RESUMO
Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability. Preclinical studies show that the systemic administration of umbilical cord blood cells (UCBCs) is beneficial for neonatal HIE. We conducted a single-arm clinical study to examine the feasibility and safety of intravenous infusion of autologous UCBCs for newborns with HIE. When a neonate was born with severe asphyxia, the UCB was collected, volume-reduced, and divided into three doses. The processed UCB was infused at 12-24, 36-48, and 60-72 hours after the birth. The designed enrolment was six newborns. All six newborns received UCBC therapy strictly adhering to the study protocol together with therapeutic hypothermia. The physiological parameters and peripheral blood parameters did not change much between pre- and postinfusion. There were no serious adverse events that might be related to cell therapy. At 30 days of age, the six infants survived without circulatory or respiratory support. At 18 months of age, neurofunctional development was normal without any impairment in four infants and delayed with cerebral palsy in two infants. This pilot study shows that autologous UCBC therapy is feasible and safe.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Sangue Fetal/citologia , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/terapia , Biomarcadores , Gasometria , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Eletroencefalografia , Feminino , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/metabolismo , Recém-Nascido , Masculino , Projetos PilotoRESUMO
Meconium obstruction (MO) in extremely low birth weight (ELBW) infants is a challenging disease to treat. We performed ultrasound-guided hydrostatic enema on six ELBW infants diagnosed with MO. We consider this procedure to be safe and effective, and recommend it as a treatment for MO in ELBW infants.
Assuntos
Enema/métodos , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/terapia , Mecônio , Ultrassonografia de Intervenção , Feminino , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Obstrução Intestinal/etiologia , MasculinoRESUMO
BACKGROUND: Chorioamnionitis (CAM) is an important risk factor for the development of bronchopulmonary dysplasia (BPD) in preterm infants. OBJECTIVES: To evaluate the effects of CAM on the development of BPD using interleukin 6 (IL-6), Krebs von den Lungen 6 (KL-6), and transforming growth factor ß1 (TGF-ß1) in the amniotic fluid as markers for inflammation, lung injury, and fibrosis/remodeling, respectively. METHODS: Amniotic fluid concentrations of IL-6, KL-6, and TGF-ß1 were measured with enzyme-linked immunosorbent assay or electro-chemiluminescence immunoassay. RESULTS: Of the 36 preterm infants, 18 were exposed to histologically confirmed CAM. Of these, 12 were later diagnosed as having BPD. The IL-6, KL-6, and TGF-ß1 levels in the amniotic fluid significantly increased with increasing histologic severity of CAM. Moreover, these markers were higher in the BPD group with histologic CAM than those without. CONCLUSIONS: Our study suggests that CAM is likely to induce inflammatory, injury, and remodeling processes in the fetal lung.
RESUMO
BACKGROUND: We investigated the effects of glucocorticoids, erythropoietin (EPO) and spironolactone (SPL) n human fetal lung fibroblasts and human alveolar epithelial cells exposed to tracheal aspirate fluid (TAF) from extremely premature infants with chronic lung disease (CLD), characterized by fibrosis and changes in the alveolar epithelium. METHODS: Fibroblasts and epithelial cells (FHs 738Lu and A549, respectively) were treated with different concentrations of hydrocortisone (HDC), dexamethasone (DEX), betamethasone (BET), SPL, and EPO in the absence or presence of TAF from infants with CLD (gestational age, 25.3 ± 0.8 weeks; birthweight, 658 ± 77 g; postnatal age, 0-28 days) and assayed for proliferation. RESULTS: Exposure to TAF resulted in a concentration-dependent proliferation of fibroblasts and epithelial cells. Proliferation of TAF-exposed fibroblasts was suppressed most significantly by 100 µmol/L DEX (21%, P = 0.046) and 300 mIU/mL EPO (18%, P = 0.02) and promoted most significantly by 0.4 µmol/L HDC (10%, P = 0.04). Epithelial proliferation was promoted by 4 µmol/L HDC (15%, P = 0.04), 10 µmol/L DEX (53%, P < 0.01), 0.2 µmol/L BET (56%, P < 0.01), and 300 mIU/mL EPO (35%, P < 0.01) in the presence of TAF. Treatment with glucocorticoids alone did not significantly affect fibroblast proliferation. CONCLUSIONS: Glucocorticoids and EPO reduced fibroproliferation while promoting epithelial cell growth in vitro within certain dose ranges. Appropriate doses of glucocorticoids and EPO may be useful in the prevention and resolution of CLD in extremely premature infants.
