Technical realization of a sensorized neonatal intubation skill trainer for operators' retraining and a pilot study for its validation.

BACKGROUND: In neonatal endotracheal intubation, excessive pressure on soft tissues during laryngoscopy can determine permanent injury. Low-fidelity skill trainers do not give valid feedback about this issue. This study describes the technical realization and validation of an active neonatal intubation skill trainer providing objective feedback. METHODS: We studied expert health professionals' performances in neonatal intubation, underlining chance for procedure retraining. We identified the most critical points in epiglottis and dental arches and fixed commercial force sensors on chosen points on a ©Laerdal Neonatal Intubation Trainer. Our skill trainer was set up as a grade 3 on Cormack and Lehane's scale, i.e. a model of difficult intubation. An associated software provided real time sound feedback if pressure during laryngoscopy exceeded an established threshold. Pressure data were recorded in a database, for subsequent analysis with non-parametric statistical tests. We organized our study in two intubation sessions (5 attempts each one) for everyone of our participants, held 24 h apart. Between the two sessions, a debriefing phase took place. In addition, we gave our participants two interview, one at the beginning and one at the end of the study, to get information about our subjects and to have feedback about our design. RESULTS: We obtained statistical significant differences between consecutive attempts, with evidence of learning trends. Pressure on critical points was significantly lower during the second session (p < 0.0001). Epiglottis' sensor was the most stressed (p < 0.000001). We found a significant correlation between time spent for each attempt and pressures applied to the airways in the two sessions, more significant in the second one (shorter attempts with less pressure, rs = 0.603). CONCLUSIONS: Our skill trainer represents a reliable model of difficult intubation. Our results show its potential to optimize procedures related to the control of trauma risk and to improve personnel retraining.

Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI): a feasibility study.

PURPOSE: To investigate the feasibility of a study based on treatment with topiramate (TPM) added to moderate hypothermia in newborns with hypoxic ischemic encephalopathy (HIE). MATERIALS AND METHODS: Multicenter randomized controlled trial. Term newborns with precocious metabolic, clinical and electroencephalographic (EEG) signs of HIE were selected according to their amplified integrated EEG pattern and randomized to receive either TPM (10 mg/kg once a day for the first three days of life) plus moderate hypothermia or hypothermia alone. Safety was assessed by monitoring cardiorespiratory parameters and blood samples collected to check renal, liver, metabolic balance and TPM pharmacokinetics. Efficacy was evaluated by the combined frequency of mortality and severe neurological disability as primary outcome. Incidence of magnetic resonance injury, epilepsy, blindness, hearing loss, neurodevelopment at 18-24 months of life was assessed as secondary outcomes. RESULTS: Forty-four asphyxiated newborns were enrolled in the study. Twenty one newborns (10 with moderate and 11 with severe HIE) were allocated to hypothermia plus TPM and 23 (12 moderate and 11 severe HIE) to hypothermia. No statistically or clinically significant differences were observed for safety, primary or secondary outcomes. However, a reduction in the prevalence of epilepsy was observed in newborns co-treated with TPM. CONCLUSIONS: Results of this pilot trial suggest that administration of TPM in newborns with HIE is safe but does not reduce the combined frequency of mortality and severe neurological disability. The role of TPM co-treatment in preventing subsequent epilepsy deserves further studies.

Two Moroccan Sisters Presenting with a Severe Salt-Wasting Form of Congenital Adrenal Hyperplasia but Normal Female Genitalia.

We report the case of 2 sisters (46,XX) born from consanguineous Moroccan parents. Both sisters had normal female genitalia, but within 2 weeks after birth, they presented with a severe salt-wasting crisis. Hormonal investigations suggested the diagnosis of congenital adrenal hyperplasia, which was confirmed by subsequent molecular analysis to be caused by 3ß-hydroxysteroid dehydrogenase type 2 deficiency. Here, we discuss the main features like onset, possible complications, genetics, and replacement therapy of this rare disease.

