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In patients with congenital diaphragmatic hernia1, nutrition can represent a challenge both in the short and long term. Its failure to resolve can have a significant impact on multiple aspects of the lives of patients with congenital diaphragmatic hernia (CDH), ranging from lung function to neurodevelopment. In this review, we will describe the causes of nutritional problems in patients with CDH, their consequences, and possible strategies to address them.
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Hernias Diafragmáticas Congénitas , Humanos , Hernias Diafragmáticas Congénitas/complicaciones , Recién Nacido , Apoyo Nutricional/métodosRESUMEN
AIM: This work explores the experiences and meaning attributed by parents who underwent the decision-making process of withholding and/or withdrawing life-sustaining treatment for their newborn. METHODS: Audio-recorded face-to-face interviews were led and analysed using interpretative phenomenological analysis. Eight families (seven mothers and five fathers) whose baby underwent withholding and/or withdrawing of life-sustaining treatment in three neonatal intensive care units from two regions in France were included. RESULTS: The findings reveal two paradoxes within the meaning-making process of parents: role ambivalence and choice ambiguity. We contend that these paradoxes, along with the need to mitigate uncertainty, form protective psychological mechanisms that enable parents to cope with the decision, maintain their parental identity and prevent decisional regret. CONCLUSION: Role ambivalence and choice ambiguity should be considered when shared decision-making in the neonatal intensive care unit. Recognising and addressing these paradoxical beliefs is essential for informing parent support practices and professional recommendations, as well as add to ethical discussions pertaining to parental autonomy and physicians' rapport to uncertainty.
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Unidades de Cuidado Intensivo Neonatal , Cuidados Paliativos , Recién Nacido , Lactante , Femenino , Humanos , Privación de Tratamiento , Toma de Decisiones , Padres/psicologíaRESUMEN
Introduction: Congenital diaphragmatic hernia (CDH) is a rare condition characterized by pulmonary hypoplasia, vascular dystrophy, and pulmonary hypertension at birth. Validation of the lamb model as an accurate representation of human CDH is essential to translating research findings into clinical practice and understanding disease mechanisms. This article emphasizes the importance of validating the lamb model to study CDH pathogenesis and develop innovative therapeutics. Material and methods: At 78 days of gestation, the fetal lamb's left forelimb was exposed through a midline laparotomy and hysterotomy, and a supra diaphragmatic thoracotomy was performed to allow the digestive organs to ascend into the thoracic cavity. At 138 ± 3 days of gestation, lambs were delivered via a cesarean section; then, with umbilical cord intact during 1 hour, the lambs were mechanically ventilated with gentle ventilation in a pressure-controlled mode for 2 h. Results: CDH lambs exhibited a lower left lung-to-body weight ratio of 5.3 (2.03), p < 0.05, and right lung-to-body weight ratio of 8.2 (3.1), p < 0.05. They reached lower Vt/kg (tidal volume per kg) during the course of the resuscitation period with 1.2 (0.7)â ml/kg at 10â min and 3 (1.65)â ml/kg at 60â min (p < 0.05). Compliance of the respiratory system was lower in CDH lambs with 0.5 (0.3)â ml/cmH2O at 60â min (p < 0.05) and 0.9 (0.26)â ml/cmH2O at 120â min (p < 0.05). Differences between pre- and postductal SpO2 were higher with 15.1% (21.4%) at 20â min and 6.7% (14.5%) at 80â min (p < 0.05). CDH lambs had lower differences between inspired and expired oxygen fractions with 4.55% (6.84%) at 20â min and 6.72% (8.57%) at 60â min (p < 0.05). CDH lamb had lower left ventricle [2.73 (0.5)â g/kg, p < 0.05] and lower right ventricle [0.69 (0.8), p < 0.05] to left ventricle ratio. Discussion: CDH lambs had significantly lower tidal volume than control lambs due to lower compliance of the respiratory system and higher airway resistance. These respiratory changes are characteristic of CDH infants and are associated with higher mortality rates. CDH lambs also exhibited pulmonary hypertension, pulmonary hypoplasia, and left ventricle hypoplasia, consistent with observations in human newborns. To conclude, our lamb model successfully provides a reliable representation of CDH and can be used to study its pathophysiology and potential interventions.
