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Secretory phospholipase A2 (sPLA2) regulates the first step of inflammatory cascade and is involved in several pathological processes. sPLA2 also plays a role in preterm labor and parturition, since they are triggered by inflammatory mediators such as prostaglandins. Interestingly, chorioamnionitis (i.e., the presence of intrauterine inflammation) is also often associated with preterm birth. We aimed to verify if chorioamnionitis with fetal involvement modifies sPLA2 activity and expression profile in mothers and neonates delivered prematurely. We collected maternal plasma and amniotic fluid, as well as bronchoalveolar lavage fluid from preterm neonates born to mothers with or without clinical chorioamnionitis with fetal involvement. We measured concentrations of sPLA2 subtype-IIA and -IB, total enzyme activity, and proteins. Urea ratio was used to obtain epithelial lining fluid concentrations. Enzyme activity measured in maternal plasma ( P < 0.001) and amniotic fluid ( P < 0.001) was higher in chorioamnionitis cases than in controls. This was mainly due to the increased production of sPLA2-IIA, as the subtype -IB was present in a smaller amount and was similar between the two groups; sPLA2-IIA was increased in epithelial lining fluid ( P = 0.045) or increased, although without statistical significance, in maternal plasma ( P = 0.06) and amniotic fluid ( P = 0.08) of chorioamnionitis cases. Cytokines that are known to increase sPLA2-IIA expression (TNF-α and IL-1β) or whose expression was increased by sPLA2-IIA (IL-8) were higher in histologically confirmed chorioamnionitis [TNF-α ( P = 0.028), IL-1β ( P < 0.001), and IL-8 ( P = 0.038)]. These data represent the basis for future studies on sPLA2-IIA inhibition to prevent deleterious consequences of chorioamnionitis and preterm birth.

Since the discovery of surfactant, a large amount of knowledge has been accumulated about its biology and pharmacology. Surfactant is the cornerstone of neonatal respiratory critical care, but its proteins and phospholipids are produced in various tissues and organs, with possible roles only partially similar to that played in the alveoli. As surfactant research is focused mainly on its respiratory applications, knowledge about the possible role of surfactant in extrapulmonary disorders has never been summarized. Here we aim to comprehensively review the data about surfactant biology and pharmacology in organs other than the lung, especially focusing in the more promising surfactant extrapulmonary roles. We also review any preclinical or clinical data available about the therapeutic use of surfactant in these contexts. We offer a summary of knowledge and research/development milestones, as possible useful guidance for researchers of multidisciplinary background.

We report the first case of life-threatening extreme neonatal-acquired methemoglobinemia that occurred during inhaled nitric oxide (iNO) at the standard 20 ppm dose in a neonate with early onset sepsis and suprasystemic pulmonary hypertension. Life-threatening methemoglobinemia has been efficaciously treated with methylene blue and ascorbic acid, while stopping iNO and starting iloprost and sildenafil. The patient was subjected to various tests (including gene sequencing and hemoglobin electrophoresis) and did not have any known genetic cause or predisposition for methemoglobinemia. Neuroimaging and the 2-year clinical follow-up were completely normal.

Background Late-presenting congenital diaphragmatic hernia (L-CDH) diagnosis is a challenge for its clinical various presentation. In literature radiologic misdiagnosis is up to 62%. The aim of this study is analyze clinical findings about our cases series in a particular setting of Pediatric Emergency Department (PED) and review of literature. Methods We retrospectively analyzed the medical records of children older than 1 month, operated for L-CDH from November 2009 to December 2019 presented to PED, with a total of 20 children (5 Morgagni and 15 Bochdaleck). Results The median age at diagnosis was 1,48 years. 50% patients had a history of previouses symtptoms with a mean duration of 243,75 days. In 30 % of cases associated anomalies were presented, mainly cardiovascular. 25% of patients had undergone to chest X-ray in past history with misdiagnosis of pneumonia, microganulia and broncovascular thickening. Misdiagnosis are manly among left sided Bochdaleck hernia. Respiratory distress alone or associated with vomiting is commonest acute symptom refered to PED. Respiratory symptoms were more common in younger children, while gastrointestinal ones in older children (not statistically differences p=0,8769). Post-operative recurrence were frequent only in cases of right sided CDH and comparing with left ones, there is a difference statistically significant (p=0.0476). Conclusions L-CDH should be suspected in cases of unexplained acute respiratory distress and vomiting, particulary when children are affected to associate cardiovascular malformation. In cases of patients with long previouses symptoms and various accesses to PED is important to emphasize history of respiratory distress, dysphagia and failure to thrive and should be considered a chest X-ray.

