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Background: Neonatal Marfan syndrome (nMFS) is a rare condition characterized by severe phenotype and poor prognosis. nMFS is caused by mutations in a specific region of the fibrillin 1 gene (FBN1). Prompt recognition of typical signs of neonatal presentation, such as characteristic facial anomalies with senile appearance, arthrogryposis, and campto-arachnodactyly, is fundamental for performing an early cardiological examination. This usually reveals rapidly progressive cardiovascular disease due to severe atrioventricular valve dysfunction., Case Presentation: Herein, we report the case of an early-onset cardiac failure in a neonate with Marfan syndrome, with a brief review of the literature of cases with cardiac involvement in neonatal age. Clinical exome sequencing identified the novel heterozygous de novo missense variant c.3152T > G in FBN1 gene (NM_000138.4), causing the aminoacidic change p.Phe1051Cys. Phenotype-genotype correlation led to a multidisciplinary diagnostic and management workflow., Conclusion: The prompt recognition of a typical phenotype such as that of Marfan syndrome should lead to a detailed evaluation and close follow-up of cardiac morphology and function. Indeed, multi-disciplinary evaluation based on genotype-phenotype correlations of nMFS cases is essential to finding out the best medical and surgical approach, predicting the relevant impact on patient prognosis, and adequately counseling their families., (© 2024. The Author(s).)

(1) Background: The literature reports a low risk of serious bacterial infections (SBIs) in febrile infants presenting with bronchiolitis or respiratory syncytial virus infection, but current microbiological techniques have a higher accuracy. (2) Methods: We assessed the risk of SBIs in neonates and infants with bronchiolitis from 2021 to 2023. We also evaluated C-reactive protein, procalcitonin, and leukocyte values. (3) Results: We included 242 infants. Blood cultures (BCs) were performed in 66/242 patients, with a positivity rate of 9.1% (including one BC with Staphylococcus hominis , considered as a contaminant). The cerebrospinal fluid culture was performed in 6/242 patients, and the results were all negative. Infection markers did not discriminate infants with positive BCs from those with negative ones. (4) Conclusions: Blood cultures should be performed in neonates and young infants with bronchiolitis fever, as the sepsis risk is not negligible. Conversely, our proposed algorithm is to wait for the respiratory panel results before decision-making for a lumbar puncture. Further studies are needed to understand lumbar puncture requirements.

Magnetic resonance imaging is currently used in the neonatal setting for assessing features of the neonatal brain. However, its utilization is constrained by logistic, technical, or clinical challenges. Brain elastography is a new research technique which enhances the diagnostic capability of traditional imaging, and can be paired with both ultrasonography and magnetic resonance imaging. In particular, brain elastography adds objective and quantitative information to traditional imaging by detecting differences in tissue elasticity/stiffness, which may represent a surrogate marker of the physiologic and pathologic features of the neonatal brain. To date, very limited experience exists about the use of brain elastography specifically in the neonatal setting. The aim of the present review was to describe the most recent information about the feasibility and diagnostic accuracy of brain ultrasound elastography (USE) in neonates, and to provide information about the possible future applications and perspectives of brain elastography.

Intracranial hemorrhage may represent a complication of the perinatal period that affects neonatal morbidity and mortality. Very poor data exist about a possible association between mutations of the type IV collagen a1 chain ( COL4A1 ) gene and the development of intracranial hemorrhage, and only sporadic reports focus on intracerebral bleedings already developing in utero or in the neonatal period in infants with such a mutation. This study presents a case series of term neonates affected by intracranial hemorrhage, with no apparent risk factors for the development of this condition, who were carriers of COL4A1 gene variants. This study also provides a review of the most recent scientific literature on this topic, specifically focusing on the available scientific data dealing with the perinatal period., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Bersani, Ronci, Savarese, Piersigilli, Micalizzi, Maddaloni, Dotta, Braguglia, Longo and Campi.)

TBX4 gene, located on human chromosome 17q23.2, encodes for T-Box Transcription Factor 4, a transcription factor that belongs to the T-box gene family and it is involved in the regulation of some embryonic developmental processes, with a significant impact on respiratory and skeletal illnesses. Herein, we present the case of a female neonate with persistent pulmonary hypertension (PH) who underwent extracorporeal membrane oxygenation (ECMO) on the first day of life and then resulted to have a novel variant of the TBX4 gene identified by Next-Generation Sequencing. We review the available literature about the association between PH with neonatal onset or emerging during the first months of life and mutations of the TBX4 gene, and compare our case to previously reported cases. Of 24 cases described from 2010 to 2023 sixteen (66.7%) presented with PH soon after birth. Skeletal abnormalities have been described in 5 cases (20%). Eleven cases (46%) were due to de novo mutations. Three patients (12%) required ECMO. Identification of this variant in affected individuals has implications for perinatal and postnatal management and genetic counselling. We suggest including TBX4 in genetic studies of neonates with pulmonary hypertension, even in the absence of skeletal abnormalities., (© 2024. The Author(s).)

