%); and treatment for retinopathy of prematurity was required in 41/472 (8.7%) vs 38/492 (7.7%). Growth at follow-up was also not significantly different between groups. Conclusions and Relevance: Among infants with birth weights of less than 1000 g, a strategy of liberal blood transfusions compared with restrictive transfusions did not reduce the likelihood of death or disability at 24 months of corrected age. Trial Registration: ClinicalTrials.gov Identifier: NCT01393496.
Asunto(s)
Trastornos del Conocimiento/etiología , Transfusión de Eritrocitos/efectos adversos , Recien Nacido con Peso al Nacer Extremadamente Bajo , Displasia Broncopulmonar/etiología , Parálisis Cerebral/etiología , Enterocolitis Necrotizante/etiología , Enterocolitis Necrotizante/cirugía , Transfusión de Eritrocitos/mortalidad , Transfusión de Eritrocitos/estadística & datos numéricos , Femenino , Trastornos de la Audición/etiología , Hematócrito/estadística & datos numéricos , Humanos , Lactante , Recien Nacido con Peso al Nacer Extremadamente Bajo/crecimiento & desarrollo , Recién Nacido , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Masculino , Evaluación de Resultado en la Atención de Salud , Retinopatía de la Prematuridad/terapia , Sensibilidad y Especificidad , Trastornos de la Visión/etiologíaRESUMEN
BACKGROUND: In 2016, an increased rate of methicillin-susceptible Staphylococcus aureus colonization was detected on a neonatal intensive care unit at the Leipzig University Hospital. Typing results showed a predominant spa-type t091. Considering nosocomial clustering, several infection prevention measures (e. g. intensified standard precautions, single-occupancy room, cohorted patients, continuing education of staff) were introduced, including staff screening followed by decolonization of colonized health care workers. METHODS: Staff members showing positive on screening carried out a 5-day decolonization program at home. Decolonization products containing octenidine as active ingredient were used first. At the earliest, 48 h after completing the procedure, the success of the intervention was tested (3 buccal and nasal swabs were taken on consecutive days). If 2 attempts at decolonization were not successful, staff members were provided with a mupirocin-containing nasal ointment instead of octenidine. RESULTS: Of 128 employees examined, 43 (33.6%) were identified as carriers of S. aureus. In 9 cases (20.9%; 9/43) the S. aureus matched with type t091. 2 carriers (4.7%; 2/43) of MRSA were detected as well. The first decolonization attempt against t091 and MRSA failed altogether. After a second decolonization, 3 cases became negative. Finally, 8 remaining staff members were decolonized successfully with mupirocin containing nasal ointment. CONCLUSIONS: Various reasons might explain the difficulties of decolonization such as the challenge of managing decolonization at home, inhibitory factors as well as inconsistent performance of decolonization measures. Additionally, differences between the preparations for the nasal decontamination may be considered.
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Infección Hospitalaria , Unidades de Cuidado Intensivo Neonatal , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Antibacterianos , Portador Sano , Alemania , Personal de Salud , Humanos , Recién Nacido , Meticilina , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureusRESUMEN
Alveolar fluid clearance mediates perinatal lung transition to air breathing in newborn infants, which is accomplished by epithelial Na+ channels (ENaC) and Na-K-ATPase. Male sex represents a major risk factor for developing respiratory distress, especially in preterm infants. We previously showed that male sex is associated with reduced epithelial Na+ transport, possibly contributing to the sexual dimorphism in newborn respiratory distress. This study aimed to determine sex-specific effects of sex steroids on epithelial Na+ transport. The effects of testosterone, 5α-dihydrotestosterone (DHT), estradiol, and progesterone on Na+ transport and Na+ channel expression were determined in fetal distal lung epithelial (FDLE) cells of male and female rat fetuses by Ussing chamber and mRNA expression analyses. DHT showed a minor effect only in male FDLE cells by decreasing epithelial Na+ transport. However, flutamide, an androgen receptor antagonist, did not abolish the gender imbalance, and testosterone lacked any effect on Na+ transport in male and female FDLE cells. In contrast, estradiol and progesterone increased Na+ transport and Na+ channel expression especially in females, and prevented the inhibiting effect of DHT in males. Estrogen receptor inhibition decreased Na+ channel expression and eliminated the sex differences. In conclusion, female sex steroids stimulate Na+ transport especially in females and prevent the inhibitory effect of DHT in males. The ineffectiveness of testosterone suggests that Na+ transport is largely unaffected by androgens. Thus, the higher responsiveness of female cells to female sex steroids explains the higher Na+ transport activity, possibly leading to a functional advantage in females.
