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Mannose binding lectin (MBL) is a soluble pattern recognition receptor of innate immunity that binds a wide range of pathogens and exerts opsonic effects. We investigated the association between serum MBL levels and development of sepsis in infants admitted to neonatal intensive care units (NICUs). Serum MBL levels on admission were measured by enzyme-linked immunosorbent assay (ELISA) in 206 neonates consecutively admitted to an NICU of whom 138 did not develop hospital-acquired sepsis and 68 did. Of these 68, 40 had confirmed sepsis with positive blood cultures, 19 clinically suspected sepsis, with negative blood cultures, and nine had clinically suspected sepsis with blood culture yielding coagulase-negative staphylococci (CoNS). Serum MBL levels on admission were significantly lower in infants with sepsis [0.45 microg/mL; interquartile range (IQR) 0.09-1.68], particularly in those with confirmed sepsis (0.17 microg/mL; IQR 0.05-0.96), compared with infants without sepsis (1.45 microg/mL; IQR 0.43-3.52), and infants with CoNS-positive blood culture (1.70 microg/mL: IQR 0.85-3.60). After adjusting for duration of exposure gestational age (GA) and birth weight (BW), the association of low MBL levels with development of sepsis was maintained [odds ratio (OR) = 0.52; 95% confidence interval (CI): 0.36-0.75]. The measurement of serum MBL levels on admission in NICU may help to identify neonates at higher risk of developing sepsis.

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.

The clinical records a years cohort of 280 newborn infants consecutively hospitalized for 48 h or more in our neonatal intensive-care unit (NICU) were reviewed. Information on the infants' conditions during the first 12h of life, and on the procedures used in the NICU, were collected. Statistical significance was tested by univariate analysis with the chi(2) test and by multivariate logistic regression analysis with the software program SPSS (Version 10). Over the one-year period reviewed, 90 hospital-acquired infections (HAIs) were contracted; 55 (19.6%) of infants had at least one infection during their stay. The overall in-hospital mortality was 7.1%, and mortality was higher in infants in whom at least one infection developed than in non-infected infants (12.7 vs. 5.8% P=0.13). Very low birthweight infants (VLBW1,501 g) who had more severe clinical conditions on admission [clinical risk index for babies (CRIB) score/=5] had an almost two-fold higher risk of contracting a HAI. In the multivariate regression analysis, the onset of a HAI was strongly associated with a low gestational age and the presence of an intravascular catheter. HAIs frequently complicate hospitalization in NICUs and are associated with increased mortality. Our findings also suggest that CRIB could be predictive for the risk of infection in VLBW infants.

Objective To review the clinical and molecular genetic characteristics of 16 patients presenting a suspected diagnosis of Kabuki syndrome (KS) in the first year of life, to evaluate the clinical handles leading to a prompt diagnosis of KS in newborns. Clinical diagnosis of KS can be challenging during the first year of life, as many diagnostic features become evident only in subsequent years. Methods All patients were clinically investigated by trained clinical geneticists. A literature review was performed using the Pubmed online database and diagnostic criteria suggested by DYSCERNE–Kabuki Syndrome Guidelines (2010) were used (a European Network of Centres of Expertise for Dysmorphology, funded by the European Commission Executive Agency for Health and Consumers (DG Sanco), Project 2006122). Molecular analysis of the known causative genes of KS, KMT2D/MLL2 and KDM6A , was performed through MiSeq-targeted sequencing platform. All mutations identified were validated by Sanger sequencing protocols. Results Mutations in KMT2D gene were identified in 10/16 (62%) of the patients, whereas none of the patients had KDM6A mutations. Facial dysmorphisms (94%), feeding difficulties (100%) and hypotonia (100%) suggested the clinical diagnosis of KS. No significative differences in terms of facial features were noticed between mutation positive and negative patients of the cohort. Brachydactyly, joint laxity and nail dysplasia were present in about 80% of the patients. Other congenital anomalies were most commonly present in the mutated group of patients, including left-sided cardiac abnormalities, skeletal, renal and anorectal malformations and hypertricosis. Conclusions We present an overview of patients with KS diagnosed during the first year of life. Early diagnosis is serviceable in terms of clinical management and for targeted genetic counselling.

