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This study aimed to prospectively evaluate the association between the appearance and evolution of retinopathy of prematurity (ROP) and selected blood parameters, focusing on platelets count. In total, 157 preterm consecutive babies screened for ROP were included and classified in: ROP necessitating treatment (group ROP1), ROP regressed without therapy (group ROP2) and no ROP (group no-ROP), divided in two phases for each group depending on gestational age. Blood parameters were weekly gathered and referred to postmenstrual age, ROP severity and phase. Platelet count mean values were statistically lower (p &lt, 0.001) during both phases in ROP1 group (179 × 109/L vs. 213 × 109/L in phase 1 and 2, respectively) vs. other groups (ROP2: 286 × 109/L vs. 293 × 109/L, no ROP: 295 × 109/L vs. 313 × 109/L). Platelet count at birth &lt, 181 × 109 was statistically associated with Type 1 ROP development and evolution (sensibility = 76.47%, 95% confidence interval 60.0–87.6, specificity = 66.12%, 95% confidence interval 57.3–73.9). In ROP 1 group, a platelets count mean value “spike” (392.6 × 109/L) was documented at 36 weeks of corrected gestational age, preceding the need for treatment performed at a median of 38.1 ± 3.2 weeks. Early birth thrombocytopenia is confirmed as a biomarker of development and progression of ROP requiring treatment. The increase of platelets count at 35–37 weeks of corrected gestational age can be considered a possible clinical biomarker anticipating Type 1 ROP progression in preterm infants.

ObjectiveEnsure access to perinatal palliative care (PnPC) to all eligible fetuses/infants/parents.DesignDuring 12 meetings in 2016, a multidisciplinary work-group (WG) performed literature review (Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method was applied), including the ethical and legal references, in order to propose shared care pathway.SettingMaternal-Infant Department of Padua’s University Hospital.PatientsPnPC eligible population has been divided into three main groups: extremely preterm newborns (first group), newborns with prenatal/postnatal diagnosis of life-limiting and/or life-threatening disease and poor prognosis (second group) and newborns for whom a shift to PnPC is appropriate after the initial intensive care (third group).InterventionsThe multidisciplinary WG has shared care pathway for these three groups and defined roles and responsibilities.Main outcome measuresPrenatal and postnatal management, symptom’s treatment, end-of-life care.ResultsThe best care setting and the best practice for PnPC have been defined, as well as the indications for family support, corpse management and postmortem counselling, as well suggestion for conflicts’ mediation.ConclusionsPnPC represents an emerging field within the paediatric palliative care and calls for the development of dedicated shared pathways, in order to ensure accessibility and quality of care to this specific population of newborns.

Objectives To compare the efficacy of intra‐tracheal (IT) surfactant/budesonide (SB) with that of surfactant alone (S) in reducing the rate of bronchopulmonary dysplasia (BPD) at 36 weeks post‐menstrual age (PMA), we included extremely preterm very low birth weight (VLBW) infants with severe respiratory distress syndrome (RDS) in our tertiary neonatal level of care unit (Padua, Italy). Study Design A retrospective chart review of two cohorts of extremely preterm VLBW neonates (

Sepsis is a major concern in neonatology, but there are no reliable biomarkers for its early diagnosis. The aim of the study was to compare the metabolic profiles of plasma and urine samples collected at birth from preterm neonates with and without earlyonset sepsis (EOS) to identify metabolic perturbations that might orient the search for new early biomarkers. All preterm newborns admitted to the neonatal intensive care unit were eligible for this proof-of-concept, prospective case-control study. Infants were enrolled as “cases” if they developed EOS, and as “controls”if they did not. Plasma samples collected at birth and urine samples collected within 24 h of birth underwent untargeted and targeted metabolomic analysis using mass spectrometry coupled with ultra-performance liquid chromatography. Univariate and multivariate statistical analyses were applied. Of 123 eligible newborns, 15 developed EOS. These 15 newborns matched controls for gestational age and weight. Metabolomic analysis revealed evident clustering of the cases versus controls, with the glutathione and tryptophan metabolic pathways markedly disrupted in the former. In conclusion, neonates with EOS had a metabolic profile at birth that clearly distinguished them from those without sepsis, and metabolites of glutathione and tryptophan pathways are promising as new biomarkers of neonatal sepsis.