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Células Epiteliales Alveolares/metabolismo , Hormonas Esteroides Gonadales/farmacología , Caracteres Sexuales , Sodio/metabolismo , Andrógenos/farmacología , Animales , Transporte Biológico/efectos de los fármacos , Canales Epiteliales de Sodio/metabolismo , Receptor beta de Estrógeno/genética , Receptor beta de Estrógeno/metabolismo , Femenino , Feto/citología , Flutamida/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Pulmón/citología , Pulmón/embriología , Masculino , Subunidades de Proteína/metabolismo , Pirazoles/farmacología , Pirimidinas/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-DawleyRESUMEN
Impairment of mucociliary clearance with reduced airway fluid secretion leads to chronically inflamed airways. Cystic fibrosis transmembrane conductance regulator (CFTR) is crucially involved in airway fluid secretion and dexamethasone (dexa) has previously been shown to elevate CFTR activity in airway epithelial cells. However, the pathway by which dexa increases CFTR activity is largely unknown. We aimed to determine whether the increase of CFTR activity by dexa is achieved by non-genomic signaling and hypothesized that the phosphoinositide 3-kinase (PI3K) pathway is involved in CFTR stimulation. Primary rat airway epithelial cells and human bronchial submucosal gland-derived Calu-3 cells were analyzed in Ussing chambers and kinase activation was determined by Western blots. Results demonstrated a critical involvement of PI3K and protein kinase B (AKT) signaling in the dexa-induced increase of CFTR activity, while serum and glucocorticoid dependent kinase 1 (SGK1) activity was not essential. We further demonstrated a reduced neural precursor cell expressed, developmentally downregulated 4-like (NEDD4L) ubiquitin E3 ligase activity induced by dexa, possibly responsible for the elevated CFTR activity. Finally, increases of CFTR activity by dexa were demonstrated within 30 min accompanied by rapid activation of AKT. In conclusion, dexa induces a rapid stimulation of CFTR activity which depends on PI3K/AKT signaling in airway epithelial cells. Glucocorticoids might thus represent, in addition to their immunomodulatory actions, a therapeutic strategy to rapidly increase airway fluid secretion.
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Células Epiteliales Alveolares/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Dexametasona/administración & dosificación , Transducción de Señal/efectos de los fármacos , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/patología , Animales , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Humanos , Proteínas Inmediatas-Precoces/genética , Proteínas Inmediatas-Precoces/metabolismo , Ubiquitina-Proteína Ligasas Nedd4/genética , Ubiquitina-Proteína Ligasas Nedd4/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Cultivo Primario de Células , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , RatasRESUMEN
PURPOSE: Glucocorticoids and progesterone exert stimulatory effects on epithelial Na(+) transport, including increased mRNA expression of the participating ion transporters (epithelial Na(+) channels [ENaC] and Na,K-ATPases) and their electrophysiological activity. Fetuses threatened by preterm labor may receive high doses of glucocorticoids to stimulate lung maturation and are naturally exposed to high levels of female sex steroids. However, it is still unknown how the combination of both hormones influences the epithelial Na(+) transport, which is crucial for alveolar fluid clearance. METHODS: Fetal distal lung epithelial cells were incubated in media supplemented with dexamethasone and progesterone. Real-time qPCR and Ussing chamber analysis were used to determine the effects on ENaC mRNA expression and channel activity. In addition, the specific progesterone receptor antagonist (PF-02367982) and the glucocorticoid receptor antagonist mifepristone were used to identify the involved hormone receptors. RESULTS: Both dexamethasone and progesterone increased ENaC subunit expression and channel activity. However, the combination of dexamethasone and progesterone reduced the α- and γ-ENaC subunit expression compared to the effect of dexamethasone alone. Furthermore, higher dexamethasone concentrations in combination with progesterone also significantly reduced Na(+) transport in Ussing chamber measurements. Hormone receptor antagonists showed that inhibition of the progesterone receptor increased the mRNA expression of α- and γ-ENaC, whereas mifepristone decreased mRNA expression of all ENaC subunits. CONCLUSION: Glucocorticoids and progesterone individually increase ENaC mRNA expression; however, the combination of both hormones decreases the stimulatory effects of dexamethasone on Na(+) transport and ENaC mRNA expression.
