RESUMEN
BACKGROUND: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. METHODS: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32+0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. FINDINGS: Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. INTERPRETATION: Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. FUNDING: Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).
Asunto(s)
Displasia Broncopulmonar , Recien Nacido con Peso al Nacer Extremadamente Bajo , Vitamina A , Humanos , Displasia Broncopulmonar/prevención & control , Displasia Broncopulmonar/mortalidad , Vitamina A/administración & dosificación , Método Doble Ciego , Recién Nacido , Masculino , Femenino , Estudios Prospectivos , Austria , Suplementos Dietéticos , Alemania , Unidades de Cuidado Intensivo Neonatal , Edad Gestacional , Vitaminas/administración & dosificación , Lactante , Resultado del TratamientoRESUMEN
BACKGROUND: Controversy exists regarding the impact of small for gestational age (SGAâ¯=â¯birth weightâ¯<â¯10th percentile) status on mortality and major morbidities. AIM: To assess the effects of SGA on mortality and major morbidities in ≤750â¯gram (g) neonates. STUDY DESIGN: Retrospective (01/2005-12/2017), single center study at a tertiary NICU. SUBJECTS: SGA neonatesâ¯≤â¯750â¯g. OUTCOME: Effect of SGA status on mortality and major morbidities. RESULTS: 183 infants were enrolled. 103 (56.3%) were non-SGA (mean gestational age 25â¯+â¯1â¯weeks⯱â¯9.9â¯days, mean birth weight 662.6⯱â¯75.2â¯g), and 80 (43.7%) SGA (mean gestational age 26â¯+â¯6â¯weeks⯱â¯14.0â¯days, mean birth weight 543.9⯱â¯114.7â¯g). Mortality was 24.1% (non-SGA: 30/103 (29.1%), SGA: 14/80 (17.5%); pâ¯=â¯0.08). Univariable logistic regression analysis revealed a significant protective effect of SGA status on pneumothoraces (OR 0.28, 95%-CI [0.11-0.69]), IVH (≥3) (OR 0.38; 95%-CI [0.15-0.67]), and seizures (OR 0.09, 95%-CI [0.01-0.76]), but NEC (≥2a) occurred more frequently in SGA neonates (pâ¯=â¯0.024). Multiple logistic regression analysis found SGA status to negatively influence ROP (≥3) (OR 2.87, 95%-CI [1.14-7.23]) and need for home monitoring (OR 2.38, 95%-CI [1.05-5.41]). Other major morbidities (IVH, PVL, RDS, BPD, NEC, FIP, sepsis, hearing impairment) and mortality rates were not significantly affected, but distinct organ-specific patterns were seen. CONCLUSION: SGA had negative effects on the rate of severe ROP and the need for home monitoring, but other major morbidities as well as mortality rates were not significantly affected. In the future, it will be important to delineate underlying pathophysiological mechanisms that contribute to this pattern.
Asunto(s)
Mortalidad Infantil , Enfermedades del Recién Nacido/epidemiología , Recién Nacido Pequeño para la Edad Gestacional , Femenino , Alemania/epidemiología , Humanos , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Enfermedades del Recién Nacido/mortalidad , Masculino , Morbilidad , Embarazo , Retinopatía de la Prematuridad/epidemiología , Estudios RetrospectivosRESUMEN
.
