Morbidity In Newborn Infants Research Articles

Validation of Hematological Markers in Early Onset Neonatal Sepsis.

BackgroundNeonatal sepsis is considered a ubiquitous worldwide cause of mortality and morbidity in newborn infants. The incidence is 10-50 per 1000 live births. Neutrophil to lymphocyte ratio (NLR) is an easily accessible and cost-effective hematological marker for prompt diagnosis of neonatal sepsis.Aim and objectivesThe purpose of this study was to analyze the clinical significance of NLR in neonates clinically diagnosed with sepsis and its impact on the management.MethodsThis retrospective study was conducted on 265 neonates diagnosed with sepsis and compared with 341 healthy controls. The statistical analysis was performed by using the Student's t-test to compare the variables.ResultMedian NLR levels were significantly higher in patients than in controls. NLR had a modest power of predicting neonatal sepsis, as suggested by an area under a curve of 0.569.ConclusionNLR is an important predictor of neonatal sepsis. There is a significant modest positive correlation between NLR and sepsis.

INTRAVENTRICULAR HEMORRHAGES OF NEWBORNS, CAUSES, COMPLICATIONS AND PREVENTION METHODS

Introduction. Intraventricular hemorrhages (IVH) occupy a prominent place in the structure of perinatal lesions of the nervous system among newborns, especially premature birth. Knowledge of risk factors and pathogenic mechanisms of development of IVH, timely prophylaxis, early diagnostic and treatment of complications will significantly reduce infant mortality and severe distant neurological effects.Objective. Conduct a retrospective analysis of medical records among infants with IVH to determine the main risk factors, complications for improving of medical care to this group of patients.Materials and methods. In the basis of this work is the analysis of 148 stories of desease among children, who had IVH of varying degrees according neurosonography and computed tomography of the brain and were treated at Chernigiv Oblast Children’s Hospital during 2015-2018.Results. The article presents the results of the analysis of the morbidity of newborn infants with intraventricular hemorrhages for the period of 2015-2018on the basis of the Chernigiv Oblast Children's Hospital. The main risk factors were identified. At the forefront are׃ asphyxia in labor gestational age(premature infants were 72.3 %), mechanical ventilation with severe parameters, mother's infection, acute hypoxia in labor, thrombocytopenia. Reliable connection between the term of gestation and the frequency of occurrence of IVH is proved. Among all children with IVH, the majority werechildren with gestational age range 29-32 weeks, one third of which requiredhard-line mechanical ventilation, but a significantly lower percentage of surfactant versus group 22-28 weeks gestational age. That testifies to insufficient use of surfactant with preventive and curative purpose in this group. Most often, there are IVH of the I – II degrees. And the first stage is the majority of full-term children, the IVH of IV degree was noted only in children with gestational age up to 32 weeks. Children of this group have a rather long period of stay in the intensive care units. Separately considered are their complications and basic methods oftreatment. Posthemorrhagic non-occlusal hydrocephalus was observedpredominantly among children with gestational age 22-28 weeks and termed infants 37-42 weeks, who suffered IVH III (52.6 %), nobody needed surgical intervention and mortality amounted to 10.5 %. Occlusion hydrocephalus is the prevailing majority of children with gestational age of 29-32 weeks (57.1 %), after IVH III (71.4 %), all of them had asphyxia at birth, meningitis and ventriculitis (71.4 %). These children required surgical treatment and a high mortality rate was observed (57.2 %).Conclusions. Looking at the long, complex, costly treatment, high mortality and the frequency of disability in this group of children, the main efforts should be directed towards prevention and timely surgical intervention for complications.

Antibiotics at the time of removal of central venous catheter to reduce morbidity and mortality in newborn infants.