Objectives: Seizures (SZ) are one of the main complications occurring in infants undergoing therapeutic hypothermia (TH) due to perinatal asphyxia (PA) and hypoxic ischemic encephalopathy (HIE). Phenobarbital (PB) is the first-line therapeutic strategy, although data on its potential side-effects need elucidation. We investigated whether: i) PB administration in PA-HIE TH-treated infants affects S100B urine levels, and ii) S100B could be a reliable early predictor of SZ., Methods: We performed a prospective case-control study in 88 PA-HIE TH infants, complicated (n=44) or not (n=44) by SZ requiring PB treatment. S100B urine levels were measured at 11 predetermined monitoring time-points from first void up to 96-h from birth. Standard-of-care monitoring parameters were also recorded., Results: S100B significantly increased in the first 24-h independently from HIE severity in the cases who later developed SZ and requested PB treatment. ROC curve analysis showed that S100B, as SZ predictor, at a cut-off of 2.78 μg/L achieved a sensitivity/specificity of 63 and 84 %, positive/negative predictive values of 83 and 64 %., Conclusions: The present results offer additional support to the usefulness of S100B as a trustable diagnostic tool in the clinical daily monitoring of therapeutic and pharmacological procedures in infants complicated by PA-HIE., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The lung ultrasound (LUS) score can be a useful tool to predict the need for respiratory support and the length of hospital stay in infants with bronchiolitis., Objective: To compare lung ultrasound features in neonates and infants up to three months of age with bronchiolitis to determine whether LUS scores (range 0-36) differ in infants with coinfections or not., Methods: Neonates and infants younger than three months admitted to neonatal units from October 2022 to March 2023, who underwent lung ultrasound evaluation on admission, were included in this retrospective study., Results: We included 60 patients who underwent LUS evaluation at admission. Forty-two infants (70.0%) had a single viral infection. Eighteen infants (30.0%) had a coinfection: fifteen infants (25.0%) had more than one virus at PCR; one infant (1.7%) had both a viral coinfection and a viral-bacteria coinfection; two infants (3.3%) had viral-bacteria coinfection. Infants with a single viral infection and those with coinfections had similar LUS scores globally and in different lung zones. An LUS score higher than 8 was identified to significantly predict the need for any respiratory support ( p  = 0.0035), whereas an LUS score higher than 13 was identified to significantly predict the need for mechanical ventilation ( p  = 0.024)., Conclusion: In our small cohort of neonates and infants younger than three months hospitalized with bronchiolitis, we found no statistically significant differences in the LUS score on admission between patients with a single viral infection and those with multiple infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor SN declared a past co-authorship with the author CM., (© 2023 De Rose, Maddaloni, Martini, Ronci, Pugnaloni, Marrocco, Di Pede, Di Maio, Russo, Ronchetti, Perno, Braguglia, Calzolari and Dotta.)

Background: Despite the latest advances in prenatal diagnosis and postnatal embolization procedures, intracranial arteriovenous shunts (AVSs) are still associated with high mortality and morbidity rates. Our aim was to evaluate the presentation and clinical course, the neurodevelopmental outcome, and the genetic findings of neonates with AVSs., Methods: In this retrospective observational study, medical records of neonates with cerebral AVSs admitted to our hospital from January 2020 to July 2022 were revised. In particular, we evaluated neuroimaging characteristics, endovascular treatment, neurophysiological features, neurodevelopmental outcomes, and genetic findings., Results: We described the characteristics of 11 patients with AVSs. Ten infants (90.9%) required embolization during the first three months of life. In 5/9 infants, pathological electroencephalography findings were observed; of them, two patients presented seizures. Eight patients performed Median Nerve Somatosensory Evoked Potentials (MN-SEPs): of them, six had an impaired response. We found normal responses at Visual Evoked Potentials and Brainstem Auditory Evoked Potentials. Eight patients survived (72.7%) and were enrolled in our multidisciplinary follow-up program. Of them, 7/8 completed the Bayley-III Scales at 6 months of corrected age: none of them had cognitive and language delays; conversely, a patient had a moderate delay on the Motor scale. The remaining survivor patient developed cerebral palsy and could not undergo Bayley-III evaluation because of the severe psychomotor delay. From the genetic point of view, we found a novel pathogenic variant in the NOTCH3 gene and three additional genomic defects of uncertain pathogenicity., Conclusion: We propose SEPs as an ancillary test to discern the most vulnerable infants at the bedside, particularly to identify possible future motor impairment in follow-up. The early identification of a cognitive or motor delay is critical to intervene with personalized rehabilitation treatment and minimize future impairment promptly. Furthermore, the correct interpretation of identified genetic variants could provide useful information, but further studies are needed to investigate the role of these variants in the pathogenesis of AVSs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Campi, De Rose, Pugnaloni, Ronci, Calì, Pro, Longo, Lucignani, Raho, Pisaneschi, Digilio, Savarese, Bersani, Amante, Conti, De Liso, Capolupo, Braguglia, Gandolfo and Dotta.)

Background: Bronchiolitis severity can be assessed using different clinical scores. Some of the most used are the Wang Bronchiolitis Severity Score (WBSS), the Kristjansson Respiratory Score (KRS), and the Global Respiratory Severity Score (GRSS), calculated on the vital parameters and the clinical conditions., Objective: To assess which of the three clinical scores better predicts the need for respiratory support and length of hospital stay in neonates and infants younger than three months, admitted to neonatal units for bronchiolitis., Methods: Neonates and infants younger than three months admitted to neonatal units from October 2021 to March 2022 were included in this retrospective study. The scores were calculated in all patients soon after admission., Results: Ninety-six patients (of whom 61 neonates) admitted for bronchiolitis were included in the analysis. Median WBSS at admission was 4.00 (interquartile range, IQR 3.00-6.00), median KRS was 4.00 (IQR 3.00-5.00), and median GRSS 4.90 (IQR 3.89-6.10). We found significant differences in all three scores between infants who needed respiratory support (72.9%) and those who did not (27.1%) ( p  < 0.001). A value >3 for WBSS, > 3 for KRS, and >3.8 for GRSS were accurate in predicting the need for respiratory support, with a sensitivity of 85.71%, 75.71%, and 93.75% and a specificity of 80.77%, 92.31%, and 88.24%, respectively. The three infants who required mechanical ventilation had a median WBSS of 6.00 (IQR 5.00-6.50), a KRS of 7.00 (IQR 5.00-7.00), and a GRSS of 7.38 (IQR 5.59-7.39). The median length of stay was 5 days (IQR 4-8). All three scores were significantly correlated with the length of stay, although with a low correlation coefficient: WBSS with an r 2 of 0.139 ( p  < 0.001), KRS with an r 2 of 0.137 ( p  < 0.001), and GRSS with an r 2 of 0.170 ( p  < 0.001)., Conclusion: Clinical scores WBSS, KRS, and GRSS calculated on admission accurately predict the need for respiratory support and the length of hospital stay in neonates and infants younger than three months with bronchiolitis. The GRSS score seems to better discriminate the need for respiratory support than the others., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 De Rose, Maddaloni, Martini, Braguglia, Dotta and Auriti.)

