Human placenta has no microbiome but can contain potential pathogens.

We sought to determine whether pre-eclampsia, spontaneous preterm birth or the delivery of infants who are small for gestational age were associated with the presence of bacterial DNA in the human placenta. Here we show that there was no evidence for the presence of bacteria in the large majority of placental samples, from both complicated and uncomplicated pregnancies. Almost all signals were related either to the acquisition of bacteria during labour and delivery, or to contamination of laboratory reagents with bacterial DNA. The exception was Streptococcus agalactiae (group B Streptococcus), for which non-contaminant signals were detected in approximately 5% of samples collected before the onset of labour. We conclude that bacterial infection of the placenta is not a common cause of adverse pregnancy outcome and that the human placenta does not have a microbiome, but it does represent a potential site of perinatal acquisition of S. agalactiae, a major cause of neonatal sepsis.

Pitfalls in the diagnosis of meningitis in neonates and young infants: the role of lumbar puncture.

Meningitis occurs frequently in neonates and can lead to a number of acute, severe complications and long-term disabilities. An early diagnosis of neonatal meningitis is essential to reduce mortality and to improve outcomes. Initial clinical signs of meningitis are often subtle and frequently overlap with those of sepsis, and current haematologic tests do not distinguish sepsis from meningitis. Thus, lumbar puncture (LP) remains the gold standard for the diagnosis of meningitis in infants, and this procedure is recommended in clinical guidelines. Nevertheless, in clinical practice, LP is frequently deferred or omitted due to concerns regarding hypothetical adverse events or limited experience of the performer. Future studies should assess whether a combination of clinical findings and select haematologic tests at disease onset can identify those neonates with the highest risk of meningitis who should undergo LP. Furthermore, clinicians should be convinced that the actual benefits of an early diagnosis of meningitis far outweigh the hypothetical risks associated with LP.

Congenital intestinal atresias with multiple episodes of sepsis: A case report and review of literature.

INTRODUCTION: Hereditary multiple intestinal atresia associated with severe combined immunodeficiency (MIA-SCID) is a very rare disease caused by deleterious mutations in the tetratricopeptide repeat domain-containing protein 7A gene TTC7A. It is characterized by intestinal obstruction, sepsis, and a poor prognosis. Insights into phenotype-genotype correlations could help to guide genetic counseling and increase our knowledge of the natural history of this disease. CASE PRESENTATION: We report the case of a newborn in which his fetal magnetic resonance imaging showed jejunal atresia and microcolon and an abdominal x-ray at birth confirmed intestinal obstruction. The clinical course was complicated by multiple episodes of sepsis, and laboratory investigations showed SCID. The genetic analysis identified a homozygous c.53344_53347 mutation in the TTC7A gene compatible with MIA-SCID syndrome. The patient required 3 operations because of new intestinal atresias in the first months of life. She underwent bone marrow transplantation at 8 months of age but died of liver failure secondary to graft-versus-host disease. CONCLUSION: Immunologic assessment and genetic screening for TTC7A mutations are important in patients with MIA. Greater knowledge of the functions of the TTC7A protein will have important therapeutic implications for patients with MIA-SCID syndrome.

Citomegalovirus y calcificaciones hepáticas en un infante / Cytomegalovirus and hepatic calcifications in a child

Se presenta el caso clínico de un infante de 2 años de edad, cuya progenitora lo llevó a consulta por presentar orinas oscuras y dolor abdominal en algunas ocasiones. Al examen físico se encontró hepatomegalia no dolorosa, que rebasaba en 2 cm el reborde costal derecho. En la ecografía abdominal se observaron múltiples calcificaciones hepáticas y la técnica de reacción en cadena de la polimerasa resultó positiva a citomegalovirus tanto en suero como en sangre. Los resultados de estos exámenes, así como los antecedentes de la madre y el niño permitieron diagnosticar una infección congénita por citomegalovirus. El paciente evolucionó favorablemente y hasta el momento de efectuado este artículo se mantenía asintomático

The case report of a 2 years child whose mother took to the outpatient service due to dark urines and abdominal pain in some occasions is presented. A non painful hepatomegaly was found in the physical examination that surpassed in 2 cm the right costal edge. Multiple hepatic calcifications were observed in the abdominal echography and the polymerase chain reaction technique, either in serum or blood, was positive to cytomegalovirus. The results of these exams, as well as the mother and child history allowed to diagnose a congenital infection due to cytomegalovirus. The patient had a favorable clinical course and he stayed asymptomatic up to the elaboration of this work

Fully non-parametric receiver operating characteristic curve estimation for random-effects meta-analysis.