RESUMEN
BACKGROUND: Parenteral and enteral nutrition are essential for both growth and development of preterm infants. Based on the results of many studies, the rate of nutritional growth and the amount of substrate delivered parenterally are under debate. OBJECTIVE: The main aim of this study was to assess parenteral nutrition in very and extremely immature preterm infants, i.e. very low birth weight (VLBW, birth weight <1500g) and extremely low birth weight (ELBW, birth weight <1000g) neonates, and to compare the amount of parenterally delivered substrate in our neonatal intensive care unit (NICU) to current German guidelines. METHODS: Retrospective audit at our tertiary NICU at the University Children's Hospital of Saarland, Homburg, Germany between 1 January 2009 and 31 December 2010. RESULTS: In total, 100 premature neonates were included. The mean gestational age was 29.6 weeks (range 24.4-34.1 weeks) and the mean birth weight was 1119 g ± 260 g (range 570 g-1490 g). Comparing the amount of fluids, glucose, amino acids, lipids and kcals with the current guidelines of the German Society for Nutritional Medicine in preterm infants, only glucose was adequately given; however, a substantial number of weight-dependent (more often in ELBW neonates) episodes of hyperglycemia requiring insulin treatment were also seen. During the first 3 weeks of life a substantial drop in body weight, length and head circumference occurred in our study cohort. In contrast, at 2 years corrected age, catch-up growth was seen in our cohort with anthropometric data now comparable to healthy term infants. Using the Bayley II test for developmental outcome assessment, at 2 years corrected age 78.6% (33/42) of infants demonstrated normal development. CONCLUSIONS: This retrospective data analysis demonstrated inadequate provision of parenteral nutrition in our NICU, which was often not in line with current German guidelines. This was associated with inadequate growth in our cohort, most notably during the first 3 weeks of life; however, implementation of current guidelines is impeded by metabolic disturbances in this cohort, most notably in ELBW neonates. Whether adherence to published guidelines will result in better early ex utero growth, and whether this normalized growth pattern will translate into better long-term outcome on a metabolic and neurological level, remains unclear.
Asunto(s)
Fenómenos Fisiológicos Nutricionales del Lactante/fisiología , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Nutrición Parenteral , Aumento de Peso , Peso al Nacer , Niño , Nutrición Enteral , Alemania , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro/crecimiento & desarrollo , Recién Nacido de muy Bajo Peso/crecimiento & desarrollo , Unidades de Cuidado Intensivo Neonatal , Estudios RetrospectivosRESUMEN
AIM: We assessed the risk factors for transient acute kidney injury in very low birth weight (VLBW) infants treated for patent ductus arteriosus (PDA) using the serum creatinine-based criteria in Kidney Disease: Improving Global Outcomes. METHOD: This retrospective study of infants requiring ibuprofen and, or, surgery for haemodynamic relevant PDAs was performed at the University Children's Hospital of Saarland, Homburg, Germany, from January 2009 to December 2015. RESULTS: We studied 422 infants with a mean birth weight of 1059 ± 308.2 g. Acute kidney injuries developed in 150/295 infants (50.9%) with spontaneous PDA closure, in 46/82 (56.1%) who received intravenous ibuprofen treatment, in 18/24 (75.0%) who had surgery and in 15/21 infants (71.4%) who received both medical and surgical treatment. Acute kidney injuries were associated with birth weight and gestational age, Apgar scores at 10 minutes, the PDA size corrected for birth weight, a PDA with three affected circulatory territories, PDA surgery and gentamicin. Multiple logistic regression analysis showed particular associations between acute kidney injury and birth weight (p = 0.001), the 10-minute Apgar score (p = 0.02) and gentamicin (p = 0.043). CONCLUSION: Birth weight, the 10-minute Apgar score and gentamicin were particularly associated with acute kidney injuries in our cohort.
Asunto(s)
Lesión Renal Aguda/etiología , Puntaje de Apgar , Peso al Nacer , Conducto Arterioso Permeable/tratamiento farmacológico , Gentamicinas/efectos adversos , Femenino , Gentamicinas/uso terapéutico , Humanos , Recién Nacido , Recién Nacido de muy Bajo Peso , Masculino , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
Breastfeeding confers multiple benefits for the health and development of very preterm infants, but there is scarce information on the duration of breastfeeding after discharge from the neonatal intensive care unit (NICU). We used data from the Effective Perinatal Intensive Care in Europe population-based cohort of births below 32 weeks of gestation in 11 European countries in 2011-2012 to investigate breastfeeding continuation until 6 months. Clinical and sociodemographic characteristics were collected from obstetric and neonatal medical records as well as parental questionnaires at 2 years of corrected age. Among 3,217 ever-breastfed infants, 34% were breastfeeding at 6 months of age (range across countries from 25% to 56%); younger and less educated mothers were more likely to stop before 6 months (adjusted relative risk [aRR] <25 years: 0.68, 95% CI [0.53, 0.88], vs. 25-34 years; lower secondary: 0.58, 95% CI [0.45, 0.76] vs. postgraduate education). Multiple birth, bronchopulmonary dysplasia (BPD), and several neonatal transfers reduced the probability of continuation but not low gestational age, fetal growth restriction, congenital anomalies, or severe neonatal morbidities. Among infants breastfeeding at discharge, mixed versus exclusive breast milk feeding at discharge was associated with stopping before 6 months: aRR = 0.60, 95% CI [0.48, 0.74]. Low breastfeeding continuation rates in this high-risk population call for more support to breastfeeding mothers during and after the neonatal hospitalization, especially for families with low socio-economic status, multiples, and infants with BPD. Promotion of exclusive breastfeeding in the NICU may constitute a lever for improving breastfeeding continuation after discharge.