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Background: Persistent pulmonary hypertension of the newborn (PPHN) is usually considered a consequence of impaired pulmonary circulation. However, little is known regarding the role of cardiac dysfunction in PPHN. In this study, we hypothesized that the tolerance for pulmonary hypertension in newborn infants depends on the biventricular function. The aim of this study is to evaluate biventricular cardiac performance by using Tissue Doppler Imaging (TDI) in an healthy newborn infants with asymptomatic pulmonary hypertension and in newborn infants with PPHN. Methods: Right and left cardiac function were investigated using conventional imaging and TDI in 10 newborn infants with PPHN ("PPHN") and 10 asymptomatic healthy newborn infants ("asymptomatic PH"). Results: Systolic pulmonary artery pressure (PAP) as assessed by TDI and the mean systolic velocity of the right ventricular (RV) free wall were similar in both groups. The isovolumic relaxation time of the right ventricle at the tricuspid annulus was significantly longer in the "PPHN" than in the "asymptomatic PH" group (53 ± 14â ms vs. 14 ± 4â ms, respectively; p < 0.05). Left ventricular (LV) function was normal in both groups with a systolic velocity (S'LV) at the LV free wall groups (6 ± 0.5â cm/s vs. 8.3 ± 5.7â cm/s, p > 0.05). Conclusion: The present results suggest that high PAP with or without respiratory failure is not associated with altered right systolic ventricular function and does not affect LV function in newborn infants. PPHN is characterized by a marked right diastolic ventricular dysfunction. These data suggest that the hypoxic respiratory failure in PPHN results, at least in part, from diastolic RV dysfunction and right to left shunting across the foramen ovale. We propose that the severity of the respiratory failure is more related to the RV diastolic dysfunction than the pulmonary artery pressure.
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BACKGROUND: Congenital diaphragmatic hernia (CDH) is a rare disease associated with major nutritional and digestive morbidities. Oral feeding autonomy remains a major issue for the care and management of these patients. The aim of this study was to specify the perinatal risk factors of delayed oral feeding autonomy in patients treated for CDH. METHODS: This monocentric cohort study included 138 patients with CDH. Eighty-four patients were analyzed after the exclusion of 54 patients (11 with delayed postnatal diagnosis, 5 with chromosomal anomaly, 9 with genetic syndrom, 13 with right-sided CDH, and 16 who died before discharge and before oral feeding autonomy was acquired). They were divided into two groups: oral feeding autonomy at initial hospital discharge (group 1, n = 51) and nutritional support at discharge (group 2, n = 33). Antenatal, postnatal, and perisurgical data were analyzed from birth until first hospital discharge. To remove biased or redundant factors related to CDH severity, statistical analysis was adjusted according to the need for a patch repair. RESULTS: After analysis and adjustment, delayed oral feeding autonomy was not related to observed/expected lung-to-head ratio (LHR o/e), intrathoracic liver and/or stomach position, or operative duration. After adjustment, prophylactic gastrostomy (OR adjusted: 16.3, IC 95%: 3.6-74.4) and surgical reoperation (OR adjusted: 5.1, IC 95% 1.1-23.7) remained significantly associated with delayed oral feeding autonomy. CONCLUSIONS: Delayed oral feeding autonomy occurred in more than one third of patients with CDH. Both prophylactic gastrostomy and surgical reoperation represent significant risk factors. Bowel obstruction might also impact oral feeding autonomy. Prophylactic gastrostomy seems to be a false "good idea" to prevent failure to thrive. This procedure should be indicated case per case. Bowel obstruction and all surgical reoperations represent decisive events that could impact oral feeding autonomy.