Late-onset sepsis is associated with increased rates of mortality and morbidity in newborn infants, in addition to poorer long-term developmental outcomes and increased length of stay and hospital costs. Central line-associated blood stream infection (CLABSI) is the most common cause of late-onset sepsis in hospitalised infants, and prevention of CLABSI is a key objective in neonatal care. Increased frequency of CLABSI around the time of removal of central venous catheters (CVCs) has been reported, and use of antibiotics at the time of removal may reduce the incidence and impact of late-onset sepsis in vulnerable newborn infants. To determine the efficacy and safety of giving antibiotics at the time of removal of a central venous catheter (CVC) for reduction of morbidity and mortality in newborn infants, in particular effects on late-onset sepsis. We used the standard search strategy of the Cochrane Neonatal Review Group without language restriction to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 3), MEDLINE via PubMed (1966 to 6 April 2017), Embase (1980 to 6 April 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 6 April 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised, quasi-randomised, and cluster-randomised trials considering use of any antibiotic or combination of antibiotics at the time of CVC removal in newborn infants compared with placebo, no antibiotics, or another antibiotic or combination of antibiotics. We extracted data using standard methods of the Cochrane Neonatal Review Group. Two review authors independently selected, assessed the quality of, and extracted data from the included study. Only one randomised controlled trial was eligible for inclusion in this analysis. Forty-four of a total of 88 infants received two doses of cephazolin at the time of removal of CVC compared with no antibiotics at the time of removal of CVC in the control group. No infant in the intervention group developed late-onset sepsis after CVC removal compared with five of 44 (11%) in the control group (risk ratio (RR) 0.09, 95% confidence interval (CI) 0.01 to 1.60). Cephazolin given at the time of removal of CVC did not statistically significantly alter late-onset sepsis rates and led to no significant differences in any of the prespecified outcomes. Review authors judged the study to be of low quality because of high risk of bias and imprecision. Randomised controlled trials have provided inadequate evidence for assessment of the efficacy or safety of antibiotics given at the time of CVC removal. The single identified trial was underpowered to address this question. Future research should be directed towards targeting use of antibiotics upon removal of CVC for those at greatest risk of complications from CVC removal-related CLABSI. Researchers should include safety data such as impact upon antibiotic use and resistance patterns. This investigation would best occur as part of a bundle of quality improvement care interventions provided by neonatal networks.

Non-invasive respiratory support in newborn infants

Abstract Respiratory failure is the most common morbidity in newborn infants, often requiring respiratory support. Traditionally, invasive mechanical ventilation was the preferred method of neonatologists. Over the last two decades, various forms of non-invasive ventilation have become popular as modes of respiratory support in newborn infants, especially if they are born preterm. These modes differ from mechanical ventilation in not needing an endo-tracheal tube, and are commonly delivered by bi-nasal prongs. We review the common modes of non-invasive respiratory support in newborn infants, including their proposed mechanisms of action and the evidence supporting their use.

Early planned removal of umbilical venous catheters to prevent infection in newborn infants.

