Ototoxic and nephrotoxic drugs in neonatal intensive care units: results of a Spanish and Italian survey.

Neonates face heightened susceptibility to drug toxicity, often exposed to off-label medications with dosages extrapolated from adult or pediatric studies. Premature infants in Neonatal Intensive Care Units (NICUs) are particularly at risk due to underdeveloped pharmacokinetics and exposure to multiple drugs. The study aimed to survey commonly used medications with a higher risk of ototoxicity and nephrotoxicity in Spanish and Italian neonatal units. A prospective cross-sectional study was conducted in Italian and Spanish neonatal units using a web-based survey with 43 questions. A modified Delphi method involved experts refining the survey through online consensus. Ethical approval was obtained, and responses were collected from January to July 2023. The survey covered various aspects, including drug-related ototoxic and nephrotoxic management, hearing screening, and therapeutic drug monitoring. Responses from 131 participants (35.9% from Spain and 64.1% from Italy) revealed awareness of drug toxicity risks. Varied practices were observed in hearing screening protocols, and a high prevalence of ototoxic and nephrotoxic drug use, including aminoglycosides (100%), vancomycin (70.2%), loop diuretics (63.4%), and ibuprofen (62.6%). Discrepancies existed in guideline availability and adherence, with differences between Italy and Spain in therapeutic drug monitoring practices. CONCLUSIONS: The study underscores the need for clinical guidelines and uniform practices in managing ototoxic and nephrotoxic drugs in neonatal units. Awareness is high, but inconsistencies in practices indicate a necessity for standardization, including the implementation of therapeutic drug monitoring and the involvement of clinical pharmacologists. Addressing these issues is crucial for optimizing neonatal care in Southern Europe. WHAT IS KNOWN: • Neonates in intensive care face a high risk of nephrotoxicity and ototoxicity from drugs like aminoglycosides, vancomycin, loop diuretics, and ibuprofen. • Therapeutic drug monitoring is key for managing these risks, optimizing dosing for efficacy and minimizing side effects. WHAT IS NEW: • NICUs in Spain and Italy show high drug toxicity awareness but differ in ototoxic/nephrotoxic drug management. • Urgent need for standard guidelines and practices to address nephrotoxic risks from aminoglycosides, vancomycin, loop diuretics, and ibuprofen.

Increased bronchiolitis burden and severity after the pandemic: a national multicentric study.

BACKGROUND: The coronavirus 2019 (COVID-19) related containment measures led to the disruption of all virus distribution. Bronchiolitis-related hospitalizations shrank during 2020-2021, rebounding to pre-pandemic numbers the following year. This study aims to describe the trend in bronchiolitis-related hospitalization this year, focusing on severity and viral epidemiology. METHODS: We conducted a retrospective investigation collecting clinical records data from all infants hospitalized for bronchiolitis during winter (1st September-31th March) from September 2018 to March 2023 in six Italian hospitals. No trial registration was necessary according to authorization no.9/2014 of the Italian law. RESULTS: Nine hundred fifty-three infants were hospitalized for bronchiolitis this last winter, 563 in 2021-2022, 34 in 2020-2021, 395 in 2019-2020 and 483 in 2018-2019. The mean length of stay was significantly longer this year compared to all previous years (mean 7.2 ± 6 days in 2022-2023), compared to 5.7 ± 4 in 2021-2022, 5.3 ± 4 in 2020-2021, 6.4 ± 5 in 2019-2020 and 5.5 ± 4 in 2018-2019 (p < 0.001), respectively. More patients required mechanical ventilation this winter 38 (4%), compared to 6 (1%) in 2021-2022, 0 in 2020-2021, 11 (2%) in 2019-2020 and 6 (1%) in 2018-2019 (p < 0.05), respectively. High-flow nasal cannula and non-invasive respiratory supports were statistically more common last winter (p = 0.001 or less). RSV prevalence and distribution did not differ this winter, but coinfections were more prevalent 307 (42%), 138 (31%) in 2021-2022, 1 (33%) in 2020-2021, 68 (23%) in 2019-2020, 61 (28%) in 2018-2019 (p = 0.001). CONCLUSIONS: This study shows a growth of nearly 70% in hospitalisations for bronchiolitis, and an increase in invasive respiratory support and coinfections, suggesting a more severe disease course this winter compared to the last five years.

