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1.
Int J Biol Macromol ; 158: 562-568, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32380112

RESUMO

Neonatal hypoxic-ischemic encephalopathy (HIE) is a complex condition that remains the leading cause of mortality and morbidity among infants. Polysaccharide has been reported to possess diverse biological activities, however, the neuro-protective activity of polysaccharide isolated from Lycium ruthenicum remains unknown so far. However, the role of Lycium ruthenicum polysaccharide 3 (LRP3) in HIE has not been evaluated. Herein, we investigated the effect of LRP3 on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced primary cortical neurons. Our results demonstrated that LRP3 significantly improved the cell viability of OGD/R-induced cortical neurons. The OGD/R-caused increase in ROS production and decrease in the activities of anti-oxidative enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were mitigated by LRP3. Besides, the caspase-3 activity in OGD/R-induced cortical neurons was markedly decreased after LRP3 treatment. The increased bax expression and decreased bcl-2 expression caused by OGD/R stimulation were alleviated by pretreatment with LRP3. In addition, LRP3 significantly induced the expressions of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in OGD/R-induced cortical neurons. However, inhibition of Nrf2/HO-1 signaling pathway through transfection with siRNA targeting Nrf2 reversed the protective effects of LRP3. In conclusion, LRP3 exerts a neuroprotective effect against OGD/R-induced neuronal injury in rat primary cortical neurons.

2.
J Pediatr Hematol Oncol ; 41(5): 355-360, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31135715

RESUMO

INTRODUCTION: The international normalized ratio (INR), a standardized method of reporting the prothrombin time, can be a surrogate marker of the vitamin K-dependent coagulation pathways. OBJECTIVE: To evaluate the relationship between INR measurements in the first 48 hours of life and subsequent development of intraventricular hemorrhage (IVH) in extremely preterm infants. MATERIALS AND METHODS: A single-center retrospective, observational cohort study of infants born at <28 weeks gestation. The main outcome measure was defined as the degree of IVH seen on cranial ultrasound examinations at day 7 postnatal age. RESULTS: Of 200 infants, 109 (mean gestational age, 25.2 wk [SD, 1.27]) had coagulation results available. Of 109, 26 developed IVH. Elevated INR was associated with increased risk of a severe IVH (odds ratio [OR] 6.50; 95% confidence interval [CI], 1.65-25.62; P=0.008) adjusted for gestation, birth weight, and sex. INR was significantly associated with severe IVH in infants who did not receive blood products (OR, 64.60; 95% CI, 1.35-3081.25; P=0.035), but not in those who did (OR, 2.93; 95% CI, 0.67-12.71; P=0.151) (Pinteraction=0.086). CONCLUSION: An elevated INR in the first 48 hours of life may be useful to identify preterm infants at risk of severe IVH and may guide strategies to prevent the development, or limit the extension, of IVH.


Assuntos
Hemorragia Cerebral Intraventricular/etiologia , Coeficiente Internacional Normatizado , Fatores de Risco , Peso ao Nascer , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores Sexuais
3.
J Pediatr ; 208: 191-197.e2, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30878207

RESUMO

OBJECTIVE: To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI. STUDY DESIGN: In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34 weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index >p97 and anterior horn width >6 mm) or high-threshold (ventricular index >p97 + 4 mm and anterior horn width >10 mm) groups. In 88 of those (80%) with a term-equivalent age-MRI, the Kidokoro Global Brain Abnormality Score and the frontal and occipital horn ratio were measured. Automatic segmentation was used for volumetric analysis. RESULTS: The total Kidokoro score of the infants in the low-threshold group (n = 44) was lower than in the high-threshold group (n = 44; median, 8 [IQR, 5-12] vs median 12 [IQR, 9-17], respectively; P < .001). More infants in the low-threshold group had a normal or mildly increased score vs more infants in the high-threshold group with a moderately or severely increased score (46% vs 11% and 89% vs 54%, respectively; P = .002). The frontal and occipital horn ratio was lower in the low-threshold group (median, 0.42 [IQR, 0.34-0.63]) than the high-threshold group (median 0.48 [IQR, 0.37-0.68], respectively; P = .001). Ventricular cerebrospinal fluid volumes could be calculated in 47 infants and were smaller in the low-threshold group (P = .03). CONCLUSIONS: More brain injury and larger ventricular volumes were demonstrated in the high vs the low-threshold group. These results support the positive effects of early intervention for posthemorrhagic ventricular dilatation. TRIAL REGISTRATION: ISRCTN43171322.