Background and Purpose: Early life microbiota plays a crucial role in human health by acting as a barrier from pathogens' invasion and maintaining the intestinal immune homoeostasis. Altered fecal microbiota (FM) ecology was reported in newborns affected by intestinal ischemia. Our purpose was to describe, in these patients, the FM, the mucosal microbiota (MM) and the mucosal immunity. Methods: Fourteen newborns underwent intestinal resection because of intestinal ischemia. FM and MM were determined through targeted-metagenomics, diversity assignment and Kruskal-Wallis analyses of Operational taxonomic units (OTUs). The mucosal immune cells were analyzed through cytofluorimetry. Results and Conclusion: Based on the severity intestinal injueris we identified two groups: extensive (EII) and focal intestinal ischemia (FII). FM and MM varied in EII and FII groups, showing in the EII group the predominance of Proteobacteria and Enterobacteriaceae and the reduction of Bacteroidetes and Verrucomicrobia for both microbiota. The MM was characterized by a statistically significant reduction of Bacteroides, Lachnospiraceae and Ruminococcaceae and by a higher diversity in the EII compared to FII group. FM showed a prevalence of Proteobacteria, while the Shannon index was lower in the EII compared to FII group. An overall increment in B- and T-lymphocytes and Natural killer (NK) T-like cells was found for EII mucosal samples associated to an increment of TNF-α and INF-γ expressing cells, compared to FII group. FM and MM carry specific signatures of intestinal ischemic lesions. Further research may be crucial to address the role of specific taxa in EII, expecially with reference to inflammation grade and ischemia extension.

BackgroundWhile porcine seems to be superior to bovine surfactants in terms of respiratory outcomes, it is unclear if a surfactant can improve extra-pulmonary outcomes in preterm neonates with respiratory distress syndrome and if there is any physiopathological/biological mechanism linking surfactant therapy to these outcomes. We aim to fill these knowledge gaps.MethodsSystematic and pragmatic review coupled with meta-analysis of randomized controlled trials of bovine or porcine surfactants administered to treat RDS in preterm neonates; common extra-pulmonary neonatal intensive care outcomes were considered. As additional analysis, animal or human translational studies about mechanisms linking surfactant replacement to extra-pulmonary neonatal outcomes were also systematically reviewed.ResultsPorcine surfactant is associated with lower incidence of patentductus arteriosus(OR:0.655; 95%CI:0.460–0.931);p = 0.018; 12 trials; 1472 patients); prenatal steroids (coeff.:-0.009, 95%CI:-0.03–0.009,p = 0.323) and gestational age (coeff.:0.079, 95%CI:-0.18–0.34,p = 0.554) did not influence this effect size. No significant differences were found between porcine and bovine surfactants on neonatal intensive care unit length of stay (mean difference (days):-2.977; 95%CI:-6.659–0.705;p = 0.113; 8 trials; 855 patients), intra-ventricular hemorrhage of any grade (OR:0.860; 95%CI:0.648–1.139);p = 0.293; 15 trials; 1703 patients), severe intra-ventricular hemorrhage (OR:0.852; 95%CI:0.624–1.163);p = 0.313; 15 trials; 1672 patients), necrotizing entero-colitis (OR:1.190; 95%CI:0.785–1.803);p = 0.412; 9 trials; 1097 patients) and retinopathy of prematurity (OR:0.801; 95%CI:0.480–1.337);p = 0.396; 10 trials; 962 patients).ConclusionsPhysiopathological mechanisms explaining the effect of surfactant have been found for patentductus arteriosusonly, while they are lacking for all other endpoints. Porcine surfactant is associated with lower incidence of PDA than bovine surfactants. As there are no differences in terms of other extra-pulmonary outcomes and no physiopathological plausibility, these endpoints should not be used in future trials.RegistrationPROSPERO n.CRD42018100906.