Fate of melatonin orally administered in preterm newborns: Antioxidant performance and basis for neuroprotection.

Preterm infants cannot counteract excessive reactive oxygen species (ROS) production due to preterm birth, leading to an excess of lipid peroxidation with malondialdehyde (MDA) production, capable of contributing to brain damage. Melatonin (ME), an endogenous brain hormone, and its metabolites, act as a free radical scavenger against ROS. Unfortunately, preterms have an impaired antioxidant system, resulting in the inability to produce and release ME. This prospective, multicenter, parallel groups, randomized, double-blind, placebo-controlled trial aimed to assess: (i) the endogenous production of ME in very preterm infants (gestational age ≤ 29 + 6 WE, 28 infants in the ME and 26 in the placebo group); (ii) the exogenous hormone availability and its metabolization to the main metabolite, 6-OH-ME after 15 days of ME oral treatment; (iii) difference of MDA plasma concentration, as peroxidation marker, after treatment. Blood was collected before the first administration (T1) and after 15 days of administration (T2). ME and 6-OH-ME were detected by liquid chromatography tandem mass spectrometry, MDA was measured by liquid chromatograph with fluorescence detection. ME and 6-OH-ME were not detectable in the placebo group at any study time-point. ME was absent in the active group at T1. In contrast, after oral administration, ME and 6-OH-ME resulted highly detectable and the difference between concentrations T2 versus T1 was statistically significant, as well as the difference between treated and placebo groups at T2. MDA levels seemed stable during the 15 days of treatment in both groups. Nevertheless, a trend in the percentage of neonates with reduced MDA concentration at T2/T1 was 48.1% in the ME group versus 38.5% in the placebo group. We demonstrated that very preterm infants are not able to produce endogenous detectable plasma levels of ME during their first days of life. Still, following ME oral administration, appreciable amounts of ME and 6-OH-ME were available. The trend of MDA reduction in the active group requires further clinical trials to fix the dosage, the length of ME therapy and to identify more appropriate indexes to demonstrate, at biological and clinical levels, the antioxidant activity and consequent neuroprotectant potential of ME in very preterm newborns.

Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study).

BACKGROUND: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. METHODS/DESIGN: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. DISCUSSION: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

Antibiotic prophylaxis for ophthalmia neonatorum in Italy: results from a national survey and the Italian intersociety new position statements.

BACKGROUND: Ophthalmia neonatorum is an acute conjunctivitis that occurs in newborns within the first month of life. The most serious infections are due to Chlamydia trachomatis and Neisseria gonorrhoeae, that may cause permanent damages. The use of ophthalmic prophylaxis varies widely around the world, according to the different health and socio-economic contexts. To date in Italy there is no a clear legislation regarding ophthalmia neonatorum prophylaxis at birth. METHODS: We invited all birth centers in Italy to carry out a retrospective survey relating the last three years. We collected data regarding demographics of neonates, drugs used for ophthalmic prophylaxis and results of the screening of pregnant women for Chlamydia trachomatis and Neisseria gonorrhoeae vaginal infections. RESULTS: Among 419 birth centers, 302 (72,1%) responded to the survey. Overall 1041384 neonates, 82,3% of those born in the three years considered, received ophthalmic prophylaxis. Only 4,585 (0,4%) of them received one of the drugs recommended by the WHO. The Centers that participated to the survey reported 12 episodes of Chlamydial conjunctivitis and no Gonococcal infection in the three years. Only 38% of the Centers performed vaginal swabs to pregnant women: 2,6% screened only for Neisseria, 9,6% only for Chlamydia and 25,8% for both germs. CONCLUSIONS: The data obtained from the survey showed a low incidence of neonatal conjunctivitis due to either Neisseria gonorrhoeae or Chlamydia trachomatis in Italy. Due to the lack of legislation regulating the prophylaxis of ophthalmia neonatorum in newborns, the Italian Society of Neonatology, the Italian Society of Obstetrics and Gynecology and the Italian Society of Perinatal Medicine have recently issued new recommendations on this topic.

Intersociety Position Statement on the Prevention of Ophthalmia Neonatorum in Italy.

There is currently no worldwide agreement on the real need to administer conjunctival antibiotics to neonates at birth to prevent neonatal conjunctivitis (usually defined as ophthalmia neonatorum) by Chlamydia trachomatis and Neisseria gonorrhoeae. Therefore, there is wide variability in antibiotic administration, conditioned mainly by the social and health context. In Italy, a law enacted in 1940 required doctors and midwives to administer ophthalmic prophylaxis with 2% silver nitrate to all newborns at birth. This law was repealed in 1975 and since then there has been no clear guidance on the use of ophthalmia neonatorum prophylaxis at birth. Since neonatal conjunctivitis caused by C. trachomatis and N. gonorrhoeae is not reported, we carried out a nationwide survey of 1,041,384 neonates across all Italian birth centers to evaluate the incidence of ophthalmia neonatorum and the current practice of prophylaxis. After analyzing the results, we formulated an intersociety position statement on the prevention of ophthalmia neonatorum to update and standardize this prevention strategy in Italy.

OPHTHALMIA NEONATORUM in Italy: it is time for change.

Ophthalmia neonatorum (ON) refers to any conjunctivitis occurring in the first 28 days of life. In the past Neisseria gonorrhoeae was the most common cause of ON. It decreased with the introduction of prophylaxis at birth with the instillation of silver nitrate 2% (the Credè's method of prophylaxis). Today, the term ON is used to define any other bacterial infection, in particular due to Chlamydia Trachomatis. Currently, the WHO reccomends topical ocular prophylaxis for prevention of gonococcal and chlamydial conjunctivitis for all neonates. On the contrary, several European countries no longer require universal prophylaxis, opting for screening and treatment of pregnant women at high risk of infection. And what about Italy? Have a look on Italian history of prophylaxis, starting by the first decree issued in 1940, signed by Benito Mussolini. In the following decades the law has undergone many changes. At the moment, legislation is unclear, therefore careful consideration is required in order to draft the correct appoach.

Neonatal Lung Ultrasound and Surfactant Administration: A Pragmatic, Multicenter Study.

BACKGROUND: Previous research shows that a lung ultrasound score (LUS) can anticipate CPAP failure in neonatal respiratory distress syndrome. RESEARCH QUESTION: Can LUS also predict the need for surfactant replacement? STUDY DESIGN AND METHODS: Multicenter, pragmatic study of preterm neonates who underwent lung ultrasound at birth and those given surfactant by masked physicians, who also were scanned within 24 h from administration. Clinical data and respiratory support variables were recorded. Accuracy of LUS, oxygen saturation to Fio2 ratio, Fio2, and Silverman score for surfactant administration were evaluated using receiver operating characteristic curves. The simultaneous prognostic values of LUS and oxygen saturation to Fio2 ratio for surfactant administration, adjusting for gestational age (GA), were analyzed through a logistic regression model. RESULTS: Two hundred forty infants were enrolled. One hundred eight received at least one dose of surfactant. LUS predicted the first surfactant administration with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, 0.81-0.91), cut off of 9, sensitivity of 0.79 (95% CI, 0.70-0.86), specificity of 0.83 (95% CI, 0.76-0.89), positive predictive value of 0.79 (95% CI, 0.71-0.87), negative predictive value of 0.82 (95% CI, 0.75-0.89), positive likelihood ratio of 4.65 (95% CI, 3.14-6.89), and negative likelihood ratio of 0.26 (95% CI, 0.18-0.37). No significant difference was shown among different GA groups: 25 to 27 weeks' GA (AUC, 0.91; 95% CI, 0.84-0.99), 28 to 30 weeks' GA (AUC, 0.81; 95% CI, 0.72-0.91), and 31 to 33 weeks' GA (AUC, 0.88; 95% CI, 0.79-0.95), respectively. LUS declined significantly within 24 h in infants receiving one surfactant dose. When comparing Fio2, oxygen saturation to Fio2 ratio, LUS, and Silverman scores as criteria for surfactant administration, only the latter showed a significantly poorer performance. The combination of oxygen saturation to Fio2 ratio and LUS showed the highest predictive power, with an AUC of 0.93 (95% CI, 0.89-0.97), regardless of the GA interval. INTERPRETATION: LUS is a reliable criterion to administer the first surfactant dose regardless of GA. Its association with oxygen saturation to Fio2 ratio significantly improves the prediction power for surfactant need.