Assuntos
Lesões Encefálicas/fisiopatologia , Encéfalo/patologia , Ventrículos Cerebrais/fisiopatologia , Derivações do Líquido Cefalorraquidiano , Hemorragias Intracranianas/fisiopatologia , Encéfalo/diagnóstico por imagem , Lesões Encefálicas/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Ventrículos Cerebrais/diagnóstico por imagem , Líquido Cefalorraquidiano , Dilatação , Feminino , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/cirurgia , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/diagnóstico por imagem , Doenças do Prematuro/fisiopatologia , Doenças do Prematuro/cirurgia , Hemorragias Intracranianas/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Substância Branca/diagnóstico por imagem
4.
Int J Dev Neurosci ; 73: 59-65, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30639393

RESUMO

BACKGROUND: Preterm infants are at risk of germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH) which leads to post-haemorrhagic hydrocephalus (PHH) in 30% of infants; this is associated with moderate-severe neurodevelopmental impairment and confers significant risk of cerebral palsy. There are however no predictive indicators of the severity or long-term outcome after GMH-IVH. In recent years, endosome-derived extracellular vesicles (EVs) or exosomes have been isolated from biofluids and shown to mediate intercellular communication via selective enrichment in proteins and micro-RNAs. METHODS: This study aimed to isolate and characterise EVs from the cerebrospinal fluid (CSF) of 3 preterm infants with PHH using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) with immunogold protein labelling, and micro-RNA analysis. RESULTS: NTA of unaltered CSF revealed a heterogeneous and dynamic population of EVs. Exosomal-sized EVs were isolated by differential ultracentrifugation and TEM confirmed the presence of CD63+ and CD81+ exosomes. The micro-RNAs miR-9, miR-17, miR-26a, miR-124 and miR-1911 were detected within the exosome-enriched fraction and profiled over time. CONCLUSION: This is the first reported characterisation of exosomes from the CSF of preterm infants with post-haemorrhagic hydrocephalus.


Assuntos
Hemorragia Cerebral/líquido cefalorraquidiano , Exossomos/metabolismo , Hidrocefalia/líquido cefalorraquidiano , MicroRNAs/líquido cefalorraquidiano , Hemorragia Cerebral/complicações , Humanos , Hidrocefalia/etiologia , Recém-Nascido , Recém-Nascido Prematuro
5.
Arch Dis Child Fetal Neonatal Ed ; 104(1): F70-F75, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29440132

RESUMO

OBJECTIVE: To compare a low versus a higher threshold for intervention in preterm infants with posthaemorrhagic ventricular dilatation. DESIGN: Multicentre randomised controlled trial (ISRCTN43171322). SETTING: 14 neonatal intensive care units in six countries. PATIENTS: 126 preterm infants ≤34 weeks gestation with ventricular dilatation after grade III-IV haemorrhage were randomised to low threshold (LT) (ventricular index (VI) >p97 and anterior horn width (AHW) >6 mm) or higher threshold (HT) (VI>p97+4 mm and AHW >10 mm). INTERVENTION: Cerebrospinal fluid tapping by lumbar punctures (LPs) (max 3), followed by taps from a ventricular reservoir, to reduce VI, and eventually a ventriculoperitoneal (VP) shunt if stabilisation of the VI below the p97+4 mm did not occur. COMPOSITE MAIN OUTCOME MEASURE: VP shunt or death. RESULTS: 19 of 64 (30%) LT infants and 23 of 62 (37%) HT infants were shunted or died (P=0.45). A VP shunt was inserted in 12/64 (19%) in the LT and 14/62 (23%) infants in the HT group. 7/12 (58%) LT infants and 1/14 (7%) HT infants required shunt revision (P<0.01). 62 of 64 (97%) LT infants and 36 of 62 (58%) HT infants had LPs (P<0.001). Reservoirs were inserted in 40 of 64 (62%) LT infants and 27 of 62 (43%) HT infants (P<0.05). CONCLUSIONS: There was no significant difference in the primary composite outcome of VP shunt placement or death in infants with posthaemorrhagic ventricular dilatation who were treated at a lower versus a higher threshold for intervention. Infants treated at the lower threshold received more invasive procedures. Assessment of neurodevelopmental outcomes will provide further important information in assessing the risks and benefits of the two treatment approaches.


