[Show abstract][Hide abstract] ABSTRACT: The identification of early noninvasive biochemical markers of disease is a crucial issue of the current scientific research, particularly during the first period of life, since it could provide useful and precocious diagnostic information when clinical and radiological signs are still silent. The ideal biomarker should be practical and sensitive in the precocious identification of at risk patients. An earlier diagnosis may lead to a larger therapeutic window and improve neonatal outcome. Brain damage and sepsis are common causes of severe morbidity with poor outcome and mortality during the perinatal period. A large number of potential biomarkers, including neuroproteins, calcium binding proteins, enzymes, oxidative stress markers, vasoactive agents, and inflammatory mediators, have been so far investigated. The aim of the present review was to provide a brief overview of some of the more commonly investigated biomarkers used in case of neonatal brain damage and sepsis.
[Show abstract][Hide abstract] ABSTRACT: Histologic chorioamnionitis (HCA) is an intrauterine status of inflammation which may lead to the fetal inflammatory response syndrome. Inflammation is a pathogenetic mechanism also of preeclampsia, although not of microbial origin. The aim of the present pilot study was to evaluate the pattern of inflammatory cytokines in mothers and high-risk preterm infants during the perinatal period. Concentrations of proinflammatory and anti-inflammatory cytokines and C-reactive protein were evaluated in maternal, cord, and neonatal blood of very preterm infants <1,500 g birth weight. Histologic examinations of placentae and umbilical cords were performed. The 65 mother-neonate pairs enrolled were subdivided into three groups: (1) HCA group (n = 15), (2) preeclampsia group (n = 17), and (3) control group, in the absence of HCA/preeclampsia (n = 33). Maternal Interleukin (IL)-6 levels were significantly higher in women of the HCA group compared with the preeclampsia and control groups (p < 0.05). IL-22 was detected in nearly all maternal samples [median value 693.115 pg/ml (599.91-809.91 pg/ml)], with no statistical difference between the groups, but with a tendency to increased levels among preeclamptic women. Increased concentrations of IL-22 were detected in cord blood of neonates exposed to preeclampsia, compared with controls and infants exposed to HCA (p < 0.05). We speculate that the tendentially higher concentrations of IL-22 in preeclamptic mothers and the significantly higher concentrations in cord blood may reflect placental dysfunction and the underlying reparative processes at the maternal-fetal interface. Therefore, IL-22 could be an important biomarker of inflammation in preeclampsia.
Full-text · Article · Nov 2014 · Immunologic Research
[Show abstract][Hide abstract] ABSTRACT: Evidence relating dietary patterns to obesity and related disorders such as non-alcoholic fatty liver disease (NAFLD) is limited in pediatric age. Aim of this study was to analyze the association between dietary patterns, obesity and development of severe steatosis and the metabolic syndrome in a series of children and adolescents referred for suspected NAFLD, and the interaction with the rs738409 I148M PNPLA3 polymorphism. Two hundred patients (112 females) had completed a food frequency and demographic questionnaire. Nearly 58 % were obese, and 32 % were overweight. Mild, moderate, and severe fatty liver was present in 60 (30 %), 87 (44 %), and 51 (26 %) participants, respectively. A great proportion of overweight/obese children and adolescents reported a correct dietary pattern. At multivariate ordinal regression analysis considering demographic, anthropometric, genetic, and behavioral determinants, the major determinant of steatosis severity was PNPLA3 I148M genotype (p < 0.0001), followed by older age (p = 0.017), higher waist circumference (p = 0.016), and less time spent practising physical exercise (p = 0.034). Furthermore, there was a significant interaction between PNPLA3 I148M and intake of sweetened beverages (p = 0.033) and of vegetables (p = 0.038). In conclusion, although dietary pattern was reportedly correct in at-risk overweight adolescents with NAFLD, we report a novel interaction between PNPLA3 I148M and dietary components with the severity of steatosis.
Full-text · Article · May 2014 · Genes & Nutrition
[Show abstract][Hide abstract] ABSTRACT: So-called lock therapy, consisting of high concentrations of antimicrobials instilled into the lumen of the catheter, has been suggested avoid central venous catheter removal during fungal infection. We report a baby who developed catheter-related candidemia. Systemic antifungal treatment did not resolve the candidemia. Lock therapy with 0.3 mL of ethanol 70% and micafungin sodium 5 mg/L was added to the therapy, and blood cultures became sterile.
