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Infections due to human herpesvirus 6 (HHV-6) are frequent during early childhood. Usually, they have a favorable clinical course. Conversely, HHV-6 congenital infections occur in about 1% of neonates and may present with more severe clinical pictures. HHV-6 can be found in lung tissues and bronchoalveolar lavage (BAL) samples from patients with pneumonia and in immunocompromised patients can cause mild to severe pneumonia. In neonates, the role of HHV-6 in the genesis of severe pneumonia is poorly defined still now. We describe a healthy infant with a late-onset (15 days of life) severe interstitial pneumonia and heavy HHV-6 genome load, persistently detected in its BAL fluid. The baby underwent high-frequency oscillatory ventilation, hydroxychloroquine, steroids, and ganciclovir for 6 weeks and at 9 months she died. Next-generation sequencing of genes known to cause neonatal respiratory insufficiency revealed the presence of a "probably pathogenetic" heterozygous variant in the autosomal recessive DRC1 gene, a heterozygous variant of unknown significance (VUS) in the autosomal recessive RSPH9 gene, and a heterozygous VUS in the autosomal recessive MUC5B gene. HHV-6 infection should be considered in the differential diagnosis of late-onset severe respiratory distress in neonates and the co-occurrence of genetic predisposing factors or modifiers should be tested by specific molecular techniques. The intensity of HHV-6 genome load in BAL fluid could be an indicator of the response to antiviral therapy.

CHARGE syndrome is a rare genetic multiple-malformation disorder characterized by wide phenotypic variability. It is often caused by heterozygous variants in CHD7 and, more rarely, SEMA3E. Although craniofacial alterations are frequent in this condition, to date craniosynostosis is not considered part of the clinical spectrum. Here, we report bi-coronal craniosynostosis in a newborn affected by CHARGE syndrome caused by the de novo heterozygous c.6157C>T, p.(Arg2053*) CHD7 variant. We found two additional subjects in the literature with different craniosynostoses and distinct CHD7 alterations. The inclusion of CHD7-related CHARGE syndrome in the group of rare causes of syndromic craniosynostoses is proposed.

Mature locomotion involves modular spinal drives generating a set of fundamental patterns of motoneuron activation, each timed at a specific phase of locomotor cycles and associated with a stable muscle synergy. How locomotor modules develop and to what extent they depend on prior experience or intrinsic programs remains unclear. To address these issues, we herein leverage the presence at birth of two types of locomotor-like movements, spontaneous kicking and weight-bearing stepping. The former is expressed thousands of times in utero and postnatally, whereas the latter is elicited de novo by placing the newborn on the ground for the first time. We found that the neuromuscular modules of stepping and kicking differ substantially. Neonates kicked with an adult-like number of temporal activation patterns, which lacked a stable association with systematic muscle synergies across movements. However, on the ground neonates stepped with fewer temporal patterns but all structured in stable synergies. Since kicking and ground-stepping coexist at birth, switching between the two behaviors may depend on a dynamic reconfiguration of the underlying neural circuits as a function of sensory feedback from surface contact. We tracked the development of ground-stepping in 4- to 48-mo-old infants and found that, after the age of 6 mo, the number of temporal patterns increased progressively, reaching adult-like conformation only after independent walking was established. We surmise that mature locomotor modules may derive by combining the multiple patterns of repeated kicking, on the one hand, with synergies resulting from fractionation of those revealed by sporadic weight-bearing stepping, on the other hand.

Listeriosis is currently the fifth most common foodborne disease in Europe. Most cases are sporadic; however, outbreaks have also been reported. Compared to other foodborne infections, listeriosis has a modest incidence but can cause life-threatening complications, especially in elderly or immunocompromised people and pregnant women. In the latter case, the pathology can be the cause of premature birth or spontaneous abortion, especially if the fetus is affected during the first months of gestation. The causative agent of listeriosis, Listeria monocytogenes, is characterized by the innate ability to survive in the environment and in food, even in adverse conditions and for long periods. Ready-to-eat food represents the category most at risk for contracting listeriosis. This study presents the result of an investigation carried out on a case of maternal-fetal transmission of listeriosis which occurred in 2020 in central Italy and which was linked, with a retrospective approach, to other cases residing in the same city of the pregnant woman. Thanks to the use of next-generation sequencing methodologies, it was possible to identify an outbreak of infection, linked to the consumption of ready-to-eat sliced products sold in a supermarket in the investigated city.