Background: Infants affected by Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) may require non-invasive ventilation (NIV) in the post-operative period after elective extubation, especially if born preterm. The aim of the paper is to evaluate the role of different ventilation strategies on anastomotic complications, specifically on anastomotic leak (AL)., Materials and Methods: Retrospective single Institution study, including all consecutive neonates affected by EA with or without TEF in a 5-year period study (from 2014 to 2018). Only infants with a primary anastomosis were included in the study. All infants were mechanically ventilated after surgery and electively extubated after 6-7 days. The duration of invasive ventilation was decided on a case-by-case basis after surgery, based on the pre-operative esophageal gap and intraoperative findings. The need for non-invasive ventilation (NCPAP, NIPPV, and HHHFNC) after extubation and extubation failure with the need for mechanical ventilation in the post-operative period were assessed. The primary outcome evaluated was the rate of anastomotic leak., Results: 102 EA/TEF infants were managed in the study period. Sixty-seven underwent primary anastomosis. Of these, 29 (43.3%) were born preterm. Patients who required ventilation (n = 32) had a significantly lower gestational age as well as birthweight (respectively p = 0.007 and p = 0.041). 4/67 patients had an AL after surgical repair, with no statistical differences among post-operative ventilation strategies., Conclusion: We found no significant differences in the rate of anastomotic leak (AL) according to post-operative ventilation strategies in neonates operated on for EA/TEF., Competing Interests: Declaration of Interests All authors state that they have no conflicts of interest or competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In patients affected by CDH, survival beyond the neonatal period continues to increase thanks to technological and pharmacological improvements. Conversely, patients, families and caregivers are more and more frequently facing "new" complex late comorbidities, including chronic pulmonary and cardiac dysfunctions, neurodevelopmental challenges, and specific nutritional requirements, that often require ongoing long-term medical or surgical care. Therefore, late morbidity is now a key focus in clinical care of CDH. The aims of this paper are to stress some of the most important "unsolved problems" for CDH patients at long-term follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Valfré, Conforti, Morini, Patel, Bevilacqua, Cianci, Bagolan and Braguglia.)

(1) Background: Massive social efforts to prevent the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have affected the epidemiological features of respiratory infections. (2) Methods: The study aims to describe the trend of hospitalizations for bronchiolitis among newborns and infants up to three months of life in Rome (Italy), in the pre-COVID-19 era and during the pandemic. (3) Results: We observed a marked decrease in the number of neonates and infants with bronchiolitis after national lockdowns in 2020 and the first months of 2021 and a similar trend in the number of bronchiolitis caused by respiratory syncytial virus (RSV). RSV was the leading pathogen responsible for bronchiolitis before the national lockdown in March 2020 (70.0% of cases), while Rhinovirus was the leading pathogen responsible for bronchiolitis (62.5%) during the pandemic while strict restrictions were ongoing. As Italy approached the COVID-19 vaccination target, the national government lifted some COVID-19-related restrictions. A surprising rebound of bronchiolitis (particularly cases caused by RSV) was observed in October 2021. (4) Conclusions: In this study, we describe for the first time the fluctuations over time of RSV bronchiolitis among newborns and young infants in Italy in relation to the restrictive measures containing the spread of the COVID-19 pandemic. Our results are in line with other countries' reports., Competing Interests: All data generated or analyzed during this study are included in this published article. Further inquiries can be directed to the corresponding author.

Objectives: The early detection and stratification of asphyxiated infants at higher risk for impaired neurodevelopment is challenging. S100B protein is a well-established biomarker of brain damage, but lacks conclusive validation according to the "gold standard" methodology for hypoxic-ischemic encephalopathy (HIE) prognostication, i.e. brain MRI. The aim of the present study was to investigate the predictive role of urinary S100B concentrations, assessed in a cohort of HIE infants receiving therapeutic hypothermia (TH), compared to brain MRI., Methods: Assessment of urine S100B concentrations was performed by immunoluminometric assay at first void and at 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120-h after birth. Neurologic evaluation, routine laboratory parameters, amplitude-integrated electroencephalography, and cerebral ultrasound were performed according to standard protocols. Brain MRI was performed at 7-10 days of life., Results: Overall, 74 HIE neonates receiving TH were included in the study. S100B correlated, already at first void, with the MRI patterns with higher concentrations in infants with the most severe MRI lesions., Conclusions: High S100B urine levels soon after birth constitute trustable predictors of brain injury as confirmed by MRI. Results support the reliability of S100B in clinical daily practice and open the way to its inclusion in the panel of parameters used for the selection of cases suitable for TH treatment., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background In congenital diaphragmatic hernia (CDH) survivors, failure to thrive is a well-known complication, ascribed to several factors. The impact of lung volume on growth of CDH survivors is poorly explored. Our aim was to evaluate if, in CDH survivors, lung volume (LV) after extubation correlates with growth at 12 and 24 months of life. Methods LV (measured as functional residual capacity-FRC) was evaluated by multibreath washout traces with an ultrasonic flowmeter and helium gas dilution technique, shortly after extubation. All CDH survivors are enrolled in a dedicated follow-up program. For the purpose of this study, we analyzed the correlation between FRC obtained shortly after extubation and anthropometric measurements at 12 and 24 months of age. We also compared growth between infants with normal lungs and those with hypoplasic lungs according to FRC values. A p < 0.05 was considered as statistically significant. Results We included in the study 22 CDH survivors who had FRC analyzed after extubation and auxological follow-up at 12 and 24 months of age. We found a significant correlation between FRC and weight Z-score at 12 months, weight Z-score at 24 months and height Z-score at 24 months. We also demonstrated that CDH infants with hypoplasic lungs had a significantly lower weight at 12 months and at 24 months and a significantly lower height at 24 months, when compared to infants with normal lungs. Conclusion We analyzed the predictive value of bedside measured lung volumes in a homogeneous cohort of CDH infants and demonstrated a significant correlation between FRC and growth at 12 and 24 months of age. An earlier identification of patients that will require an aggressive nutritional support (such as those with pulmonary hypoplasia) may help reducing the burden of failure to thrive., (Copyright © 2021. Published by Elsevier Inc.)