Lengthy duration of use may be a risk factor for umbilical venous catheter-associated bloodstream infection in newborn infants. Early planned removal of umbilical venous catheters (UVCs) is recommended to reduce the incidence of infection and associated morbidity and mortality. To compare the effectiveness of early planned removal of UVCs (up to two weeks after insertion) versus an expectant approach or a longer fixed duration in preventing bloodstream infection and other complications in newborn infants.To perform subgroup analyses by gestational age at birth and prespecified planned duration of UVC placement (see "Subgroup analysis and investigation of heterogeneity"). We used the standard Cochrane Neonatal search strategy including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 4), Ovid MEDLINE, Embase, and the Maternity & Infant Care Database (until May 2017), as well as conference proceedings and previous reviews. Randomised and quasi-randomised controlled trials that compared effects of early planned removal of UVCs (up to two weeks after insertion) versus an expectant approach or a longer fixed duration in preventing bloodstream infection and other complications in newborn infants. Two review authors assessed trial eligibility and risk of bias and independently undertook data extraction. We analysed treatment effects and reported risk ratio (RR) and risk difference (RD) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We planned to use a fixed-effect model in meta-analyses and to explore potential causes of heterogeneity in sensitivity analyses. We assessed the quality of evidence for the main comparison at the outcome level using GRADE methods. We found one eligible trial. Participants were 210 newborn infants with birth weight less than 1251 grams. The trial was unblinded but otherwise of good methodological quality. This trial compared removal of an umbilical venous catheter within 10 days after insertion (and replacement with a peripheral cannula or a percutaneously inserted central catheter as required) versus expectant management (UVC in place up to 28 days). More infants in the early planned removal group than in the expectant management group (83 vs 33) required percutaneous insertion of a central catheter (PICC). Trial results showed no difference in the incidence of catheter-related bloodstream infection (RR 0.65, 95% CI 0.35 to 1.22), in hospital mortality (RR 1.12, 95% CI 0.42 to 2.98), in catheter-associated thrombus necessitating removal (RR 0.33, 95% confidence interval 0.01 to 7.94), or in other morbidity. GRADE assessment indicated that the quality of evidence was "low" at outcome level principally as the result of imprecision and risk of surveillance bias due to lack of blinding in the included trial. Currently available trial data are insufficient to show whether early planned removal of umbilical venous catheters reduces risk of infection, mortality, or other morbidity in newborn infants. A large, simple, and pragmatic randomised controlled trial is needed to resolve this ongoing uncertainty.

Antimicrobial-impregnated central venous catheters for prevention of catheter-related bloodstream infection in newborn infants.

Central venous catheter-related bloodstream infection is an important cause of mortality and morbidity in newborn infants cared for in neonatal units. Potential strategies to prevent these infections include the use of central venous catheters impregnated with antimicrobial agents. To determine the effect of antimicrobial-impregnated central venous catheters in preventing catheter-related bloodstream infection in newborn infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 8), MEDLINE (1966 to September 2015), EMBASE (1980 to September 2015), CINAHL (1982 to September 2015), conference proceedings and previous reviews. Randomised or quasi-randomised controlled trials comparing central venous catheters impregnated or coated with any antibiotic or antiseptic versus central venous catheters without antibiotic or antiseptic coating or impregnation in newborn infants. We extracted data using the standard methods of the Cochrane Neonatal Group, with independent evaluation of risk of bias and data extraction by two review authors. We found only one small trial (N = 98). This trial found that silver zeolite-impregnated umbilical venous catheters reduced the incidence of bloodstream infection in very preterm infants (risk ratio 0.11, 95% confidence interval 0.01 to 0.87; risk difference -0.17, 95% CI -0.30 to -0.04; number needed to treat for benefit 6, 95% CI 3 to 25]. Although the data from one small trial indicates that antimicrobial-impregnated central venous catheters might prevent catheter-related bloodstream infection in newborn infants, the available evidence is insufficient to guide clinical practice. A large, simple and pragmatic randomised controlled trial is needed to resolve on-going uncertainty.

Standardised formal resuscitation training programmes for reducing mortality and morbidity in newborn infants.