Assuntos
Hemorragia Cerebral/cirurgia , Ventrículos Cerebrais/cirurgia , Doenças do Prematuro/cirurgia , Derivação Portossistêmica Cirúrgica/métodos , Derivação Portossistêmica Cirúrgica/estatística & dados numéricos , Circulação Cerebrovascular , Dilatação Patológica , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Índice de Gravidade de Doença , Punção Espinal
6.
Medicine (Baltimore) ; 97(7): e9875, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29443752

RESUMO

RATIONALE: Enterococcus gallinarum meningitis (EGM) is rarely found in normal adults and even rarer in children. To our knowledge, EGM in neonate has not been reported previously. PATIENTS CONCERNS: Here we reported the first case of EGM in neonate. Prolonged fever was the only manifestation for the case after admission. DIAGNOSES: Cerebrospinal fluid cultures showed that the isolate was Enterococcus gallinarum and sensitive to linezolid. INTERVENTIONS: Ceftriaxone, beta lactam type, and vancomycin were used respectively, but not effective. OUTCOMES: The temperature went down to normal after linezolid was used and the baby was discharged in good condition in the end. LESSONS: This case indicated that EGM could also occur in neonate and fever could be the only obvious manifestation. Thus, the effective antibiotics and adequate duration are very important and linezolid is a potential good choice, especially for vancomycin-resistant patients.


Assuntos
Infecções por Bactérias Gram-Positivas , Linezolida/administração & dosagem , Meningites Bacterianas , Enterococos Resistentes à Vancomicina , Antibacterianos/administração & dosagem , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/fisiopatologia , Humanos , Recém-Nascido , Masculino , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Meningites Bacterianas/fisiopatologia , Testes de Sensibilidade Microbiana/métodos , Resultado do Tratamento , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/isolamento & purificação
7.
Childs Nerv Syst ; 34(3): 473-479, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29067501

RESUMO

PURPOSE: Ventriculitis is a known complication during external CSF drainage in preterm infants with posthaemorrhagic ventricular dilatation. Staphylococci are most frequently isolated in device-associated ventriculitis, and hence, intraventricular vancomycin is a commonly used therapy. Our aim was to study the CSF vancomycin level pattern and drug safety in ventriculostomy access device infection in preterm infants less than 28 weeks gestation. METHODS: This single-centre, retrospective case series included seven infants with a median gestational age of 25 + 4 weeks (range 23 + 6 to 27 + 5 weeks). Ventriculitis was defined as elevated CSF white cell count of > 20/mm3 or positive CSF culture. The CSF vancomycin concentrations following intraventricular vancomycin administration were studied. RESULTS: Forty treatment episodes of intraventricular vancomycin administration were studied in seven preterm infants. Maximum CSF vancomycin concentrations were 24.9 mg/L (3 mg, n = 8, observed concentration-time (OCT), hours (h) = 19), 96.3 mg/L (5 mg, n = 17, OCT(h) = 14), 94 mg/L (10 mg, n = 14, OCT(h) = 24), and 230.7 mg/L (15 mg, n = 1, OCT(h) = 24). The threshold for re-dosage is set at CSF vancomycin level of < 10 mg/L. In all patients, ventriculitis resolution (defined as sterile CSF and CSF WCC of < 20/mm3) was achieved in a median of 5.5 days (range 2-31 days). Individual microbiology data is provided in the online resource. CONCLUSION: Intraventricular vancomycin is an effective treatment for ventriculostomy access device infection in preterm infants. In doses ranging from 3 to 15 mg, sufficient CSF vancomycin level is generated to achieve microbiological cure without any reported adverse effects. Daily CSF drug monitoring is recommended to define dosage interval to maintain drug concentration above breakpoint of minimum inhibitory concentration.