Lung Ultrasound Score Progress in Neonatal Respiratory Distress Syndrome.

BACKGROUND AND OBJECTIVES: The utility of a lung ultrasound score (LUS) has been described in the early phases of neonatal respiratory distress syndrome (RDS). We investigated lung ultrasound as a tool to monitor respiratory status in preterm neonates throughout the course of RDS. METHODS: Preterm neonates, stratified in 3 gestational age cohorts (25-27, 28-30, and 31-33 weeks), underwent lung ultrasound at weekly intervals from birth. Clinical data, respiratory support variables, and major complications (sepsis, patent ductus arteriosus, pneumothorax, and persistent pulmonary hypertension of the neonate) were also recorded. RESULTS: We enrolled 240 infants in total. The 3 gestational age intervals had significantly different LUS patterns. There was a significant correlation between LUS and the ratio of oxygen saturation to inspired oxygen throughout the admission, increasing with gestational age (b = -0.002 [P < .001] at 25-27 weeks; b = -0.006 [P < .001] at 28-30 weeks; b = -0.012 [P < .001] at 31-33 weeks). Infants with complications had a higher LUS already at birth (12 interquartile range 13-8 vs 8 interquartile range 12-4 control group; P = .001). In infants 25 to 30 weeks' gestation, the LUS at 7 days of life predicted bronchopulmonary dysplasia with an area under the curve of 0.82 (95% confidence interval 0.71 to 93). CONCLUSIONS: In preterm neonates affected by RDS, the LUS trajectory is gestational age dependent, significantly correlates with the oxygenation status, and predicts bronchopulmonary dysplasia. In this population, LUS is a useful, bedside, noninvasive tool to monitor the respiratory status.

Oral melatonin as a new tool for neuroprotection in preterm newborns: study protocol for a randomized controlled trial.

BACKGROUND: Prevention of neurodevelopmental impairment due to preterm birth is a major health challenge. Despite advanced obstetric and neonatal care, to date there are few neuroprotective molecules available. Melatonin has been shown to have anti-oxidant/anti-inflammatory effects and to reduce brain damage, mainly after hypoxic ischemic encephalopathy. The planned study will be the first aiming to evaluate the capacity of melatonin to mitigate brain impairment due to premature birth. METHOD: In our planned prospective, multicenter, double-blind, randomized vs placebo study, we will recruit, within 96 h of birth, 60 preterm newborns with a gestational age ≤ 29 weeks + 6 days; these infants will be randomly allocated to oral melatonin, 3 mg/kg/day, or placebo for 15 days. After the administration period, we will measure plasma levels of malondialdehyde, a lipid peroxidation product considered an early biological marker of melatonin treatment efficacy (primary outcome). At term-equivalent age, we will evaluate neurological status (through cerebral ultrasound, cerebral magnetic resonance imaging, vision and hearing evaluations, clinical neurological assessment, and screening for retinopathy of prematurity) as well as the incidence of bronchodysplasia and sepsis. We will also monitor neurodevelopmental outcome during the first 24 months of corrected age (using the modified Fagan Test of Infant Intelligence at 4-6 months and standardized neurological and developmental assessments at 24 months). DISCUSSION: Preterm birth survivors often present long-term neurodevelopmental sequelae, such as motor, learning, social-behavioral, and communication problems. We aim to assess the role of melatonin as a neuroprotectant during the first weeks of extrauterine life, when preterm infants are unable to produce it spontaneously. This approach is based on the supposition that its anti-oxidant mechanism could be useful in preventing neurodevelopmental impairment. Considering the short- and long-term morbidities related to preterm birth, and the financial and social costs of the care of preterm infants, both at birth and over time, we suggest that melatonin administration could lead to considerable saving of resources. This would be the first study addressing the role of melatonin in very low birth weight preterm newborns, and it could provide a basis for further studies on melatonin as a neuroprotection strategy in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04235673 . Prospectively registered on 22 January 2020.