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.

As described in animal models, the lectin-complement pathway is central to the propagation of ischemia-reperfusion injuries in many tissues, including the brain. Similarly, it might affect the genesis of brain damage in preterm infants. MBL2 gene single-nucleotide polymorphisms (SNPs), regulating mannose-binding lectin (MBL) serum levels, could predict the risk of adverse neurological outcome in these infants.To evaluate the association between SNPs of the MBL2 gene and long-term neurological outcomes in preterm infants, 75 infants (gestational age (GA) ≤ 32 wk) were observed in a prospective longitudinal study and assessed by clinical and instrumental exams at 12 and 24 mo of corrected age (CA). They were genotyped for the promoter polymorphism -221 and for the exon-1 variant alleles (at codons 52, 54, and 57) of the MBL2 gene.The MBL2 exon-1 OO genotype was more frequent in children with an adverse neurological outcome (5/35; 7%) than in controls (0/40; 0%), P = 0.045. The risk of intraventricular hemorrhage in carriers of the genotype OO was marked, without reaching statistical significance (odds ratio: 8.67; 95% confidence interval: 0.87-86.06; P = 0.07).Preterm infants who are carriers of MBL2 exon-1 OO genotype are exposed to an increased risk of adverse neurological outcomes.

UNLABELLED Acute liver failure is a rare heterogeneous syndrome in neonates. We report of a newborn with haemophagocytic lymphohistiocytosis presenting as acute liver failure. Pancytopenia and multi-organ failure occurred later in the course. He carried two mutations of the perforin gene (PRF-1), one of which not previously described, causing a complete loss of perforin expression and natural killer cell function. CONCLUSION Perforin expression and function should be promptly assessed in neonatal/infantile acute liver failure, as haemophagocytic lymphohistiocytosis requires specific treatment and represents a contra-indication to liver transplant.

Objective To investigate the accuracy of procalcitonin (PCT) as a diagnostic marker of nosocomial sepsis (NS) and define the most accurate cut-off to distinguish infected from uninfected neonates. Setting Six neonatal intensive care units (NICUs). Patients 762 neonates admitted to six NICUs during a 28-month observational study for whom at least one serum sample was taken on admission. Main outcome measures Positive and negative predictive values at different PCT cut-off levels. Results The overall probability of an NS was doubled or more if PCT was >0.5 ng/ml. In very-low-birth-weight (VLBW) infants, a cut-off of >2.4 ng/ml gave a positive predictive value of NS near to 50% with a probability of a false-positive diagnosis of NS in about 10% of the patients. Conclusions In VLBW neonates, a serum PCT value >2.4 ng/ml prompts early empirical antibiotic therapy, while in normal-birth-weight infants, a PCT value ≤2.4 ng/ml carries a low risk of missing an NS.

We report the case of a vesiculopustular eruption associated with a transient myeloproliferative disorder (TMD) in a neonate with trisomy 21 syndrome. Examination of a skin biopsy showed a dermal mixed inflammatory infiltrate including atypical megakaryoblasts. As the white blood cell count spontaneously normalized, the eruption disappeared. This case report and review of the literature demonstrates that a vesiculopustular eruption could be an important clue to identify TMD in a neonate.

A female neonate with Beckwith-Wiedemann syndrome (BWS) presented at birth with a swelling on the right cheek and multiple nodular and vesicular lesions on the face, limbs and abdomen, resembling the condition referred to as ‘blueberry muffin baby’ (figure 1). Figure 1 Swelling on the right cheek and blueberry muffin-like lesions on the abdomen and limbs. A biopsy was …

Infantile myofibromatosis is the most common fibrous tumor of infancy. Solitary or generalized myofibromas without visceral involvement usually regress within a few months. The multifocal disease infantile generalized myofibromatosis, with visceral involvement, is associated with a significant mortality due to the effect of tumors on vital organs. We report a case of infantile generalized myofibromatosis with visceral involvement, including 2 right atrium tumors. The infant expressed high circulating vascular endothelial growth factor and fibroblast growth factor-2 levels, and interferon alpha-2b was started as antiangiogenic treatment, aimed at triggering regression of the life-threatening cardiac lesions. The tumors regressed and vascular endothelial growth factor and fibroblast growth factor-2 levels were reduced after treatment discontinuation.