Asunto(s)
Lactancia Materna/estadística & datos numéricos , Recien Nacido Prematuro/fisiología , Adulto , Displasia Broncopulmonar , Estudios de Cohortes , Europa (Continente) , Femenino , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Madres/estadística & datos numéricos , Progenie de Nacimiento Múltiple , Factores Socioeconómicos , Adulto JovenRESUMEN
BACKGROUND: Tuberous Sclerosis Complex (TSC) is a rare multisystem disorder. In 2012 diagnostic criteria for TSC were revised. However, data on the incidence of TSC are limited. METHODS: Prospective, national surveillance study in Germany over a 2-year-period (03/2015-02/2017) using current revised criteria for TSC. Patients up to the age of 18 years with a new diagnosis of definite or possible TSC (clinical and/or genetic) were included. The aims of this study were 1) to generate up-to-date data on the incidence of definite or possible TSC, 2) to assess age at first diagnosis, and 3) to compare these data with previous epidemiologic data. RESULTS: In total, 86 patients met inclusion criteria (definite or possible TSC) with a median age at diagnosis of 6 months (range: 5 months before birth - 197 months of age). Among patients identified with features of TSC, 73.3% met criteria for definite diagnosis (median age: 7 months) and 26.7% met criteria for a possible diagnosis (median age: 3 months). 55.8% of patients were male. When excluding prenatally diagnosed patients, median age at diagnosis was 11 months with a range of 0 to 197 months. The 3 most common clinical features at diagnosis of TSC were central nervous system involvement in 73.3% patients (of these 95.2% experienced seizures), cutaneous involvement in 58.1% patients (with the most common lesion being hypomelanotic macules in 92%) and cardiac rhabdomyoma in half of the patients. Cardiac rhabdomyoma were detected by prenatal ultrasonography in 22.1% of patients. The presence of cardiac rhabdomyoma was associated with cardiac arrhythmias in 25.6% (about 13% of all diagnosed patients) in our cohort. The overall prevalence of seizure disorders was 69.8%. The annual incidence rate of TSC is estimated at a minimum of 1:17.785 live births. However correcting for underreporting, the estimated incidence rate of definite or possible TSC is approximately 1:6.760-1:13.520 live births in Germany. CONCLUSIONS: This is the first study that assessed prospectively the incidence rate of TSC in children and adolescents using the updated diagnostic criteria of 2012. This prospective surveillance study demonstrates a low age at first diagnosis (median: 6 months), likely due to antenatal detection of cardiac rhabdomyoma. Early diagnosis bears the potential for implementing effective therapies at an earlier stage.