In this study, the onset and shaping of the salivary and gut microbiota in healthy newborns during the first period of life has been followed, evaluating the impact of salivary microbiota on the development of early fecal microbial communities. The microbiota of 80 salivary and 82 fecal samples that were collected from healthy newborns in the first six months of life, was investigated by 16S rRNA amplicon profiling. The microbial relationship within and between the saliva and gut ecosystems was determined by correlation heatmaps and co-occurrence networks. Streptococcus and Staphylococcus appeared as early commensals in the salivary microbiota, dominating this ecosystem through the time, while Fusobacterium, Prevotella, Porphyromonas, Granulicatella, and Veillonella were late colonizers. Enterobacteriaceae, Staphylococcus and Streptococcus were gut pioneers, followed by the anaerobic Bifidobacterium, Veillonella, Eggerthella, and Bacteroides. Streptococcus, Staphylococcus, and Veillonella were shared by the gut and saliva ecosystems. The saliva and gut microbiota seem to evolve independently, driven by local adaptation strategies, except for the oral Streptococcus and Veillonella that are involved in gut microbiota development as seeding species. This study offers a piece of knowledge on how the oral microbiota may affect the gut microbiota in healthy newborns, shedding light onto new microbial targets for the development of therapies for early life intestinal dysbiosis.

Purpose: To describe the prevalent clinical, laboratory, and radiological features of otogenic lateral sinus thrombosis (OLST) in children; to identify clinical predictors of outcome; to propose a management algorithm derived from experience. Methods: A retrospective review was conducted of the clinical records of patients with OLST, treated in a single tertiary care referral center for pediatric disease from 2006 to 2017. The inclusion criteria were pediatric age (0–16years) and OLST diagnosis confirmed by a pre- and post-contrast CT or venography–MRI scan. Primary outcome measures were early (1–2months) and late (6months) sinus recanalization assessed by means of neuroimaging. Results: Twenty-five patients (8 females and 17 males; mean age = 6 ± 3years) were included. A genetic abnormality associated with thrombophilia was found in 24 (96%) patients. At diagnosis, anticoagulant treatment with low-molecular-weight heparin (LMWH) was started in all subjects, while surgical treatment (mastoidectomy and tympanostomy tube insertion) was performed in 16/25 (64%) patients. Follow-up neuroimaging showed lateral sinus recanalization in 12/25 (48%) patients after 1–2months and in 17/25 (68%) after 6months. At multivariate logistic regression analysis, no significant predictors of the early and late neuroradiological outcome were found. Conclusions: All children with OLST should be screened for thrombophilia to decide on treatment duration and to assess the need for future antithrombotic prophylaxis. Immediately after diagnosis, anticoagulant treatment with LMWH should be started according to the international guidelines. Instead, our experience suggests that surgical treatment should not be indicated in all patients, but decided on a case-to-case basis.