Assuntos
Antibacterianos/administração & dosagem , Ventriculite Cerebral/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Recém-Nascido Prematuro , Vancomicina/administração & dosagem , Ventriculostomia/métodos , Ventriculite Cerebral/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos
8.
Ir J Med Sci ; 187(3): 713-718, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29101642

RESUMO

This is a transcript of a scientific conference on the subject of prenatal surgery for spina bifida. It represents the views of three patients, an obstetrician, a postnatal neurosurgeon, a neonatologist, a paediatric neurologist, two surgeons who practice open spina bifida foetal surgery, a fetoscopic surgeon and an obstetrician experienced in randomised trials and systematic reviews. Implications for current practice and recommendations for future research are also discussed in detail.


Assuntos
Cuidado Pré-Natal/métodos , Disrafismo Espinal/cirurgia , Feminino , Humanos , Irlanda , Gravidez , Disrafismo Espinal/patologia
9.
J Matern Fetal Neonatal Med ; 31(6): 791-796, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28274150

RESUMO

OBJECTIVE: To determine the usefulness of measures, available shortly after birth, as predictors of hypoxic-ischemic encephalopathy (HIE) following perinatal asphyxia. PATIENTS: All inborn patients at Southmead Hospital between January 2012 and March 2014 at ≥36 weeks gestation with a pH <7 or BE >16 on cord or baby's blood within one hour of birth or 10-minute Apgar score ≤5 or requiring intermittent positive pressure ventilation at 10 minutes were eligible for inclusion. METHODS: ROC curves were derived for the perinatal clinical and biochemical measures to establish their predictive values for the development of HIE and the area under the curve (AUC) used as the measure of prediction. RESULTS: We identified 79 eligible babies. Infants qualifying for therapeutic hypothermia (TH) based on aEEG abnormalities were considered to have HIE (n = 13; 16.5%), whereas babies with normal aEEG were classified as "non-HIE" (n = 66; 83.5%). The highest AUC measure was associated with the five-minute Apgar score (0.89 (0.79-0.99)). Troponin T (0.81 (0.64-0.98)) and ALT (0.78 (0.60-96)) also showed high values. CONCLUSIONS: In this work, the Apgar score, troponin T and ALT were found to be strong and useful predictors of HIE.


Assuntos
Alanina Transaminase/sangue , Índice de Apgar , Asfixia Neonatal/sangue , Hipóxia-Isquemia Encefálica/sangue , Troponina T/sangue , Asfixia Neonatal/complicações , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/etiologia , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Gravidez , Curva ROC , Estudos Retrospectivos
10.
J Neonatal Perinatal Med ; 10(4): 347-353, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29286930

RESUMO

BACKGROUND: Mothers are increasingly given greater control over many of the choices around birth, although there is little robust evidence to inform these choices. After an infant is born with HIE the question of whether it was predictable, or preventable, is often raised. Intrapartum 'sentinel' events and antenatal predictors of HIE have been well described, however there is little evidence how antenatal and intrapartum factors interact. This is particularly important when elective delivery by lower segment caesarean section (LSCS) has been shown to be beneficial in high risk groups. AIM: To develop a clinical risk score to identify women with a higher risk of having an infant with HIE. PATIENTS AND METHODS: This study is based on the Avon Longitudinal Study of Parents and Children (ALSPAC). This dataset was split into two halves: with each infant being randomly allocated to either cohort one or two. The first cohort was used for the derivation of the model, while it was tested exclusively on the second. Logistic regression modelling was then performed to develop a predictive model. The final model was used to predict the outcome of infants in the second cohort and infants divided into four risk quartiles. To give some indication of possible avoidable disease, the proportion of infants with HIE, potentially avoided by earlier delivery, was estimated by assuming that medicalized delivery by elective LSCS at 37 weeks would remove intrapartum risk of HIE for those infants undelivered at this point. RESULTS: In the final model seven covariates remained (parity, preeclampsia, polyhydramnios, prelabor rupture of membranes, gender, concerns over fetal growth and prematurity). When applied to the second cohort, a ROC curve for the prediction of developing HIE in the newborn period showed good evidence for association (AUC 0.68 (0.60 to 0.77)) and the risk score derived was strongly associated with the risk of HIE, resuscitation and stillbirth, and neonatal death (all p < 0.05). Elective delivery of high risk infants at 37 weeks gestation could prevent 14% of all HIE, with a NNT of 41. CONCLUSION: It is possible to combine routine antenatal findings to identify infants at higher risk of neonatal HIE, thereby recognizing those infants who may benefit most from delivery by elective caesarean section. This work suggests a clinical risk score permits antenatal identification of high-risk infants whose outcome may be amenable to changes in clinical practice to potentially reduce HIE rates, and its devastating consequences.