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective: Echocardiographic flow patterns of patent ductus arteriosus (PDA) are useful to predict the development of haemodynamically significant ductus in premature infants. N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations seem to be useful to detect PDA. We investigated how NT-proBNP levels change on the basis of different flow patterns during the first day of life, and whether NT-proBNP might represent a reliable decision tool in PDA management. Methods: Neonates with gestational age <32 weeks were assessed prospectively, using paired Doppler-echocardiographic evaluation and NT-proBNP values, at T0 (6-24 hours of life), and daily until ductal closure. Results: At T0, NT-proBNP concentrations of 41 neonates correlated to the kind of pattern (p=0.018) with the highest values in neonates with pulsatile or growing patterns. A value <9854 pg/ml identified neonates with spontaneous closure (sensitivity 71.8%, specificity 100%). Overall, 32 infants needed treatment. Pre-treatment NT-proBNP values increased compared to those at T0, significantly in neonates with growing pattern at T0 (p=0.001). After treatment, NT-proBNP concentrations decreased compared to pre-treatment values (p=0.0024), more markedly in the responders than in the non-responders (p=0.042). Conclusions: NT-proBNP concentrations at T0 show a good agreement with different flow patterns and represent a useful tool to identify neonates at risk of developing hemodicamically significant PDA.
No preview · Article · Jan 2014 · The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
[Show abstract][Hide abstract] ABSTRACT: The treatment of neonatal limb ischemia (LI) is challenging for neonatologists. Peripheral nerve blockade (PNB), alone or in association with other therapies, represents a valid therapy in case of vascular spasm or thromboembolic events responsible for LI. In the present case report, we describe the clinical history of a preterm neonate with catheter-related thrombosis of the left leg. PNB was not performed according to the traditional technique but rather by a peridural catheter left in situ for 9 days with a continuous infusion of ropivacaine. In conclusion, the effectiveness of this approach was confirmed by the contemporary near-infrared spectroscopy monitoring, documenting gradual improvement of leg perfusion.
Full-text · Article · Sep 2013 · European Journal of Pediatrics
[Show abstract][Hide abstract] ABSTRACT: Surfactant replacement significantly decreased acute pulmonary morbidity and mortality among preterm neonates with respiratory distress syndrome. Besides improving lung function and oxygenation, surfactant is also a key modulator of pulmonary innate and acquired immunity regulating lung inflammatory processes. In this review, we describe the immunomodulatory features of surfactant preparations. Various surfactant preparations decrease the proinflammatory cytokine and chemokine release, the oxidative burst activity, and the nitric oxide production in lung inflammatory cells such as alveolar neutrophils, monocytes and macrophages; they also affect lymphocyte proliferative response and immunoglobulin production, as well as natural killer and lymphokine-activated killer cell activity. In addition, surfactant preparations are involved in airway remodeling, as they decrease lung fibroblast proliferation capacity and the release of mediators involved in remodeling. Moreover, they increase cell transepithelial resistance and VEGF synthesis in lung epithelial cells. A number of different signaling pathways and molecules are involved in these processes. Because the inhibition of local immune response may decrease lung injury, surfactant therapeutic efficacy may be related not only to its biophysical characteristics but, at least in part, to its anti-inflammatory features and its effects on remodeling processes. However, further studies are required to identify which surfactant preparation ensures the highest anti-inflammatory activity, thereby potentially decreasing the inflammatory process underlying respiratory distress syndrome. In perspective, detailed characterization of these anti-inflammatory effects could help to improve the next generation of surfactant preparations.
No preview · Article · Feb 2013 · Expert Review of Anti-infective Therapy
[Show abstract][Hide abstract] ABSTRACT: Administration of glucocorticoids and caffeine is a common therapeutic intervention in the neonatal period, but possible interactions between these substances are still unclear. The present study investigated the effect of caffeine and different glucocorticoids on expression of surfactant protein (SP)-B, crucial for the physiological function of pulmonary surfactant. We measured expression levels of SP-B, various SP-B transcription factors including erythroblastic leukemia viral oncogene homolog 4 (ErbB4) and thyroid transcription factor-1 (TTF-1), as well as the glucocorticoid receptor (GR) after administering different doses of glucocorticoids, caffeine, cAMP, or the phosphodiesterase-4 inhibitor rolipram in the human airway epithelial cell line NCI-H441. Administration of dexamethasone (1 µM) or caffeine (5 mM) stimulated SP-B mRNA expression with a maximal of 38.8±11.1-fold and 5.2±1.4-fold increase, respectively. Synergistic induction was achieved after co-administration of dexamethasone (1 mM) in combination with caffeine (10 mM) (206±59.7-fold increase, p<0.0001) or cAMP (1 mM) (213±111-fold increase, p = 0.0108). SP-B mRNA was synergistically induced also by administration of caffeine with hydrocortisone (87.9±39.0), prednisolone (154±66.8), and betamethasone (123±6.4). Rolipram also induced SP-B mRNA (64.9±21.0-fold increase). We detected a higher expression of ErbB4 and GR mRNA (7.0- and 1.7-fold increase, respectively), whereas TTF-1, Jun B, c-Jun, SP1, SP3, and HNF-3α mRNA expression was predominantly unchanged. In accordance with mRNA data, mature SP-B was induced significantly by dexamethasone with caffeine (13.8±9.0-fold increase, p = 0.0134). We found a synergistic upregulation of SP-B mRNA expression induced by co-administration of various glucocorticoids and caffeine, achieved by accumulation of intracellular cAMP. This effect was mediated by a caffeine-dependent phosphodiesterase inhibition and by upregulation of both ErbB4 and the GR. These results suggested that caffeine is able to induce the expression of SP-transcription factors and affects the signaling pathways of glucocorticoids, amplifying their effects. Co-administration of caffeine and corticosteroids may therefore be of benefit in surfactant homeostasis.
