Mariarosa Colnaghi

Prophylactic nasal continuous positive airways pressure in newborns of 28–31 weeks gestation: multicentre randomised controlled clinical trial

Background: The role of nasal continuous positive airways pressure (nCPAP) in the management of respiratory distress syndrome in preterm infants is not completely defined. Objective: To evaluate the benefits and risks of prophylactic nCPAP in infants of 28–31 weeks gestation. Design: Multicentre randomised controlled clinical trial. Setting: Seventeen Italian neonatal intensive care units. Patients: A total of 230 newborns of 28–31 weeks gestation, not intubated in the delivery room and without major malformations, were randomly assigned to prophylactic or rescue nCPAP. Interventions: Prophylactic nCPAP was started within 30 minutes of birth, irrespective of oxygen requirement and clinical status. Rescue nCPAP was started when Fio2 requirement was > 0.4, for more than 30 minutes, to maintain transcutaneous oxygen saturation between 93% and 96%. Exogenous surfactant was given when Fio2 requirement was > 0.4 in nCPAP in the presence of radiological signs of respiratory distress syndrome. Main outcome measures: Primary end point: need for exogenous surfactant. Secondary end points: need for mechanical ventilation and incidence of air leaks. Results: Surfactant was needed by 22.6% in the prophylaxis group and 21.7% in the rescue group. Mechanical ventilation was required by 12.2% in both the prophylaxis and rescue group. The incidence of air leaks was 2.6% in both groups. More than 80% of both groups had received prenatal steroids. Conclusions: In newborns of 28–31 weeks gestation, there is no greater benefit in giving prophylactic nCPAP than in starting nCPAP when the oxygen requirement increases to a Fio2 > 0.4.

Closed versus Open Endotracheal Suctioning in Preterm Infants: Effects on Cerebral Oxygenation and Blood Volume

The aim of our study was to compare, using near-infrared spectroscopy (NIRS), the effects on cerebral intracellular oxygenation and cerebral blood volume (CBV) of closed endotracheal suctioning (CS), which permits continuous ventilation of the patient, with open endotracheal suctioning (OS), which requires disconnection from the ventilator. Eleven preterm infants were studied. Each patient underwent one CS, followed, after 60 min, by one OS, or vice versa, three times during the same day. Modifications in CBV and oxidized cytochrome oxidase (CytO2) were continuously detected by NIRS; arterial oxygen saturation (SaO2) heart rate (HR), transcutaneous carbon dioxide tension and mean arterial blood pressure were simultaneously recorded. Significant reductions in HR and SaO2 were observed following OS; the magnitude and duration of these negative effects of suctioning were significantly reduced with CS. In addition, the decrease in CBV was more pronounced than following CS. No changes in CytO2 concentration were seen.

Respiratory mechanics during NCPAP and HHHFNC at equal distending pressures

Objective To compare the effect of heated, humidified, high-flow nasal cannula (HHHFNC) and nasal continuous positive airways pressure (NCPAP) on lung function and mechanics in preterm infants with respiratory distress syndrome (RDS) at the same level of retropharyngeal pressure (Prp). Design Randomised crossover trial. Setting Neonatal intensive care unit, Ospedale Maggiore Policlinico, Milan, Italy. Patients 20 preterm infants (gestational age: 31±1 wks) with mild-moderate RDS requiring non-invasive respiratory support within 96 h after birth. Interventions Infants were exposed to a randomised sequence of NCPAP and HHHFNC at different settings (2, 4 and 6 cmH2O for NCPAP and 2, 4, 6 L/min for HHHFNC) to enable comparison at the same level of Prp. Main outcome measures Tidal volume by respiratory inductance plethysmography, pleural pressure estimated by oesophageal pressure, and gas exchange were evaluated at each setting and used to compute breathing pattern parameters, lung mechanics and work of breathing (WOB). Results A poor linear regression between flow and Prp was found during HHHFNC (Prp=0.3+0.7*flow; r2=0.37). Only in 15 out of 20 infants it was possible to compare HHHFNC and NCPAP at a Prp of 2 and 4 cmH2O. No statistically significant differences were found in breathing pattern, gas exchange, lung mechanics and total WOB. Resistive WOB in the upper airways was slightly but significantly higher during HHHFNC (0.65 (0.49;1.09) vs 1.57 (0.85;2.09) cmH2O median (IQR)). Conclusions Despite differing mechanisms for generating positive airway pressure, when compared at the same Prp, NCPAP and HHHFNC provide similar effects on all the outcomes explored.

BPD: old and new problems

Bronchopulmonary dysplasia (BPD) is still one of the main long term complication of preterm birth, and it is the most common chronic respiratory disease in infants. Due to advances in perinatal care and neonatal respiratory therapy the clinical characteristics and the natural history of infants affected by BPD have widely changed in the last decades. The sever presentation of the old form of BPD has been replaced by a milder clinical form, without or with mild respiratory distress syndrome in the first days of life, that responds rapidly to surfactant therapy and instead requires prolonged ventilator support because of poor respiratory effort. “Old” and “new” BPD, are also histologically different, being two morphologic outcomes of variable combinations of factors injuring lungs of differing maturity. New BPD is characterized by diffusely reduced alveolar development, with airway injury, inflammation and fibrosis that are usually milder than in old form. Such “new” form of BPD is interpreted as a developmental disorder. The development of BPD is a multifactorial process with pathogenesis being linked to immature lung tissue, barotrauma and volutrauma resulting from mechanical ventilation, oxidant injury, and proinflammatory mediators.and inflammatory regulation may also have a role in the development of the new form. There is growing evidence that BPD results from an imbalance between proinflammatory and anti-inflammatory mechanisms, with a persistent imbalance that favors proinflammatory mechanisms. Reduction of the incidence and severity of BPD may be possible through a reduction of the amount of injury induced by respiratory support interventions.