Catheter and Laryngeal Mask Endotracheal Surfactant Therapy: the CALMEST approach as a novel MIST technique.

PURPOSE: Neonatal respiratory distress syndrome (RDS) is a major cause of mortality and morbidity among preterm infants. Although the INSURE (INtubation, SURfactant administration, Estubation) technique for surfactant replacement therapy is so far the gold standard method, over the last years new approaches have been studied, i.e. less invasive surfactant administration (LISA) or minimally invasive surfactant therapy (MIST). Here we propose an originally modified MIST, called CALMEST (Catheter And Laryngeal Mask Endotracheal Surfactant Therapy), using a particular laryngeal mask as a guide for a thin catheter to deliver surfactant directly in the trachea. MATERIALS AND METHODS: We performed a preliminary study on a mannequin and a subsequent in vivo pilot trial. RESULTS AND CONCLUSIONS: This novel procedure is quick, effective and well tolerated and might represent an improvement in reducing neonatal stress. Ultimately, CALMEST offers an alternative approach that could be extremely useful for medical staff with low expertise in laryngoscopy and intubation.

Effect of high-fidelity shoulder dystocia simulation on emergency obstetric skills and crew resource management skills among residents.

OBJECTIVE: To determine the effect of a simulation training program for residents in obstetrics and gynecology in terms of technical and nontechnical skills for the management of shoulder dystocia. METHODS: A prospective study was performed at a center in Italy in April-May 2015. Thirty-two obstetrics and gynecology residents were divided into two groups. Residents in the control group were immediately exposed to an emergency shoulder dystocia scenario, whereas those in the simulation group completed a 2-hour training session with the simulator before being exposed to the scenario. After 8weeks, the residents were again exposed to the shoulder dystocia scenario and reassessed. Participants were scored on their demonstration of technical and nontechnical skills. RESULTS: In the first set of scenarios, the mean score was higher in the simulation group than the control group in terms of both technical skills (P=0.008) and nontechnical skills (P<0.001). This difference was retained after 8weeks. CONCLUSION: High-fidelity simulation programs could be used for the training of residents in obstetrics and gynecology to diagnose and manage obstetric emergencies such as shoulder dystocia.

Revised recommendations concerning palivizumab prophylaxis for respiratory syncytial virus (RSV).

Respiratory Syncytial Virus infections are one of the leading causes of severe respiratory diseases that require hospitalization and, in some cases, intensive care. Once resolved, there may be respiratory sequelae of varying severity. The lack of effective treatments for bronchiolitis and the lack of vaccines for RSV accentuate the role of prevention in decreasing the impact of this disease. Prevention of bronchiolitis strongly relies on the adoption of environment and the hygienic behavior measures; an additional prophylactic effect may be offered, in selected cases, by Palivizumab, a humanized monoclonal antibody produced by recombinant DNA technology, able to prevent RSV infection by blocking viral replication.After many years the Italian Society of Neonatology, on the basis of the most recent scientific knowledge, has decided to revise recommendations for the use of palivizumab in the prevention of RSV infection.

A novel simulator for mechanical ventilation in newborns: MEchatronic REspiratory System SImulator for Neonatal Applications.

Respiratory problems are among the main causes of mortality for preterm newborns with pulmonary diseases; mechanical ventilation provides standard care, but long-term complications are still largely reported. In this framework, continuous medical education is mandatory to correctly manage assistance devices. However, commercially available neonatal respiratory simulators are rarely suitable for representing anatomical and physiological conditions; a step toward high-fidelity simulation, therefore, is essential for nurses and neonatologists to acquire the practice needed without any risk. An innovative multi-compartmental infant respirator simulator based on a five-lobe model was developed to reproduce different physio-pathological conditions in infants and to simulate many different kinds of clinical scenarios. The work consisted of three phases: (1) a theoretical study and modeling phase, (2) a prototyping phase, and (3) testing of the simulation software during training courses. The neonatal pulmonary simulator produced allows the replication and evaluation of different mechanical ventilation modalities in infants suffering from many different kinds of respiratory physio-pathological conditions. In particular, the system provides variable compliances for each lobe in an independent manner and different resistance levels for the airway branches; moreover, it allows the trainer to simulate both autonomous and mechanically assisted respiratory cycles in newborns. The developed and tested simulator is a significant contribution to the field of medical simulation in neonatology, as it makes it possible to choose the best ventilation strategy and to perform fully aware management of ventilation parameters.