Background: Vascular rings (VR) may cause severe tracheomalacia and upper airway obstruction (UAO). Increased pulmonary artery pressure and cardiac dysfunction have been described in patients with chronic UAO, but has not been investigated in infants with obstruction associated with VR. The aim of this study is to evaluate myocardial strain in infants with UAO due to VR., Method: Demographic characteristics, respiratory symptoms, percentage of tracheal obstruction measured and classified using Computer Tomography, and lung function testing (LFT) were collected. Left (LV) and right ventricle (RV) systolic functions were measured using speckle tracking echocardiography longitudinal strain analysis (LS). Pulmonary artery pressure was evaluated using maximal tricuspid regurgitation jet velocity (TR) and LV end-systolic eccentricity index (EI)., Results: Fifteen cases were included in the study, six had mild tracheal obstruction (<50%), nine moderate-severe obstruction (≥50%). LV LS and RV LS were significantly reduced in cases with moderate to severe airway obstruction cases compared to those with mild airway obstruction (LV LS -15.9 versus -19.9%; RV LS -15.7 versus -20.5%, p  = .04 and p  = .02, respectively). Respiratory symptoms were more pronounced in moderate-severe cases. No significant differences in TR, EI, and LFT were observed., Conclusions: In cases of VR with severe tracheomalacia RV and LV myocardial strain is reduced, suggesting secondary cardiac dysfunction.

Background: Pediatric medical traumatic stress (PMTS) is a psychological and physiological response of children and their families to pain, serious illness, and invasive medical procedures. We aimed to apply the PMTS model to parents of newborns operated at birth for a congenital malformation and to identify clinical and sociodemographic risk factors associated with PMTS symptoms at 6 months., Methods: We designed a cross-sectional study to assess PMTS symptoms (avoidance, arousal, reexperiencing) in parents of six months children operated on for a congenital anomaly, with the Italian version of the Impact of Event Scale - Revised (IES-R)., Results: One-hundred-seventy parents form the object of the study. Eighty-two parents (48.2%) fell over the clinical cut-off. Ventilatory time (p = 0.0001), length of hospital stay (p = 0.0001), associated anomalies (p = 0.0002), medical devices at discharge (p = 0.0001) and Bayley motor scale (p = 0.0002) were significantly correlated with IES-R Total and Subscale Scores. Multivariate linear regression showed length of hospital stay and number of associated anomalies as significant predictors of IES-R Scores., Conclusions: Regardless the type of anomaly and sociodemographic factors, it is the clinical history of the child which seems to predict the severity of PMTS symptoms in this population of parents. PMTS represents a useful model to describe the psychological reactions of parents of newborns operated at birth for a congenital malformation. NICU and outpatient pediatric staff should be aware of risk factors to identify families who may request early multidisciplinary interventions since the first admission., Level of Evidence: Prognosis study, level II., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess cardiac function in infants with bronchiolitis and the association with disease severity and outcomes., Working Hypothesis: Cardiac function may be impaired in bronchiolitis and represent an early predictor of disease severity., Study Design: A prospective cohort study., Patient Selection: Infants with suspected bronchiolitis were included., Methodology: All cases received antigen detection and viral genome detection from nasal lavage or swabs and echocardiography within 24 hours from admission. Systolic and diastolic function in left ventricle (LV) and right ventricle (RV) were assessed using longitudinal strain (LS), a measure of myocardial deformation. Pulmonary artery pressures were estimated using tricuspid regurgitation jet (TR), when present, and end-systolic eccentricity index (EI ES). Main outcomes (duration of respiratory support, length of stay [LOS], and type of respiratory support) were collected. Data were compared to normative existing data, and a group of healthy infants, matched in age., Results: Twenty-eight infants with bronchiolitis and 10 healthy comparators were included. Cases with bronchiolitis showed significantly lower values of RV LS and LV LS compared to healthy comparators (LV: p0.04 and RV: P < .001). Ten infants (36%) had a normal biventricular function, nine (32%) had LV impairment, and nine (32%) had a biventricular impairment. No significant differences were found in TR and EI ES. Infants with biventricular impairment demonstrated a significant increase in LOS (p0.04) and higher levels of respiratory support compared to the healthy comparators (P = .03)., Conclusions: Bronchiolitis is associated with myocardial impairment. Cardiac function is related to disease severity and outcome., (© 2020 Wiley Periodicals, Inc.)

Objective: The objective of this study was to assess the presence of posttraumatic stress disorder (PTSD) symptoms in parental couples of newborn requiring early surgery at 6 and 12 months after birth., Study Design: A longitudinal study was set up from January 2014 to June 2015. As a measure of PTSD, we used the Italian version of the Impact of Event Scale-Revised (IES-R)., Results: Thirty-four couples form the object of the study. At 6 months, half of mothers (52.9%) and fathers (44.1%) reported traumatic stress symptoms above the clinical cutoff. Percentages remained stable at 12 months. When parental gender and length of follow-up were compared with two-factor analysis of variance, none had an impact on IES-R score, nor an interaction between these factors was found. A significant correlation of IES-R total score was present within the couple both at 6 and 12 months (6 months- r : 0.6842, p  < 0.0001 and 12 months- r : 0.4045, p  = 0.0177)., Conclusion: Having a child with a repaired malformation represents a complex prolonged stressful situation with persistent burden for both parents who are at high risk of developing PTSD symptoms., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Treatment modalities for neonates born with congenital diaphragmatic hernia (CDH) have greatly improved in recent times with a concomitant increase in survival. In 2008, CDH EURO consortium, a collaboration of a large volume of CDH centers in Western Europe, was established with a goal to standardize management and facilitate multicenter research. However, limited knowledge on long-term outcomes restricts the identification of optimal care pathways for CDH survivors in adolescence and adulthood. This review aimed to evaluate the current practice of long-term follow-up within the CDH EURO consortium centers, and to review the literature on long-term outcomes published from 2000 onward. Apart from having disease-specific morbidities, children with CDH are at risk for impaired neurodevelopmental problems and failure of educational attainments which may affect participation in society and the quality of life in later years. Thus, there is every reason to offer them long-term multidisciplinary follow-up programs. We discuss a proposed collaborative project using standardized clinical assessment and management plan (SCAMP) methodology to obtain uniform and standardized follow-up of CDH patients at an international level.

