Neonatal persistent pulmonary hypertension related to a novel TBX4 mutation: case report and review of the literature.

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.

Elevated S100B urine levels predict seizures in infants complicated by perinatal asphyxia and undergoing therapeutic hypothermia.

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.

Neurodevelopmental and genetic findings in neonates with intracranial arteriovenous shunts: A case series.

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.

Comparison of three clinical scoring tools for bronchiolitis to predict the need for respiratory support and length of stay in neonates and infants up to three months of age.

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 r2 of 0.139 (p < 0.001), KRS with an r2 of 0.137 (p < 0.001), and GRSS with an r2 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.

Are lung ultrasound features more severe in infants with bronchiolitis and coinfections?

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.

Unsolved problems in CDH follow-up.

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.

Lessons from SARS-CoV-2 Pandemics: How Restrictive Measures Impacted the Trend of Respiratory Infections in Neonates and Infants up to Three Months of Age.

(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.

Early predictors of abnormal MRI patterns in asphyxiated infants: S100B protein urine levels.

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.

Post-operative ventilation strategies after surgical repair in neonates with esophageal atresia: A retrospective cohort study.

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.

Myocardial strain in newborn infants with tracheomalacia due to vascular rings, a pilot study.

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.

Growth and morbidity in infants with Congenital Diaphragmatic Hernia according to initial lung volume: A pilot study.

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.

Pediatric medical traumatic stress (PMTS) in parents of newborns with a congenital anomaly requiring surgery at birth.

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.

Myocardial strain on admission predicts disease severity in infants hospitalized for bronchiolitis.

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.

Defining outcomes following congenital diaphragmatic hernia using standardised clinical assessment and management plan (SCAMP) methodology within the CDH EURO consortium.

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.

Couples Facing the Birth of a Newborn with a Congenital Anomaly: PTSD Symptoms in the First Year.

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.

Outcome of infants operated on for congenital pulmonary malformations.

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.

Neurodevelopmental Outcome in High-Risk Congenital Diaphragmatic Hernia Patients: An Appeal for International Standardization.

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.

Factors affecting short-term neurodevelopmental outcome in children operated on for major congenital anomalies.

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.

Kabuki syndrome: clinical and molecular diagnosis in the first year of life.

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.