Terrestrial locomotion requires coordinated bilateral activation of limb muscles, with left–right alternation in walking or running, and synchronous activation in hopping or skipping. The neural mechanisms involved in interlimb coordination at birth are well known in different mammalian species, but less so in humans. Here, 46 neonates (of either sex) performed bilateral and unilateral stepping with one leg blocked in different positions. By recording EMG activities of lower-limb muscles, we observed episodes of left–right alternating or synchronous coordination. In most cases, the frequency of EMG oscillations during sequences of consecutive steps was approximately similar between the two sides, but in some cases it was considerably different, with episodes of 2:1 interlimb coordination and episodes of activity deletions on the blocked side. Hip position of the blocked limb significantly affected ipsilateral, but not contralateral, muscle activities. Thus, hip extension backward engaged hip flexor muscle, and hip flexion engaged hip extensors. Moreover, the sudden release of the blocked limb in the posterior position elicited the immediate initiation of the swing phase of the limb, with hip flexion and a burst of an ankle flexor muscle. Extensor muscles showed load responses at midstance. The variable interlimb coordination and its incomplete sensory modulation suggest that the neonatal locomotor networks do not operate in the same manner as in mature locomotion, also because of the limited cortical control at birth. These neonatal mechanisms share many properties with spinal mammalian preparations (i.e., independent pattern generators for each limb, and for flexor and extensor muscles, load, and hip position feedback). SIGNIFICANCE STATEMENT Bilateral coupling and reciprocal activation of flexor and extensor burst generators represent the fundamental mechanisms used by mammalian limbed locomotion. Considerable progress has been made in deciphering the early development of the spinal networks and left–right coordination in different mammals, but less is known about human newborns. We compared bilateral and unilateral stepping in human neonates, where cortical control is still underdeveloped. We found neonatal mechanisms that share many properties with spinal mammalian preparations (i.e., independent pattern generators for each limb, the independent generators for flexor and extensor muscles, load, and hip-position feedback. The variable interlimb coordination and its incomplete sensory modulation suggest that the human neonatal locomotor networks do not operate in the same manner as in mature locomotion.

Human neonatal motoneurons show high synchronized discharge timings that modulate the generation of fast movements., Motoneurons of neonatal rodents show synchronous activity that modulates the development of the neuromuscular system. However, the characteristics of the activity of human neonatal motoneurons are largely unknown. Using a noninvasive neural interface, we identified the discharge timings of individual spinal motoneurons in human newborns. We found highly synchronized activities of motoneurons of the tibialis anterior muscle, which were associated with fast leg movements. Although neonates’ motor units exhibited discharge rates similar to those of adults, their synchronization was significantly greater than in adults. Moreover, neonatal motor units showed coherent oscillations in the delta band, which is directly translated into force generation. These results suggest that motoneuron synchronization in human neonates might be an important mechanism for controlling fast limb movements, such as those of primitive reflexes. In addition to help revealing mechanisms of development, the proposed neural interface might monitor children at risk of developing motor disorders.

The baby hatch is a prefabricated structure, easily reachable, formed by two small rooms; it offers total anonymity to the women who leave their baby, and maximum security to the small child. The mother who decides to leave a child enters a room without passing through control, must open a tilting window and lay him in a cradle located in an adjoining room, which is maintained at a constant temperature in all four seasons. An alarm, activated by a volumetric and contact sensor, immediately draws the attention of the first aid triage operators. A camera frames only the bed where the child lies and does not take a picture of the face of the person who puts the child in it.

Introduction Melatonin has been studied and used for several years as a sleep-wake cycle modulator in patients with sleep disorders. Experimental evidence has demonstrated the multiple neuroprotective benefits of this indoleamine secreted by the pineal gland. Melatonin is also used in neurological investigations, for its ability to induce sleep in children. In fact, it favors falling asleep during electroencephalogram, Magnetic Resonance Imaging (MRI), and during brainstem auditory evoked potentials. Previous studies are focused on infants and children. No investigation have been performed in neonates, before or during instrumental assessments. Material and methods One hundred ten newborns (term and preterm) undergoing brain MRI were enrolled in the study. Thirty minutes before the planned time for the examination, we administered a single dose solution of melatonin- tryptophan-vitamin B6. Twenty minutes after the initial administration of 2 mg, a second dose of 1 mg was administered, if the baby was still awake. If after further 15 min the baby was still not sleeping, an additional dose of 1 mg was administered. Results In 106 patients we obtained adequate sedation without adverse events, allowing us to perform an adequate quality MRI, with a median time of 25 min to reach sleeping. Only in three patients MRI could not be performed. In patients having a large weight, higher doses of melatonin were necessary to reach sleeping. Considering the pro kg dose of melatonin, the average dose that induced sleepiness in neonates was 0,64 ± 0.16 mg/Kg. Conclusion A solution based on Melatonin- tryptophan-vitamin B6 can be a helpful sedative to administer to neonates undergoing brain MRI, avoiding the use of anesthetics and achieving adequate assessments.