Introduction: Patients operated on for congenital pulmonary malformations (CPM) have excellent survival rates, but little is known about long-term morbidity. Our aim is to report the sequelae in patients operated on for CPM in infancy and to define factors that may influence their outcome., Methods: All patients operated on for major congenital anomalies are followed in a dedicated outpatient program and evaluated at 6, 24, and 48 months of life (corrected for gestational age) and at school age at 4, 6, 8, and 12 years of life. The data are prospectively collected. Patients operated on for CPM and enrolled in the follow-up clinic between January 2004 and December 2010 are compared with a control group of term infants operated on for inguinal hernia, without other major congenital or acquired abnormalities. The two groups were compared for auxological, respiratory, and orthopedic outcome., Results: In the study period, 76 consecutive patients with CPM attended our dedicated follow-up clinic. Eight non-operated patients were excluded from the study. Age at follow-up was 82.0 (56.1-103.7) months in CPM patients and 83.5 (75.2-90.4) months in controls (P = 0.79). Fifty-three patients with CPM (78%) had one or more clinical or radiological abnormality versus six (16%) control patients (OR [95%CI] 16.5 [5.8-47.2]; P < 0.0001)., Conclusions: Over 50% of patients with CPM present long-term sequelae, regardless type of malformation. Therefore, long-term follow-up of patients operated on for CPM is recommended. Further studies are needed to define if, in asymptomatic patients, surgery may modify the natural history of CPM. Pediatr Pulmonol. 2016;51:1367-1372. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Since mortality in congenital diaphragmatic hernia (CDH) is decreasing, morbidity such as neurodevelopmental outcome is becoming increasingly important., Objectives: We evaluated neurodevelopmental outcome in high-risk CDH patients treated according to the CDH EURO Consortium standardized treatment protocol., Methods: This observational, prospective cohort study was conducted in two European centers. Neurodevelopment of 88 patients (Rotterdam n = 49; Rome n = 39) was assessed at 12 and 24 months with the Bayley Scales of Infant Development (BSID)-II-NL (Rotterdam) or BSID-III (Rome). Data of the centers were analyzed separately., Results: Cognition was normal in 77.8% of children from Rotterdam and in 94.8% from Rome at 12 months, and in 70.7 and 97.4%, respectively, at 24 months. Motor function was normal in 64.3% from Rotterdam and in 81.6% from Rome at 12 months and in 45.7 and 89.8%, respectively, at 24 months. Longer length of hospital stay (LoS) was associated with worse cognitive outcome and motor function; LoS, low socioeconomic status, and ethnicity were associated with lower cognition., Conclusions: At 2 years, most CDH patients have normal cognition, but are at risk for motor function delay. Due to differences in outcomes between centers, careful interpretation is needed before conclusions can be drawn for other centers. Future multicenter collaboration should not only focus on standardization of postnatal care, but also on international standardization of follow-up to identify risk factors and thereby reduce morbidity., (© 2015 S. Karger AG, Basel.)

Purpose: Identify clinical and socio-demographic risk-factors affecting short-term neurodevelopmental outcome (NDO) in children operated on for abdominal and thoracic congenital anomalies (CA)., Methods: Prospective cohort observational study on newborns operated on for non-cardiac major CA. Evaluations were conducted at 6 and 12 months of age. Univariate linear regression and multivariate regression were conducted to analyze the impact on NDO of clinical and sociodemographic variables. Infants were evaluated with the Bayley Scales of Infant and Toddler Development-3rd Edition., Results: One-hundred-fifty-five children were enrolled. They were affected by the following anomalies: Esophageal Atresia (N=41), Congenital Diaphragmatic Hernia (N=42), Midgut Malformations (N=34), Abdominal Wall Defects (N=18), Colorectal Malformations (N=20). There were no statistically significant differences among the five groups of CA as to NDO. Variables which reached statistical significance at multivariate regression (p≤0.001) at 6 and 12 months as to cognitive and motor development were: ventilatory time, associated malformations, medical appliances for feeding, number of surgery and length of hospital stay., Conclusions: On the average, children born with CA show a NDO within normal range. The identified risk-factors could prompt health care professionals to conduct a close surveillance on most vulnerable children giving them the best chance to reach their full potential., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To review the clinical and molecular genetic characteristics of 16 patients presenting a suspected diagnosis of Kabuki syndrome (KS) in the first year of life, to evaluate the clinical handles leading to a prompt diagnosis of KS in newborns. Clinical diagnosis of KS can be challenging during the first year of life, as many diagnostic features become evident only in subsequent years., Methods: All patients were clinically investigated by trained clinical geneticists. A literature review was performed using the Pubmed online database and diagnostic criteria suggested by DYSCERNE-Kabuki Syndrome Guidelines (2010) were used (a European Network of Centres of Expertise for Dysmorphology, funded by the European Commission Executive Agency for Health and Consumers (DG Sanco), Project 2006122). Molecular analysis of the known causative genes of KS, KMT2D/MLL2 and KDM6A, was performed through MiSeq-targeted sequencing platform. All mutations identified were validated by Sanger sequencing protocols., Results: Mutations in KMT2D gene were identified in 10/16 (62%) of the patients, whereas none of the patients had KDM6A mutations. Facial dysmorphisms (94%), feeding difficulties (100%) and hypotonia (100%) suggested the clinical diagnosis of KS. No significative differences in terms of facial features were noticed between mutation positive and negative patients of the cohort. Brachydactyly, joint laxity and nail dysplasia were present in about 80% of the patients. Other congenital anomalies were most commonly present in the mutated group of patients, including left-sided cardiac abnormalities, skeletal, renal and anorectal malformations and hypertricosis., Conclusions: We present an overview of patients with KS diagnosed during the first year of life. Early diagnosis is serviceable in terms of clinical management and for targeted genetic counselling., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Data on the neurodevelopmental outcome of esophageal atresia (EA) survivors are scarce, controversial, and based on small samples. This is an observational prospective longitudinal study on a selected cohort of low-risk EA survivors. We considered a low-risk EA survivor a patient with the following characteristics: gestational age >32 weeks, no long gap, no genetic or chromosomic anomaly associated with neurodevelopmental delay, and no further major surgical congenital anomalies. Infants were evaluated with scales derived from the Bayley Scales of Infant and Toddler Development - 3rd Edition at 6 and 12 months, with a score of 100 considered normal for each scale. Analysis of variance was used to assess differences of cognitive and motor development. Linear regression was used to assess the impact of the following clinical and sociodemographic variables: gender, birthweight, gestational age, length of hospital stay, number of surgeries and number of esophageal dilatations during first hospitalization, days of mechanical ventilation, weight at follow up, number of surgeries and esophageal dilatations at follow up, parental age, educational level, and socioeconomic status. Thirty children form the object of the study. The mean (standard deviation [SD]) cognitive scale's score was 93.7 (7.5) and 98.2 (9.6) at 6 and 12 months, respectively (P < 0.05). The mean (SD) motor scale's score was 97.6 (9.3) and 98.0 (12.1) at 6 and 12 months, respectively (P = n.s.). Children with a body weight <5° percentile at 12 months showed a mean (SD) cognitive score significantly lower when compared with those with a body weight >5° percentile: 88.8 (6.3) and 100.5 (8.9), respectively. At 12 months, children with unemployed mothers had a mean (SD) motor score significantly lower when compared with those in the other socioeconomic classes: 87.7 (9.8) and 100.6 (12.4), respectively. In conclusion, parents of babies operated on for low-risk EA can be reassured about neurodevelopmental outcome at least up to 1 year of age. When offering a multidisciplinary follow-up program, underweight patients should deserve particular attention to promote their quality of life and support their global development., (© 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Objective: To describe short-term neurodevelopmental outcome of infants operated on for congenital anomalies (CA) and assess the impact of type of CA on the outcome., Study Design: From 2008 to 2010 newborns operated on for CA were enrolled in a cross-sectional follow-up study including three distinct groups: infants of 6 months (group A), infants of 12 months (group B), and children of 24 months (group C). Each group was divided into five subgroups: (1) esophageal atresia; (2) congenital diaphragmatic hernia; (3) midgut malformations; (4) abdominal wall defects; (5) colorectal malformations. Each group of patients underwent a neurodevelopmental evaluation with Bayley III., Results: In all, 150, 156, and 84 babies were enrolled in groups A, B, and C, respectively. Mean (standard deviation) Mental Scale score was 94.65 (8.75), 98.76 (11.03), and 100.60 (12.04) in groups A, B, and C. Mean (standard deviation) Motor Scale score was 96.89 (11.62), 99.23 (14.83), and 103.60 (12.90) in groups A, B, and C. No significant differences were found among the five subgroups considered., Conclusion: Regardless of type of malformation, short-term neurodevelopmental outcome of children with gastrointestinal anomalies including diaphragmatic hernia falls within normal range, suggesting that neither being born with a CA nor its type is per se a risk factor for neurodevelopmental delay., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