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Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia and respiratory morbidity. To assess whether respiratory morbidity during the first 2 years of life in infants with left-sided CDH is associated with fetal lung volume (FLV) evaluated by the observed-to-expected FLV ratio (o/e FLV) on antenatal magnetic resonance imaging (MRI). In this retrospective study, o/e FLV measures were collected. Respiratory morbidity in the first 2 years of life was studied according to two endpoints: treatment with inhaled corticosteroids for >3 consecutive months and hospitalization for any acute respiratory disease. The primary outcome was a favorable progression defined by the absence of either endpoint. Forty-seven patients were included. The median o/e FLV was 39% (interquartile range, 33-49). Sixteen (34%) infants were treated with inhaled corticosteroids and 13 (28%) were hospitalized. The most efficient threshold for a favorable outcome was an o/e FLV ≥ 44% with a sensitivity of 57%, specificity of 79%, negative predictive value of 56%, and positive predictive value of 80%. An o/e FLV ≥ 44% was associated with a favorable outcome in 80% of cases. These data suggest that lung volume measurement on fetal MRI may help to identify children at lower respiratory risk and improve information during pregnancy, patient characterization, decisions about treatment strategy and research, and personalized follow-up.
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Our objective is to determine perinatal factors contributing to the development of pulmonary hypertension (PH) in patients with isolated giant omphaloceles (GO). All cases of omphaloceles that underwent prenatal and postnatal care at the University Hospital of Lille between 1996 and 2021 were reviewed. We included all infants with isolated GO, including at least a part of the liver, who were treated by delayed surgical closure. Prenatal and postnatal data were recorded and correlated with postnatal morbidities. We compared outcomes between a group of infants with GO who developed PH and infants with GO with no PH. We identified 120 infants with omphalocele. Fifty isolated GO cases fulfilled the inclusion criteria of our study. The incidence of PH was 30%. We highlighted a prolonged inflammatory state, defined as a CRP superior to 15 mg/L, platelets higher than 500 G/L, and white blood cells higher than 15 G/l for more than 14 days in patients who developed PH. This event occurred in 73% of patients with PH versus 21% of patients without PH (p < 0.05). Late-onset infection was not different between the two groups. We speculate that prolonged inflammatory syndrome promotes PH in infants with GO treated with delayed surgical closure.
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Congenital diaphragmatic hernia (CDH) is associated with abnormal pulmonary development, which is responsible for pulmonary hypoplasia with structural and functional abnormalities in pulmonary circulation, leading to the failure of the cardiorespiratory adaptation at birth. Despite improvement in treatment options and advances in neonatal care, mortality remains high, at close to 15 to 30%. Several risk factors of mortality and morbidities have been validated in fetuses with CDH. Antenatal assessment of lung volume is a reliable way to predict the severity of CDH. The two most commonly used measurements are the observed/expected lung to head ratio (LHRo/e) and the total pulmonary volume (TPV) on MRI. The estimation of total pulmonary volume (TPVo/e) by means of prenatal MRI remains the gold standard. In addition to LHR and TPV measurements, the position of the liver (up, in the thorax or down, in the abdomen) also plays a role in the prognostic evaluation. This prenatal prognostic evaluation can be used to select fetuses for antenatal surgery, consisting of fetoscopic endoluminal tracheal occlusion (FETO). The antenatal criteria of severe CDH with an ascended liver (LHRo/e or TPVo/e < 25%) are undoubtedly associated with a high risk of death or significant morbidity. However, despite the possibility of estimating the risk in antenatal care, it is difficult to determine what is in the child's best interest, as there still are many uncertainties: (1) uncertainty about individual short-term prognosis; (2) uncertainty about long-term prognosis; and (3) uncertainty about the subsequent quality of life, especially when it is known that, with a similar degree of disability, a child's quality of life varies from poor to good depending on multiple factors, including family support. Nevertheless, as the LHR decreases, the foreseeable "burden" becomes increasingly significant, and the expected benefit is increasingly unlikely. The legal and moral principle of the proportionality of medical procedures, as well as the prohibition of "unreasonable obstinacy" in all investigations or treatments undertaken, is necessary in these situations. However, the scientific and rational basis for assessing the long-term individual prognosis is limited to statistical data that do not adequately reflect individual risk. The risk of self-fulfilling prophecies should be kept in mind. The information given to parents must take this uncertainty into account when deciding on the treatment plan after birth.
