[Necrotizing enterocolitis (nec): risk factors and genetic susceptibility]. / Enterocolite necrotizzante (NEC): fattori di rischio e suscettibilitá genetica.

Necrotizing enterocolitis (NEC) is a main cause of morbidity and mortality in neonatal intensive care units. Etiology is likely to be multifactorial and prematurity and low birth weight (<1500 g) are risk factors already recognized. The studies conducted on the role of genetic factors in the pathogenesis of the disease led to contradictory outcomes, even if interesting hints emerged to encourage future research. The aim of the present review was to update on genetic research in NEC, focusing on the evidences arisen from the studies on the main risk factors (prematurity and ischaemia) and inflammatory mediators.

Fatal respiratory failure in a full-term newborn with two ABCA3 gene mutations: a case report.

Genetic mutations associated with pulmonary surfactant protein deficiency are associated with diverse clinical phenotypes. Mutations of the surfactant protein B and C genes were the first to be described. In 2004, fatal surfactant deficiency in newborns due to mutations of the gene encoding the adenosine triphosphate-binding cassette transporter A3 (ABCA3) was first reported. Few cases of lethal adenosine triphosphate-binding cassette transporter A3 mutations have been described to date. In our report, we describe a full-term newborn that died because of respiratory failure secondary to an uncommon ABCA3 genetic configuration.

[Three cases of congenital cutaneous candidosis]. / Tre casi di Candidosi Cutanea Congenita.

We report three cases of term newborns with Congenital Cutaneous Candidosis (CCC) occured in a ten months period. Two of these showed respiratory distress that require mechanical ventilation and the administration of exogenous surfactant in one case. All the three cases recovered after therapy with fluconazole. Early onset of severe respiratory distress may require intubation and mechanical ventilation, and systemic involvement requires systemic antimichotic therapy. We did not find any predisposing factors of such a rare disease, in spite of the occurrence of three cases in a short period of time.

[Respiratory diseases associated to surfactant proteins B and C deficiency]. / Malattie respiratorie associate a deficit delle proteine B e C del surfattante.

Pulmonary surfactant is a mixture of lipids and proteins necessary to reduce alveolar surface tension and prevent end expiratory atelectasis. The hydrophobic surfactant proteins B and C are essential for lung function and pulmonary homeostasis after birth. Mutations in the genes encoding surfactant proteins B and C are associated with acute respiratory failure and interstitial lung disease. Diagnosis is possible through DNA analysis from blood leucocytes and immunostaining from lung tissue.

Congenital misalignment of pulmonary vessels and alveolar capillary dysplasia: how to manage a neonatal irreversible lung disease?

Congenital misalignment of pulmonary vessels (MPV) with alveolar capillary dysplasia is a rare condition consisting of anomalous veins in bronchovascular bundles, a decreased number of alveolar capillaries, and increased muscularization of pulmonary arterioles. In the literature, infants reported as having such a malformation developed respiratory distress with persistent pulmonary hypertension and ultimately died. We report the case of an infant with MPV and alveolar capillary dysplasia who was unresponsive to maximal cardiorespiratory support, including high-frequency oscillatory ventilation and inhaled nitric oxide; the infant died of pulmonary hemorrhage after 19 days, during venoarterial extracorporeal membrane oxygenation bypass. We conclude that the diagnosis of MPV and alveolar capillary dysplasia should be considered during autopsy of infants who have died of irreversible persistent pulmonary hypertension. If a lung biopsy in infants with prolonged refractory hypoxemia confirms such diagnosis before death, expensive and invasive treatments such as extracorporeal membrane oxygenation could be avoided.

Hereditary surfactant protein B deficiency resulting from a novel mutation.

Hereditary surfactant protein B (SP-B) deficiency is an autosomal recessive disease in which affected infants are unable to produce normally functional surfactant, resulting in neonatal respiratory failure and death within the first year of life. The most common cause of SP-B deficiency is a frameshift mutation in exon 4 (121ins2) of the SP-B gene. We report a newborn infant who had onset of respiratory distress during the first days, was unresponsive to exogenous surfactant, corticosteroids, prostacyclin, high frequency oscillatory ventilation and inhaled nitric oxide, and died after 27 days. Immunostaining of lung tissue obtained at biopsy demonstrated absent staining for SP-B, and robust extracellular staining for proSP-C, findings characteristic for SP-B deficiency. DNA analysis revealed the 121ins2 mutation on one of her SP-B alleles and a novel mutation, 122delC, on her other SP-B allele. The proximity of the novel mutation in exon 4 allele found in this infant to the 121ins2 supports the notion that this region may represent a "hot spot" for SP-B gene mutations and confirms the heterogeneity of mechanisms which lead to SP-B deficiency. Hereditary SP-B deficiency is a rare, newly diagnosable and probably under-recognized disease, which should be suspected in term newborn infants with unexplained respiratory failure.

Impact of new treatments for respiratory failure on outcome of infants with congenital diaphragmatic hernia.