Assuntos
Células Epiteliais/patologia , Eritropoetina/uso terapêutico , Glucocorticoides/uso terapêutico , Doenças do Prematuro/tratamento farmacológico , Recém-Nascido Prematuro , Alvéolos Pulmonares/patologia , Traqueia/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Doença Crônica , Células Epiteliais/efeitos dos fármacos , Feminino , Fibroblastos/patologia , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Prematuro/patologia , Pneumopatias , Masculino , Alvéolos Pulmonares/efeitos dos fármacos , Traqueia/efeitos dos fármacosRESUMO
Chorioamnionitis (CAM) can initiate fetal lung injury resulting in neonatal bronchopulmonary dysplasia (BPD). While neonates with BPD have higher amniotic fluid concentrations of proinflammatory cytokines, overexpression of transforming growth factor (TGF)-beta(1) also appears important in the pathogenesis of BPD. The aim of this study was to investigate the relationship between TGF-beta(1) and CAM-induced fetal lung injury. Forty-four amniotic fluid samples were obtained at delivery of preterm infants (median gestation, 28 weeks; birth weight, 908 g). TGF-beta(1) and interleukin (IL)-6 concentrations in the amniotic fluid were measured with ELISA. Both TGF-beta(1) and IL-6 concentrations in the amniotic fluid increased with increasing histological severity of CAM (each p < 0.0001). The presence of both BPD and histological CAM was associated with significantly higher amniotic fluid TGF-beta(1) and IL-6 concentrations than the presence of BPD without histological CAM, or the absence of both (each p < 0.0001). Both concentrations also correlated with the duration of oxygen administration in the neonates (each p < 0.0001). Amniotic fluid TGF-beta(1) seems to be important in CAM-induced fetal lung injury progressing to neonatal BPD.
Assuntos
Líquido Amniótico/metabolismo , Displasia Broncopulmonar/metabolismo , Corioamnionite/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/patologia , Corioamnionite/patologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Interleucina-6/metabolismo , Valor Preditivo dos Testes , Gravidez , Fatores de RiscoRESUMO
Lung injury alters the expression and release of growth factors that disrupt postnatal pulmonary development in newborns and causes chronic lung disease (CLD). The effect of these factors, released into the airways of newborns with CLD, on cell proliferation and collagen production was characterized in vitro. Human fetal lung fibroblast and alveolar-epithelial-like cell lines (FHs 738Lu and A549, respectively) were exposed to tracheal effluents from infants with CLD (mean gestation, 24.7 +/- 0.9 wk; birth weight, 666 +/- 85 g; postnatal age, 0-62 d). In both cell types, proliferation was assessed by measuring [(3)H]-thymidine uptake; in fibroblasts, collagen production was analyzed by measuring [(3)H]-proline incorporation. The activity of specific growth factors in effluents was determined using anti-growth factor antibodies and the growth factors themselves. Growth factors in tracheal effluents promoted proliferation in a dose-dependent manner and caused up to a 10.2- and 3.1-fold increase in thymidine uptake by fibroblasts and epithelial cells, respectively. Collagen production by fibroblasts increased dose dependently, peaking at 177% of baseline. Antibody against transforming growth factor beta-1 (TGF-beta(1)) inhibited proliferation and the increase in collagen production by 31% (p = 0.01) and 14% (p = 0.045), respectively. Antibody against hepatocyte growth factor (HGF) inhibited proliferation of epithelial cells (25%, p = 0.039). The effects of exogenous TGF-beta(1) on fibroblasts and HGF on epithelial cells resembled those of tracheal effluents. Potent mitogenic and differentiating substances are released into the tracheal effluents of newborns with CLD. TGF-beta(1) may worsen CLD by inducing fibrosis whereas HGF may favor resolution by promoting epithelialization.
Assuntos
Pneumopatias/fisiopatologia , Mitógenos/isolamento & purificação , Traqueia/fisiopatologia , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Doença Crônica , Colágeno/biossíntese , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Substâncias de Crescimento/farmacologia , Humanos , Técnicas In Vitro , Recém-Nascido , Recém-Nascido Prematuro , Lesão Pulmonar , Mitógenos/farmacologia , Alvéolos Pulmonares/citologia , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/metabolismoRESUMO
BACKGROUND: The present study describes the outcome at 3 years in term and near-term infants treated with inhaled nitric oxide (iNO) for persistent pulmonary hypertension of the newborn (PPHN). METHODS: The study population consisted of 18 infants delivered at 34 weeks by best obstetric estimate who were admitted to the neonatal intensive care units with a diagnosis of PPHN. RESULTS: Eighteen infants (mean gestational age 38.5 +/- 2.6 weeks, mean birthweight 3015 +/- 587 g) were treated with iNO. The mean oxygenation index before iNO was 27.2 +/- 15.2. Responses to iNO were classified into three groups: (i) early response in eight infants; (ii) late response in two; and (iii) poor response in eight infants. Three infants died within seven postnatal days. Fifteen surviving infants were followed up to 3 years. The mean developmental scale was 98.4 +/- 9.0. One infant was diagnosed with severe neurodevelopmental disability due to cerebral palsy. Another infant was diagnosed with mild neurodevelopmental disability because of a low developmental scale. No infant showed significant hearing loss. Five infants had reactive airway disease (RAD) at 18 months, these infants required a significantly longer duration of mechanical ventilation in their neonatal period than non-RAD infants (P = 0.02). The frequency of survival with normal neurodevelopmental outcome was significantly higher in the early response group than the late or poor response groups (P = 0.03). CONCLUSION: In iNO-treated PPHN, mortality and neurodevelopmental outcome were associated with response to iNO, and pulmonary outcome was associated with duration of mechanical ventilation.