Asunto(s)
Esclerosis Tuberosa/metabolismo , Niño , Preescolar , Everolimus/uso terapéutico , Femenino , Alemania , Humanos , Lactante , Recién Nacido , Masculino , Estudios Prospectivos , Rabdomioma/tratamiento farmacológico , Rabdomioma/metabolismo , Convulsiones/tratamiento farmacológico , Convulsiones/metabolismo , Espasmos Infantiles/tratamiento farmacológico , Espasmos Infantiles/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Esclerosis Tuberosa/tratamiento farmacológicoRESUMEN
BACKGROUND: Vitamin A (VA) is crucial for lung growth and development. In premature infants, inadequate VA levels are associated with an increased risk of bronchopulmonary dysplasia (BPD). Intramuscular VA supplementation has been shown to decrease the incidence of BPD, but is not widely used in the clinical setting due to concerns about feasibility and pain. We studied VA kinetics, distribution, and the induction of early genetic expression of retinoid homeostatic genes in the lung after endotracheal and intravenous application in a preterm lamb model. METHODS: Lambs were delivered prematurely after 85% of gestation, intubated, and ventilated for 3 hours. The animals were randomized to receive no VA ("control"), a bolus of VA intravenously ("i.v."), or VA endotracheally directly after administration of surfactant ("e.t."). RESULTS: Animals treated with VA endotracheally directly after administration of surfactant showed significant increases of VA in serum and lung compared to controls. Animals treated with a bolus of VA intravenously showed significant increases of VA in serum, lung, and liver; however, peak serum concentrations and mRNA levels of homeostatic genes raised concerns about toxicity in this group. CONCLUSIONS: Endotracheal VA supplementation in preterm lambs is feasible and might offer advantages in comparison to i.v. Further studies are warranted to explore biological effects in the context of BPD.
Asunto(s)
Displasia Broncopulmonar/prevención & control , Pulmón/efectos de los fármacos , Surfactantes Pulmonares/administración & dosificación , Vitamina A/administración & dosificación , Vitamina A/farmacocinética , Administración por Inhalación , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Femenino , Edad Gestacional , Humanos , Recién Nacido , Infusiones Intravenosas , Intubación Intratraqueal , Pulmón/crecimiento & desarrollo , Embarazo , Distribución Aleatoria , Sensibilidad y Especificidad , OvinosRESUMEN
Tuberous sclerosis complex (TSC) is a genetic disease with a significant morbidity and mortality. We conducted a retrospective analysis of two cohorts (Vall d'Hebron University Hospital [HVH], Barcelona, Spain, 1982-2015, and at Saarland University Medical Center [UKS], Homburg, Germany, 1998-2015) to assess prevalence and treatment of TSC associated manifestations and to evaluate if the follow-up was in line with published recommendations. This was considered if more than 15% of patients did not receive adequate examination with regard to potential organ involvement. A definite diagnosis was made in 52 patients (96%), and a possible diagnosis was made in 2 patients (4%). Thirty-four (63%) patients were from HVH and 20 (37%) from UKS. Median age at first presentation was 6 months (interquartile range: 0-38 months), and median time of follow-up was 6 years (interquartile range: 2-13 years). Clinical symptoms that led to a diagnosis of TSC were cardiac rhabdomyoma (22/54), epilepsy (20/54), and cutaneous manifestations (4/54). Assessment of neuropsychiatric, renal, and ocular manifestations was inadequate in both hospitals, whereas cutaneous manifestation was inadequate at UKS only. Our data demonstrate insufficient examinations in a substantial number of TSC patients with regard to neuropsychiatric, renal, ocular, and cutaneous manifestations. The recently published guidelines may prove valuable in establishing a more comprehensive approach.
Asunto(s)
Esclerosis Tuberosa/diagnóstico , Esclerosis Tuberosa/terapia , Adolescente , Encéfalo/diagnóstico por imagen , Niño , Preescolar , Diagnóstico Diferencial , Epilepsia/diagnóstico , Epilepsia/etiología , Epilepsia/genética , Epilepsia/terapia , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Esclerosis Tuberosa/genéticaRESUMEN
Although prenatal exposure to opioids, cannabinoids and cocaine is a frequent problem, only scarce data have been published on the long-term outcome in affected children and adolescents. While opioid-exposed children up to the age of 2 years show a reduced motor developmental pattern, data from meta-analyses up to adolescence show a strong trend for reduced performance with regard to cognitive function and behavior. Follow-up data after intrauterine cannabinoid exposure indicate reduced cognitive and reading abilities as well as abnormal findings in complex planning tests. Externalizing pathologies have been observed more frequently in boys. Prenatal cocaine exposure results in reduced cognitive and verbal development up to adolescence; however, differences are small but significant in meta-analyses. Interpretation of follow-up data with partially contradictory results may reflect methodological differences and a number of modifying co-factors, e.g., social conditions during the childhood period. These data should encourage further primary and secondary preventive attempts.