Meta-analyses, broadly defined as the quantitative review and synthesis of the results of related but independent comparable studies, allow to know the state of the art of one considered topic. Since the amount of available bibliography has enhanced in almost all fields and, specifically, in biomedical research, its popularity has drastically increased during the last decades. In particular, different methodologies have been developed in order to perform meta-analytic studies of diagnostic tests for both fixed- and random-effects models. From a parametric point of view, these techniques often compute a bivariate estimation for the sensitivity and the specificity by using only one threshold per included study. Frequently, an overall receiver operating characteristic curve based on a bivariate normal distribution is also provided. In this work, the author deals with the problem of estimating an overall receiver operating characteristic curve from a fully non-parametric approach when the data come from a meta-analysis study i.e. only certain information about the diagnostic capacity is available. Both fixed- and random-effects models are considered. In addition, the proposed methodology lets to use the information of all cut-off points available (not only one of them) in the selected original studies. The performance of the method is explored through Monte Carlo simulations. The observed results suggest that the proposed estimator is better than the reference one when the reported information is related to a threshold based on the Youden index and when information for two or more points are provided. Real data illustrations are included.

Plasma lactoferrin levels in newborn preterm infants with sepsis.

INTRODUCTION: 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. METHODS: A total of 15 (8 females, 7 males) newborn preterm infants with a postnatal age >72 h of life, underwent to blood culture and others markers of infection, for suspected sepsis, were enrolled in the study. RESULTS: 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). CONCLUSIONS: 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.

Infectious Complications and Morbidities After Neonatal Bloodstream Infections: An Observational Cohort Study.

Few data are available on the clinical characteristics of complications and morbidities after neonatal bloodstream infections (BSIs), understood as any newly infectious focus or organ dysfunction directly related to BSIs but not occur concurrently. However, these bloodstream-associated infectious complications (BSICs) contribute significantly to increased hospital stay, cost, and final mortality. We performed an observational cohort study of unselected neonatal intensive care unit (NICU) patients based on records in a large clinical database. All neonates hospitalized in our NICU with BSI between 2006 and 2013 were reviewed, and those who developed BSICs were analyzed to identify the clinical characteristics and outcomes. Multivariate logistic regression was used to identify independent risk factors for BSICs. Of 975 episodes of neonatal BSI, 101 (10.4%) BSICs occurred in 93 neonates with a median interval of 3 days (range, 0-17 days) after onset of BSI and included newly infectious focuses in 40 episodes (39.6%), major organ dysfunctions after septic shock in 36 episodes (35.6%), and neurological complications after meningitis or septic shock in 34 episodes (33.7%). All patients with BSICs encountered various morbidities, which subsequently resulted in in-hospital death in 30 (32.3%) neonates, critical discharge in 4 (4.3%), and persistent sequelae in 17 (18.3%). After multivariate logistic regression analysis, independent risk factors for BSICs included initial inappropriate antibiotics (odds ratio [OR], 5.54; 95% confidence interval [CI], 3.40-9.01), BSI with septic shock (OR, 5.75; 95% CI, 3.51-9.40), and BSI concurrent with meningitis (OR, 9.20; 95% CI, 4.33-19.56). It is worth noting that a percentage of neonates with BSI encountered subsequent sequelae or died of infections complications, which were significantly associated with initial inappropriate antibiotic therapy, septic shock, and the occurrence of meningitis. Further investigation is warranted to decrease the occurrence of BSICs due to their significant contribution toward final mortality.

Incidence and risk factors of urinary tract infection in very low birth weight infants.

OBJECTIVES: To describe the incidence and associated risk factors of urinary tract infection (UTI) in very low birth weight (VLBW) infants and to determine the value of diagnostic imaging studies after the first UTI episode before discharge from the neonatal intensive care unit (NICU). METHODS: VLBW infants born during 2003-2012 were reviewed for UTI. In a nested case-control study, potential risk factors of UTI were compared between infants with UTI (cases) versus birth weight and gestational age matched controls. Renal ultrasonography (USG) and voiding cystourethrography (VCUG) results were reviewed in cases. RESULTS: During the study period, 54.7% of urine culture specimens were collected by sterile methods. 3% (45/1,495) of VLBW infants met the study definition for UTI. UTI was diagnosed at mean postnatal age of 33.1±22.9 days. There was no significant difference in gender, ethnicity, antenatal steroid exposure, blood culture positive sepsis, ionotropic support, respiratory support and enteral feeding practices between cases and controls. Cases had a significantly higher cholestasis compared to controls (22% vs. 9% ; p = 0.03). However, cholestasis was not a significant predictor of UTI in the adjusted analysis [adjusted OR 2.38 (95% CI 0.84 to 6.80), p = 0.11]. Cases had higher central line days, parenteral nutrition days, total mechanical ventilation days, chronic lung disease, and length of stay compared to controls. Renal USG was abnormal in 37% and VCUG was abnormal in 17% of cases. CONCLUSIONS: The incidence of UTI in contemporary VLBW infants is relatively low compared to previous decades. Since no significant UTI predictors could be identified, urine culture by sterile methods is the only reliable way to exclude UTI. The majority of infants with UTI have normal renal anatomy. UTI in VLBW infants is associated with increased morbidity and length of stay.