A woman contracted chickenpox in the 12th week of gestation. Her general practitioner and later the consultant obstetrician warned her about the small risk of giving birth to a disabled child. She decided to continue the pregnancy without undergoing invasive tests to diagnose fetal intrauterine infection. Symptoms of congenital varicella syndrome (CVS) were detected by ultrasound in the 29th and 34th weeks of gestation. On admission to hospital, the baby was not considered infectious and was not isolated because polymerase chain reaction analysis to detect varicella zoster virus (VZV) DNA in the blood, cerebrospinal fluid, saliva, skin scrapings and feces gave negative results. He was also not separated from his mother. The mother was without clinical complications. Varicella during pregnancy may result in VZV transmission to the fetus or newborn. Intrauterine VZV infection in the first 28 weeks of gestation may result in CVS with limb deformities, brain abnormalities and mental retardation. Usually the newborn is not infectious, and therapy and isolation are unnecessary. When the mother catches the infection in the second trimester, the newborn may manifest shingles in the first 2 years of life. A maternal rash erupting 5 days before to 2 days after delivery is frequently associated with clinically severe varicella in the newborn, leading to high mortality if untreated. Then the newborn is infectious and must be isolated. This case report underlines the need for expert medical counseling for women who contract chickenpox at any time during pregnancy. It also underlines the importance of immunizing susceptible women of childbearing age before they become pregnant.

The receptor TLR9, recognizing unmethylated bacterial DNA (CpG), is expressed by B cells and plays a role in the maintenance of serological memory. Little is known about the response of B cells stimulated with CpG alone, without additional cytokines. In this study, we show for the first time the phenotypic modification, changes in gene expression, and functional events downstream to TLR9 stimulation in human B cell subsets. In addition, we demonstrate that upon CpG stimulation, IgM memory B cells differentiate into plasma cells producing IgM Abs directed against the capsular polysaccharides of Streptococcus pneumoniae. This novel finding proves that IgM memory is the B cell compartment responsible for the defense against encapsulated bacteria. We also show that cord blood transitional B cells, corresponding to new bone marrow emigrants, respond to CpG. Upon TLR9 engagement, they de novo express AID and Blimp-1, genes necessary for hypersomatic mutation, class-switch recombination, and plasma cell differentiation and produce Abs with anti-pneumococcal specificity. Transitional B cells, isolated from cord blood, have not been exposed to pneumococcus in vivo. In addition, it is known that Ag binding through the BCR causes apoptotic cell death at this stage of development. Therefore, the ability of transitional B cells to sense bacterial DNA through TLR9 represents a tool to rapidly build up the repertoire of natural Abs necessary for our first-line defense at birth.

We compared the effectiveness of a single dose and a three-day course of antibiotic prophylaxis in preventing bacterial infections in high-risk neonates. The study was a prospective, randomized controlled trial conducted in a 20-bed tertiary referral neonatal intensive care unit (NICU). A series of 130 neonates admitted consecutively to the NICU, fulfilling risk factors for infection, were assigned at random to receive intravenous antibiotic prophylaxis with ampicillin and netilmicin either in two daily doses for 72 h (three-day-administration group, 67 infants) or in a single bolus injection on admission (bolus group, 63 infants). Hospital-acquired infection, the main outcome measure, was defined as infection that developed at least 48 h after admission, and vertical infection (maternally transmitted) was considered to be present when clinical symptoms and abnormal laboratory findings became evident within 48 h of birth. Infections were considered as suspected when clinical and laboratory findings of infection were present, without positive cultures, and as confirmed when positive cultures were also present. No significant differences were found between the two groups of neonates studied in mean birth weight, gestational age or postnatal age on admission. The incidence of vertical infection was similar in the two groups (16/67, 23.9% vs. 14/63, 22.2%). Of the 130 newborns studied, 29 (22.3%) acquired at least one nosocomial infection during their NICU stay; total hospital-acquired infections, calculated as the incidence density of infection (the number of infective episodes divided by the number of days in the NICU), were less frequent among newborns who received the three-day course than the bolus (relative risk 0.69). This difference, although not statistically significant, depended on the different incidence density of confirmed nosocomial infections rather than on suspected infections (relative risk 0.59; 95% confidence interval 0.32-1.09; P=0.1). There were no significant differences between the two groups in overall mortality. A single bolus administration on admission is therefore likely to be as effective as a three-day course of antibiotic prophylaxis in preventing bacterial infection in high-risk infants admitted to an NICU.