Assuntos
Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Área Sob a Curva , Cesárea , Procedimentos Cirúrgicos Eletivos , Feminino , Desenvolvimento Fetal , Ruptura Prematura de Membranas Fetais/epidemiologia , Humanos , Hipóxia-Isquemia Encefálica/prevenção & controle , Recém-Nascido , Modelos Logísticos , Estudos Longitudinais , Masculino , Paridade , Poli-Hidrâmnios/epidemiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Curva ROC , Medição de Risco/métodos , Fatores de Risco , Fatores Sexuais , Adulto Jovem
11.
PLoS One ; 12(1): e0169392, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28076368

RESUMO

BACKGROUND: Functional magnetic resonance imaging (fMRI) in neonates has been introduced as a non-invasive method for studying sensorimotor processing in the developing brain. However, previous neonatal studies have delivered conflicting results regarding localization, lateralization, and directionality of blood oxygenation level dependent (BOLD) responses in sensorimotor cortex (SMC). Amongst the confounding factors in interpreting neonatal fMRI studies include the use of standard adult MR-coils providing insufficient signal to noise, and liberal statistical thresholds, compromising clinical interpretation at the single subject level. PATIENTS / METHODS: Here, we employed a custom-designed neonatal MR-coil adapted and optimized to the head size of a newborn in order to improve robustness, reliability and validity of neonatal sensorimotor fMRI. Thirteen preterm infants with a median gestational age of 26 weeks were scanned at term-corrected age using a prototype 8-channel neonatal head coil at 3T (Achieva, Philips, Best, NL). Sensorimotor stimulation was elicited by passive extension/flexion of the elbow at 1 Hz in a block design. Analysis of temporal signal to noise ratio (tSNR) was performed on the whole brain and the SMC, and was compared to data acquired with an 'adult' 8 channel head coil published previously. Task-evoked activation was determined by single-subject SPM8 analyses, thresholded at p < 0.05, whole-brain FWE-corrected. RESULTS: Using a custom-designed neonatal MR-coil, we found significant positive BOLD responses in contralateral SMC after unilateral passive sensorimotor stimulation in all neonates (analyses restricted to artifact-free data sets = 8/13). Improved imaging characteristics of the neonatal MR-coil were evidenced by additional phantom and in vivo tSNR measurements: phantom studies revealed a 240% global increase in tSNR; in vivo studies revealed a 73% global and a 55% local (SMC) increase in tSNR, as compared to the 'adult' MR-coil. CONCLUSIONS: Our findings strengthen the importance of using optimized coil settings for neonatal fMRI, yielding robust and reproducible SMC activation at the single subject level. We conclude that functional lateralization of SMC activation, as found in children and adults, is already present in the newborn period.


Assuntos
Potencial Evocado Motor/fisiologia , Lateralidade Funcional/fisiologia , Recém-Nascido Prematuro , Córtex Sensório-Motor/fisiologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Mapeamento Encefálico/instrumentação , Mapeamento Encefálico/métodos , Feminino , Idade Gestacional , Cabeça/crescimento & desenvolvimento , Cabeça/fisiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Recém-Nascido Prematuro/psicologia , Imagem por Ressonância Magnética , Masculino , Triagem Neonatal/instrumentação , Triagem Neonatal/métodos
12.
Neonatology ; 111(1): 22-29, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27509264