Asunto(s)
Drogas Ilícitas/efectos adversos , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Psicotrópicos/efectos adversos , Adolescente , Analgésicos Opioides/efectos adversos , Cannabinoides/efectos adversos , Niño , Preescolar , Cocaína/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , EmbarazoRESUMEN
Surfactant treatment of neonatal respiratory distress syndrome (RDS) was introduced in Europe during the 1990s. Meta-analyses have indicated that using less invasive surfactant administration techniques on preterm neonates receiving continuous positive airway pressure (CPAP) results in improved survival rates without bronchopulmonary dysplasia. Surfactant should be administered early and ventilator settings adapted to changing oxygen requirements and lung mechanics. Side effects including initial bradycardia, oxygen desaturation, tube obstruction and isolated cases of pulmonary haemorrhage have been reported. CONCLUSION: Less invasive surfactant therapy improves pulmonary outcomes in preterm neonates with RDS and should ideally be administered in combination with CPAP.
Asunto(s)
Surfactantes Pulmonares/administración & dosificación , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Presión de las Vías Aéreas Positiva Contínua , Humanos , Recién Nacido , Recien Nacido Prematuro , Surfactantes Pulmonares/efectos adversos , Factores de TiempoRESUMEN
BACKGROUND: Intraventricular hemorrhage (IVH) is one of the most serious complications in preterm infants and is associated with neurological sequelae and mortality. Over the past few decades, the rate of IVH has decreased due to improved neonatal intensive care. However, up to 15-25% of very and extremely premature infants (<32 and <28weeks of pregnancy (WOP) respectively) still suffer from IVH. STUDY PURPOSE: The aim of this study was to perform an updated, multicenter analysis to identify ante-, peri, and postnatal factors other than gestational age/birth weight associated with IVH of any grade in a large cohort of very and extremely premature infants. METHODS: We performed a retrospective analysis in a prospectively conducted multicenter cohort study between 01/01/1998-31/12/2012 at 5 level 3 perinatal centers. All relevant ante-, peri- and neonatal data were collected and univariate as well as multivariate logistic regression analysis was performed. RESULTS: 765 inborn infants with a gestational age<32 WOP were enrolled into this study (369 (48.2%) female; 396 (51.8%) male). Birth weight ranged from 315g to 2200g (mean 1149.7g, SD 371.9g); 279 (36.5%) were born ≤27+6 WOP and 486 (63.5%)≥28+0 WOP. IVH was seen in 177 (23.1%) patients. Multivariate analysis revealed that in addition to higher gestational age (OR 0.7, CI [0.6-0.8]), antenatal steroid treatment (OR 0.3, CI [0.2-0.6]) and caesarian section without uterine contraction (OR 0.6, CI [0.4-0.9]) were associated with a lower rate of IVH while RDS (OR 5.6, CI [1.3-24.2]), pneumothorax (OR 2.8, CI [1.4-5.5]) and use of catecholamines (OR 2.7, CI [1.7-4.5]) were associated with an increased risk of IVH. After exclusion of gestational age and birth weight from multivariate analysis, early onset sepsis (OR 1.6, CI [1.01-2.7]) and patent ductus arteriosus (OR 1.9, CI [1.1-3.1]) were associated with a higher rate of IVH. In addition, univariate analysis revealed that Apgar scores at 5min (p<0.001), BDP/ROP/NEC (p<0.001), mechanical ventilation (p<0.001) and inhalative nitric oxide (p<0.001) were significantly associated with IVH. CONCLUSIONS: Our comprehensive analysis demonstrated that the occurrence of IVH in very premature infants is significantly associated with ante-, peri- and postnatal factors being either related to the degree of immaturity or indicating a critical clinical course after birth. The analysis reiterates the necessity for a very close cooperation between obstetricians and neonatologists to reduce the incidence of IVH in this susceptible cohort.