Human saliva as route of inter-human infection for mouse mammary tumor virus.

Etiology of human breast cancer is unknown, whereas the Mouse Mammary Tumor Virus (MMTV) is recognized as the etiologic agent of mouse mammary carcinoma. Moreover, this experimental model contributed substantially to our understanding of many biological aspects of the human disease. Several data strongly suggest a causative role of MMTV in humans, such as the presence of viral sequences in a high percentage of infiltrating breast carcinoma and in its preinvasive lesions, the production of viral particles in primary cultures of breast cancer, the ability of the virus to infect cells in culture. This paper demonstrates that MMTV is present in human saliva and salivary glands. MMTV presence was investigated by fluorescent PCR, RT-PCR, FISH, immunohistochemistry, and whole transcriptome analysis. Saliva was obtained from newborns, children, adults, and breast cancer patients. The saliva of newborns is MMTV-free, whereas MMTV is present in saliva of children (26.66%), healthy adults (10.60%), and breast cancer patients (57.14% as DNA and 33.9% as RNA). MMTV is also present in 8.10% of salivary glands. RNA-seq analysis performed on saliva of a breast cancer patient demonstrates a high expression of MMTV RNA in comparison to negative controls. The possibility of a contamination by murine DNA was excluded by murine mtDNA and IAP LTR PCR. These findings confirm the presence of MMTV in humans, strongly suggest saliva as route in inter-human infection, and support the hypothesis of a viral origin for human breast carcinoma.

Comparative performances analysis of neonatal ventilators.

BACKGROUND: Mechanical ventilation is a therapeutic action for newborns with respiratory diseases but may have side effects. Correct equipment knowledge and training may limit human errors. We aimed to test different neonatal mechanical ventilators' performances by an acquisition module (a commercial pressure sensor plus an isolated chamber and a dedicated software). METHODS: The differences (ΔP) between peak pressure values and end-expiration pressure were investigated for each ventilator. We focused on discrepancies among measured and imposed pressure data. A statistical analysis was performed. RESULTS: We investigated the measured/imposed ΔP relation. The ΔP do not reveal univocal trends related to ventilation setting parameters and the data distributions were non-Gaussian. CONCLUSIONS: Measured ΔP represent a significant parameter in newborns' ventilation, due to the typical small volumes. The investigated ventilators showed different tendencies. Therefore, a deep specific knowledge of the intensive care devices is mandatory for caregivers to correctly exploit their operating principles.

Sustained lung inflation at birth for preterm infants: a randomized clinical trial.

BACKGROUND: Studies suggest that giving newly born preterm infants sustained lung inflation (SLI) may decrease their need for mechanical ventilation (MV) and improve their respiratory outcomes. METHODS: We randomly assigned infants born at 25 weeks 0 days to 28 weeks 6 days of gestation to receive SLI (25 cm H2O for 15 seconds) followed by nasal continuous positive airway pressure (nCPAP) or nCPAP alone in the delivery room. SLI and nCPAP were delivered by using a neonatal mask and a T-piece ventilator. The primary end point was the need for MV in the first 72 hours of life. The secondary end points included the need for respiratory supports and survival without bronchopulmonary dysplasia (BPD). RESULTS: A total of 148 infants were enrolled in the SLI group and 143 in the control group. Significantly fewer infants were ventilated in the first 72 hours of life in the SLI group (79 of 148 [53%]) than in the control group (93 of 143 [65%]); unadjusted odds ratio: 0.62 [95% confidence interval: 0.38-0.99]; P = .04). The need for respiratory support and survival without BPD did not differ between the groups. Pneumothorax occurred in 1% (n = 2) of infants in the control group compared with 6% (n = 9) in the SLI group, with an unadjusted odds ratio of 4.57 (95% confidence interval: 0.97-21.50; P = .06). CONCLUSIONS: SLI followed by nCPAP in the delivery room decreased the need for MV in the first 72 hours of life in preterm infants at high risk of respiratory distress syndrome compared with nCPAP alone but did not decrease the need for respiratory support and the occurrence of BPD.