Advantages of prenatal diagnosis and early surgery for congenital cystic disease of the lung

Prenatal ultrasonography makes possible the diagnosis of congenital cystic lung disease in utero, enabling elective surgery for the lesions early in infancy before development of respiratory distress or potentially life-threatening infection. From 1986 to 1994, ten infants with congenital lung cyst underwent corrective surgery. Nine of them had a prenatal diagnosis of congenital lung cyst confirmed by ultrasound or computed tomography (CT) after birth. In 7 of these infants, congenital adenomatoid malformation (CAM) was found at surgery, and pulmonary sequestration was found and removed in two other infants. Two of the nine infants had respiratory distress at birth; the seven others were asymptomatic when surgery was performed (between 2 and 6 months of age). In 4 out of 9 newborn a plain chest radiography at birth was normal and a CT scan only showed the cysts prenatally observed at ultrasound. Intraoperative measurement of pulmonary function in the asymptomatic infants demonstrated significant improvement after resection of the affected lobe. One other infant had normal lung fields at the time of prenatal diagnosis. However, a severe acute pneumonia with abscess of the lobe became life-threatening at 4.5 months. CT showed a large congenital lung cyst, treated initially with antibiotics and extirpated at age 6 months with great difficulty. Pulmonary function did not improve postoperatively. Examinations on follow-up (8 months-8 years; 5 of 10 infants longer than 4 years) have shown that all 10 of the infants are healthy and have normal pulmonary function. Pneumonia in the controlateral lung was found in 3 children (3-6 years after the operation), one of them had respiratory distress at birth and another had the life-threatening pneumonia preoperatively. Thus, early surgery is indicated when prenatal diagnosis of congenital cystic disease has been confirmed after birth.

Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns: A pilot study

BACKGROUND Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infancy, affecting preterm children with low birth weight. The disease has a multifactorial aetiology with a significant genetic component; until now published association studies have identified several candidate genes but only few of these data has been replicated. In this pilot study, we approached exome sequencing aimed at identifying non-common variants, which are expected to have a stronger phenotypic effect. MATERIALS AND METHODS We performed this study on 26 Italian severely affected BPD preterm unrelated newborns, homogeneously selected from a large prospective cohort. We used an Illumina HiSeq 2000 for sequencing. Data analysis was focussed on genes previously associated to BPD susceptibility and to new candidates in related pathways, highlighted by a prioritization analysis performed using ToppGene Suite. RESULTS By exome sequencing, we identified 3369 novel variants, with a median of 400 variations per sample. The top candidate genes highlighted were NOS2, MMP1, CRP, LBP and the toll-like receptor (TLR) family. All of them have been confirmed with Sanger sequencing. CONCLUSIONS Potential candidate genes have been discovered in this preliminary study; the pathogenic role of identified variants will need to be confirmed with functional and segregation studies and possibly with further methods, able to evaluate the collective influence of rare variants. Moreover, additional candidates will be tested and genetic analysis will be extended to all affected children.

Lung lavage with a saline volume similar to functional residual capacity followed by surfactant administration in newborns with severe meconium aspiration syndrome

We speculated that lung lavage with an FRC (Functional Residual Capacity)dike volume of saline (30 ml/kg) would reduce obstruction of the airways and prevent subsequent non-homogeneous distribution and inactivation of exogenous surfactant in infants with meconium aspiration syndrome (MAS). We report the tolerance of lung lavage with an FRC-like saline volume and the improvement after surfactant administration in two newborns with MAS.

Endogenous Nitric Oxide Production in the Airways of Preterm and Term Infants

Few studies have measured endogenous nitric oxide exhaled from the respiratory system of newborn infants. We measured exhaled nitric oxide (eNO) in the first 48 h of life in 24 (13 preterm, 11 term) spontaneously breathing (online method) newborns using a chemoluminescence analyzer. There was a significant difference in the eNO concentration between term and preterm healthy infants in the first 2 days of life (repeated measures analysis of variance, p < 0.05). In term infants there is a peak eNO production in the first hours of life, suggesting a potential role in postnatal adaptation, while in preterm infants eNO production is almost absent at birth, and then gradually increases.

A case of congenital peripheral primitive neuroectodermal tumor presenting with multiple metastases

The report describes a case of a newborn with a huge congenital abdominal peripheral primitive neuroectodermal tumor, with peritoneal dissemination and cutaneous involvement, and discusses literature data. Peripheral primitive neuroectodermal tumor is an exceedingly uncommon tumor in this age group and is characterized by very aggressive behavior and poor prognosis.

Nasal Continuous Positive Airway Pressure With Heliox in Preterm Infants With Respiratory Distress Syndrome

OBJECTIVE: To assess the therapeutic effects of breathing a low-density helium and oxygen mixture (heliox, 80% helium and 20% oxygen) in premature infants with respiratory distress syndrome (RDS) treated with nasal continuous positive airway pressure (NCPAP). METHODS: Infants born between 28 and 32 weeks of gestational age with radiologic findings and clinical symptoms of RDS and requiring respiratory support with NCPAP within the first hour of life were included. These infants were randomly assigned to receive either standard medical air (control group) or a 4:1 helium and oxygen mixture (heliox group) during the first 12 hours of enrollment, followed by medical air until NCPAP was no longer needed. RESULTS: From February 2008 to September 2010, 51 newborn infants were randomly assigned to two groups, 24 in the control group and 27 in the heliox group. NCPAP with heliox significantly decreased the risk of mechanical ventilation in comparison with NCPAP with medical air (14.8% vs 45.8%). CONCLUSIONS: Heliox increases the effectiveness of NCPAP in the treatment of RDS in premature infants.