Asunto(s)
Hemorragia Cerebral/etiología , Enfermedades del Prematuro/etiología , Catecolaminas/uso terapéutico , Hemorragia Cerebral/epidemiología , Cesárea , Femenino , Humanos , Recien Nacido Extremadamente Prematuro , Enfermedades del Prematuro/epidemiología , Recién Nacido de muy Bajo Peso , Masculino , Preeclampsia/etiología , Embarazo , Complicaciones Infecciosas del Embarazo/etiología , Respiración Artificial/estadística & datos numéricos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O2). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O2 In the context of MV-O2, attenuated PDGF signaling independently contributes to defective septation and endothelial cell apoptosis stemming from a PDGF-Rα-dependent reduction in lung VEGF-A. TGF-ß contributes to the PDGF-Rα-dependent decrease in myofibroblast function. Remarkably, endotracheal treatment with exogenous PDGF-A rescues both the lung defects in haploinsufficient mice undergoing MV-O2 Overall, our results establish attenuated PDGF signaling as an important driver of nCLD pathology with provision of PDGF-A as a protective strategy for newborns undergoing MV-O2.
Asunto(s)
Enfermedades Pulmonares/patología , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Animales , Animales Recién Nacidos , Células Cultivadas , Enfermedad Crónica , Fibroblastos/citología , Fibroblastos/metabolismo , Haploinsuficiencia , Células Endoteliales de la Vena Umbilical Humana , Humanos , Recién Nacido , Pulmón/metabolismo , Enfermedades Pulmonares/metabolismo , Enfermedades Pulmonares/prevención & control , Ratones , Ratones Endogámicos C57BL , Oxígeno/metabolismo , Factor de Crecimiento Derivado de Plaquetas/farmacología , Factor de Crecimiento Derivado de Plaquetas/uso terapéutico , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Respiración Artificial , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismoAsunto(s)
Antivirales/uso terapéutico , Palivizumab/uso terapéutico , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones del Sistema Respiratorio/prevención & control , Anticuerpos Monoclonales , Anticuerpos Monoclonales Humanizados , Hospitalización , Humanos , Lactante , Recién Nacido , Infecciones del Sistema Respiratorio/virologíaRESUMEN
BACKGROUND: Neurological dysfunction may occur after corrective cardiac surgery using cardio-pulmonary bypass (CPB) with or without circulatory arrest. Different neurophysiological monitoring systems have been employed to detect neurological complications and possible brain injury in infants and children during and after cardiac surgery. The value of Elecetroencephalogram (EEG) in infants and children at risk for neurological sequelae has not been systematically studied. METHODS: Sequential performance of two EEGs before and after cardiac surgery at a tertiary University Hospital to screen for possible brain injury after cardiac surgery in neonates and children undergoing CPB surgery. In addition, a complete neurological examination and assessment by a physiotherapist was performed. RESULTS: Over a 4-year period, in 313 patients (age: 54.2 ± 55.7 months; normal initial EEG) after cardiac surgery CPB (duration of surgery: 146.0 ± 58.9 min; aortic cross clamp time: 34.1 ± 19.1 min), a 19-channel EEG recording was performed 2.4 ± 1.8 days prior to and 11.6 ± 5.3 days after cardiac surgery. An abnormal EEG was detected in only 8 of 313 patients (2.5%; focal slowing: 1, generalised slowing: 5, epiletiform discharges: 2) after cardiac surgery, while the EEG was normal in the remaining 305 patients (97.5%). In 1 patient, an intra-cerebral pathology was seen on MRI (ischemic); in 5 patients, follow-up EEGs were performed, which revealed normalized findings. None of the 8 patients demonstrated new focal neurological deficits on physical examination, but 33 (9.7%) children demonstrated minor abnormalities (e.g., subtle motor asymmetry, increase in muscle tone, etc.), which were unrelated to abnormal EEG findings. CONCLUSIONS: According to the used protocol, pathological EEG findings were very infrequent in our study cohort. The routine and indiscriminative recording of EEGs in children before and after corrective or palliative cardiac surgery for congenital heart disease using CPB is not recommended. Further intra-operative neuromonitoring methods with immediate intervention should be evaluated.