UNLABELLED: Term and near-term newborn infants with congenital diaphragmatic hernia (CDH), symptomatic in the first 24 h of life or diagnosed antenatally, without other significant malformations were treated at our hospital with high-frequency oscillatory ventilation (HFOV) as a primary modality of ventilation and elective delay in surgical repair after a period of stabilisation. When unresponsive to HFOV, infants were treated with surfactant, inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) to achieve pre-operative stabilisation. From October 1994 to August 1998, 28 newborn infants with CDH were managed with such treatment; mean birth weight was 3184 +/- 535 g and gestational age 38.5 +/- 1.85 weeks. Age at operation was 68 +/- 35 h. In 9 cases, large diaphragmatic defects required the use of a prosthetic patch (Gore-tex). HFOV was used for primary ventilation in inborn patients (n = 16); outborn infants (n = 12) were placed on HFOV at admittance. A total of 15 patients (53%) were stabilised using only HFOV. Bovine surfactant was administered in 12 infants and 4 responded. iNO was used in eight infants and five responded. ECMO was used in three outborn patients and one survived. Overall, out of 28 infants, 25 survived (89%). Neurological examination (Amiel-Tison and Grenier) of 15 infants showed transient anomalies at 6 months in 40% of infants, while a normal neurological examination was present in all patients at 1 year. The development quotient (Griffiths scales) was within normal values in ten and mildly abnormal in two infants tested at 1 year. CONCLUSION: Management based on early HFOV, eventually associated with surfactant, iNO and ECMO to achieve preoperative stabilisation, resulted in a good survival rate (89%) and good neurodevelopmental outcome at 1 year of age in infants with CDH.

Imaging of neonatal hemangiomas, two cases.

Hemangiomas are the most common tumor of infancy. Most hemangiomas are harmless and follow a benign clinical course and undergo regression with time. Sometimes they can destroy vital organs and become life-threatening. We report two cases of neonatal hemangiomas which presented very different clinical aspects and course.

Extracorporeal membrane oxygenation with veno-venous bypass and apneic oxygenation for treatment of severe neonatal respiratory failure.

Seven newborn infants with life-threatening respiratory failure were treated with veno-venous (V-V) extracorporeal lung support and apneic oxygenation after maximal ventilatory and pharmacological treatment failed. Diagnosis were meconium aspiration syndrome in 3 cases, respiratory distress syndrome in 2, sepsis in 1, congenital diaphragmatic hernia in 1. Before ECMO 6 infants received tolazoline, 4 surfactant, 3 high frequency ventilation, 1 prostaglandin E, 1 epoprostenol, 2 nitric oxide. Newborns were highly hypoxemic at admission and all but one underwent rescue cannulation. V-V bypass was performed with a single lumen single cannula and tidal flow was generated by an alternating clamp using a non-occlusive roller pump. The mean duration of bypass was 162.4 +/- 162.3 hours and infants were extubated 94.5 +/- 74.8 hours after decannulation. Five newborns survived and two died. Growth and neurologic development of the older children is normal. The extracorporeal lung support with V-V bypass associated with apneic oxygenation was effective in reversing severe neonatal respiratory failure unresponsive to maximal ventilatory and pharmacological support. An early referral, prior to meeting ECMO criteria, is important in order to avoid hypoxic complications preceding ECMO.

Reduction of haemorrhagic complications during mechanically assisted circulation with the use of a multi-system anticoagulation protocol.

Two different anticoagulation protocols were used in 49 consecutive patients mechanically supported either for bridge to transplantation (11) or for recovery of myocardial function after cardiac surgery (35). In 46 patients a Biomedicus centrifugal pump was used and in 3 patients a Pierce-Donachy ventricles. Mechanical support was provided to the left ventricle in 14 patients, to the right ventricle in 6 and to both ventricles in 12 patients; an extra-corporeal membrane oxygenator (ECMO) support was used in 17 patients. Thirty-seven males and 12 females, aged 0.2 to 58 years, were supported for an average time of 6.3 days (range 1-43). Anticoagulation was either based on a continuous infusion of heparin in the first 27 patients (group A) or on a multi-system therapy ("La Pitié" protocol) in the other 22 patients (group B). Overall survival rate was 47%. Patients in group A had a 30% (8/27) survival rate, whereas in group B a 68% (15/22) survival rate was observed (p = 0.006). Transplantation and ventricular assist device (VAD) removal was successfully obtained in 59% (16/27) and 91% (20/22) of patients in group A and group B respectively (p = 0.05). Significant bleeding occurred in 21 patients (81%) in group A and in 2 (9%) of group B (p = 0.001). In these patients bleeding averaged 230 +/- 231 ml/kg in group A versus 55 +/- 18 ml/kg in group B (p = 0.001). Surgical revision was necessary for cardiac tamponade or persistent bleeding in 12 patients of group A (25 procedures: mean 0.9/patient) and in 3 patients of group B (one each patient: mean 0.1/patient) (p = 0.01). Infection, thrombo-embolism and brain hemorrhage were also less frequent in group A than in group B. Our data suggest that the "La Pitié" protocol provides a better control of bleeding than the conventional heparin infusion in patients receiving assist device. this reduction in thrombo-hemorrhagic complications might improve the results of mechanical circulatory support.

[Evaluation of arterial pressure in the first 3 days of life in a group of healthy newborn infants weighing between 2000 and 4600 g at birth]. / Valutazione della pressione arteriosa nei primi tre giorni di vita in un gruppo di neonati sani con peso alla nascita da 2000 a 4600 g.

Systolic, mean and diastolic arterial pressure (AP) was measured on the first and third days of life in a group of 270 infants born in our Hospital. The aim of this work is to see if there are modifications of AP in the first 3 days of life, and correlations between AP and weight at birth, gestational age, and different methods of delivery. Gestational age was between 34 and 42 weeks and birth weight between 2000 and 4600 grams. We excluded infants who developed any illness, those with a low Apgar score, and those whose mothers were given antihypertensive drugs. None of the examined infants received transfusion or drug which could affect the AP. Blood pressure was measured using the automatic oscillometric method. The infant's group was divided into 6 subgroups according to weight (table 1). For statistical analysis we used linear regressions and Student's "t" test. According to our data no correlation was found between birth weight and AP, nor between AP and gestational age; results obtained from other studies concerning this subject didn't agree. On the other and, we found an increase of values of AP in the third day; this agrees with the results of other Authors and is considered a consequence of the rise in peripheral vascular resistance in the postanal period. No difference was observed between the AP values of infants born by normal delivery and cesarean section.