Pathophysiology of retinopathy of prematurity (ROP) still presents a gap. Lately blood tests parameters of premature infants have been measured at different times of ROP, attempting to detect correlations with ROP development and progression. So far, very early post-natal biomarkers, predictive of ROP outcome, have not been detected. Our purpose is to evaluate, in the earliest post birth blood sample, the correlation between routinely dosed blood parameters and ROP outcome. 563 preterm babies, screened according to ROP guidelines, were included and classified in conformity with ET-ROP study in “Group 1” (ROP needing treatment), “Group 2” (ROP spontaneously regressed) and “noROP” group (never developed ROP). The earliest (within an hour after delivery) blood test parameters routinely dosed in each preterm infant were collected. Platelet count was decreased in Group 1 versus noROP group (p = 0.0416) and in Group 2 versus noROP group (p = 0.1093). The difference of thrombocytopenic infants among groups was statistically significant (p = 0.0071). CRP was higher in noROP versus all ROPs (p = 0.0331). First post-natal blood sample revealed a significant thrombocytopenia in ROP needing treatment, suggesting a role of platelets in the pathophysiology and progression of ROP, possibly considering it as a predictive parameter of ROP evolution.

Background and Objective: Placing an endotracheal tube (ETT) in neonates is challenging and currently requires timely radiographic confirmation of correct tip placement. The objective was to establish the reliability of ultrasound (US) for assessing ETT position in the neonatal intensive care unit (NICU), time needed to do so, and patients’ tolerance. Methods: A prospective study on 71 newborns admitted to our NICU whose ETT placement was evaluated with US (ETT-echo) and confirmed on chest X-rays (CXR). Data were collected by 3 operators (2 neonatologists and a resident in pediatrics). The right pulmonary artery (RPA) was used as a landmark for US. The distance between the tip of the ETT and the upper margin of the RPA was measured using US and compared with the distance between the tube’s tip and the carina on the CXR. Results: Seventy-one intubated newborns were included in the study (n = 34 < 1,000 g, n = 18 1,000–2,000 g, n = 19 > 2,000 g). Statistical analysis (Bland-Altman plot and Lin’s concordance correlation coefficient) showed an excellent consistency between ETT positions identified on US and chest X-ray. The 2 measures (ETT-echo and CXR) were extremely concordant both in the whole sample and in the subgroups. Minimal changes in patients’ vital signs were infrequently observed during US, confirming the tolerability of ETT-echo. The mean time to perform US was 3.2 min (range 1–13). Conclusions: ETT-echo seems to be a rapid, tolerable, and highly reliable method worth further investigating for future routine use in neonatology with a view to reducing radiation exposure.

Background The optimal management of PDA in very low birth weight (VLBW) infants is still controversial. Aim of our study was to investigate the management of PDA in the Italian neonatal intensive care units (NICU). Methods We conducted an on-line survey study from June to September 2017. A 50-items questionnaire was developed by the Italian Neonatal Cardiology Study Group and was sent to Italian NICUs. Results The overall response rate was 72%. Diagnosis of PDA was done by neonatologists, cardiologists or both (62, 12 and 28% respectively). PDA significance was assessed by a comprehensive approach in all centers, although we found a heterogeneous combination of parameters and cut-offs used. None used prophylactic treatment. 19% of centers treated PDA in the first 24 h, 60% after the first 24 h, following screening echocardiography or clinical symptoms, 18% after the first 72 h and 2% after the first week. In the first course of treatment ibuprofen, indomethacin and paracetamol were used in 87, 6 and 7% of centers respectively. Median of surgical ligation was 3% (1–6%). Conclusions Significant variations exist in the management of PDA in Italy. Conservative strategy and targeted treatment to infants older than 24 h with echocardiographic signs of hemodynamic significance seemed to be the most adopted approach.