Lactoferrin and neonatology - role in neonatal sepsis and necrotizing enterocolitis: present, past and future.

Neonatal sepsis and necrotizing enterocolitis (NEC) are two most important neonatal problems in nursery which constitute the bulk of neonatal mortality and morbidity. Inflammatory mediators secondary to sepsis and NEC increases morbidity, by affecting various system of body like lung, brain and eye, thus causing long term implications. Lactoferrin (LF) is a component of breast milk and multiple actions that includes antimicrobial, antiviral, anti-fungal and anti-cancer and various other actions. Few studies have been completed and a number of them are in progress for evaluation of efficacy and safety of LF in the prevention of neonatal sepsis and NEC in field of neonatology. In future, LF prophylaxis and therapy may have a significant impact in improving clinical outcomes of vulnerable preterm neonates. This review analyse the role of lactoferrin in prevention of neonatal sepsis and NEC, with emphasis on mechanism of action, recent studies and current studies going on around the globe.

The current and future roles of neonatal infection surveillance programmes in combating antimicrobial resistance.

Neonatal sepsis is an important cause of morbidity and mortality, particularly in premature or low birth weight babies. Hospital-acquired blood stream infections represent a significant and largely preventable cause of disease in this population. Neonatal units have been identified as a common site for the development and transmission of antimicrobial-resistant pathogens, a significant issue in modern medicine. Neonatal surveillance programmes collect prospective data on infection rates and may be used to optimise therapy, benchmark practice and develop quality improvement programmes. Despite this, the number of networks is relatively few and these are largely concentrated in resource-rich nations. Furthermore, surveillance definitions may vary between programmes impairing our ability to draw comparisons between them. Better harmonisation is required between networks to ensure that they achieve their potential as a valuable tool for benchmarking of hospital-acquired infection rates between units.

CRP levels in extremely low birth weight (ELBW) septic infants.

OBJECTIVE: Testing the validity of C-reactive protein (CRP) in extremely low birth weight (ELBW) infants. METHODS: During a five-year period, 483 infants with probable (36%) and definite sepsis (64%) were enrolled in the study. RESULTS: ELBW infants with definitive sepsis had CRP levels comparable with full-terms (p=0.992). However, the highest (hs) values were observed in infants >2500 g, 24 h after the septic work up whereas in those with birth weight (BW) <1000 g after 48 h. Highest CRP levels of infants with early sepsis were similar to those of the late onset ones (p=0.825). The causative microorganism had a strong influence on CRP values, as Gram negative germs produced significantly higher CRP levels in comparison to infants with Gram positive sepsis. CONCLUSIONS: Highest CRP values in <1000 g infants increase in levels comparable to full terms, but with a 24-h delay.

Neonatal sepsis is mediated by maternal fever in labour epidural analgesia.

Women delivering with EA (EA group) were matched on parity with 453 women with deliveries without EA (non-EA group). Significantly more neonates born in the EA-group had fever ≥ 38.0°C (11.6% vs 1.8%, p < 0.001) at birth. The overall incidence of neonatal sepsis, based on clinical symptoms and defined as proven (by a positive blood culture) or suspected (no positive blood culture), was significantly higher in the EA group (6.0% vs 2.2%; p = 0.002), but the incidence of proven neonatal sepsis alone was not (0.4% vs 0%; p = 0.250). EA turned out to be an independent risk factor for neonatal sepsis (adjusted OR 2.43, 95% CI 1.15-5.13; p = 0.020). However, in the EA group as well as the non-EA group, the incidence of neonatal sepsis was significantly higher in mothers with intrapartum fever compared with afebrile mothers (11.0% vs 2.9% in the EA group; p = 0.004; 8.2% vs 1.3% in the non-EA group; p = 0.006). Therefore we conclude, that the positive association between neonatal sepsis and labour EA is possibly mediated by maternal intrapartum fever.

Comparison of hematologic indices and markers of infection in umbilical cord and neonatal blood.

OBJECTIVE: Evaluation of a neonate for suspected early neonatal sepsis routinely includes blood tests such as complete blood count, C-reactive protein (CRP) and culture. In order to obviate the need for venepuncture, we prospectively compared these tests in paired samples from umbilical cord and peripheral venous blood drawn during the first hours after birth in both preterm and term infants. METHODS: Paired blood samples were studied from asymptomatic neonates with risk factors for early sepsis. Data were collected on maternal and neonatal factors that may have influenced the correlation between the tests. RESULTS: Three hundred fifty pairs of samples were studied. Significant correlation between umbilical cord and peripheral venous samples was found for white blood cell (WBC; r = 0.683) and platelets (PLT) (r = 0.54). Correlation for hemoglobin was lower (r = 0.36). No cases of early neonatal sepsis were detected. However, contamination rates were 12% in umbilical cord blood and 2.5% in peripheral venous blood cultures. WBC rose after birth and the 90th percentile rose from 22 500 in umbilical cord blood to 29 700 in peripheral blood. CONCLUSIONS: Screening for sepsis with umbilical cord CBC may be useful provided normal ranges are adjusted accordingly.

The use of continuous positive airway pressure in preterm babies with respiratory distress syndrome: a report from Baghdad, Iraq.

OBJECTIVES: To study maternal and neonatal risk factors related to outcome of preterm babies with respiratory distress syndrome (RDS) on Continuous Positive Airway Pressure (CPAP) in a tertiary Iraqi NICU. METHODS: A prospective case study carried out from January 5, 2011 to January 5, 2012, on 70 preterm neonates with RDS who were started on CPAP. Maternal and infant variables of preterm babies with successful or failed CPAP therapy were compared. RESULTS: Seventy neonates, 44 (63%) males and 26 (37%) females were included. Mean (SD) gestation was 32.8 (2.8) weeks and mean (SD) birth weight was 1860 (656) g. Thirty-seven (52.9%) babies failed CPAP, of them 29 (78.3%) were started on mechanical ventilation. The variables associated with failure of CPAP were: Birth weight ≤1500 g, gestational age ≤30 weeks, white out on the chest X-ray, FiO2 ≥50% at 20 min of CPAP, PEEP ≥5.5 cm H2O. Mortality rates were 94.6% in CPAP failures versus 5.4% in CPAP successes (p = 0.001). In infants surviving till discharge, duration of hospital stay was longer in babies who were CPAP successes (9.6 ± 3.7 versus 3.0 ± 2.7 days, p = 0.001). CONCLUSIONS: Gestational age, birth weight, whiteout chest X-ray, and FiO2 are important predictive values for success of CPAP therapy. A larger prospective multicenter controlled trial is needed to determine the benefits and risks of CPAP and predictors of its failure in our setting. Our results may be useful for others practicing in similar settings as us.

Serum ischemia-modified albumin levels at diagnosis and during treatment of late-onset neonatal sepsis.

Sepsis is one of the most common infectious conditions in the neonatal period, and continues as a major source of morbidity and mortality. The aim of this study is to determine serum ischemia-modified albumin (IMA) levels in late-onset neonatal sepsis at the time of diagnosis and after therapy, and to show the meaningful on the follow-up. Also, it is aimed to compare serum IMA levels with serum C-reactive protein (CRP), procalcitonin (PCT) levels and white blood cell count. The study was performed on 33 premature babies with sepsis and 21 healthy premature controls at 7-28 days of age. In the sepsis group, biochemical parameters and blood culture samples were obtained from the blood at the onset and on the fifth day of treatment for each patient. Serum IMA, CRP, PCT and white blood cell count were significantly higher in the sepsis group before treatment when compared with the control group. In addition, the levels of IMA were positively correlated with white blood cell count, CRP and PCT in the sepsis group before treatment. In conclusion, serum IMA levels may be useful in late-onset neonatal sepsis at the time of diagnosis and after therapy. As far as we know this is the first report about the assesment of illness diagnosis and after therapy using serum IMA levels, and further studies are needed to confirm our results in larger groups of patients.

The specific characteristics of DIC syndrome vary with different clinical settings in the newborn.