Propafenone, an antiarrhythmic drug that is effective for treating supraventricular tachycardias, can induce well-known proarrhythmic and systemic adverse effects. We describe a previously unreported adverse effect in 3 newborns: oral propafenone-induced profuse oral secretions and respiratory distress of sufficient severity to necessitate discontinuation of propafenone.

Objective: Preterm infants often require mechanical ventilation (MV) and admission to neonatal intensive care unit (NICU). However, the use of MV, and other external stimuli can cause them pain. Pain in preterm infants may lead to developmental changes. Few non-invasive and nonpharmacological techniques are used in the NICU to avoid it. Therefore, the aim of this study is to demonstrate that aquatic therapy, a technique developed by our team can be an extremely effective tool to provide comfort and immediate relief of pain in preterm infants receiving MV. Methods: Nine preterm infants who were undergoing MV and had pain were submitted to this technique, which consisted of a hot bath tub with high temperature (36–36.5°C) followed by therapeutic exercises done by a physical therapist for 10 minutes. The babies were monitored during the whole procedure. Demographic data, vital signs, mechanical ventilation parameters and scales of pain NFCS and NIPS were collected at three time points: before, after 15 and after 60 minutes of therapy. Results: There were no complications related to the procedure performed, nor there was any change in body temperature. Other signs such as heart rate, respiratory rate and mean arterial pressure decreased to normal values after therapy. All babies showed a statistically significant reduction (p ≤0.01) in pain scores taken Before/After 15 and after 60 min (NIPS: 5.67/0/0, NFCS:5.34/0/0).

Cocaine abuse in pregnancy has been evaluated through toxicological analysis of hair from 123 pathological new-borns admitted in an intensive care division. The new-borns were affected with malformations, low gestational age, low birth weight, respiratory distress. A control group of 39 healthy new-borns was also analysed. Hair samples (about 50 mg) were enzymatically digested and directly analysed by RIA. Samples positive to the preliminary screening were extracted by SPE columns and injected in GC/MS. Results obtained showed 3 positive samples (2.4%). All cocaine babies had low gestational age, low birth weight, two of them showed heart malformation, one kidney malformation and one genital malformation. None of the control new-born resulted positive for cocaine. These results show a worrying trend of cocaine diffusion in the Italian population.

Background: Necrotizing Enterocolitis (NEC) is a leading cause of morbidity and mortality among preterm neonates. To identify subsets of neonates at high risk of NEC is a challenge. Local pro-inflammatory response of the host could be of relevance in the still unclear pathogenesis of NEC. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine, implicated in the pathophysiology of inflammatory bowel diseases, such as chronic colitis and gastric inflammation. The MIF promoter contains a functionally relevant single nucleotide polymorphism (SNP) G/C at position -173. The MIF -173 C allele is associated with higher MIF expression in vitro.