Congenital leukemia is rare disease with an incidence of one to five cases per million births. Transient abnormal myelopoiesis (TAM), also called transient myeloproliferative disorder, is a pre-leukemia disorder that may occur in Down syndrome (DS) or non-DS infants. TAM may enter spontaneous remission; however, continual monitoring is required, as this disorder has been observed to develop into acute megakaryoblastic leukemia in 16-30% of cases. In the literature, 16 cases of TAM in non-DS infants have been reported. The case presented in the current study is, to the best of our knowledge, the first case of an Italian non-DS newborn presenting with clinical manifestations of acute leukemia at five days after birth, exhibiting a normal karyotype, trisomy 21 only in blast cells, and spontaneous remission. Chromosomal analyses on peripheral blood cells, bone marrow cells and dermal fibroblasts were conducted using a G-banding technique, and fluorescence in situ hybridization (FISH) was used to identify the critical regions of DS. Amplification of GATA binding protein 1 (GATA1) exon 2 genomic DNA was performed using polymerase chain reaction. Cytogenetic analysis of 50 peripheral blood cells and dermal fibroblasts from the patient revealed a normal karyotype: 46, XX. Conversely, cytogenetic analysis of the patient's bone marrow revealed an abnormal karyotype 47, XX+21. In order to investigate this result, FISH was performed, which identified the presence of three signals in 70% of the cells and two signals in 30% of bone marrow cells. GATA1 sequencing revealed the substitution of a single base (c.150delG) in exon 2. Seven months after the initial analysis, FISH and cytogenetic analyses of the stimulated/unstimulated peripheral blood cells and bone marrow cells were performed, revealing that each exhibited diploid signals, as observed in a normal karyotype.

A mother&rsquo, s milk offers several benefits to infant&rsquo, s health, but, some factors may lead to a reduction in the duration of breastfeeding, such as maternal stress. The objective of our study is to determine if the rate of breastfeeding can be influenced by stress induced by infants&rsquo, hospitalization. A preliminary observational non-randomized study was carried out in Bambino Ges&ugrave, Children&rsquo, s Hospital between October 2016 and January 2017, in order to elucidate a possible relationship between breastfeeding and maternal stress, linked to hospitalization. We modeled the modified version of the PSS NICU (Parental Stressor Scale&mdash, neonatal intensive care unit) questionnaire, which investigated parental stress during hospitalization. This included 33 items with a score from 0 to 5. The overall score, high stress, was established at 85 points or higher. The principal statistically significant correlation was between &lsquo, high PSS score&rsquo, and reduced breastfeeding during hospitalization (p-value: 0.048, OR: 2.865, 95%, CI: 1.008&ndash, 8.146). This relation was not influenced by other descriptive characteristics of the mother. The PSS questionnaire can be an instrument to evaluate the influence of stress in breastfeeding and to monitor the rate and success of lactation. Our study highlights that the stress from hospitalization could influence the success of breastfeeding, mostly in intensive settings and during long hospitalizations.

Background Newborns with congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) might experience breastfeeding difficulties. The aim of this study was to detect the prevalence of breastfeeding in newborns with CDH and EA at different time points. Methods We performed an epidemiological study and retrospective survey on the prevalence of breastfeeding in CDH and EA affected newborns. We identified 40 CDH and 25 EA newborns who were fed through breastfeeding procedures according to WHO categorized definitions, and compared the breastfeeding procedures at the beginning of hospitalization and at three months of life. Results Although all the mothers attempted breastfeeding after birth, only 44 (67.7%) were still breastfeeding at the time of discharge. Exclusive breastfeeding was successful for only 19 (29%) mothers. The rate of exclusive breastfeeding at three months of life did not differ statistically from discharge and between the two groups of study. Conclusion A large percentage of mothers of children with CDH and EA who breastfed at the beginning of hospitalization did not continue at three months. It would be important to increase the breastfeeding rate in CDH and EA affected newborns by following specific steps for vulnerable infants and sustaining breastfeeding after discharge.

South Africa is an emerging market for publishing; it has a number of small and medium-sized local publishers but is dominated by publishing groups and multinationals that import international trends. Along with textbooks, imported trade books are the heart of South African publishing. The major obstacles the industry faces are linked to the poor distribution network as well as the lack of access to financial resources for local publishers, and a readership characterized by the plurality of official languages and an educational gap left over from the social inequalities of the apartheid era. Digital publishing, although not yet thriving, appears to be a promising opportunity to deal with both production costs and distribution and may provide a pathway towards the democratization of reading. A number of commercial platforms and non-profit initiatives are already in place in South Africa to support the development of the publishing market.