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Dexametasona/farmacología , Canales Epiteliales de Sodio/efectos de los fármacos , Preñez , Progesterona/farmacología , Análisis de Varianza , Animales , Transporte Biológico/efectos de los fármacos , Transporte Biológico/fisiología , Células Cultivadas , Medios de Cultivo Condicionados , Interacciones Farmacológicas , Electrofisiología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/fisiología , Canales Epiteliales de Sodio/fisiología , Femenino , Feto/citología , Reacción en Cadena de la Polimerasa/métodos , Embarazo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Sensibilidad y EspecificidadRESUMEN
Objective: To evaluate the association between different types of human milk feeds and bronchopulmonary dysplasia (BPD) in preterm infants. Methods: Data on dispensed mother's own milk (MOM) and donor human milk (DHM) from Leipzig Milk Bank for hospitalized infants with a gestational age (GA) ≤32 weeks observed from birth to 36 weeks' postmenstrual age or prior discharge were used. BPD was assessed based on documented International Statistical Classification of Diseases and Related Health Problems (ICD) diagnosis and on electronic hospital records (EHR) of data on ventilation and oxygen supplementation. Associations of dispensed milk feed variations with BPD were investigated using logistic regressions in crude and adjusted models. Results: 866 infants were included with a BPD prevalence of 15.4% (EHR) and 23.2% (ICD). The mean GA was 29.1 weeks. The majority (84.4%, n = 746) of infants were nurtured with a mix of MOM, DHM supplemented by formula or parenteral (other) nutrition during hospitalization. For which, MOM comprised the highest median [Q1-Q3] percentage proportion (53[31-81] %) of this mix. Exclusive fresh milk and exclusive MOM feeds were dispensed on a mean of 40 and 34% patient-days, respectively. Statistically significant associations with lower BPD incidence were only observed for 70-80% MOM vs. DHM, and 60% fresh vs. frozen milk, in crude and adjusted models. Conclusion: Our findings suggest a protective association of MOM and fresh milk with lower odds of BPD, which may be dependent on the proportion of MOM or fresh milk administered. These results highlight the importance of MOM as an ideal source of nutrition during early infancy.
RESUMEN
BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Very different models using clinical parameters at an early postnatal age to predict BPD have been developed with little extensive quantitative validation. The objective of this study is to review and validate clinical prediction models for BPD. METHODS: We searched the main electronic databases and abstracts from annual meetings. The STROBE instrument was used to assess the methodological quality. External validation of the retrieved models was performed using an individual patient dataset of 3229 patients at risk for BPD. Receiver operating characteristic curves were used to assess discrimination for each model by calculating the area under the curve (AUC). Calibration was assessed for the best discriminating models by visually comparing predicted and observed BPD probabilities. RESULTS: We identified 26 clinical prediction models for BPD. Although the STROBE instrument judged the quality from moderate to excellent, only four models utilised external validation and none presented calibration of the predictive value. For 19 prediction models with variables matched to our dataset, the AUCs ranged from 0.50 to 0.76 for the outcome BPD. Only two of the five best discriminating models showed good calibration. CONCLUSIONS: External validation demonstrates that, except for two promising models, most existing clinical prediction models are poor to moderate predictors for BPD. To improve the predictive accuracy and identify preterm infants for future intervention studies aiming to reduce the risk of BPD, additional variables are required. Subsequently, that model should be externally validated using a proper impact analysis before its clinical implementation.
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Displasia Broncopulmonar/epidemiología , Modelos Teóricos , Área Bajo la Curva , Sesgo , Peso al Nacer , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/prevención & control , Calibración , Diuresis , Diagnóstico Precoz , Femenino , Edad Gestacional , Humanos , Hipoxia/epidemiología , Hipoxia/terapia , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Masculino , Estudios Observacionales como Asunto , Valor Predictivo de las Pruebas , Curva ROC , Pérdida de PesoRESUMEN
OBJECTIVES: An increased frequency of intermittent hypoxemia (IH) is associated with a higher risk for poor developmental outcomes, disability, or death in extremely preterm infants. The objective of the prFesent study is to quantify the effect of hands-on medical and parental interventions on the incidence of IH in extremely preterm infants. METHODS: An observational design with intraindividual comparisons was used. Blood oxygen saturation levels (SpO2) and time-lapse video were recorded. Frequency, duration, and time to occurrence of IH (SpO2 <80% for ≥10 s) were compared between nursing and medical care (NMC), health care by parents, skin-to-skin contact (SSC), touch in incubator, physiotherapy, and rest. Each infant was observed for six consecutive 24-h periods. Inclusion criteria were as follows: gestational age ≤28 weeks, birth weight <1500 g, postnatal age 0-6 weeks, gavage feeding, no severe illnesses or invasive procedures, no mechanical ventilation. RESULTS: The highest proportion of time with IH occurred during NMC (2.49%) and incubator touch (1.32%), the lowest during SSC (0.74%) and health care by parents (0.67%). IH frequency per hour was highest during NMC (2.95, IQR 1.19-4.01) and lowest during SSC (0.88, IQR 0.37-2.32, p < 0.001). While an increase in IH during NMC was expected, the high incidence during incubator touch was surprising. Parental touch in the incubator is intended to be soothing, not stressful. CONCLUSIONS: Future studies need to clarify how preterm infants process touch, which attributes of touch are fundamental trigger mechanisms of IH, and which handling strategies are most effective in lowering the incidence of IH during hands-on medical care.