Serum cortisol concentrations during induced hypothermia for perinatal asphyxia are associated with neurological outcome in human infants.

Birth asphyxia is a cause of neonatal death or adverse neurological sequelae. Biomarkers can be useful to clinicians in order to optimize intensive care management and communication of prognosis to parents. During perinatal adverse events, increased cortisol secretion is due to hypothalamo-pituitary-adrenal axis activation. We aimed to investigate if cortisol variations during therapeutic hypothermia are associated with neurodevelopmental outcome. We compared 18 cases (neonates with birth asphyxia) with 18 controls (healthy term newborns) and confirmed increased serum cortisol concentrations following the peri-partum adverse event. Among cases, we stratified patients according to neurological outcome at 18 months (group A - good; group B - adverse) and found that after 24 h of therapeutic hypothermia serum cortisol concentration was significantly lower in group A vs group B (28.7 ng/mL vs 344 ng/mL, *p = 0.01). In group B serum, cortisol concentration decreased more gradually during therapeutic hypothermia. We conclude that monitoring serum cortisol concentration during neonatal therapeutic hypothermia can add information to clinical evaluation of neonates with birth asphyxia; cortisol values after the first 24 h of hypothermia can be a biomarker associated with neurodevelopmental outcome at 18 months of age.

Iodine supplementation in the newborn.

Iodine deficiency can be defined as the world's greatest single cause of preventable brain damage. Fetal and neonatal hypothyroidism, caused by iodine deficiency can be prevented prior to conception and then during pregnancy and lactation when an adequate iodine supplementation is ensured. Extremely low birth weight preterm babies risk having a negative iodine balance status in the first weeks of life, exacerbating the hypothyroxinaemia of the prematurity. It is important to ensure that these babies are provided with an adequate iodine intake from the first days of life. Mothers and newborns should avoid environmental iodine excess during pregnancy or lactation.

An active one-lobe pulmonary simulator with compliance control for medical training in neonatal mechanical ventilation.

Mechanical ventilation is a current support therapy for newborns affected by respiratory diseases. However, several side effects have been observed after treatment, making it mandatory for physicians to determine more suitable approaches. High fidelity simulation is an efficient educational technique that recreates clinical experience. The aim of the present study is the design of an innovative and versatile neonatal respiratory simulator which could be useful in training courses for physicians and nurses as for mechanical ventilation. A single chamber prototype, reproducing a pulmonary lobe both in size and function, was designed and assembled. Volume and pressure within the chamber can be tuned by the operator through the device control system, in order to simulate both spontaneous and assisted breathing. An innovative software-based simulator for training neonatologists and nurses within the continuing medical education program on respiratory disease management was validated. Following the clinical needs, three friendly graphic user interfaces were implemented for simulating three different clinical scenarios (spontaneous breathing, controlled breathing and triggered/assisted ventilation modalities) thus providing physicians with an active experience. The proposed pulmonary simulator has the potential to be included in the range of computer-driven technologies used in medical training, adding novel functions and improving simulation results.

MEchatronic REspiratory System SImulator for Neonatal Applications (MERESSINA) project: a novel bioengineering goal.