RESUMO

BACKGROUND: Induction of lung maturation by prenatal steroid treatment has become the standard of care for pregnant women at risk for preterm birth. In addition to the beneficial effects on lung maturation, prenatal steroids have been shown to reduce the incidence of neonatal death, necrotizing enterocolitis, sepsis, and intraventricular hemorrhage. However, little is known about the role of interindividual differences in corticoid sensitivity arising from polymorphisms in the glucocorticoid receptor (GR) gene. OBJECTIVES: To assess the impact of GR polymorphisms N363S (rs56149945), R23K (rs6190), and BclI (rs41423247) on neonatal outcome. METHODS: The GR polymorphisms N363S, R23K, and BclI were examined in 10,490 very-low-birth-weight (VLBW) preterm infants from 49 German tertiary level neonatal units (German Neonatal Network, GNN) with respect to neonatal outcome. RESULTS: Infants carrying the BclI genotype were at higher risk to develop bronchopulmonary dysplasia (BPD) (OR 1.12 per BclI allele, 95% CI: 1.02-1.23, p = 0.013) in a logistic regression model adjusted for gestational age, mechanical ventilation, and small for gestational age status. A similar relative risk was seen in the children (89.4%) who received antenatal betamethasone treatment (OR 1.16, 95% CI: 1.05-1.27, p = 0.003), whereas no such effect was detectable in infants without antenatal steroids. N363S and R23K did not show any stable association with neonatal outcome parameters. CONCLUSION: Except for a slightly higher risk of BPD in carriers of the GRBclI variant, the GR gene polymorphisms BclI, N363S, and R23K did not affect neonatal outcome parameters in this large multicenter cohort of VLBW preterm infants.


Assuntos
Betametasona/uso terapêutico , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/genética , Glucocorticoides/uso terapêutico , Receptores de Glucocorticoides/genética , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Modelos Logísticos , Polimorfismo Genético , Gravidez , Reino Unido
13.
J Matern Fetal Neonatal Med ; 29(10): 1581-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26115229

RESUMO

OBJECTIVE: To evaluate the relationship between superior vena cava flow (SVCF) measurements within the first 24 h of life, and development of intraventricular haemorrhage (IVH) in extremely preterm infants. STUDY DESIGN: Single centre retrospective cohort study of 108 preterm infants born less than 28 weeks' gestation. Main outcome measure was degree of IVH at day 7 postnatal age. RESULTS: The mean GA of the study group was 25.4 weeks. Mean SVCF was lower (75 ml/kg/min) in infants later diagnosed with IVH (n = 46) compared to infants, who did not develop IVH (87.7 ml/kg/min, p = 0.055). PDA diameter was inversely associated with SVCF (p = 0.024) and reversal of flow in the descending aorta (p = 0.001). Sensitivity analysis did not confirm an independent association of SVCF with development of IVH [OR 0.990 (0.978-1.002), p = 0.115]. CONCLUSION: Our study describes early SVCF in extremely preterm infants is associated with the extent of ductal shunting, but insensitive in predicting IVH.


Assuntos
Circulação Cerebrovascular , Hemorragias Intracranianas/etiologia , Veia Cava Superior/fisiologia , Ecocardiografia , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Estudos Retrospectivos , Veia Cava Superior/diagnóstico por imagem
14.
Hum Brain Mapp ; 36(7): 2483-94, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25787931

RESUMO

Understanding how spatially remote brain regions interact to form functional brain networks, and how these develop during the neonatal period, provides fundamental insights into normal brain development, and how mechanisms of brain disorder and recovery may function in the immature brain. A key imaging tool in characterising functional brain networks is examination of T2*-weighted fMRI signal during rest (resting state fMRI, rs-fMRI). The majority of rs-fMRI studies have concentrated on slow signal fluctuations occurring at <0.1 Hz, even though neuronal rhythms, and haemodynamic responses to these fluctuate more rapidly, and there is emerging evidence for crucial information about functional brain connectivity occurring more rapidly than these limits. The characterisation of higher frequency components has been limited by the sampling frequency achievable with standard T2* echoplanar imaging (EPI) sequences. We describe patterns of neonatal functional brain network connectivity derived using accelerated T2*-weighted EPI MRI. We acquired whole brain rs-fMRI data, at subsecond sampling frequency, from preterm infants at term equivalent age and compared this to rs-fMRI data acquired with standard EPI acquisition protocol. We provide the first evidence that rapid rs-fMRI acquisition in neonates, and adoption of an extended frequency range for analysis, allows identification of a substantial proportion of signal power residing above 0.2 Hz. We thereby describe changes in brain connectivity associated with increasing maturity which are not evident using standard rs-fMRI protocols. Development of optimised neonatal fMRI protocols, including use of high speed acquisition sequences, is crucial for understanding the physiology and pathophysiology of the developing brain.