Background and aims Preterm newborns undergo hemodynamic challenges in the postnatal period. The aim of this study was to investigate myocardial mechanics changes in the postnatal period in preterm infants using speckle tracking echocardiography (STE). Material and methods Thirty-nine preterm infants ≤34 weeks' gestation underwent cardiac ultrasound evaluation during the first 96 hours of life. A repeated echocardiogram at 3 weeks of age was performed. Echocardiographic assessment involved left ventricular ejection fraction, mitral E/A ratio, S' and E' velocities, E/E' ratio, tricuspid annular plane systolic excursion (TAPSE), left atrium-to-aorta ratio, ductal diameter and ductal shunt pattern. Left ventricular longitudinal, circumferential and radial strain, apex-basal rotation and twist were measured from the apical 4-chamber and short-axis views using STE. Results The mean gestational age was 30 ± 2.7 weeks with a mean birth weight of 1318 ± 485 g. Apical segments demonstrated higher longitudinal strain than basal and mid-ones. In all gestational ages, endocardial longitudinal strain was higher than the epicardial. Epicardial longitudinal strain significantly increased during the first 3 weeks, resulting in the change in basal rotation from counterclockwise to clockwise and thus in the acquisition of twist. Deformation parameters were higher in infants with a hemodynamic significant patents ductus arteriosus. Conclusions Echocardiographic assessment of myocardial deformation parameters is feasible in preterm infants. Our data suggest that the maturational process of the myocardium is due to the development of the epicardial layer after birth, which allows the acquisition of the twist.

Antimicrobial prescriptions in neonatal intensive care units (NICUs) represent a point of concern for the emergence of MDROs and for morbidity associated with prolonged antibiotic exposure (e.g., invasive candidiasis, necrotizing enterocolitis, and late-onset sepsis). Antimicrobial stewardship programs (ASPs) have shown to be a valuable tool for the prevention of resistance with the goals of optimizing clinical outcomes while decreasing unnecessary prescribing. The most frequent ASP strategies include the correct collection and interpretation of microbiological specimens, prescription of the narrowest-spectrum antibiotic appropriate for a particular case, and de-escalation or discontinuation of therapy in defined situations. A robust ASP requires everyday multidisciplinary collaboration between ID physicians, neonatologist, clinical pharmacists, clinical microbiologists, infection control professionals, hospital epidemiologists, and information services specialists. Education and clinical pathways (e.g., sepsis or surgical prophylaxis pathways) are an excellent starting point if followed by proactive interventions such as prospective audits and feedback and formulary restriction with prior antimicrobial authorization. The current review outlines the problems faced in NICU antimicrobial prescribing and presents various solutions from the literature.

Background Neonatologist performed echocardiography (NPE) has increasingly been used to assess the hemodynamic status in neonates. Aim of this survey was to investigate the utilization of NPE in Italian neonatal intensive care units (NICUs). Methods We conducted an on-line survey from June to September 2017. A questionnaire was developed by the Italian neonatal cardiology study group and was sent to each Italian NICU. Results The response rate was 77%. In 94% of Italian NICUs functional echocardiography was used by neonatologists, cardiologists or both (57, 15 and 28% respectively). All the respondents used NPE in neonates with patent ductus arteriosus and persistent pulmonary hypertension, 93% in neonates with hypotension or shock, 85% in neonates with perinatal asphyxia, 78% in suspicion of cardiac tamponade, and 73% for line positioning. In 30% of center, there was no NPE protocol. Structural echocardiography in stable and critically ill neonates was performed exclusively by neonatologists in 46 and 36% of center respectively. Conclusions NPE is widely used in Italian NICUs by neonatologists. Structural echocardiography is frequently performed by neonatologists. Institutional protocols for NPE are lacking. There is an urgent need of a formal training process and accreditation to standardize the use of NPE.