Objective This report discusses the neurological involvement in respiratory syncytial virus (RSV) infection in neonates. Study Design We present a case report of a 2-month-old infant affected by a bronchiolitis RSV-positive, with syndrome of inappropriate antidiuretic hormone secretion (SIADH) correlated seizure and encephalopathy. Results RSV infection can be associated as a serious disease in newborns involving the central nervous system (CNS) and causing seizures or acute encephalopathy. RSV may be also responsible for SIADH and seizures associated with hyponatremia. The RSV related encephalopathy could be caused by different mechanisms, such as direct viral invasion of the CNS or by indirect mechanism mediated by inflammatory cytokines. In addition, it can be favored by severe hyponatremia and SIADH that can cause cerebral edema. Some studies highlight that this virus-related encephalopathy lead to sudden infant death syndrome. Conclusion In presence of neurological involvement during RSV-infection must be taken in consideration to performing instrumental test to detect cerebral edema. In addiction could be useful to dose inflammatory cytokines, and to consider the immune-modulatory therapy.

Background: Infants born at 23–24 weeks' gestation have the highest risk of developing a hemodynamically significant patent ductus arteriosus (hsPDA), that is refractory to pharmacological closure requiring surgical ligation. Thus, these patients might have the greatest benefits from hsPDA closure, although previous studies on PDA closure were not focused on this population. Aim: To compare the occurrence of hsPDA, failure rate of the first course of ibuprofen in closing hsPDA, and need of surgical closure in infants born at 23+0–24+6 weeks' gestation to those in infants born at 25+0–28+6 weeks' gestation. Study design: This is a retrospective multicenter study including infants born at 23+0–28+6 weeks of gestation admitted to the neonatal care units from January 2013 to December 2017. All infants underwent echocardiographical assessment for hsPDA diagnosis and eventually pharmacological treatment, and surgical closure. Results: We studied a total of 842 infants of which 562 (67%) developed a PDA. Among those with PDA, 511 (91%) received a pharmacological treatment for a hsPDA. We found that a hsPDA occurred in 70% (106/151) of infants born at 23–24 weeks and in 59% (405/691) of infants born at 25–28 weeks of gestation (P < 0.001). Failure of closure with the first-treatment cycle (69 vs. 40%; P < 0.001) and need of surgical closure (19 vs 10%) were more frequent (P < 0.011) in infants born at 23–24 than 25–28 gestational weeks. Paracetamol vs. ibuprofen treatment and gestational age of 23–24 versus 25–28 weeks increased closure failure, while less severe RDS and maternal clinical chorioamnionitis decreased it. Conclusions: Among extremely preterm infants, infants born at 23–24 weeks of gestation have the highest risk of developing a hsPDA refractory to pharmacological treatment requiring surgical closure. Our findings support the need of individualized more careful strategies for hsPDA management in this special population.

During the last epidemic season of bronchiolitis (S2, years 2016–2017) we performed a single Centre analysis in inborn infant of 30+ 0–32+ 6 gestational age and age 30 weeks gestational age, we decided to repeat our observation during the last epidemic season (S3, years 2017–2018), in order to compare ours infants of 30+ 0–32+ 6 gestational age with preterm of the same gestational age born in our unit in the previous seasons (S1 and S2), to evaluate the clinical impact of the different prophylaxis approaches. The new observation confirmed the clinical efficacy of PLV in this delicate group of newborns in preventing almost completely new episodes of bronchiolitis. Of the 6 newborns who developed bronchiolitis, 4 had received only a single dose of PLV, providing suboptimal protection, before the onset of bronchiolitis; furthermore 3 developed a mild form allowing to be treated at home.

The accomplishment of mature locomotor movements relies upon the integrated coordination of the lower and upper limbs and the trunk. Human adults normally swing their arms and a quadrupedal limb coordination persists during bipedal walking despite a strong corticospinal control of the upper extremities that allows to uncouple this connection during voluntary activities. Here we investigated arm–leg coordination during stepping responses on a surface in human neonates. In eight neonates, we found the overt presence of alternating arm–leg oscillations, the arms moving up and down in alternation with ipsilateral lower limb movements. These neonates moved the diagonal limbs together, and the peak of the arm-to-trunk angle (i.e., maximum vertical excursion of the arm) occurred around the end of the ipsilateral stance phase, as it occurs during typical adult walking. Although episodes of arm–leg coordination were sporadic in our sample of neonates, their presence provides significant evidence for a neural coupling between the upper and lower limbs during early ontogenesis of locomotion in humans.

Objective: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. Study design: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. Results: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. Conclusion: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. Trial registration: isrctn.org: ISRCTN53107700.

Lutein (LT) is a naturally occurring xanthophyll carotenoid most predominant in the central nervous system (CNS), but its neurotrophic role is still debated. We therefore investigated whether cord blood concentrations correlated with a well-established neurobiomarker, namely activin A.We conducted a prospective study on the distribution of LT and activin A in arterial cord blood of healthy preterm (n=50) and term (n=82) newborns according to weeks of gestational age (wGA) and gender.LT and activin A showed a pattern of concentration characterized by higher levels (P0.01, for all) at 33-36 wGA followed by a progressive decrease (P0.01, for all) from 37 onwards with a dip at term. Both LT and activin A were gender-dependent with significantly (P0.01, for all) higher levels in all recruited females and after sub-grouping for preterm and term births. LT (R=0.33; P0.001) correlated with wGA at sampling. There were significant positive correlations between lutein and activin A in male (R=0.93; P0.001) and female (R=0.89; P0.001) groups.The present data showing a correlation between LT and activin A support the notion of a neurotrophic role gender-dependent for LT and open the way to further investigations correlating LT with well-established biochemical markers of CNS development/damage.