Assuntos
Encéfalo/fisiologia , Desenvolvimento Infantil/fisiologia , Imagem por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Encéfalo/crescimento & desenvolvimento , Mapeamento Encefálico/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Rede Nervosa/crescimento & desenvolvimento
16.
BMC Pediatr ; 14: 219, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25179312

RESUMO

BACKGROUND: Pathogenesis of intraventricular hemorrhage (IVH) in premature infants is multifactorial. Little is known about the impact of genetic variants in the vitamin K-dependent coagulation system on the development of IVH. METHODS: Polymorphisms in the genes encoding vitamin K epoxide reductase complex 1 (VKORC1 -1639G>A) and coagulation factor 7 (F7 -323Ins10) were examined prospectively in 90 preterm infants <32 weeks gestational age with respect to coagulation profile and IVH risk. RESULTS: F7-323Ins10 was associated with lower factor VII levels, but not with individual IVH risk. In VKORC1-wildtype infants, logistic regression analysis revealed a higher IVH risk compared to carriers of the -1639A allele. Levels of the vitamin K-dependent coagulation parameters assessed in the first hour after birth did not differ between VKORC1-wildtype infants and those carrying -1639A alleles. CONCLUSIONS: Our data support the assumption that genetic variants in the vitamin K-dependent coagulation system influence the coagulation profile and the IVH risk in preterm infants. Further studies focussing on short-term changes in vitamin K-kinetics and the coagulation profile during the first days of life are required to further understand a possible link between development of IVH and genetic variants affecting the vitamin K-metabolism.


Assuntos
Coagulação Sanguínea/genética , Fator VII/genética , Doenças do Prematuro/genética , Hemorragias Intracranianas/genética , Polimorfismo de Nucleotídeo Único , Sangramento por Deficiência de Vitamina K/genética , Vitamina K Epóxido Redutases/genética , Biomarcadores/sangue , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/sangue , Hemorragias Intracranianas/sangue , Modelos Logísticos , Masculino , Estudos Prospectivos , Sangramento por Deficiência de Vitamina K/sangue
18.
Neonatology ; 102(4): 270-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22906886

RESUMO

BACKGROUND: Pathogenesis of intraventricular hemorrhage (IVH) in premature infants is multifactorial. Little is known about the influence of pro-inflammatory cytokine activation on the coagulation system in extremely preterm infants and its impact on the development of IVH. OBJECTIVE: To determine the interaction between serum interleukin-6 (IL-6) and the coagulation system in preterm infants predisposed to the development of IVH. METHODS: Vitamin K-dependent coagulation factors were examined retrospectively in 132 extremely preterm infants prior to vitamin K administration at the first day of life. Patients were grouped according to the occurrence of IVH and serum concentration of IL-6 >/<100 pg/ml. RESULTS: Occurrence of IVH was associated with clinical diagnosis of chorioamnionitis, low gestational age, high CRIB score, air leak, catecholamine treatment, low initial hematocrit and increased serum concentration of IL-6. Infants developing IVH showed a diminished coagulation profile. Multivariable logistic regression analysis revealed decreased activity of coagulation factor VII, development of pneumothorax and low hematocrit as independent risk factors for the development of IVH. An increased IL-6 serum concentration was associated with a significantly decreased activity of coagulation factor VII and increased levels of fibrinogen. CONCLUSIONS: The association of elevated IL-6 levels with alterations of the coagulation profile and development of IVH found in our study supports the assumption of a close pathophysiological relation between inflammation and IVH.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Fatores de Coagulação Sanguínea/análise , Hemorragia Cerebral/sangue , Lactente Extremamente Prematuro , Interleucina-6/sangue , Adulto , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/epidemiologia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiologia , Corioamnionite/sangue , Corioamnionite/diagnóstico , Corioamnionite/epidemiologia , Comorbidade , Fator VII/análise , Feminino , Fibrinogênio/análise , Alemanha/epidemiologia , Hematócrito , Humanos , Recém-Nascido , Masculino , Pneumotórax , Gravidez , Estudos Retrospectivos , Fatores de Risco
19.
Dev Med Child Neurol ; 54(1): 15-22, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22126123