Respiratory function is mandatory for extrauterine life, but is sometimes impaired in newborns due to prematurity, congenital malformations, or acquired pathologies. Mechanical ventilation is standard care, but long-term complications, such as bronchopulmonary dysplasia, are still largely reported. Therefore, continuous medical education is mandatory to correctly manage devices for assistance. Commercially available breathing function simulators are rarely suitable for the anatomical and physiological realities. The aim of this study is to develop a high-fidelity mechatronic simulator of neonatal airways and lungs for staff training and mechanical ventilator testing. The project is divided into three different phases: (1) a review study on respiratory physiology and pathophysiology and on already available single and multi-compartment models; (2) the prototyping phase; and (3) the on-field system validation.

Lutein administration to pregnant women with gestational diabetes mellitus is associated to a decrease of oxidative stress in newborns.

Oxidative stress (OS) is defined as an imbalance between pro- and antioxidant factors that can lead to cellular and tissue damage. Under condition of gestational diabetes, OS is exacerbated and can cause vascular dysfunction in the placenta, leading to fetal and perinatal complications. We investigated the oxidative status of diabetic pregnant women and of their babies. A group of those diabetic women received lutein, and another group did not receive anything. In order to verify a possible antioxidant function of lutein, we compared the OS values of the two groups. OS appeared lower in treated gravidas than in untreated ones; however, there was not a statistically significant difference between the two groups. As far as newborns are concerned, there was a significant difference of OS values between babies born to mothers treated with lutein and newborns to mothers untreated at 2 h of life. However, at 48 h, there was not a significant difference between the two groups. In conclusion, lutein administration during pregnancy significantly reduced neonatal OS at birth. Further studies are necessary to evaluate the effects of combined administration to mother and infants.

Skin conductance variations compared to ABC scale for pain evaluation in newborns.

OBJECTIVES: To validate spontaneous skin conductance variations as a specific reliable mean to measure pain in full-term healthy newborns during heel stick, comparing it with the ABC scale. To compare oral sucrose to wrapping effectiveness for non-pharmacological analgesia during the same procedure. METHOD: All recruited newborns (n = 158) underwent a heel stick for metabolic screening at 48 h of life with non-pharmacological analgesia by oral sucrose (group A) or wrapping (group B) according to randomization. Their pain was estimated by ABC scale score (standard method) and measured by skin conductance variations. RESULTS: A positive correlation was founded between peaks per sec measure and ABC score (rs = 0.303, p < 0.005). ABC score in group A was lower than in group B (p < 0.001). Difference in mean ABC score among newborn subgroups treated by different nurses was not statistically significant for wrapping while it was significant for sucrose (p = 0.001). CONCLUSIONS: Skin conductance measurement device is a reliable method to evaluate pain. Novel technological devices may be a useful support to clinical observation in this field. Oral sucrose is more effective than wrapping in reducing pain. Operators should be well periodically re-trained in performing non pharmacological analgesia during minor procedure on newborns.

Feto-placental vascular dysfunction as a prenatal determinant of adult cardiovascular disease.

Low birthweight is associated with increased rates of coronary heart disease, stroke, hypertension and non-insulin-dependent diabetes during adult life. This is thought to be the consequence of a 'programming', whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology and metabolism. Programming of the fetus may, hence, result from adaptations to a condition where placental nutrient supply fails to match fetal demand. Recently, compensatory feto-placental up-regulation of the nitric oxide system during fetal growth restriction (FGR) was shown. Particularly, restricted hypoxic fetuses present an elevation of nitrites and a reduction of asymmetric dimethylarginine. S-nitrosohemoglobin is consumed under hypoxic conditions. These events are followed by nitric oxide pathway down-regulation postnatally, increasing susceptibility to cardiovascular disorders later in life. The relative hyperoxia would favor any such occurrence through depletion of tetrahydrobiopterin secondary to oxygen radical formation. This concept may lead to new therapeutic strategies, based on tetrahydrobiopterin supplementation, free-radical scavenging, L-arginine administration and/or inhaled NO therapy in FGR hypoxic newborns, to improve their postnatal adaptation and to reduce the risk of metabolic pathologies in adult age.