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Conventional mechanical ventilation (CMV) has been recommended as the first-line mode of respiratory support for neonates born with a congenital diaphragmatic hernia (CDH). However, older studies suggested that protective high-frequency oscillatory ventilation (HFOV) with low-mean airway pressure (MAP) may limit lung injury. We aimed to compare low-MAP HFOV with CMV in neonates with CDH in terms of patient outcomes. This retrospective cohort study was conducted in two French neonatal intensive care units: center 1 mainly used CMV, and center 2 mainly used HFOV with a low MAP. All term neonates with CDH born between 2010 and 2018 in these two centers were included. The primary outcome was the duration of oxygen therapy. Secondary outcomes were survival and duration of mechanical ventilation. A total of 170 patients (105 in center 1, 65 in center 2) were included. In center 2, 96% of patients were ventilated with HFOV versus 19% in center 1. After adjustment for perinatal data, there was no significant difference regarding duration of oxygen therapy (SHR 0.83, 95% CI [0.55-1.23], p = 0.35) or survival (HR 1.73, 95% CI [0.64-4.64], p = 0.28). Center 2 patients required longer mechanical ventilation and sedation. CONCLUSION: First-line mode of mechanical ventilation was not associated with the duration of oxygen therapy or survival in neonates with CDH. WHAT IS KNOWN: ⢠Recommendations were given in favour of using the conventional mechanical ventilation in first intention in neonates with a congenital diaphragmatic hernia, since High frequency oscillation (HFO) has been associated with a higher morbidity. WHAT IS NEW: ⢠No differences between HFO and conventional mechanical ventilation were observed concerning the length of oxygen supply and the survival..
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Infecciones por Citomegalovirus , Hernias Diafragmáticas Congénitas , Ventilación de Alta Frecuencia , Femenino , Hernias Diafragmáticas Congénitas/terapia , Humanos , Recién Nacido , Oxígeno , Embarazo , Respiración Artificial , Estudios RetrospectivosRESUMEN
Background: The use of non-steroidal anti-inflammatory drugs (NSAIDs) during the third trimester of pregnancy can cause premature constriction of the ductus arteriosus. This report describes a case of in utero narrowing of the ductus arteriosus (DA) diagnosed postnatally in a baby with Persistent Pulmonary Hypertension of the Newborn (PPHN), after maternal use of Diclofenac-Epolamine 140 mg patch during the second and third trimester. Case Presentation: A fetal ultrasounds revealed an enlarged hypertrophic right ventricle at 32 weeks of gestation. Detailed questioning of the mother highlighted that topical Diclofenac (FLECTOR®) had been used at 26 and at 31 weeks of gestation. An echocardiography performed 8 h postnatally showed supra-systemic pulmonary hypertension, a restrictive ductus arteriosus and a dilated right ventricle. The newborn was treated by inhaled nitric oxide and oral Sildenafil and was discharged from hospital on day 24. He had a complete normalization of his pulmonary vascular resistance on day 48. Conclusion: This case illustrates the potential fetal and neonatal complications associated with maternal topical Diclofenac medication during pregnancy resulting in antenatal closure of the DA.