Increasing recent evidence favors paracetamol use for patent ductus arteriosus (PDA) closure in preterms. Our study aims were (1) to assess efficacy and safety of intravenous (i.v.) paracetamol for PDA closure in a 23-32-week preterm population, as "first-line" (when traditional ibuprofen treatment was contraindicated) or "rescue" treatment (after ibuprofen failed), and (2) to identify predictors of PDA closure. The cumulative efficacy of consecutive cycles of i.v. paracetamol on PDA closure was confirmed after both "first-line" and "rescue" treatment, the overall PDA closure rates being, respectively, 56.7 and 61.1 % (p = 0.7624) after two cycles and 63.3 and 77.8 % (p = 0.2959) after three cycles. No toxicity was apparent after either "first-line" or "rescue" i.v. paracetamol treatment. On multivariate analysis, gestational age (GA) emerged as an independent predictor of PDA closure in the "first-line" i.v. paracetamol treatment group, while clinical risk index for babies (CRIB) score (a patient risk index based on birth weight, GA at birth, sex, patient's temperature on admission, and maximum base excess in first 12 h of life) was an independent predictor of PDA closure failure in the "rescue" group.I.V. paracetamol proved effective in our study population. Randomized control trials (RCTs) are warranted to further investigate the efficacy and safety of i.v. paracetamol for PDA closure in preterms.• Oral paracetamol has been judged as effective as oral ibuprofen for PDA closure in the preterm. • To date, only a handful of non-randomized studies exist to support the effectiveness of i.v. paracetamol in PDA closure. What is New: • Our observations confirm the clinical efficacy of i.v. paracetamol for PDA closure in a very low birth weight (VLBW)/extremely low birth weight (ELBW) preterm population. • Gestational age and CRIB score emerge as independent predictors of PDA closure.

Bronchopulmonary dysplasia (BPD) is a major complication of premature birth that significantly affects mortality and long-term morbidity in numerous immature infants. Corticosteroids are particularly suitable for treating BPD, as lung inflammation is central to its pathogenesis. Corticosteroids have considerable, fast beneficial effects on lung function in premature infants with lung disease, but they are also associated with several serious adverse effects, which may have a detrimental impact on long-term outcome. Dexamethasone is the most often used corticosteroid for systemic administration. Despite its value in preventing and treating BPD, its use is associated with several alarming short-term effects and, worst of all, with an increased rate of cerebral palsy in the long term. Dexamethasone nonetheless remains an important therapeutic option for infants with severe lung disease beyond the second to third week of life. Hydrocortisone is an important alternative to dexamethasone, as its use does not appear to be associated with any neurotoxic effects. Its efficacy in the prevention and treatment of BPD has yet to be clearly demonstrated, however. Inhaled corticosteroids might reduce lung inflammation with fewer systemic adverse effects; however, a recent, large randomized trial showed that inhaled budesonide was associated with an excess mortality, despite its beneficial respiratory effects. In another study, instilling budesonide together with surfactant in the trachea of intubated infants with severe respiratory distress appeared safe and achieved a significant reduction in the rate of BPD at 36 postmenstrual weeks. This important finding needs to be confirmed in a larger trial currently underway.

In recent years, the diagnostic-therapeutic developments in fetal and neonatal medicine have profoundly changed the medical and ethical context in which pediatric healthcare professionals work.

Aim The aim of this report is to present a brief review of the current literature on the management of EEC. Case Report A term male neonate presented at birth with classic bladder exstrophy, a variant of the exstrophy-epispadias complex (EEC). The defect was covered with sterile silicon gauzes and waterproof dressing; at 72 hours of life, primary closure without osteotomy of bladder, pelvis, and abdominal wall was successfully performed. Discussion EEC incidence is approximately 2.15 per 1,00,000 live births; several urological, musculocutaneous, spinal, orthopedic, gastrointestinal, and gynecological anomalies may be associated to EEC. Initial medical management includes use of occlusive dressings to prevent air contact and dehydration of the open bladder template. Umbilical catheters should not be positioned. Surgical repair stages include initial closure of the bladder and abdominal wall with or without osteotomy, followed by epispadias repair at 6 to 12 months, and bladder neck repair around 5 years of life. Those who fail to attain continence eventually undergo bladder augmentation and placement of a catheterizable conduit. Conclusion Modern-staged repair of EEC guarantees socially acceptable urinary continence in up to 80% of cases; sexual function can be an issue in the long term, but overall quality of life can be good.