Background: MBL initiates complement activation and could have a role in the pathogenesis of ischemia-reperfusion pathologies, such as NEC. We investigated the association between MBL2 genotype, the development of NEC and the MBL expression on specimens of bowel tissue in a cohort of preterm neonates in NICU. Material and methods: We determined the MBL2 genotype in 118 preterm neonates admitted in NICU. The exon 1 SNPs 52,54, 57 and SNPs -550 and - 221 of the promoter region of the MBL2 gene were also determined. Immunoistochemical analysis was performed on 16 bowel bioptic paraffin-embedded specimens, collected during surgery in neonates with NEC. Clinical cases and summary results:21/118 neonates developed NEC. The analysis of the polymorphisisms in the promoter region at -221(variant X/Y) showed that the frequency of the YY genotype was 85.7% in the neonates with NEC and 53.6% in the controls(p=0.013). Adjusting for gestational age, the association between YY genotype and the development of NEC was still significant(OR=5.02;p=0.015). MBL was highly expressed in anastomotic healthy tissue, in enterocytes and istiocytes. No MBL staining was detectable in the necrotic bowel tissue. Neonates MBL low and deficient producer showed negligible or weak staining for MBL. Conclusions: YY genotype of the promoter of the MBL2 gene appeared to increase the risk of developing NEC. The epithelial localization of MBL in the bowel is consistent with a role for MBL in developing full-thickness necrosis during NEC.

We report the use of regional nerve blockade in the management of arterial limb ischaemia. A female infant weighing 815 g was born spontaneously at 26 weeks' gestation. At birth the baby required resuscitation with endotracheal intubation. Soon after birth she underwent arterial blood gas analysis by direct puncture of the right radial artery. At 5 h of life her right hand was cool, with oedema of the third, fourth and fifth fingers and cyanotic discoloration of the fourth and fifth distal phalanges. The radial pulse was absent. As a cerebral ultrasound examination showed no intraventricular haemorrhage, systemic fibrinolytic treatment was started. However, this had to be discontinued after 24 h because …

As care improves many neonates with life-threatening disorders now survive. Nonetheless Nosocomial Infections (NI) are still a major cause of morbidity and mortality in NICUs. A prospective multicentric surveillance study was conducted in six Italian NICUs to describe the epidemiologic profile and determinants of NI in NICU. 1692 neonates, consecutively admitted to the NICUs from July 2000 to October 2002 and monitored for the development of NI were enrolled into the study. The standard definition criteria for NI formulated by the Centers for Disease Control in Atlanta were used. The cumulative probability and hazard ratios (HR) for the first episode of infection were estimated by the Kaplan-Meier method and the Cox model. A total of 217 neonates had 255 episodes of NI. The incidence rate of NI was 7 per 1000 patient-days. The cumulative probability of first infection was 20% (95% CI, 7.50–23.30) and 27.6% (95 CI, 23.20–32.80) at 30 and 60 days after admission to the NICU. After adjustment for the severity of illness, the main risk factors related to NI in very-low-birth-weight neonates (VLBW) were surgical procedures (HR 2.69;95% CI 0.60–12.08), nasal ventilation (CPAP) (HR, 2.51; 95% CI, 0.93–6.76), continuous enteral feeding (HR 1.89; 95% CI, 0.20–17.50), mechanical ventilation (HR, 1.70; 95%CI, 0.72–4.00) and intravenous infusions (HR 1.46; 95% CI, 0.32–6.52). Among neonates with a birth weight over 1500 g, risk factors for NI were parenteral nutrition with lipid emulsion (HR, 12.41; 95% CI, 4.19–36.78), surgical procedures (HR 2.78; 95% CI, 0.82–9.44), and intravenous infusions (HR, 2.63; 95% CI, 0.27–25.53). Risk factors for NI were related more to the severity of illness than to healthcare procedures in VLBW babies and more to medications among neonates weighing more than 1500 g at birth.

Background: MBL is a serum lectin, synthesised by the liver, that is part of the innate immune system; it behaves as an acute phase reactant and plays an auxiliary rather than a critical role in host defence. Individuals with MBL deficiency may experience an increased number of infections, particularly in the course of immunodeficiency (e.g. chemotherapy). A MBL concentration of 0.5 mcg/ml has been suggested as a cut-off level for MBL deficiency. Serum MBL levels in term neonates are similar to those in adults, but values in preterms are approximately 50% lower. HAI are an important cause of neonatal morbidity and mortality. Known risk factors account only in part of the (inter)individual variability of the frequency and severity of neonatal infections. Part of this variability could be related to individual differences in the maturation of the innate immune system.