Human milk has been traditionally considered germ free, however, recent studies have shown that it represents a continuous supply of commensal and potentially probiotic bacteria to the infant gut. Mammary microbioma may exercise anti-infective, anti-inflammatory, immunomodulatory and metabolic properties. Moreover human milk may be a source of pathogenic microorganism during maternal infection, if contaminated during expression or in case of vaccination of the mother. The non-sterility of breast milk can, thus, be seen as a protective factor, or rarely, as a risk factor for the newborn.

Summary We report the case of a 31-week gestational age neonate with Candida albicans sepsis and a hepatic abscess. Diagnosis relied on clinical and radiological signs of sepsis, liver function impairment and culture isolation of Candida spp. from sterile sites. Liver ultrasound documented the presence of a multiloculated abscess. Treatment with micafungin (3 mg/kg/day) resulted in normalization of liver function and inflammatory laboratory values and improvement of clinical condition. After 30 days of treatment, the liver abscess resolved and at the 8-month follow up the infant is doing well. Prompt diagnosis and antifungal treatment avoided surgical drainage and liver surgery in this high-risk neonate.

[Accessibilty and safety of drugs in pediatrics] Many of pediatric drugs have not been tested and evaluate in children. The risks associated with the off-label use of drugs without pediatric indications include adverse effects, inefficacy, and improper formulation. Furthermore the use of magistral or officinal formulations to treat the pediatric population may be of poor quality. The objectives of EU Regulation 1901/2006 on medicinal products for pediatric are to improve the health of children by facilitating the development and availability of medicines for children, ensuring that medicines for use in children are of high quality, ethically researched and authorised appropriately, and improving the availability of information on the use of medicines for children. Peyona (caffeine citrate) is authorised for the treatment of primary apnea of premature newborns and it’s a good example of drug tested and evaluate in children.

Lactoferrin (Lf) is one of the major proteins of all exocrine secretions with a role in the antinfective process. Our aim was to evaluate how plasma Fl levels may change in response to infection in newborn preterm infants.A total of 15 (8 females, 7 males) newborn preterm infants with a postnatal age72 h of life, underwent to blood culture and others markers of infection, for suspected sepsis, were enrolled in the study.We found that Lf serum concentration was significantly lowest in four neonates (26.7%) with confirmed sepsis than in 11 (73.3%) with clinical sepsis. The AUC was 0.90 (95%CI: 0.63-0.99). The optimal cutoff for Lf was 1.2 μg/ml with a sensibility of 100% and a specificity of 81.8%. Lf serum concentration was positively correlated with WBC or neutrophil (Spearman rho = 0.69 and 0.49, respectively).Serum Lf could prove a promising, sensitive and specific marker in the diagnostic approach to infants with suspected sepsis, thanks to its role in defense mechanisms and physiological functions of the immune system. Low levels of Lf in sepsis may suggest an immature response due to suboptimal leukocites activity in newborn preterm infants.

Objective We aimed at assessing the association between superior vena cava flow (SVCf), regional (cerebral) tissue oxygen saturation (rSO2), and cerebral fractional oxygen extraction (CFOE) during the first 48 hours of life and 2-years neurodevelopmental outcome of very low-birth-weight infants (VLBW). Methods We prospectively studied 60 VLBW infants admitted to our neonatal intensive care unit; rSO2 was continuously monitored with near-infrared spectroscopy during the first 48 hours of life, SVCf was measured at 4 to 6, 12, 24, and 48 hours, and CFOE was calculated. Neurodevelopmental outcome was assessed at 24 months corrected age. Results The mean gestational age at birth was 27.9 weeks (standard deviation: 2.4); 8 infants died in the first 3 months of life, 6 were lost to follow-up, 46 survived and were followed up. At 24 months, 6 (13%) and 7 (15.2%) infants developed minor and major sequelae, respectively. Infants who died had higher CFOE (p Conclusion SVCf, rSO2, and CFOE patterns in the first days of life suggest cerebral hyperperfusion, related to loss of autoregulation and/or use of inotropic drugs, as a potential mechanism of cerebral injury.