RESUMO

AIM: Our aim was to compare the effect of prenatal endoscopic with postnatal myelomeningocele closure (fetally operated spina bifida aperta [fSBA]) versus neonatally operated spina bifida aperta [nSBA]) on segmental neurological leg condition. METHOD: Between 2003 and 2009, the fetal surgical team (Department of Obstetrics, University of Bonn, Germany) performed 19 fetal endoscopic procedures. Three procedures resulted in fetal death, three procedures were interrupted by iatrogenic hemorrhages and 13 procedures were successful. We matched each successfully treated fSBA infant with another nSBA infant of the same age and level of lesion, resulting in 13 matched pairs (mean age 14 mo; SD 16 mo; f/m=1.6; female-16, male-10). Matched fSBA and nSBA pairs were compared in terms of segmental neurological function and leg muscle ultrasound density (MUD). We also determined intraindividual difference in MUD (dMUD) between myotomes caudal and cranial to the myelomeningocele (reflecting neuromuscular damage by the myelomeningocele) and compared dMUD between fSBA and nSBA infants. Finally, we correlated dMUD with segmental neurological function. RESULTS: We found that, on average, the fSBA group were born at a lower gestational age than the nSBA group (median 32 wks [range 25-34 wks] vs 39 wks [34-41 wks]; p=0.001) and experienced more complications (chorioamnionitis, premature rupture of the amniotic membranes, oligohydramnios, and infant respiratory distress syndrome necessitating intermittent positive-pressure ventilation). Neurological function was better preserved after fSBA than after nSBA (median motor and sensory gain of two segments; better preserved knee-jerk [p=0.006] and anal [p=0.032] reflexes). The dMUD was smaller in fSBA than in nSBA infants (mean difference 24, 95% confidence interval [CI] 15-33; p<0.05), which was associated with better preserved segmental muscle function. INTERPRETATION: Fetal endoscopic surgery is associated with spinal segmental neuroprotection, but it results in more complications. Before considering clinical implementation of fetal endoscopic myelomeningocele closure as standard care, the frequency of complications should be appropriately reduced and results assessed in larger groups over a longer period of time.


Assuntos
Fetoscopia/métodos , Meningomielocele/fisiopatologia , Meningomielocele/cirurgia , Espinha Bífida Cística/cirurgia , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/mortalidade , Malformação de Arnold-Chiari/fisiopatologia , Malformação de Arnold-Chiari/cirurgia , Comorbidade , Avaliação da Deficiência , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Complicações Intraoperatórias/diagnóstico por imagem , Complicações Intraoperatórias/mortalidade , Complicações Intraoperatórias/fisiopatologia , Complicações Intraoperatórias/cirurgia , Masculino , Meningomielocele/diagnóstico por imagem , Meningomielocele/mortalidade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiopatologia , Exame Neurológico , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Prognóstico , Fatores de Risco , Espinha Bífida Cística/diagnóstico por imagem , Espinha Bífida Cística/mortalidade , Espinha Bífida Cística/fisiopatologia , Resultado do Tratamento , Ultrassonografia Pré-Natal
20.
Child Psychiatry Hum Dev ; 43(1): 137-51, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21927969

RESUMO

The aim of the present study was to develop and validate the Children's Depression Screener (ChilD-S) for use in pediatric care. In two pediatric samples, children aged 9-12 (N(I) = 200; N(II) = 246) completed an explorative item pool (subsample I) and a revised item pool (subsample II). Diagnostic accuracy of each of the 22 items from the revised pool was evaluated in order to select the best items for the brief instrument ChilD-S. Areas under the curve (AUCs) of the revised item pool and the ChilD-S were compared. A diagnostic interview, the Kinder-DIPS, served as gold standard. For the purpose of screening for depressive disorders in children, the eight-item ChilD-S (AUC = 0.97) performed just as well as the revised 22-item pool (AUC = 0.94). For the ChilD-S the optimal cut-off point of ≥11 yielded a sensitivity of 0.91 and a specificity of 0.89. The ChilD-S shows high potential for depression screening of children in pediatric care.


Assuntos
Transtorno Depressivo/diagnóstico , Programas de Rastreamento , Inventário de Personalidade/estatística & dados numéricos , Criança , Transtorno Depressivo/psicologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Entrevista Psicológica , Masculino , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes
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