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Some previous studies reported a benefit to cardiopulmonary transition at birth when starting resuscitation maneuvers while the cord was still intact for a short period of time. However, the best timing for umbilical cord clamping in this condition is unknown. The aim of this study was to explore the duration of effective umbilico-placental circulation able to promote cardiorespiratory adaptation at birth during intact cord resuscitation. Umbilico-placental blood flow and vascular resistances were measured in an experimental neonatal lamb model. After a C-section delivery, the lambs were resuscitated ventilated for 1 h while the cord was intact. The maximum and mean umbilico-placental blood flow were respectively 230 ± 75 and 160 ± 12 mL·min-1 during the 1 h course of the experiment. However, umbilico-placental blood flow decreased and vascular resistance increased significantly 40 min after birth (p < 0.05). These results suggest that significant cardiorespiratory support can be provided by sustained placental circulation for at least 1 h during intact cord resuscitation.
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Resuscitation at birth of infants with Congenital Diaphragmatic Hernia (CDH) remains highly challenging because of severe failure of cardiorespiratory adaptation at birth. Usually, the umbilical cord is clamped immediately after birth. Delaying cord clamping while the resuscitation maneuvers are started may: (1) facilitate blood transfer from placenta to baby to augment circulatory blood volume; (2) avoid loss of venous return and decrease in left ventricle filling caused by immediate cord clamping; (3) prevent initial hypoxemia because of sustained uteroplacental gas exchange after birth when the cord is intact. The aim of this trial is to evaluate the efficacy of intact cord resuscitation compared to immediate cord clamping on cardiorespiratory adaptation at birth in infants with isolated CDH. The Congenital Hernia Intact Cord (CHIC) trial is a prospective multicenter open-label randomized controlled trial in two balanced parallel groups. Participants are randomized either immediate cord clamping (the cord will be clamped within the first 15 s after birth) or to intact cord resuscitation group (umbilical cord will be kept intact during the first part of the resuscitation). The primary end-point is the number of infants with APGAR score <4 at 1 min or <7 at 5 min. One hundred eighty participants are expected for this trial. To our knowledge, CHIC is the first study randomized controlled trial evaluating intact cord resuscitation on newborn infant with congenital diaphragmatic hernia. Better cardiorespiratory adaptation is expected when the resuscitation maneuvers are started while the cord is still connected to the placenta.
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AIM: To assess quality of life (QoL) in children with congenital diaphragmatic hernia (CDH) and to compare it with oesophageal atresia (OA). METHODS: A cross-sectional study in CDH children (≥7 years) was conducted in Lille University Hospital, France, from January 2013 to April 2014. History, lung function (rest, exercise) and Pediatric Quality of Life Inventory questionnaires (PedsQoL 4.0) were collected. Data of OA children were previously published. RESULTS: Fifty-four CDH patients (male: 53%, median age: 11 years, IQR 9-14) were compared to 54 OA patients (male: 61%, median age: 13 years, IQR: 11-15). CDH children had significantly more frequent history of pneumonia (30% vs 13%), exercise limitation (54% vs 35%) and chest deformity (39% vs 11%); 46% had an obstructive pattern and 66% an abnormal cardiopulmonary exercise test. The median PedsQoL total score in children was 81 (IQR 73-90) in CDH and 81 (IQR 72-91) in OA (P = .8). In CDH, duration of neonatal oxygen therapy, hospitalisation for respiratory disease, exercise limitation, inhaled corticosteroids treatment, chest deformity, abnormal cardiopulmonary exercise test and lower forced expiratory volume in one second were significantly associated with lower QoL scores. CONCLUSION: PedsQoL scores remained satisfactory in CDH children with CDH, with no difference compared to OA. Patients with respiratory morbidity and lung function impairment, who displayed lower scores, should be identified in order to optimise their management in reference centres.
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Atresia Esofágica , Hernias Diafragmáticas Congénitas , Adolescente , Niño , Estudios Transversales , Atresia Esofágica/complicaciones , Francia , Hernias Diafragmáticas Congénitas/complicaciones , Humanos , Recién Nacido , Masculino , Morbilidad , Calidad de VidaRESUMEN
OBJECTIVE: In the emergency department (ED), the early identification of patients suspected of infection is a challenge for emergency physicians. Sepsis prevalence among patients with suspected infection in the ED remains uncertain. Our objective was to determine how many cases of sepsis occurred among patients with suspected infections in the ED. METHODS: This multi-center, prospective, observational study was conducted in 19 EDs in France. For 1 week, all consecutive ED patients with suspected infection (according to the emergency physician) were included. The primary endpoint was the prevalence of sepsis in the ED according to the 'sepsis-3' definition. Secondary endpoints involved comparisons among patients with and without sepsis. RESULTS: During the study period, 13 904 patients were screened; 494 (3.6%) consulted for suspected infection and were included in the study. Among them, 172 patients [39%, 95% confidence interval (CI) (34-44)] were diagnosed with sepsis. The total hospital mortality for patients with a suspected infection was 4.7% and the hospital mortality for sepsis patients was 9.9%. CONCLUSION: In the ED, among patients with a suspected infection, the prevalence of sepsis as per the 'sepsis-3' definition was 39% [95% CI (34-44)].
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Sepsis , Servicio de Urgencia en Hospital , Francia/epidemiología , Mortalidad Hospitalaria , Humanos , Prevalencia , Estudios Prospectivos , Sepsis/diagnóstico , Sepsis/epidemiologíaRESUMEN
BACKGROUND: Suprasystemic pulmonary hypertension (PH) is highly predictive of pulmonary morbidity and death in infants with congenital diaphragmatic hernia (CDH). OBJECTIVES: To report the effects and tolerability of Prostaglandin E1 (PGE1) in newborns with severe CDH and life-threatening PH. METHODS: Newborn infants with isolated CDH and life-threatening PH defined by an acute worsening of the cardiorespiratory function, and bidirectional or exclusive right-to-left shunting across the ductus arteriosus (DA) with an acceleration of the blood flow >1.5â¯m.s-1 assessed by Doppler echocardiography. Serial measurements of cardiorespiratory variables have been recorded before and after PGE1. RESULTS: 18 infants (out of 102 in the cohort) were included in the study (gestational age: 39⯱â¯2â¯weeks). The median FiO2, and preductal and postductal SpO2 were 80% [50; 100], 91% [88; 95] and 86% [82; 91], respectively, before treatment. FiO2 decreased to 35% [30-40] (pâ¯=â¯0.001) at H6. Maximal blood flow velocities in the DA decreased after starting PGE1 from 2.2â¯m.s-1 [1.5-2.5] to 1â¯m.s-1 [0.55-1.2] (pâ¯<â¯0.001). CONCLUSIONS: PGE1 treatment improved oxygenation and circulatory function in newborn infants with severe CDH and life-threatening PH. Our data provide evidence that restrictive DA may result in suprasystemic pulmonary hypertension in CDH infants, and that PGE1 may improve cardiorespiratory failure through reopening of the DA. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.
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Alprostadil/uso terapéutico , Conducto Arterial , Hernias Diafragmáticas Congénitas , Hipertensión Pulmonar , Vasodilatadores/uso terapéutico , Edad Gestacional , Humanos , Recién NacidoRESUMEN
OBJECTIVE: To investigate the effects of distending pressures on respiratory mechanics and pulmonary circulation in newborn infants with congenital diaphragmatic hernia (CDH) and persistent pulmonary hypertension (PPHN). STUDY DESIGN: In total, 17 consecutive infants of ≥37 weeks of gestational age with CDH and PPHN were included in this prospective, randomized, crossover pilot study. Infants were assigned randomly to receive 2 or 5 cmH2O of positive end-expiratory pressure (PEEP) for 1 hour in a crossover design. The difference between peak inspiratory pressure and PEEP was kept constant. Respiratory mechanics, lung function, and hemodynamic variables assessed by Doppler echocardiography were measured after each study period. RESULTS: At 2 cmH2O of PEEP, tidal volume and minute ventilation were greater (P < .05), and respiratory system compliance was 30% greater (P < .05) than at 5 cmH2O. PaCO2 and ventilation index were lower at 2 cmH2O than at 5 cmH2O (P < .05). Although preductal peripheral oxygen saturation was similar at both PEEP levels, postductal peripheral oxygen saturation was lower (median [range]: 81% [65-95] vs 91% [71-100]) and fraction of inspired oxygen was greater (35% [21-70] vs 25% [21-60]) at 5 cmH2O. End-diastolic left ventricle diameter, left atrium/aortic root ratio, and pulmonary blood flow velocities in the left pulmonary artery were lower at 5 cmH2O. CONCLUSIONS: After surgical repair, lower distending pressures result in better respiratory mechanics in infants with mild-to-moderate CDH. We speculate that hypoplastic lungs in CDH are prone to overdistension, with poor tolerance to elevation of distending pressure.
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Hernias Diafragmáticas Congénitas/fisiopatología , Hipertensión Pulmonar/etiología , Rendimiento Pulmonar/fisiología , Pulmón/fisiopatología , Respiración con Presión Positiva/métodos , Estudios Cruzados , Ecocardiografía Doppler , Femenino , Estudios de Seguimiento , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/terapia , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/fisiopatología , Recién Nacido , Masculino , Proyectos Piloto , Estudios Prospectivos , Presión Esfenoidal Pulmonar/fisiologíaRESUMEN
CHARGE syndrome is a rare genetic disorder mainly due to de novo and private truncating mutations of CHD7 gene. Here we report an intriguing hot spot of intronic mutations (c.5405-7G > A, c.5405-13G > A, c.5405-17G > A and c.5405-18C > A) located in CHD7 IVS25. Combining computational in silico analysis, experimental branch-point determination and in vitro minigene assays, our study explains this mutation hot spot by a particular genomic context, including the weakness of the IVS25 natural acceptor-site and an unconventional lariat sequence localized outside the common 40 bp upstream the acceptor splice site. For each of the mutations reported here, bioinformatic tools indicated a newly created 3' splice site, of which the existence was confirmed using pSpliceExpress, an easy-to-use and reliable splicing reporter tool. Our study emphasizes the idea that combining these two complementary approaches could increase the efficiency of routine molecular diagnosis.
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Síndrome CHARGE/genética , ADN Helicasas/genética , Proteínas de Unión al ADN/genética , Mutación , Sitios de Empalme de ARN , Niño , Biología Computacional/métodos , Humanos , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Análisis de Secuencia de ADN/métodosRESUMEN
BACKGROUND: Starting resuscitation before clamping the umbilical cord at birth may progressively increase pulmonary blood flow while umbilical venous blood flow is still contributing to maintenance of oxygenation and left ventricle preload. OBJECTIVE: To evaluate the feasibility, safety, and effects of intact cord resuscitation (ICR) on cardiorespiratory adaptation at birth in newborn infants with CDH. STUDY DESIGN: Prospective, observational, single-center pilot study. METHODS: Physiologic variables and outcomes were collected prospectively in 40 consecutive newborn infants with an antenatal diagnosis of isolated CDH. RESULTS: Infants were managed with immediate cord clamping (ICC group) from 1/2012 to 5/2014 or the cord was clamped after initiation of resuscitation maneuvers (ICR group) from 6/2014 to 4/2016 (20 in each group). Ante- and postnatal markers of CDH severity were similar between groups. Resuscitation before cord clamping was possible for all infants in the ICR group. No increase in maternal or neonatal adverse events was observed during the period of ICR. The pH was higher and the plasma lactate concentration was significantly lower at one hour after birth in the ICR than in the ICC group (pH=7.17±0.1 vs 7.08±0.2; lactate=3.6±2.3 vs 6.6±4.3mmol/l, p<0.05). Mean blood pressure was significantly higher in the ICR than in the ICC group at H1 (52±7.7 vs 42±7.5mmHg), H6 (47±3.9 vs 40±5.6mmHg) and H12 (44±2.9 vs 39±3.3mmHg) (p<0.05). CONCLUSION: Commencing resuscitation and initiating ventilation while the infant is still attached to the placenta is feasible in infants with CDH. The procedure may support the cardiorespiratory transition at birth in infants with CDH.