We assessed whether physical activity could influence the performance and perception of dyspnea in children who were operated on for high risk congenital diaphragmatic hernia (CDH). We hypothesized that CDH children with normal activity would have better lung function and exercise performance level when compared to sedentary CDH subjects. We studied 18 children (11 males and 7 females, mean age 6.6 ± 2.6 years) who were surgically corrected. All children underwent physical examination, ECG at rest, and a maximal exercise stress test on a treadmill to measure the duration of exercise, maximal heart rate and blood pressure, maximal oxygen uptake (VO(2)  max and VO(2)  ml/kg/min). Lung function testing to measure forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1) ), and peak expiratory flow (PEF) was also performed. Following the stress test, the Dalhousie dyspnea and effort scale was shown to children as a pictorial panel with three groups of increasing (from 1 to 7) levels of effort perception, throat discomfort, and chest dyspnea. Children were divided into group A (sedentary) and group B (regular physical participation). There was no difference in CDH severity between the two groups. Group A had a statistically significant lower duration of exercise (P < 0.01), maximal oxygen consumption (VO(2)  max P < 0.0001), VO(2)  ml/kg/min (P < 0.001), higher throat closing feeling (P < 0.004), chest dyspnea (P < 0.001), and effort perception (P < 0.04) compared to group B. No differences were found in lung function tests. In conclusion, our data may suggest that children with a history of CDH who are active maintain a higher level of performance with less perception of dyspnea and effort., (Copyright © 2011 Wiley-Liss, Inc.)

In neonatology unit 40 to 80% of the drugs are used as off-label or unlicensed, particularly in Neonatal Intensive Care Unit (NICU), where it has been described that in a single patient up to 60 parenteral drugs can be administered. The course of a drug inside the organism can be defined in 4 different phases: absorption, distribution, metabolism, elimination; for each of these phases the newborn infant has different characteristics than child and adult. In the last years much more attention has been put in pharmacological research specific for the neonatal age and a good trial design should take into account the following points: (1) to define the pediatric disease in terms of natural history, prevalence, severity, treatment and impact of the new drug; (2) to avoid the "try and error" method based on the adult dose corrected for weight or age; (3) to use adapted methodologies (pharmacokinetics); (4) to avoid small clinical trials (limited number of patients), the use of Randomized Controlled Trials rather than observational studies; (5) to consider ethics providing clear information and reducing pain and stress to the baby and its family.