Asunto(s)
Daño Encefálico Crónico/diagnóstico , Isquemia Encefálica/diagnóstico , Electroencefalografía , Cardiopatías Congénitas/cirugía , Complicaciones Intraoperatorias/diagnóstico , Monitoreo Intraoperatorio , Complicaciones Posoperatorias/diagnóstico , Puente Cardiopulmonar , Niño , Preescolar , Femenino , Paro Cardíaco Inducido , Humanos , Imagen por Resonancia Magnética , Masculino , Examen Neurológico , Tempo Operativo , Factores de RiesgoRESUMEN
Dravet syndrome is often caused by SCN1A mutations and has a wide variation in clinical appearance. Indication for genetic analysis should be an epileptic encephalopathy or severe clinical course of seizures in infants with episodes of fever before the first year of life.
RESUMEN
AIM: This study assessed the prevalence of small for gestational age (SGA) among very preterm (VPT) infants using national and European intrauterine references. METHODS: We generated country-specific and common European intrauterine growth references for 11 European countries, according to Gardosi's approach and Hadlock's foetal growth model, using national data on birthweights by sex. These references were applied to the Effective Perinatal Intensive Care in Europe (EPICE) cohort, which comprised 7766 live VPT births without severe congenital anomalies under 32 weeks of gestation in 2011-2012, to estimate the prevalence of infants with SGA birthweights, namely those below the 10th percentile. RESULTS: The SGA prevalence was 31.8% with country-specific references and 34.0% with common European references. The European references yielded a 10-point difference in the SGA prevalence between countries with lower term birthweights (39.9%) - Portugal, Italy and France - and higher term birthweights, namely Denmark, the Netherlands, Sweden (28.9%; p < 0.001). This was not observed with country-specific references, where the respective figures were 32.4% and 33.9% (p = 0.34), respectively. CONCLUSION: One-third of VPT infants were SGA according to intrauterine references. Common European references showed significant differences in SGA prevalence between countries with high and low-term birthweights.
Asunto(s)
Peso al Nacer , Retardo del Crecimiento Fetal/epidemiología , Recien Nacido Prematuro , Recién Nacido Pequeño para la Edad Gestacional , Europa (Continente)/epidemiología , Femenino , Humanos , Recién Nacido , Masculino , PrevalenciaRESUMEN
Background: Infections and autoimmune disorders are more frequent in Down syndrome, suggesting abnormality of adaptive immunity. Although the role of B cells and antibodies is well characterized, knowledge regarding T cells is limited. Methods: Lymphocyte subpopulations of 40 children and adolescents with Down syndrome and 51 controls were quantified, and phenotype and functionality of antigen-specific effector T cells were analyzed with flow cytometry after polyclonal and pathogen-specific stimulation (with varicella-zoster virus [VZV] and cytomegalovirus [CMV]). Results were correlated with immunoglobulin (Ig) G responses. Results: Apart from general alterations in the percentage of lymphocytes, regulatory T cells, and T-helper 1 and 17 cells, all major T-cell subpopulations showed higher expression of the inhibitory receptor PD-1. Polyclonally stimulated effector CD4+ T-cell frequencies were significantly higher in subjects with Down syndrome, whereas their inhibitory receptor expression (programmed cell death 1 [PD-1] and cytotoxic T-lymphocyte antigen 4 [CTLA-4]) was similar to that of controls and cytokine expression profiles were only marginally altered. Pathogen-specific immunity showed age-appropriate levels of endemic infection, with correlation of CMV-specific cellular and humoral immunity in all subjects. Among VZV IgG-positive individuals, a higher percentage of VZV-specific T-cell-positive subjects was seen in those with Down syndrome. Conclusions: Despite alterations in lymphocyte subpopulations, individuals with Down syndrome can mount effector T-cell responses with similar phenotype and functionality as controls but may require higher effector T-cell frequencies to ensure pathogen control.