AIM: Despite advances in perinatal management, there is a flat trend in incidences of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants. The main feature of BPD development in preterm infants is an imbalance between increased exposure to free radicals and inadequate antioxidant defences. We investigated the associations between BPD and lipid hydro-peroxide (LOOH) and glutathione (GSH) concentrations in bronchoalveolar lavage fluid (BALF). METHODS: In this prospective study, BALF samples were collected from 44 preterm infants with RDS and oxidative stress markers were measured in 11 with BPD and 33 controls without BPD. RESULTS: LOOH levels were significantly higher (p

The efficacy of caffeine in an episode of Apnoea of Prematurity (AOP) has been known for over thirty years. Its use over long periods of time has not only found it to be manageable within the field of neonatology, but it has also been found to have other favourable actions, such as reducing the incidence of extubation failure, preventing Bronchopulmonary Dysplasia (BPD), reducing the need for Patent Ductus Arteriosus treatment and the beneficial effect it has on Retinopathy of Prematurity. Recent in vitro trials have highlighted the neuroprotective role that caffeine plays, which has already partly been observed from in vivo trials. Just recently, caffeine citrate has become a "label" drug and it would be beneficial if more studies could confirm the more significant effects it has on the more severe conditions of prematurity.

Background Transcutaneous bilirubin (TcB) measurement is widely used as screening for neonatal hyperbilirubinaemia. Aims To prospectively validate TcB measurement using hour-specific nomogram in identifying newborn infants not at risk for severe hyperbilirubinaemia. Study design prospective, observational, multicenter. Subjects 2167 term and late preterm infants born in 5 neonatal units in the Lazio region of Italy. Methods All neonates had simultaneous TcB and total serum bilirubin (TSB) measurements, when jaundice appeared and/or before hospital discharge. TcB and TSB values were plotted on a percentile-based hour-specific transcutaneous nomogram previously developed, to identify the safe percentile able to predict subsequent significant hyperbilirubinaemia defined as serum bilirubin > 17 mg/dL or need for phototherapy. Results Fifty-five babies (2.5%) developed significant hyperbilirubinaemia. The 50th percentile of our nomogram was able to identify all babies who were at risk of significant hyperbilirubinaemia, but with a high false positive rate. Using the 75th percentile, two false negatives reduced sensitivity in the first 48 hours but we were able to detect all babies at risk after the 48th hour of age. Conclusions: This study demonstrates that the 75th percentile of our TcB nomogram is able to exclude any subsequent severe hyperbilirubinaemia from 48 h of life ahead.

Objective: Metabolomics is a technique used to non-invasively determine a snapshot of the current metabolic status of an organism by analyzing intact tissue or bio-fluids. The aim of the present preliminary study was to analyze metabolic profiles in preterm infants complicated by respiratory distress syndrome (RDS) trough bronchoalveolar lavage fluid (BALF) measurement. Methods: Twelve BALF samples collected at birth prior surfactant, post-surfactant during mechanical ventilation and at extubation time-points, were analyzed by proton nuclear magnetic resonance spectroscopy and Gas chromatography-Mass Spectrometry (GC-MS). Results: GC-MS analysis identified 25 metabolites of whom 10 had a known molecular structure. They were: undecane, decanoic acid, dodecanoic acid, hexadecanoic acid, octadecanoic acid, hexadecanoic acid methyl ester, 9-octadecanoic acid, tetracosanoic acid, myristic acid, phosphate. These metabolites were over-expressed in BALF collected during mechanical ventilation after surfactant administration. Conclusions: The present preliminary data suggest that metabolic profile in BALF of RDS infants is becoming possible opening a new cue of metabolomics as promising tool in management of sick premature infants.

Early discharge from the maternity hospital is almost becoming the rule: it is not clear if this practice actually increases the rate of newborn rehospitalization, but it surely poses some problems for jaundice management, since hyperbilirubinemia is the most frequent reason for hospital readmission. Available guidelines for jaundice management and early discharge are reviewed. Evidence-based update is given about four new points: use of gestational age as predictor jointly with the nomogram evaluation, two-point bilirubin assay, and rate of rise evaluation; choice of the "right" curve and unforeseen jaundice risk factors. In conclusion, available predictive tools allow reliable jaundice prediction and safe early discharge if adequate follow-up is planned according to the prediction. Advice about things to avoid is provided together with a practical flowchart based on guidelines and recent evidence-based data.

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.

Background Late preterm (LP) infants [gestational age (GA): 3436 weeks] are at increased risk of neonatal acute respiratory morbidity compared with term infants (GA: 3741) [1,2]. The observed rate of acute respiratory morbidity, in a population of about 20,000 LP infants, was 10-12% vs 1.4% of term infants [1]. Transient tachypnea of the newborn (TTN) and respiratory distress syndrome (RDS) are the most common diagnosis, with RDS rate reaching 10.5% in infants born at 34 weeks of GA [1,2]. Major causes of respiratory morbidity in LP are: prematurity and birth by Cesarean Section (CS) [1,3]. Material and methods We retrospectively studied 830 LP and moderate preterm (MP) infants (GA: 33-36 weeks) admitted to our unit from June 2009 to December 2013. Infants were classified according to GA: 33 weeks (n = 129), 34 weeks (n = 176), 35 weeks (n = 225), 36 weeks (n = 300). Clinical charts for each patient were reviewed and main diagnosis recorded.

Multiple organ failure (MOF), or multiple organ dysfunction syndrome (MODS) as more recently known, is a clinical syndrome characterized by the failure of two, or more, organs which are unable to maintain homeostasis without intervention. Described causative factors for MODS in the neonatal period are sepsis, shock due to any cause, tissue hypoperfusion, prematurity, hypoxic ischemic encephalopathy, necrotizing enterocolitis (NEC), surgery, congenital heart disease and others. MOF can be considered as the final common pathway of immunological, cytokine and hormonal changes, occurred as physiologic re- sponse to different infectious or non-infectious inflammatory insults, who lead to systemic inflammation, a procoagulant state and progressive organ dysfunction. The clinical presentation of MODS can widely vary, depending on the primary causes, nature, number and severity of the organ systems involved. Pre-MODS conditions should be promptly identified and treated. In case of severe sepsis and septic shock, the available guidelines should be followed. When MODS already occurred, supportive care for single organ dysfunction should be provided and adequate oxygenation and organ perfusion maintained. More studies in term and preterm infants (with the development of specific neonatal scoring systems) are needed, to further understand neonatal MODS and assess strategies for early prevention and treatment. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014) · Cagliari (Italy) · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

Background Late preterm (LP) are at higher risk than term infants to develop infections due to their more immature immune system. Little data about the risks and incidence of infection and sepsis in LP are present in literature. Aims To evaluate treated infection rates and risk factors for infection in moderate and late preterm infants (gestational age=32–36 weeks). Study design We retrospectively studied a population of 771 moderate and late preterm infants consecutively admitted to our unit from June 2008 to November 2013. Results Treated infections were 128, with an incidence of 16.6%; the 90% (n = 115) occurred during the first 72 hours of life. Blood cultures were positive in 22% of cases, umbilical venous catheter cultures were positive in 26% of cases; Coagulase-negative staphylococci were the most frequently isolated pathogens. Patients of the sepsis group had a C-reactive protein (CRP) mean value of 28.27 mg/L and a procalcitonin mean value of 25.3 μg/L. Risk factors for infections were umbilical venous catheter (UVC) insertion (χ 2 = 15.9; p ≤ 0.05), prophylaxis with antenatal corticosteroids (χ 2 = 16.7; p ≤ 0.05) and birth by cesarean section, with observed values very similar to the expected values (χ 2 = 15.9; p = 0.1). Respiratory symptoms were found in 47 of the 60 patients in the sepsis group (78.3%). Conclusions Late and moderate preterm infants have an increased significant risk of infection compared to term infants. Infections, given the high frequency of negative cultures in neonates, should be often suspected and treated on the basis of clinical features and inflammatory markers, trying always to avoid a possible overtreatment.

Healthcare systems in low- and middle-income countries (LMIC), due to scarcity of economic resources, often lack appropriate health technologies necessary for the prevention, diagnosis and treatment of many curable diseases.1 WHO acknowledges that most of the current global health targets and goals would be impossible to achieve without an increase in access to essential medical devices,2 hence promotes the development and local production of appropriate devices.3 Nonetheless, despite the increasing interest and efforts, prices of devices, as well as prices of patents for local producers, continue to not be appropriate for many LMIC. Research, development and production of biomedical devices are mostly performed by companies in high-income countries for high-income markets, and it has been estimated that only 13% of manufacturers are located in LMIC.2 Consequences are that high prices, along with inefficient local production and distribution, among other factors, contribute to set back commercialisation and availability of final products in low-resource settings. This problem has been recently highlighted and defined as the last mile translation.4 In the past …

Apnea of prematurity (AOP) is one of the most frequent pathologies in the Neonatal Intensive Care Unit, with an incidence inversely related to gestational age. Its etiology is often multi factorial and diagnosis of idiopathic forms requires exclusion of other underlying diseases. Despite being a self-limiting condition which regresses with the maturation of the newborn, possible long-term effects of recurring apneas and the degree of desaturation and bradycardia who may lead to abnormal neurological outcome are not yet clarified. Therefore AOP needs careful evaluation of its etiology and adequate therapy that can be both pharmacological and non-pharmacological. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy) · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

Lutein is an antioxidant carotenoid exerting a key role in eye health, but no reference curve in the perinatal period is available.We conducted a prospective study on the distribution of lutein and its metabolite 3'-oxolutein in arterial cord blood of preterm (n=40) and term (n=76) newborns according to gestational age, sex and delivery modalities.Lutein and 3'-oxolutein concentrations peaked at the beginning of third trimester (P0.01, for both) being higher in the preterm than in term group. From 36 weeks onwards, lutein and 3'-oxolutein levels progressively decreased reaching the lowest levels at term between 41 and 42 weeks (P0.01, for both). Lutein and 3'-oxolutein significantly (P0.01, for all) correlated with each other (R=0.33) and with gestational age at sampling (R=0.31 and R=0.38 for lutein and 3-oxolutein, respectively) (P0.001, for all). Indeed, lutein and 3'-oxolutein concentrations were significantly higher (P0.05, for all) in female than in male and significantly lower (P0.01, for both) in newborns delivered by caesarean section when compared to vaginal delivery.Since macula densa and retina are sites of lutein accumulation, the present findings open-up a new cue on the potential role of lutein in the prevention of the retinopathy of prematurity.

BackgroundEarly discharge of healthy late preterm and full term newborn infants has become common practice because of the current social and economic necessities. Severe jaundice, and even kernicterus, has developed in some term infants discharged early. This study was designed to elaborate a percentile-based hour specific total serum bilirubin (TSB) nomogram and to assess its ability to predict the absence of risk for subsequent non physiologic severe hyperbilirubinaemia before discharge.MethodsA percentile-based hour-specific nomogram for TSB values was performed using TSB data of 1708 healthy full term neonates. The nomogram's predictive ability was then prospectively assessed in five different first level neonatal units, using a single TSB value determined before discharge.ResultsThe 75thpercentile of hour specific TSB nomogram allows to predict newborn babies without significant hyperbilirubinemia only after the first 72 hours of life. In the first 48 hours of life the observation of false negative results did not permit a safe discharge from the hospital.ConclusionThe hour-specific TSB nomogram is able to predict all neonates without risk of non physiologic hyperbilirubinemia only after 48 to 72 hours of life. The combination of TSB determination and risk factors for hyperbilirubinemia could facilitate a safe discharge from the hospital and a targeted intervention and follow-up.

Preterm newborns may be discharged when clinical conditions are stable and maturity of physiological functions has been gained, but no precise indications on weight and GA to be reached before discharge are available. In our NICU we have observed in the last five years 234 newborns32 weeks of GA; we have decided to transfer from incubators at the mean weight of 1737 g, regardless of their GA and birth weight and to discharge at a mean weight of 1966 g, the lowest mean weight in comparison to the other twelve NICUs of the Lazio region. We have analyzed if the major diseases affecting those newborns (RDS, mechanical ventilation, PDA, IVH/PVL, PHH, NEC, ROP, sepsis ) have influenced weight at discharge in 13 NICUs of Lazio region.in our NICU the discharge of ELBW/VLBW preterm newborns32 weeks GA and/or1500 g can be feasible at a mean weight close to 1900 g. An early transfer from incubator at a mean weight of 1737 g promotes an early discharge from hospital. Major diseases affecting those newborn haven't influenced weight at discharge.

Few data exist about patient-triggered ventilation techniques in neonatal critical care. Our aim was to compare pressure-limited synchronised intermittent positive pressure (or assist/control) ventilation (sIPPV) in the classical time-cycled (TC-sIPPV) mode against flow-cycled (FC-sIPPV) modality. In this latter, typical sIPPV full respiratory support is provided but both the initiation and the end of inflation are determined by the infant's spontaneous respiratory efforts by using airway flow changes.A third-level neonatal intensive care unit.Ten preterm babies (32 weeks' gestation) were randomised to receive 1 h FC-sIPPV followed by 1 h TC-sIPPV or the inverse shift, according to a computer-created randomisation table. Eligible babies had hyaline membrane disease and received 200 mg/kg surfactant at least 6 h before the study period. Respiratory mechanics, ventilatory and vital parameter data were registered real time.FC-sIPPV resulted in lower-rate volume ratio, pressure x rate product, mean airway pressure and heart rate; tidal volume and oxygen saturation were higher (all p0.001). Spontaneous inspiratory time was lower than usually set by the physician and it was directly correlated to birth weight (rho = 0.5, p = 0.001) and gestational age (rho = 0.32, p = 0.001). No differences were noticed in the mechanics and blood gas and vital parameters during the two study phases.FC-sIPPV may safely result in a better patient ventilator synchrony. Inspiratory time usually set in neonatal critical care is higher than that decided by the baby during spontaneous effort. This should be considered when establishing time-cycled ventilation.

Vitamin D and fluoride are two typical examples of dietary supplements given to infants, children and adolescents. They allow to prevent specific diseases as rickets and dental caries, respectively, but questions have been suggested about adequate dosages and risk of excess. Neonates, particularly preterm, are a special risk class because of possible nutritional deficiency during hospitalization and post-discharge.

Even if breast milk is the natural and optimal food for infants, toxic pollutants of the environment can be transferred from mothers to neonates through breastfeeding. Among chemical contaminants, phthalates are ubiquitous and in animals studies produce developmental and/or reproductive toxicity in a wide range of mammalian species with a period of susceptibility extending from fetal to pubertal stage of life. Preliminary studies support the hypothesis that prenatal exposure at environmental levels can adversely affect male reproductive development in humans. Further studies are needed to evaluate possible risks for infants due to this contaminants.

Apnea of prematurity is a developmental disorder that frequently affects preterm infants, especially those with lower gestational age. Even if apnea of prematurity is by definition a self-limiting condition, it can cause serious problems during the hospital stay and can potentially have long-term neurological and cognitive consequences depending on the severity and inten- sity of the episodes. The diagnosis of apnea of prematurity can be made only after excluding a number of diseases of the preterm infant in which apnea may be an epiphenomenon. Etiological diagnosis is essential for selection of appropriate treatment, which may be nonpharmacological or involve use of drugs.