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Recien Nacido Extremadamente Prematuro , Tacto , Lactante , Humanos , Recién Nacido , Incidencia , Hipoxia/epidemiología , Hipoxia/etiología , Padres , Recién Nacido de muy Bajo PesoRESUMEN
Background: Human milk banking has become an important aspect of Nutritional medicine. It is not just about the provision of mother's own milk (MOM) or donor human milk (DHM) in the hospital, but also a strategy to encourage breastfeeding in the clinical setting and beyond. Objective: To describe the feeding patterns of hospitalised infants including human milk dispensed by the Leipzig Donor Human Milk Bank (LMB). Design: A descriptive analysis of daily data on milk feeds dispensed by LMB for hospitalised infants distinguishing between MOM or DHM, either fresh or frozen, and raw/pasteurised milk from 2012-2019. Results: We included 2,562 infants with median hospitalisation of 23 days, for whom human milk was dispensed on median 76% of those days and other nutrition on the remaining days. Raw MOM and raw DHM comprised 52% and 8% of the dispensed milk, respectively. Dispensing exclusive DHM instead of MOM for at least one full day was required for 55% of the infants, mostly at the beginning but also later during hospitalisation. Exclusive raw DHM was dispensed on at least 1 day for 37% of the infants, in different birthweight strata <1,000 g: 10%, 1,000-1500 g: 11%, 1,500-2500 g: 13% and > 2,500 g: 3%. At discharge, MOM was dispensed for more than 60% of the infants. Conclusion: During an infant's hospital stay, LMB dispenses various human milk feeds with interspersed DHM resulting in complex intra-individual and time-variant feeding patterns. LMB dispenses raw MOM and especially raw DHM with the intention to retain the properties of human milk unlike a diet containing pasteurised DHM and/or formula. Although raw DHM comprises a small percentage of all dispensed milk, raw DHM is dispensed for a substantial portion of infants. Our results document that dispensing raw DHM, is possible in routine settings.
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Background: Randomized controlled trials have indicated reduced mortality rates in very preterm infants assigned to high compared to low oxygen saturation (SpO2) target levels, accompanied by higher rates of retinopathy of prematurity and bronchopulmonary dysplasia. However, the benefit-to-harm ratio may depend on the local background mortality risk. We therefore aimed to quantify the risk-benefit ratios of different SpO2 target ranges in 10 tertiary newborn intensive care units (NICUs) in East Germany. Methods: In a retrospective multicenter study, 1,399 infants born between 2008 and 2012 at a gestational age between 24 0/7 and 27 6/7 weeks and with a birthweight below 1,250â g were grouped according to the hospital's target SpO2 range [high oxygen saturation group (HOSG) above 90%], low oxygen saturation group (LOSG) below 90%] and the compliance of units with their target SpO2 range. The association between neonatal morbidities, neurodevelopmental outcomes, selected treatment strategies, and target SpO2 ranges was calculated using chi-squared and Mann Whitney U tests. Results: Nine of the ten participating NICUs met their SpO2 target ranges. Five units were considered as HOSG, and five units were considered as LOSG. Necrotizing enterocolitis and intraventricular hemorrhage grade ≥ 2 occurred significantly more frequently in the HOSG than in the LOSG (8.4% vs. 5.1%, p = 0.02; and 26.6% vs. 17.7%, p < 0.001). No significant differences in the mortality rate and the rate of retinopathy of prematurity were found. Conclusion: In our patient population, a lower SpO2 target range was not associated with increased safety risks in extremely preterm infants. We cannot be sure that our outcome differences are associated with differences in oxygen saturations due to the retrospective study design and the differences in site practices.