[Show abstract][Hide abstract] ABSTRACT: Considering the high frequency of bleeding complications following fibrinolytic treatment in neonates, peripheral nerve blockade (PNB) has been proposed alone or in association with lower doses of tissue plasminogen activator, as a possible new therapeutic approach in the management of neonatal limb ischemia (LI) secondary to vasospasm and/or thrombosis. The present article provides a review of the current knowledge about the topic, in order to evaluate the efficacy and safety of this therapeutic approach. According to the few case reports documented in literature and to our experience, PNB could be considered as valid procedure for the treatment of LI, especially during neonatal period, when the risk of serious bleeding associated with fibrinolytic or anticoagulant therapy is higher. Peripheral nerve blockade resulted in a safe and effective procedure for the treatment of neonatal vascular spasm and thrombosis.
No preview · Article · Sep 2012 · Clinical and Applied Thrombosis/Hemostasis
[Show abstract][Hide abstract] ABSTRACT: Arterial oxygen saturation (SaO(2)) and partial arterial pressure of carbon dioxide (PaCO(2)) are important respiratory parameters in critically ill neonates. A sensor combining a pulse oximeter with the Stow-Severinghaus electrode, required for the measurement of peripheral oxygen saturation (SpO(2)) and transcutaneous partial pressure of carbon dioxide (PtcCO(2)), respectively, has been recently used in neonatal clinical practice (TOSCA(500Ò)Radiometer). We evaluated TOSCA usability and reliability in the delivery room (DR), throughout three different periods, on term, late-preterm, and preterm neonates. During the first period (period A), 30 healthy term neonates were simultaneously monitored with both TOSCA and a MASIMO pulse oximeter. During the second period (period B), 10 healthy late-preterm neonates were monitored with both TOSCA and a transcutaneous device measuring PtcCO(2) (TINA(Ò) TCM3, Radiometer). During the third period (period C), 15 preterm neonates were monitored with TOSCA and MASIMO after birth, during stabilization, and during transport to the neonatal intensive care unit (NICU). Blood gas analyses were performed to compare transcutaneous and blood gas values. TOSCA resulted easily and safely usable in the DR, allowing reliable noninvasive SaO(2) estimation. Since PtcCO(2) measurements with TOSCA required at least 10 min to be stable and reliable, this parameter was not useful during the early resuscitation immediately after birth. Moreover, PtcCO(2) levels were less precise if compared to the conventional transcutaneous monitoring. However, PtcCO(2) measurement by TOSCA was useful as trend-monitoring after stabilization and during transport to NICU.
[Show abstract][Hide abstract] ABSTRACT: Very low birth weight (VLBW) infants are at high risk to develop a neonatal nosocomial sepsis. The incidence of neonatal nosocomial, late-onset sepsis (LOS) is about 20-30%, but a rate of up to 43% has been reported among neonates with a birth weight of 400-750 g. Preventive and treatment strategies for neonatal sepsis in VLBW infants are aiming to enhance the infant's host defence mechanisms. Neonatal immunodeficiencies include quantitative and qualitative deficits in phagocytes, complement components, and immunoglobulins. A considerable number of immune strategies has been investigated in carefully designed multicentre trials. These include exchange transfusion, neutrophil transfusion, hematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), intravenous immunoglobulins (IVIG), and others. Since none of these interventions was able to reduce the mortality rate of immature preterm infants, the current evidence does not support the use of any of the immune strategies for prevention or treatment of neonatal sepsis. Decreasing the burden of intensive care and following strict hygiene programs at NICUs may be the most promising current strategies to minimise nosocomial infection.