Purpose: Congenital diaphragmatic hernia (CDH) presents with a broad spectrum of severity, depending on the degree of pulmonary hypoplasia and persistent pulmonary hypertension (PPH). It is currently not clear whether pulmonary hypertension may affect late morbidity. Aim of the present study was to evaluate the influence of PPH on mid-term morbidity in high-risk CDH survivors., Methods: All high-risk (prenatal diagnosis and/or respiratory symptoms within 6 h of life) CDH survivors, treated between 2004 and 2008 in our Department were followed up in a multidisciplinary outpatient clinic as part of a longitudinal prospective study. Auxological, gastroesophageal, pulmonary and orthopedic evaluations were done at specific time-points (at 6, 12, and 24 months of age). Patients were grouped depending on the presence/absence of pulmonary hypertension (defined by expert pediatric cardiologists after echocardiography). Paired t-test and Fisher's exact test were used as appropriate. P < 0.05 was considered significant., Results: 70 survivors out of a total of 95 high-risk CDH infants treated in our Department attended our follow-up clinic and were prospectively evaluated. 17 patients were excluded from the present study because no clear data was available regarding the presence/absence of PPH during the perinatal period. Moreover, 9 infants were not enrolled because they did not reach at least 6 months of age. A total of 44 survivors were finally enrolled since they met the inclusion criteria. 26 infants did not present with PPH during the first hospital admission, while 18 had PPH. The 2 groups did not differ with regard to any of the outcomes considered at follow-up (p > 0.2)., Conclusion: In our cohort of high-risk CDH survivors, PPH was not found to affect late sequelae at mid-term follow-up. This may indicate that postnatal pulmonary development is not (always) influenced by perinatal PPH. Nevertheless, a longer follow-up and more patients are needed to properly quantify possible late problems in high-risk CDH survivors with associated neonatal PPH., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background/purpose: The increased survival rate reached in infants with congenital diaphragmatic hernia (CDH) has shown a concomitant increase in late morbidity. A recent report from CDH Study Group showed that dimension of diaphragmatic defect is the only independent risk factor of mortality. However, the influence of defect size on late morbidity is still controversial. The aim of the study was to evaluate the influence of patch repair (proxy of diaphragmatic defects size) on midterm morbidity., Methods: All high-risk (prenatal diagnosis and/or respiratory symptoms within 6 hours of life) CDH survivors treated at our institution from 2004 to 2008 were followed up in a multidisciplinary outpatient clinic as part of a longitudinal prospective study. Auxological, gastroesophageal, pulmonary, and orthopedic evaluations were performed at 6, 12, and 24 months of age. Patient outcomes were compared with respect to +/- patch repair., Results: Of 70 survivors, 61 (87%) were enrolled and prospectively evaluated in follow-up. Poorer auxological outcome, increased rate of gastroesophageal reflux, and altered pulmonary function test were observed during follow-up., Conclusions: Patch repair correlates with higher pulmonary, auxological, and gastroesophageal morbidity without increasing chest wall deformities at long-term follow-up., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Unlabelled: The assessment of lung volumes, particularly functional residual capacity (FRC), is crucial for understanding lung development during infancy in CDH patients., Aim: To evaluate changes in lung function during infancy in subjects with CDH treated with a "gentle ventilation" technique and delayed surgery strategy in the neonatal period., Methods: 13 CDH infants were studied twice and compared with a population of 28 healthy infants (HI). Tidal-Volume (Vt), respiratory rate (RR) and time to peak expiratory flow/expiratory time ratio (tPTEF/Te) were measured with an ultrasonic flow meter; Compliance (Crs) and Resistance (Rrs) of the respiratory system were studied with the single occlusion technique; FRC and Lung Clearance Index (LCI), were assessed with the sulfur hexafluoride (SF6) wash-in/wash-out technique. The differences between the first (T1) and second (T2) measurement in the CDH group were assessed by the Student's t-test for paired values. For each set of measurement (T1 and T2) the values were compared with HI by Student's t-test., Results: Mean age at test was 7.5 +/- 5.2 months for HI, 4.5 +/- 2.5 at T1 and 11.9 +/- 4.5 months at T2 for CDH infants. At T1 there were no significant differences between CDH infants and HI in Vt, Crs, and FRC, while tPTEF/te ratio was lower and RR, Rrs, and LCI were higher in CDH patients than in HI. At T2 Vt, Crs, and FRC remained normal in CDH patients as well as RR that, at this time was not different between CDH and healthy infants; tPTEF/te remained below and Rrs and LCI remained above normal ranges, indicating a persistent impairment in lower airways patency., Conclusions: Lung function in infants with severe CDH is characterized by a persistent impairment in airways patency and significant inhomogeneity of ventilation, suggesting a peripheral bronchial obstruction even if the other lung function tests are within normal ranges.

Background/purpose: Despite surgical refinements, perioperative use of tracheobronchoscopy (TBS) as part of surgical approach to esophageal atresia (EA) is still controversial. The purpose of this study was to evaluate the influence of preoperative TBS in newborns with EA in preventing complications and improving diagnosis and surgical treatment., Methods: In the period ranging from 1997 to 2003, 62 patients with EA underwent preoperative TBS. The procedure was carried out with flexible bronchoscope maintaining spontaneous breathing. When a wide carinal fistula was found, this was mechanically occluded by Fogarty catheter and cannulated with rigid bronchoscopy. Type of EA, surgical procedure variations caused by TBS, and associated anomalies not easily detectable were recorded., Results: Before TBS, the Gross classification of the 62 patients was as follows: type A, 9 patients; type B, none; type C, 51 patients. At TBS, however, 3 of 9 type A patients had an unsuspected proximal fistula (type B). These 3 patients, plus the 2 with H-type fistula, were repaired through a cervical approach. In 4 patients, previously undetected malformations of the respiratory tree (2 aberrant right upper bronchus and 2 hypoplastic bronchi) were found at TBS. Carinal fistulas in 14 type C patients were occluded by Fogarty catheter to improve ventilation during repair. No complications were observed. Overall, TBS was clinically useful in 28 (45.2%) of 62 patients, including 15 (24.2%) of 62 infants in whom it was crucial in modifying the surgical approach., Conclusion: Tracheobronchoscopy is a useful and safe procedure and should be recommended in tertiary centers for babies with EA before surgical repair.

Background: Wolf-Hirschhorn syndrome (WHS) is a well-known genetic condition characterized by typical facial anomalies, midline defects, skeletal anomalies, prenatal and postnatal growth retardation, hypotonia, mental retardation, and seizures. Affected patients with a microdeletion on distal 4p present a milder phenotype that lacks congenital malformations. WHS is rarely associated with congenital diaphragmatic hernia (CDH), and only 8 cases are reported in the literature. In almost all cases of CDH and WHS a large deletion of the short arm of chromosome 4 is present., Case: A microdeletion of 2.6 Mb on distal 4p associated with CDH and multiple congenital malformations (i.e., cleft palate) is reported for the first time., Conclusions: Such a microdeletion should prompt a molecular study for WHS when in a fetus/newborn with CDH the association with cleft lip/palate and typical facial appearance (flat facial profile, hypertelorism) is found., (Copyright 2006 Wiley-Liss, Inc.)

Background: Despite improvements in clinical management, mortality of congenital diaphragmatic hernia (CDH) remains high. Early prediction of mortality risk helps in comparing strategies and/or performances of different centers. Birth weight (BW), Apgar Score at 5 minutes, and modified McGoon Index (MGI) calculated by the ratio between the diameters of pulmonary arteries and the descending aorta have been used to determine mortality of CDH., Aim: The purpose of this study is to evaluate the relationship between early detectable variables and survival in newborns with CDH intubated at birth, managed with "gentle" ventilation and delayed surgery., Methods: All medical records of patients affected by high-risk CDH and treated with a standardized protocol at Bambino Gesù Children's Hospital, Rome, Italy, between January 2002 and September 2004 were reviewed. Prenatal diagnosis, gestational age, BW, sex, side of hernia, and MGI were recorded on admission. The relationship with mortality of each variable was evaluated by univariate analysis. Subsequently, a predictive model of mortality was developed using a logistic regression: the explanatory variables, BW, and MGI were dichotomized in high (HBW and HMGI) and low (LBW and LMGI) according to the best cutoff found with receiver-operating characteristic curves., Results: Thirty-four newborns with CDH, treated with a standardized protocol, were studied. The main characteristics of the 34 patients were BW, 2886 g (1500-3620 g); gestational age, 37.7 weeks (32-42 weeks); male/female, 22/12; right/left, 8/26; prenatal diagnosis, 29; MGI, 1.31 (0.9-1.85). Only BW and MGI were significantly (P < .05) associated with mortality at the univariate analysis. The best cutoff values were 2755 g for BW (sensitivity, 70%; specificity, 74%) and 1.25 for MGI (sensitivity, 73%; specificity, 78%). Using these limits, BW and MGI resulted independently associated with mortality in the multivariate analysis. Using the 4 possible combinations, the LBW associated with the LMGI presented the highest prediction of mortality (80%)., Conclusions: Birth weight and MGI, variously combined, were predictive of mortality. Because they are not influenced by subsequent modalities of care, they can be considered as valid early severity scores in CDH and used for comparing strategies and/or performances of different centers.

Background: Cardiorespiratory stabilization is recommended before surgical repair of congenital diaphragmatic hernia (CDH) because surgery may induce a transitory deterioration of chest compliance and gas exchange. It is not known if surgical intervention can affect cerebral circulation and oxygenation., Aim: The aim of the study was to assess noninvasively, by near-infrared spectroscopy, the possible changes in cerebral hemodynamics and oxygenation associated with surgical repair of CDH., Subjects: Twenty-five newborns with severe CDH (birth weight, 3057 +/- 354 g; gestational age, 37.8 +/- 1.8 weeks; male/female newborns, 15/10; left/right CDH, 19/6) were sedated, paralyzed, and mechanically ventilated by conventional gentle ventilation and surgically corrected at a median age of 2.7 days (min-max, 2-14 days) after cardiorespiratory stabilization., Methods: Heart rate (HR [beats per minute]), preductal transcutaneous oxygen saturation (tcSaO2 [%]), carbon dioxide tension (tcPCO2 [Torr]), and mean arterial blood pressure (mm Hg) were continuously monitored. Inspired fractional oxygen concentration (FIO2) was adjusted to maintain and preductal tcSaO2 of greater than 80%, whereas the ventilator's settings were kept unchanged throughout the surgical procedure. Cerebral hemodynamics was assessed by near-infrared spectroscopy (NIRO 300, Hamamatsu Photonics, Japan), recording continuously and noninvasively the relative changes in concentration of oxygenated (DeltaO2Hb [micromol/L]), deoxygenated (DeltaHHb [micromol/L]), and total (DeltatHb [micromol/L]) hemoglobin; the tissue oxygenation index (TOI [%]) was also calculated (TOI = O2Hb/O2Hb + HHb). Total hemoglobin concentration is considered to be representative of cerebral blood volume. Arterial blood gases were also measured at the beginning (T1) and at the end of surgery (T2). For all measurements, results at T1 and at T2, as well as the differences between T1 and T2, have been expressed as means or medians and SDs or 95% confidence intervals or ranges. The differences between T1 and T2 were considered statistically significant for a P value of less than .05 by the Student t test for paired values., Results: At T1, mean tcSaO2% was 94.1 % (SD, 4.6) with a FIO2 of 0.25 (SD, 0.1); at T2, to obtain similar values of tcSaO2 (93.4%; SD, 4.4), it was necessary to increase the FIO2 to 0.37 (SD, 0.14; P < .001). Mean HR at T1 was 149.5 beats per minute (SD, 9.1) and increased significantly (P < .05) at T2 (165.2 beats per minute; SD, 14.2). Mean arterial blood pressure was 54.7 mm Hg (SD, 7.7) at T1 and did not change appreciably at T2 (55.6 mm Hg; SD, 8.1). Moreover, tcPCO2 did not change significantly during the procedure (mean tcPCO2 = 49.9 Torr [SD, 12.8] at T1 and 57.3 mm Hg [SD, 17.9] at T2). O2Hb and tHb decreased (P < .001 and <.005) and HHb increased (P < .05) significantly during the surgical procedure (mean Delta [SD]: DeltaO2Hb= -10.9 micromol/L [9.7], DeltatHb = -7.5 micromol/L [11.7], and DeltaHHb = -3.5 micromol/L [6.8]). Mean TOI was 70% at T1 (normal values >60%) and decreased significantly at T2 (mean DeltaTOI = -6.1% [SD, 10.6]). In all infants, the greatest changes occurred when the viscera were positioned into the abdomen., Conclusions: Notwithstanding the initial cardiorespiratory stabilization, surgical repair of CDH was associated with a rise in HR and oxygen requirement and a drop in cerebral tHb and O2Hb, suggesting a reduction in cerebral blood volume and oxygenation. These events were probably due to the combined effects of an increase in right to left shunting (as indicated by the increased oxygen requirement) and a decrease in venous return (possibly due to compression of the inferior vena cava by the viscera positioned into the abdomen). These preliminary results reinforce the importance of achieving a good cardiorespiratory stability before undertaking surgical correction of CDH to minimize the possible interference of the procedure with cerebral circulation and oxygenation.