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Within this review, sex-specific differences in alveolar epithelial functions are discussed with special focus on preterm infants and the respiratory disorders associated with premature birth. First, a short overview about fetal lung development, the challenges the lung faces during perinatal lung transition to air breathing and respiratory distress in preterm infants is given. Next, clinical observations concerning sex-specific differences in pulmonary morbidity of human preterm infants are noted. The second part discusses potential sex-specific causes of pulmonary complications, including pulmonary steroid receptors and local lung steroid metabolism. With regard to pulmonary steroid metabolism, it is important to highlight which steroidogenic enzymes are expressed at which stage during fetal lung development. Thereafter, we review the knowledge concerning sex-specific aspects of lung growth and maturation. Special focus is given to alveolar epithelial Na+ transport as a driver of perinatal lung transition and the sex differences that were noted in this process.
Asunto(s)
Síndrome de Dificultad Respiratoria del Recién Nacido , Femenino , Feto/metabolismo , Humanos , Recién Nacido , Recien Nacido Prematuro , Pulmón/metabolismo , Masculino , Embarazo , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Síndrome de Dificultad Respiratoria del Recién Nacido/metabolismo , Caracteres SexualesRESUMEN
Background: Neonatal sepsis is one of the most important causes of elevated morbidity and mortality rates in neonatal intensive care units worldwide. While the clinical manifestations of neonatal sepsis tend to be nonspecific, its rapid development and life-threatening potential call for reliable markers for early detection. Methods: We conducted a retrospective single-center study including all neonates suspected of having developed neonatal sepsis from 2013 to 2016. Perinatal and clinical characteristics as well as microbiological and laboratory findings were evaluated. Neonatal sepsis was defined as either culture-proven sepsis (positive blood culture) or clinical sepsis (at least one symptom and elevated C-reactive protein (CRP) concentrations within 72 h with negative blood culture). We further differentiated between early-onset (EOS) and late-onset (LOS) sepsis. Results: Microbiological colonization screening by throat and rectal swabs frequently did not detect the organism that subsequently caused the sepsis. Depending on the age of the newborn with sepsis (EOS or LOS), associations between different anamnestic and clinical factors (prenatal or postnatal ones) were found. In particular, the central−peripheral temperature difference showed a strong association with LOS. Laboratory results useful for the early detection of neonatal sepsis included interleukin-6 (IL-6) and CRP concentrations. Conclusions: Elevated IL-6 >100 ng/L was a strong marker for neonatal sepsis. When choosing the antibiotics for treatment, data from microbiological colonization screening should be considered but not solely relied on. Some indicators of infection also depended on postnatal age.
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BACKGROUND AND OBJECTIVE: Results of five randomized controlled trials (RCT) sequentially published in 2010-2013 suggested that aiming for higher, as opposed to lower oxygen saturation targets, reduces rates of mortality in infants <28 weeks of gestation, while increasing rates of severe retinopathy of prematurity (ROP). Two further RCTs published in 2011 and 2015 demonstrated that avoiding endotracheal intubation by minimally invasive surfactant administration reduces respiratory morbidity. Assuming that such data are likely to affect clinical practice and ultimate outcome, we analyzed population-level results in extremely preterm infants born across Germany during 2010-2017. METHODS: We used mandatory German quality surveillance data to compare mortality and morbidities in preterm infants born between 24 weeks 0 days and 27 weeks 6 days of gestation in 2010-2013 versus 2014-2017. RESULTS: Mortality decreased from 15.1% (1,366/9,058) in 2010-2013 to 12.7% (1,385/10,924) in 2014-2017, risk ratio (RR) 0.845 (95% confidence interval [CI], 0.784-0.901). Rates of severe ROP (≥grade 3) per survivor increased from 12.1% (930/7,692) to 13.3% (1.269/9,539), RR 1.100 (95% CI: 1.017-1.191). The lowest mortality and highest ROP rates were found in infants born in 2014. There was no change in rates of necrotizing enterocolitis, while those of bronchopulmonary dysplasia (BPD) decreased steadily between 2010 and 2017, alongside the increased proportion of infants who were never intubated. CONCLUSIONS: There was a moderate decline in mortality, an insignificant increase in severe ROP, and a steady decline of BPD in Germany during 2010-2017. Avoiding endotracheal intubation may have contributed to lowered BPD rates.