Human milk and breastfeeding represent the nutritional normative standards for term and preterm newborns. With the term "surgical infants" we refer to all newborns who undergo surgery during the first days of life and who are assisted in the neonatal intensive care unit during the postoperative period and then in the neonatal surgery unit. There are many obstacles to breastfeeding these newborns. The "barriers" include the unstable clinical conditions before and after surgery, the period of separation between the mother and child, and often the lack of attention to breastfeeding. Few studies have assessed if newborns with surgical diseases are breastfeed and if human milk is beneficial for their outcome. We believe that the best option is to offer them their own mother's milk through the promotion and support of breastfeeding. A specific program focused on the needs of these vulnerable children should be created. Furthermore the surgical and pediatric staff of the neonatal surgery unit should be informed and trained to increase such a program's feasibility.

The 80% of bone mineralisation occurs in the third trimester of pregnancy. The daily fetal requirement is 310 mg of calcium and 170 mg of phosphorus[1]. The bone mineral density (BMD) correlates positively with gestational age, weight and length[2]. At birth, extremely premature infants (ELBWI)canpresent hypocalcaemiabecause of interruption of the maternal calcium supply, high level of calcitoninand immature response to PTH. Early parenteral nutrition solutionisnecessary to maintain normal serum calcium and phosphorus levels. Indeed, the exclusive use of dextrose and calcium gluconate leads to thehypophosphatemia, deleterious to intermediary metabolism, intracellular energy transfer and bone mineral homeostasis[3]. The ELBWI are at risk of Osteopenia of prematurity, also known as neonatal metabolic bone disease (MBD). The pathophysiology includesreduction in organic protein matrix (osteopenia) and/or a reduction in mineral component (osteomalacia). MBD causes rickets, fractures and may affect growth in infancy and childhood. The structural basis of osteopenia is decreased thickness or number of trabeculae and/or decreased thickness of the bone cortex. Osteomalaciais a disorder of the physiological process of mineralisation, when the incorporation of mineral into the organic bone matrix is disturbed, whereas “rickets” describes defective mineralisation of growth plate cartilage and its morphological consequences[4]. The ethiology is multifactorial: placental dysfunction, prolonged (>4 weeks) parenteral nutrition, diureticsand steroids treatment, immobilization and inadequate nutrient intake of calcium, phosphorus, and vitamin D[5]. The main ethiology factor is deficit of mineral substrates, whereas the critical factor is lack of phosphorus[4]. It should be needed an adequate mineral supplementation with parenteral and enteral nutrition, although the difficulties to fortify appropriately the human milk. The dosage recommended of vitamin D is between, 400 IU/d (AAP) and 1000 IU/d (ESPGHAN)[6]. Moreover hypotonia and immobilization are an additional risk factors [7], daily passive exercise canimproves the bone mineral content [8]. MBD could be detected by X-Ray, dual-energy x-ray absorptiometry (DEXA) or quantitative ultrasound. The serumdiagnostic markers are alkaline phosphatases, calcium and phosphateserum levels. Preterm infants with low serum phosphate (

The Cavum Septi Pellucidi represent the normal transitional finding from 24 to 36 weeks post-conceptional age in prenatal ultrasonography. Usually it closes between the second and sixth month of life. Haemorrhage of CSP is a rare entity. Only two cases of hemorrhage in the abnormal dilated CSP have been previously reported in full term neonate. We describe a case of Cavum Septi Pellucidi and lateral ventricles haemorrhage associated with familiar macrocrania, in a full term neonate. Our baby was discharge at hospital a 16 days of life in good clinical conditions and the MRI at 3.5 months of life showed improvement brain anatomy.

Background Medical errors are particularly frequent in Neonatal Intensive Care Units (NICUs) [1], increasing morbidity and mortality of newborns [2]. This category of patients requires the application of high technology and needs individualized medical prescription mainly based on body weight and gestational age[3]. The most frequent event categories are wrong medication, dose, schedule, or infusion rate; error in administration or method of using a specific treatment; patient misidentification