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Parto Obstétrico/métodos , Hernias Diafragmáticas Congénitas , Resucitación/métodos , Cordón Umbilical , Adulto , Puntaje de Apgar , Estudios de Factibilidad , Femenino , Edad Gestacional , Humanos , Recién Nacido , Intubación Intratraqueal/métodos , Masculino , Proyectos Piloto , Embarazo , Estudios Prospectivos , Seguridad , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Postnatal adaptation requires liquid clearance and lung aeration. However, their relative contribution to the expansion of functional residual capacity (FRC) has not been fully investigated. We studied evolution of lung liquid removal and lung aeration after birth in preterm lambs. METHODS: Lung liquid content and lung volume were assessed at birth and every 30 min over 2 h using magnetic resonance imaging (MRI) in three groups of lambs delivered by cesarean: preterm, late preterm, and late preterm with antenatal steroids. Lung function and mechanics of the respiratory system were also measured. RESULTS: Lung liquid content increased by approximately 30% in the preterm group (P < 0.05), whereas it did not change significantly in the late preterm lambs. Antenatal steroids induced a 50% drop in the lung liquid content (P < 0.05). Total lung volume increased in all groups (P < 0.05) but was higher in the late preterm + steroids group relative to other groups (P < 0.05). Compliance and resistances of the respiratory system were significantly correlated with lung liquid content (P < 0.05). CONCLUSION: FRC expansion results mainly from an increase in lung volume rather than a decrease in lung liquid in preterm and late preterm lambs. Antenatal steroids promote FRC expansion through increases in lung volume and liquid clearance.
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Capacidad Residual Funcional , Pulmón/diagnóstico por imagen , Pulmón/fisiología , Animales , Animales Recién Nacidos , Peso al Nacer , Rendimiento Pulmonar , Imagen por Resonancia Magnética , Nacimiento Prematuro , Respiración , Pruebas de Función Respiratoria , Ovinos , Oveja Doméstica , Volumen de Ventilación Pulmonar , Factores de TiempoRESUMEN
CONTEXT: The neonatal period, notably in preterm infants, is characterized by high sodium wasting, implying that aldosterone, the main hormone regulating sodium reabsorption, is unable to maintain sodium homeostasis. OBJECTIVE: This study sought to assess aldosterone secretion and action in neonates according to gestational age (GA). DESIGN AND SETTING: This was a multicenter prospective study (NCT01176162) conducted between 2011 and 2014 at five neonatology departments in France. Infants were followed during their first 3 months. PARTICIPANTS: The 155 newborns included were classified into three groups: Group 1 (n = 46 patients), <33 gestational weeks (GW); Group 2 (n = 67 patients), 33-36 GW; and Group 3 (n = 42 patients), ≥37 GW. MAIN OUTCOME MEASURES: Plasma aldosterone was measured in umbilical cord blood. Urinary aldosterone (UAldo) was assessed at day 0, day 3, month 1, and month 3 postnatal. The correlation between UAldo and the urinary Na/K ratio was determined as an index of renal aldosterone sensitivity. RESULTS: UAldo significantly increased with GA: from 8.8 ± 7.5 µg/mmol of creatinine (Group 1) to 21.1 ± 21.0 (Group 3) in correlation with plasma aldosterone levels in all groups (P < .001), demonstrating its reliability. The aldosterone/renin ratio significantly increased with GA, suggesting an aldosterone secretion defect in preterm infants. UAldo and urinary Na/K were correlated in very preterm but not in term neonates, consistent with very preterm neonates being renal-aldosterone sensitive and term neonates being aldosterone resistant. CONCLUSIONS: Very preterm infants have a previously unrecognized defective aldosterone secretion but conserved renal aldosterone sensitivity in the neonatal period, which modifies the current view of sodium balance in these infants and suggests alternative management approaches.