No preview · Article · Aug 2012 · Zeitschrift für Geburtshilfe und Neonatologie
[Show abstract][Hide abstract] ABSTRACT: We describe a case of neonatal cerebral sinovenous thrombosis associated with the presence of anti-phospholipid antibodies (aPL). We recommend that in all cases of neonatal thrombosis, the couple mother-infant should be extensively tested for the presence of both acquired (aPL) and congenital thrombophilia.
Full-text · Article · May 2012 · Indian pediatrics
[Show abstract][Hide abstract] ABSTRACT: Immaturity of the pulmonary and immune systems represents an important risk factor for increased morbidity and mortality in neonates. Surfactant protein (SP)-A and SP-D, linking molecules between these two systems, are critical for lung homeostasis as they regulate surfactant metabolism and host immunodefense activities in innate and adaptive immunity. Preterm neonates with respiratory distress syndrome showed lower concentrations of SP-A and SP-D, and the administration of exogenous surfactant was found to strengthen the secretion of SPs. Low levels of SP-A and SP-D also correlated with a higher risk of infection and development of bronchopulmonary dysplasia. Moreover, SP-A- and SP-D-enriched surfactant formulations were more resistant to the inhibitory action of the plasmatic proteins in animal models. Based on these assumptions, new-generation surfactants, enriched with SP-A and/or SP-D, may enhance the function of immune system and lungs in neonates, potentially improving the clinical outcome.
No preview · Article · May 2012 · Expert Review of Anti-infective Therapy
[Show abstract][Hide abstract] ABSTRACT: Chorioamnionitis represents a major risk factor for preterm birth and contributes to prematurity-associated morbidity and mortality. Comparison of studies addressing neonatal outcome after exposure to either histological or clinical chorioamnionitis is hampered by the great heterogeneity regarding study cohorts and disease definitions which were applied. Moreover, the impact of exposure to inflammation in utero on neonatal outcome has become less evident with major advances in perinatal and neonatal care. Histologic chorioamnionitis evidently is associated with a reduction of incidence and severity of respiratory distress syndrome. Short-term maturational effects on the lungs of ventilated extremely premature infants are, however, accompanied by a greater susceptibility of the lung, eventually contributing to an increased risk of bronchopulmonary dysplasia. Chorioamnionitis has been shown associated with increased rate of early-onset sepsis but, according to recent data, histological chorioamnionitis might be protective against late-onset sepsis. Inconsistent data exist concerning the true role of chorioamnionitis in the development of brain lesions such as cystic periventricular leukomalacia, diffuse white matter disease, and intraventricular hemorrhage. However, an association with the development of cerebral palsy has been reported.
No preview · Article · Mar 2012 · The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
[Show abstract][Hide abstract] ABSTRACT: This retrospective, study compared the efficacy and safety of Ibuprofen-Lysinate (Arfen, intramuscular formulation, Group I, n=156) used during 2000-2005 and Sodium-ibuprofen (Pedea, intravenous solution, Group II, n=60) used during 2006-2008, for the prophylaxis of Patent Ductus Arteriosus in inborn neonates with gestational age ≤ 28 weeks. Ductus closure rate after prophylaxis was significantly higher (73.1% vs 50%; P=0.002) and surgical ligation significantly lower (8.2% vs 23.3%; P=0.005) in Group I. A smaller number of neonates of Group I vs Group II showed oliguria and hemorrhagic disease.
No preview · Article · Jan 2012 · Indian pediatrics
[Show abstract][Hide abstract] ABSTRACT: We report the successful and safe use of levosimendan, a new calcium-sensitizing agent with positive inotropic and vasodilatory action, in 2 critically ill term newborns with acute heart failure and pulmonary hypertension in the absence of any underlying heart malformation and/or previous cardiosurgical procedures. During the neonatal period, levosimendan may represent an ideal drug for immature myocardium characterized by a higher calcium-dependent contractility than in adults. Copyright (C) 2011 S. Karger AG, Basel
[Show abstract][Hide abstract] ABSTRACT: Patent ductus arteriosus (PDA) complicates the clinical course of preterm infants. Nonsteroidal anti-inflammatory drugs, especially Indomethacin and Ibuprofen, have been widely used for both prevention and treatment of PDA. Short-term efficacy of Indomethacin or Ibuprofen is equivalent, while Ibuprofen results show a higher safety profile. Ibuprofen is associated with fewer clinical gastrointestinal and renal side effects with respect to Indomethacin even if subclinical potential effects are reported. When administered as prophylaxis, Ibuprofen has no effects on prevention of intraventricular haemorrhage unlike Indomethacin. Considering the potential adverse effects of both these drugs, a careful monitoring during and after the treatment period is highly recommended.
No preview · Article · Jul 2011 · The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians