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

Neonato con tumore miofibroblastico infiammatorio associato a trombocitopenia

Neonato di sesso maschile, nato a termine da parto eutocico. Gravidanza insorta da ICSI omologa, normodecorsa. IgG materne per CMV positive, IgM negative. Sierologia materna per toxoplasma, treponema, HIV e HCV, HBsAg, tamponi vagino-rettali negativi. Apgar 9-10, riscontro di tumefazione ovalare dell’avambraccio sinistro, dura, disomogenea, calda, con cute sovrastante integra. Contemporaneo riscontro di piastrinopenia (PLT 9000). PCR per CMV, EBV, ADV su sangue, indici infiammatori ed emocoltura negativi. Principali anticorpi anti-piastrine assenti. Eco-encefalo, eco-addome e radiografia del torace nella norma. Un’ecodoppler della tumefazione evidenziava una formazione espansiva di 35x21x25 mm, con margini lineari, ecostruttura disomogenea e accentuati segnali vascolari, in sede sovrafasciale. Una RM confermava un quadro suggestivo per anomalia vascolare. Veniva formulata l’ipotesi che si trattasse di emangioendotelioma kaposiforme e si attribuiva la trombocitopenia ad una verosimile sindrome di Kasabach-Merritt. Dopo l’asportazione della lesione all’analisi istologica veniva posta diagnosi di tumore miofibroblastico infiammatorio infantile. Normalmente la sindrome di Kasabach-Merritt si associa all’emangioendotelioma kaposiforme, mentre il tumore miofibroblastico infiammatorio si presenta spesso associato a trombocitosi, veniva quindi meno l’ipotesi diagnostica posta per l’eziologia della piastrinopenia. Per il persistere della piastrinopenia si approfondiva con: antigeni/anticorpi HIV, sottopopolazioni linfocitarie ed immunità umorale, dosaggio di LDH, creatinina, tutti risultati nella norma. L’aspirato midollare metteva in evidenza midollo a cellularità discreta, non elementi indifferenziati, rari megacariociti, numerosi aggregati piastrinici (recente terapia trasfusionale con concentrati piastrinici), esami genetici in corso. All’esame istologico della biopsia midollare si riscontrava midollo emopoietico con normale rappresentazione delle popolazioni cellulari. PCR per CMV, EBV, Parvovirus B19 e HHV6 su midollo osseo negative. All’immunofenotipo su aspirato midollare non rilevate popolazioni anomale. Venivano quindi escluse altre cause più rare di piastrinopenia quali la trombocitopenia amegacariocitica congenita (TAMC). Considerata l’origine periferica, venivano somministrate immunoglobuline endovena per due giorni consecutivi, con risoluzione della piastrinopenia. Discussione: Nel nostro caso i principali anticorpi antipiastrine risultavano assenti e si era ipotizzato che la piastrinopenia fosse dovuta alla sindrome di Kasabach-Merritt. La diagnosi istologica della lesione è risultata però essere di tumore miofibroblastico infiammatorio, normalmente non associato a trombocitopenia; quest’ultima tra l’altro persisteva nonostante l’escissione della lesione. Esami di secondo livello hanno permesso di identificare la condizione come periferica. Nonostante l’assenza dei principali anticorpi antipiastrine, si è deciso di somministrare immunoglobuline. Tale strategia ha portato alla immediata e persistente risalita dei valori delle piastrine, confermando quindi la diagnosi di trombocitopenia causata da anticorpi antipiastrine. Si ribadisce quindi la possibilità di interpretare la piastrinopenia come alloimmune anche se gli autoanticorpi principali dovessero risultare negativi. Nei laboratori generalmente vengono valutati i principali e non tutti i possibili anticorpi antipiastrine, tale esame rappresenta quindi un primo screening e per quanto la sua normalità ci possa far protendere verso altre diagnosi non dovrebbe far escludere a priori dalle possibili diagnosi differenziali la trombocitopenia causata da anticorpi contro le piastrine. Nel nostro specifico caso vista l’età del paziente si trattava verosimilmente di una NATP (Neonatal Alloimmune Thrombocytopenic Purpura), considerando anche il fatto che l’anamnesi patologica materna negativa per trombocitopenia permetteva teoricamente di escludere una ITP (Idiopathic Thrombocytopenic Purpura) materna

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

Abstract 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

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.status: publishe