Background: Ibuprofen (IBU) has proved as effective as indomethacin in the pharmacological closure of hemodynamically significant patent ductus arteriosus (HsPDA), with an efficacy inversely related to gestational age (57-89%). Objective: This study aimed to establish whether continuous infusions of IBU could be more effective in very low birth weight infants with no additional adverse effects and reduce the need for surgical ligation. Methods: A prospective, randomized, double-dummy study was conducted on 112 very low birth weight infants (mean gestational age 27.2 weeks, SD 2; birth weight 1,019 g, SD 330) with HsPDA, 56 of whom were given IBU in conventional 15-min intermittent boluses, while the other 56 were administered IBU as a 24-hour continuous infusion, both at standard doses (10/5/5 mg/kg). Extensive echocardiography was performed before and after treatment, and adverse effects were monitored. Results: Pharmacological PDA closure was achieved after 1 or 2 IBU courses in 36 of 56 infants (64.3%) after bolus administration and in 46 of 55 (83.6%) after continuous infusion (p = 0.020), and in 9 of 26 (34.6%) and 24 of 30 (80.0%), respectively, in the infants with a gestational age of 23-27 weeks (p = 0.006). Sustained pharmacological closure was observed in 38 of 56 infants (67.9%) after bolus IBU and in 47 of 55 (85.5%) after continuous infusion (p = 0.029). Surgical ligation was used less after continuous infusion than after bolus IBU (5.5 vs. 19.6%; p = 0.024). The continuous infusion group had fewer symptoms of necrotizing enterocolitis (NEC), especially in the more preterm infants, while other neonatal morbidity and mortality rates were similar. Conclusion: Continuous IBU infusion is more effective than standard boluses for sustained closure of HsPDA, with fewer NEC symptoms and less need for surgical ligation in very low birth weight infants.

Despite notable advances in the survival and management of preterm infants in recent decades, chronic lung disease remains a common complication. Approximately one in three infants born preterm (< 32 weeks of gestation) are hospitalized with respiratory problems (mainly due to infections) in their first 2 years of life, and the risk of childhood wheezing is three times higher in this population. By comparison with infants born at term, there seems to be a higher incidence of respiratory morbidity in those born preterm, even in the absence of bronchopulmonary dysplasia (BPD) and in late-preterm babies. Although long-term follow-up data are still not collected systematically, there is evidence of preterm infants' respiratory symptoms, lung function impairments, and radiological abnormalities, tending to persist throughout childhood and into early adulthood. Respiratory conditions associated with preterm birth are often diagnosed and treated as asthma, but the pathophysiological patterns of BPD and asthma are very different. Future research should focus on characterizing preterm infants' pathological pulmonary features by gestational age at birth, and presence or absence of BPD. Improving our current knowledge of the respiratory disorder associated with prematurity might hopefully prompt targeted follow-up protocols, and novel prevention strategies and treatment approaches.

Heart transplantation, formerly the final option for terminally ill children, has now become the treatment of choice for a number of serious acquired or congenital cardiac conditions, which cannot be treated conservatively. Nevertheless, several problems remain unsolved. First of all the shortage of donors, mainly in the first months and years of life, which has become more and more significant with time, regardless of the country, religious belief or culture of the people. Secondly, the long-term impact of immunosuppression in a developing organism, and its possible inter-relation with the primary disorder, which leads to intractable heart failure. Whether a heart transplant is a cure or an ongoing disease for both the child and the family is another matter of concern. These and other topics are covered in this article.

Summary Background: The efficacy of a Neonatal Resuscitation Program (NRP) has been previously evaluated in developed countries, but there is a lack of information regarding the impact of this teaching program in developing countries. Our aim was to compare the knowledge gained by University of Khartoum (Sudan) and University of Padova (Italy) pediatric residents following participation in the NRP course. Methods: An 80-item questionnaire derived from the standard test contained in the American Heart Association and American Academy of Pediatrics Neonatal Resuscitation Manual was given to participants before and after the course. Results: Twenty-five Sudanese and 26 Italian pediatric residents answered the pre- and postcourse questionnaire. The percentages of correct answers significantly improved from before to immediately after the course for both Sudanese (51.9 ± 10.5% vs 84.9 ± 5.8%; P

A 2-day old girl with status epilepticus, unresponsive to maximum pharmacological intervention, is reported. Findings of brain and cardiac lesions pointed to the diagnosis of tuberous sclerosis. One of the brain lesions was unusually large, occupying most of the right temporo-parietal lobe.

Indomethacin (INDO) and, more recently, ibuprofen (IBU) have been used to treat haemodynamically significant patent ductus arteriosus (PDA) in preterm infants. Both are cyclo-oxygenase blockers, but seem to have a different influence on regional circulation. In a prospective, randomised, controlled study, we compared INDO and IBU with regard to efficacy and safety for the early non-invasive treatment of PDA. Doppler echocardiography was used to study 232 preterm infants (gestational age 23-34 weeks) with respiratory distress syndrome of whom 175 had persistent, haemodynamically significant PDA at 48-72 h of life. They were randomised to receive three intravenous doses of either INDO (0.2 mg/kg, at 12 h intervals) or IBU (a first 10 mg/kg dose followed by two doses of 5 mg/kg at 24 h intervals), recording rate of ductal closure, need for additional treatment, side-effects and clinical course. The efficacy of the pharmacological treatment was similar in the two groups (56/81, 69% INDO; 69/94, 73% IBU). Patients treated with INDO showed a significant increase in serum creatinine (89 +/- 24 versus 82 +/- 20 mmol/l, P = 0.03) and a near-significant tendency for a lower fractional excretion of sodium (3 +/- 3 versus 4 +/- 2%, P = 0.08); moreover, 12/81 (15%) INDO patients versus 1/94 (1%) IBU patients became oliguric (1 ml/kg per h) during treatment (P = 0.017).Our findings confirm that, by comparison with indomethacin, ibuprofen has fewer effects on renal function in terms of urine output and fluid retention, with much the same efficacy and safety in closing patent ductus arteriosus in preterm infants with respiratory distress syndrome. In particular, no increased incidence of intracranial haemorrhage was observed after ibuprofen treatment.

Prenatal diagnosis can show masses of the fetal neck, mouth, and face that can potentially cause respiratory distress at birth. To prevent such an emergency, the EXIT (ex utero intrapartum technique) is performed: it is the intrapartum intubation of the fetus at term while still connected to the placenta. The EXIT procedure was first performed in a case of cervical teratoma. Up to now a total of 34 cases are described, mostly cervical teratomas (13 cases), lymphangiomas (7), epignathus (3); babies' outcome has been successful in 25 of them, with one death related to the procedure. Among the reported cases we are aware of only one where EXIT was performed in a twin gestation, in which the normal twin was delivered first. In our case the normal fetus was posterior to the twin with cervical malformation, requiring us to work on the latter while the former was still in the uterus. After having safely secured the airway in twin A, twin B was prompt delivered with excellent general conditions. Our limited experience enlarges the possibility to perform this prenatal procedure even in "nonstandard" conditions, such as a twin gestation, and may prove useful to those who are going to deal with such issues.

Effect of Administering Low-Dose Fentanyl Infusion on Respiratory Dynamics in the Premature Ventilated for Respiratory Distress Syndrome-A Randomized Double-Blind Trial

The purpose of this study is to better define seizure activity and to make anticonvulsant therapy optimal. During a period of 4.5 years, 57 infants with clinical evident seizures underwent continuous EEG monitoring (C.F.M., Device Instrument, Ltd, London). C.F.M. tracing showed seizure activity in 31 (54.4 %), and none in 26 (45.6 %). 20 of the 31 subjects with C.F.M. documented activity and 20 of those 26 without, had already begun anticonvulsant therapy at the beginning of C.F.M. monitoring. The efficacy of the anti-convulsant drugs was evaluated in 31 infants having both clinical and C.F.M. documented seizure activity. 20 infants began C.F.M. monitoring after, and 11 before beginning anticonvulsant therapy. Phenobarbital, the drug of first choise, was efficacious in 4 out of the 27 cases, but useless in 16 of the 27. The best responce was obteined with lidocaine, efficacious in 14 out of 20 patients treated. In conclusion, 45.6 % of the clinical seizures have no C.F.M. equivalent. In the large pan of the cases, commonly used anti-convulsant drugs did not eliminate the seizure activity found on C.F.M. The persistent electrical seizures are considered to be damaging. Continuous neurophysiologies! monitoring is a very usefull means for evaluating the efficacy of anticonvulsant therapy.

We report a case of a 750 grams premature female who was scheduled for surgical ligation of a patent arterial duct. Intra-operative findings showed a patent arterial duct in association to a retro-esophageal aortic arch creating a complete vascular ring around the trachea, which was successfully divided. A vascular ring should be ruled-out in premature infants prior to ductal ligation at bidimensional echocardiography. _______________________________________________________________________________________ Keywords: congenital heart disease; premature infant; surgery; vascular ring. ____________________________________________________________________________