Congenital leukemia is a very rare severe condition and leukemia cutis may represent the presenting sign of this malignancy, sometimes preceding hematological findings of weeks. Typical clinical features include multiple red to purple papules, macules and nodules due to direct infiltration of the skin by malignant cells. We illustrate these cutaneous findings in a patient with congenital leukemia and tetralogy of Fallot.

Bronze baby syndrome (BBS) is an extremely rare dyschromia occurring in neonates with a raised conjugated bilirubin level under phototherapy treatment.1 Rubaltelli et al 1 demonstrated it to be due to the phototransformation of Cu(II)-protoporphyrin upon irradiation,2 but BBS has never been pictorially described. We illustrate comprehensive visible findings of newborn …

Background The increased number of childbearing women with autoimmune diseases leads to a growing interest in studying relationship among maternal disease, therapy, pregnancy and off-spring. The aim of this study was to determine the impact of autoimmune disease on pregnancy and on neonatal outcome, taking into account the maternal treatment and the transplacental autoantibodies passage. Methods We studied 70 infants born to 70 pregnant women with autoimmune disease attended in Fondazione IRCCS Policlinico San Matteo, Pavia, Italy from June 2005 to June 2012. Maternal and neonatal characteristics were collected and relevant clinical, laboratory, therapeutics, sonographic and electrocardiographic investigations were recorded and analyzed. Results We observed a high rate of spontaneous abortions in medical history, 29 %, and 18.6 % of preterm births and 22.9 % of low birth weight (< 2500 g). Transplacental autoantibodies passage wasn’t related to maternal or obstetrical complication, but anti-Ro/SSA positive pregnancies correlated with abnormal fetal heart rate (P = 0.01). Pregnant women on therapy showed an higher incidence of maternal (p = 0.002), obstetric (p = 0.007) complications and an increased rate of intrauterine growth restriction (p = 0.01) than the untreated ones. Conclusions Autoimmune diseases in pregnancy require to be carefully monitored to ensure the best possible management of mothers, fetuses and newborns due to the high rate of morbidity specially in case of maternal polytherapy and/or anti-Ro/SSA positivity.

An appropriate stabilization before transport is essential to reduce adverse events [1-5]. The aim of this study was to describe the characteristics of a cohort of newborns transported and to evaluate the association between stabilization time and change of Transport Risk Index of Physiologic Stability (TRIPS score)[6].

Cortisol production by the human fetal adrenal cortex has been shown to be not adequate at early gestation. This is due to an inefficient expression of 3β-hydroxysteroid dehydrogenase, the enzyme that catalyzes the synthesis of progesterone from pregnenolone, before about 23 weeks of gestation. Whereas, the fetal adrenal cortex it is able to produce dehydroepiandrosterone sulphate for placental estrogen synthesis and to convert placental progesterone to cortisol [1,2]. During the last trimester of pregnancy the fetal adrenal gland undergoes significant anatomical and functional maturation for adaptation to extra-uterine life and cortisol production increases greatly in the last two months of gestation. Cortisol increases synthesis of surfactant, enhances the reabsorption of lung fluid, promotes the conversion of T4 to T3, favors the closure of the ductus arteriosus and maturation of liver and intestinal enzymes [2]. Adrenal insufficiency can be caused by rare conditions such as adrenocortical hypoplasia or congenital enzymatic deficiencies of steroidogenesis, with clinical variables depending on the hormone involved. In preterm infants, the developmental immaturity, combined with increased demands in critical illness, may result in insufficient cortisol production to maintain homeostasis in the face of acute stress or illness, despite apparently normal cortisol levels. This condition is known as “transient or relative adrenal insufficiency” (TAI) [3,4]. TAI usually appears in the first week of life and normalizes in the second week. Infants with TAI can exhibit refractory hypotension (hypotension not responsive to volume expanders and inotropic drugs, but responsive to corticosteroids), respiratory distress, patent ductus arteriosus and bronchopulmonary dysplasia (BPD) [2,3]. Diagnosis of TAI is not easy because many other conditions can cause hypotension in VLBW infants: hypovolemia, myocardial dysfunction, deficient vascular tone, hyaline membrane disease, infection or a combinations of these factors. In addition, normal basal cortisol levels are extremely variable in preterms and to date there is no consensus on the diagnosis of adrenal insufficiency based on tests with adrenocorticotropic hormone (ACTH) [5-8]. Appropriate dose and duration of steroid therapy have not been established yet. On the other hand refractory and persistent hypotension is associated with intraventricular hemorrhage, periventricular leukomalacia, increased mortality and neurological disability [9]. Poor adrenal response has been shown to be associated with later development of BPD and with death [10,11]. For these reasons further studies are needed to evaluate the efficacy and safety of glucocorticoids in the treatment of cardiovascular failure due to TAI in ill preterm and term infants [12,13].