Abstract Two hundred fourteen newborns with serious perinatal pathology (posthypoxic syndrome, sepsis, surgical intervention, etc.) were examined in progress, according to 27 parameters including coagulative, trombocitic, anti-coagulative and fibrinolitic parts of hemostasis system. It was proved, that neonatal disseminated intravascular coagulation (DIC) syndrome had different hemostasiological patterns, which were connected with the genesis: sepsis, surgical intervention or posthypoxic syndrome. Precise periods of DIC syndrome are not always presented in newborns. DIC syndrome with neonatal sepsis has two different patterns (overcompensated and decompensated). The manifestation of trombo-hemorrhagic disorders and their characteristics depend on the genesis of DIC syndrome (e.g. an infection process and hyperbilirubinemia can provide the appearance of hemorrhagic syndrome).

[Epidemiology of infections in very low birth weight infants. Polish Neonatology Network research]. / Epidemiologia Zakazen Noworodkówz Bardzo Mala Masa Urodzeniowa.badania Polskiej Sieci Neonatologicznej.

AIM OF STUDY: 1. prospective record of infections; 2. prevention of nosocomial infections by providing current data about infections, which are significant for making therapeutic decisions. MATERIAL AND METHODS: Recorded infections: early-onset sepsis (congenital), late-onset sepsis (acquired in hospital), necrotising enterocolitis (NEC), pneumonia. Infections were diagnosed and qualified on the basis of definitions of infections based on the National Nosocomial Infections Surveillance (NNIS) criteria, developed by CDC, USA, including modifications of German Neo-KISS programme. Infection control was realised as a part of common research project of "Polish Neonatology Network", appointed by the decision of the Minister of Science and Higher Education no. 669/E-215/BWSN- 0180/2008 dated 20.05.2008 r. The study was conducted by 6 Polish neonatology units, Microbiology Chair of Jagiellonian University Collegium Medicum and Institute of Theoretical and Applied Computer Science. Infants with birth weight lower than 1500 g were qualified for the study. RESULTS: Between 1.01.2009 and 31.12.2009, 910 patients were registered, i.e. 19.1% of VLBW infants born in that period. The conducted analysis showed significant differences between centres in gestational age, birth weight, hospitalisation, use of invasive procedures, antibiotics and parenteral feeding. Cumulative morbidity rate was 68.5% total. Blood infection (sepsis) was the most commonly observed type of infection: 268 cases - 43.1% of all recorded forms of infection. Pneumonia was diagnosed in 242 cases, 38.8% total. NEC constituted 12.7% studied infections (79 cases). Apart from NEC, the risk of other forms of infection differed between centres. Dominant etiologic factor of all infections were Gram-positive cocci, which constituted 565 isolated microorganisms. Among them coagulase-negative staphylococci (CNS) were the most common (41.7%), while Staphylococcus aureus was fourth most frequent etiologic factor of infections (6.3% total). CONCLUSIONS: 1. Introduction of unified definition and criteria for diagnosing infections and the use of morbidity rates enables comparative analysis of epidemiology of infections in neonatal intensive care units. 2. Due to significant differences observed between prophylactic and therapeutic procedures in various units, it is essential to propose Polish recommendations regarding control over etiology of infections and use of invasive procedures, such as intravenous catheters and ventilation. 3. It is essential to undertake action leading to fully rational antibiotic therapy, because overuse of antibiotics leads to bacterial resistance and increases incidence of infections.

In search of biomarkers for diagnosing and managing neonatal sepsis: the role of angiopoietins.

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are antagonistic ligands that bind to the extracellular domain of the Tie-2 receptor, which is almost exclusively expressed by endothelial cells. Angiopoietins can directly stimulate both endothelial cells and neutrophils for an overall proinflammatory and proangiogenic response. An increasing number of experimental and clinical studies gave evidence that in the course of sepsis the serum levels of Ang-1 and Ang-2 as well as their ratio significantly differ from those in healthy subjects, in non-septic hospitalized patients, and in patients with non-infectious systemic inflammatory response syndrome (SIRS) or critical illness. Further evidences have demonstrated that the magnitude of Ang-2 dysregulation correlates with the severity of sepsis and the mortality rate. Since the onset of neonatal sepsis is often subtle and the diagnosis occurs later, Ang-1 and Ang-2 appear to be very promising biomarkers for improving the diagnosis and the management of septic newborns.

Congenital tuberculosis because of misdiagnosed maternal pulmonary tuberculosis during pregnancy.

We report the death of an infant due to severe sepsis caused by congenital tuberculosis following treatment with antituberculous drugs and antibiotics, who was born to a mother with misdiagnosed symptomatic pulmonary tuberculosis during pregnancy. Therefore, pregnant women with chronic cough and constitutional symptoms must be examined for pulmonary tuberculosis, particularly in tuberculosis endemic areas.