Possible Coronavirus Disease 2019 Pandemic and Pregnancy: Vertical Transmission Is Not Excluded.

Coronavirus disease 2019 outbreak has a growing impact on global health; vertical transmission of severe acute respiratory syndrome coronavirus 2 infection is still controversial. In this article, we describe a case of vertical transmission of severe acute respiratory syndrome coronavirus 2 in a newborn with respiratory and gastrointestinal symptoms.

[Ready-to-use parenteral nutrition in a preterm infant with necrotizing enterocolitis and related complications: case report]. / Nutrizione parenterale con sacche precostituite nel nato pretermine con enterocolite necrotizzante complicata: un caso clinico.

INTRODUCTION: Necrotizing enterocolitis (NEC) is a very aggressive, destructive and sometimes lethal disease, which mainly affects infants born with severe prematurity. These patients need a complex multidisciplinary approach. The clinical course is often long and complicated, and nutritional approach should ensure a balance between the need for nutrients and the risk of complications. CLINICAL CASE: We describe the case of a preterm female infant born at 24 weeks and 5 days of gestational age transferred to our intensive care unit for NEC complicated with intestinal perforation. Subsequently, she developed short bowel syndrome. In terms of nutrition, the baby was treated with the use of standard parenteral nutrition (PN) solutions for preterm infants, which were prescribed immediately after passing the critical and metabolically unstable phase of disease. It was possible to use these standard PN solutions also during a period of cholestasis and after the hospital discharge. CONCLUSIONS: The use of ready-to-use bags with standard solutions for PN in preterm infants complicated with surgical pathology is possible, feasible, safe and effective; it is recommendable to perform periodic clinical and laboratory evaluations.

Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study.

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. Propranolol 0.1% eye micro-drops administered to newborns with stage 2 ROP are well-tolerated, but not sufficiently effective. Methods: A multi-center open-label trial was conducted to assess the safety and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1 ROP. The progression of the disease was evaluated with serial ophthalmologic examinations. Hemodynamic, respiratory, biochemical parameters, and propranolol plasma levels were monitored. Demographic and perinatal characteristics, co-morbidities and co-intervention incidences, together with ROP progression, were compared with a historical control group in the same centers participating in the trial. Results: Ninety-eight newborns were enrolled and compared with the historical control group. Populations were not perfectly homogeneous (as demonstrated by the differences in the Apgar score and the different incidence rate in surfactant administration and oxygen exposure). The progression to ROP stage 2 or 3 plus was significantly lower than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI 0.297- 0.916). No adverse effects related to propranolol were observed and the mean propranolol plasma level was significantly lower than the safety cut-off of 20 ng/mL. Unexpectedly, three newborns treated with oral propranolol before the appearance of ROP, showed a ROP that was unresponsive to propranolol eye micro-drops and required laser photocoagulation treatment. Conclusion: Propranolol 0.2% eye micro-drops were well-tolerated and appeared to reduce the ROP progression expected on the basis of a comparison with a historical control group. Propranolol administered too early appears to favor a more aggressive ROP, suggesting that a ß-adrenoreceptor blockade is only useful during the proliferative phase. Further randomized placebo-controlled trials are required to confirm the current results. Clinical Trial Registration  The trial was registered at ClinicalTrials.gov with Identifier NCT02504944 and with EudraCT Number 2014-005472-29.

Caudal Regression and Encephalocele: Rare Manifestations of Expanded Goldenhar Complex.

Oculoauriculovertebral spectrum, or Goldenhar Syndrome, is a condition characterized by variable degrees of uni- or bilateral involvement of craniofacial structures, ocular anomalies, and vertebral defects. Its expressivity is variable; therefore, the term "expanded Goldenhar complex" has been coined. The Goldenhar Syndrome usually involves anomalies in craniofacial structures, but it is known that nervous system anomalies, including encephalocele or caudal regression, may, rarely, occur in this condition. We report two rare cases of infants affected by Goldenhar Syndrome, associated with neural tube defects, specifically caudal regression syndrome and nasal encephaloceles, to underline the extremely complex and heterogeneous clinical features of this oculoauriculovertebral spectrum. These additional particular cases could increase the number of new variable spectrums to be included in the "expanded Goldenhar complex."

Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial.

BACKGROUND: Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). METHODS: A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. DISCUSSION: Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014-005472-29.

Lung Ultrasound for Diagnosing Pneumothorax in the Critically Ill Neonate.

OBJECTIVES: To evaluate the accuracy of lung ultrasound for the diagnosis of pneumothorax in the sudden decompensating patient. STUDY DESIGN: In an international, prospective study, sudden decompensation was defined as a prolonged significant desaturation (oxygen saturation <65% for more than 40 seconds) and bradycardia or sudden increase of oxygen requirement by at least 50% in less than 10 minutes with a final fraction of inspired oxygen ≥0.7 to keep stable saturations. All eligible patients had an ultrasound scan before undergoing a chest radiograph, which was the reference standard. RESULTS: Forty-two infants (birth weight = 1531 ± 812 g; gestational age = 31 ± 3.5 weeks) were enrolled in 6 centers; pneumothorax was detected in 26 (62%). Lung ultrasound accuracy in diagnosing pneumothorax was as follows: sensitivity 100%, specificity 100%, positive predictive value 100%, and negative predictive value 100%. Clinical evaluation of pneumothorax showed sensitivity 84%, specificity 56%, positive predictive value 76%, and negative predictive value 69%. After sudden decompensation, a lung ultrasound scan was performed in an average time of 5.3 ± 5.6 minutes vs 19 ± 11.7 minutes required for a chest radiography. Emergency drainage was performed after an ultrasound scan but before radiography in 9 cases. CONCLUSIONS: Lung ultrasound shows high accuracy in detecting pneumothorax in the critical infant, outperforming clinical evaluation and reducing time to imaging diagnosis and drainage.

Ventilation strategies for preventing oxidative stress-induced injury in preterm infants with respiratory disease: an update.

Reactive oxygen and nitrogen species are produced by several inflammatory and structural cells of the airways. The lungs of preterm newborns are susceptible to oxidative injury induced by both reactive oxygen and nitrogen species. Increased oxidative stress and imbalance in antioxidant enzymes may play a role in the pathogenesis of inflammatory pulmonary diseases. Preterm infants are frequently exposed to high oxygen concentrations, infections or inflammation; they have reduced antioxidant defense and high free iron levels which enhance toxic radical generation. Multiple ventilation strategies have been studied to reduce injury and improve outcomes in preterm infants. Using lung protective strategies, there is the need to reach a compromise between satisfaction of gas exchange and potential toxicities related to over-distension, derecruitment of lung units and high oxygen concentrations. In this review, the authors summarize scientific evidence concerning oxidative stress as it relates to resuscitation in the delivery room and to the strategies of ventilation.

Visfatin: New marker of oxidative stress in preterm newborns.

BACKGROUND: Oxidative stress is involved in several neonatal conditions characterized by an upregulation in the production of oxidative or nitrative free radicals and a concomitant decrease in the availability of antioxidant species. Oxygen, which is obviously vital to survival, can be highly damaging to neonatal tissue which is known to be poorly equipped to neutralize toxic derivatives. Thus, exposure of the newborn infant to high oxygen concentrations during resuscitation at birth increases oxidative damage. Visfatin is an adipocytokine involved in oxidative stress and an important mediator of inflammation that induces dose-dependent production of both pro-inflammatory and anti-inflammatory cytokines. To our knowledge, the diagnostic value of visfatin as a marker of oxidative stress in preterm newborns has not been investigated. OBJECTIVE: The aim of this study was to evaluate visfatin levels in preterm neonates resuscitated with different concentrations of oxygen in the delivery room. PATIENTS: Fifty-two preterm newborns with gestational age less than 32 weeks, resuscitated randomly with different oxygen concentrations (40%, 60%, or 100%) were enrolled at the University Hospital of Messina, over a 12-month period to evaluate serum visfatin levels at T0 (within 1 h after birth), T24 h, T72 h, and T168 h of life. RESULTS: At T72 h and T168 h, higher serum visfatin values in the high-oxygen group compared to the low- and mild-oxygen subjects (P=0.002 and P<0.001, respectively) were noted. CONCLUSION: The results of this study suggest that visfatin could be a new marker of oxidative stress in preterm newborns.