Approximately 10% of all newborns require resuscitation at birth. Training healthcare providers in standardised formal neonatal resuscitation training (SFNRT) programmes may improve neonatal outcomes. Substantial healthcare resources are expended on SFNRT. To determine whether SFNRT programmes reduce neonatal mortality and morbidity, improve acquisition and retention of knowledge and skills, or change teamwork and resuscitation behaviour. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PREMEDLINE, EMBASE, CINAHL, Web of Science and the Oxford Database of Perinatal Trials, ongoing trials and conference proceedings in April 2014 and updated in March 2015. Randomised or quasi-randomised trials including cluster-randomised trials, comparing a SFNRT with no SFNRT, additions to SFNRT or types of SFNRT, and reporting at least one of our specified outcomes. Two authors extracted data independently and performed statistical analyses including typical risk ratio (RR), risk difference (RD), mean difference (MD), and number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH) (all with 95% confidence intervals (CI)). We analysed cluster-randomised trials using the generic inverse variance and the approximate analysis methods. We identified two community-based and three manikin-based trials that assessed the effect of SFNRT compared with no SFNRT. Very low quality evidence from one study suggested improvement in acquisition of knowledge (RR 5.96, 95% CI 3.60 to 9.87) and skills (RR 170, 95% CI 10.8 to 2711) and retention of knowledge (RR 3.60, 95% CI 2.43 to 5.35) and the other study suggested improvement in resuscitation and behavioural scores.We identified three community-based cluster-randomised trials in developing countries comparing SFNRT with basic resuscitation training (Early Newborn Care). In this setting, there was moderate quality evidence that SFNRT decreased early neonatal mortality (typical RR 0.88, 95% CI 0.78 to 1.00; 3 studies, 66,162 neonates) and when analysed by the approximate analysis method (typical RR 0.85, 95% CI 0.75 to 0.96; RD -0.0044, 95% CI -0.0082 to -0.0006; NNTB 227, 95% CI 122 to 1667). Low quality evidence from one trial showed that SFNRT may decrease 28-day mortality (typical RR 0.55, 95% CI 0.33 to 0.91) but the effect on late neonatal mortality was more uncertain (typical RR 0.47, 95% CI 0.20 to 1.11). None of our a priori defined neonatal morbidities were reported. We did not identify any randomised studies in the developed world.We identified two trials that compared SFNRT with team training to SFNRT. Teamwork training of physician trainees with simulation may increase any teamwork behaviour (assessed by frequency) (MD 2.41, 95% CI 1.72 to 3.11) and decrease resuscitation duration (MD -149.54, 95% CI -214.73 to -84.34) but may lead to little or no difference in Neonatal Resuscitation Program (NRP) scores (MD 1.40, 95% CI -2.02 to 4.82; 98 participants, low quality evidence).We identified two trials that compared SFNRT with booster courses to SFNRT. It is uncertain whether booster courses improve retention of resuscitation knowledge (84 participants, very low quality evidence) but may improve procedural and behavioural skills (40 participants, very low quality evidence).We identified two trials on decision support tools, one on a cognitive aid that did not change resuscitation scores and the other on an electronic decision support tool that improved the frequency of correct decision making on positive pressure ventilation, cardiac compressions and frequency of fraction of inspired oxygen (FiO2) adjustments (97 participants, very low quality evidence). SFNRT compared to basic newborn care or basic newborn resuscitation, in developing countries, results in a reduction of early neonatal and 28-day mortality. Randomised trials of SFNRT should report on neonatal morbidity including hypoxic ischaemic encephalopathy and neurodevelopmental outcomes. Innovative educational methods that enhance knowledge and skills and teamwork behaviour should be evaluated.

Two novel genetic variants in the mineralocorticoid receptor gene associated with spontaneous preterm birth.

BackgroundPreterm birth is the leading cause of mortality and morbidity in newborn infants. Its etiology is multifactorial with genes and environmental factors, including chronic maternal stress, contributing to its risk. Our objective was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in the stress response are associated with spontaneous preterm birth using a candidate gene approach.MethodsA total of 210 cases (singleton spontaneous preterm birth at <37 weeks) and 412 controls (singleton term birth at 38–42 weeks without a history of preterm birth) were studied. High quality maternal DNA was available from saliva samples of 190 cases and 369 controls and compared. Sociodemographic and medical data were collected. Sixteen SNPs, either tag SNPs located in key genes involved in the stress response identified in the Preterm Birth Genome Project database or SNPs found to be associated with adverse mental health outcomes in the published literature, were selected for genotyping and sequencing. SNPs were genotyped using Taqman® SNP genotyping assays. Univariate and multivariate logistic regression were performed.ResultsMultivariate analysis showed that two SNPs located in the mineralocorticoid receptor gene were significantly associated with spontaneous preterm birth: rs17484063 (OR 0.50, p = 0.038) and rs2883929 (OR 0.49, p = 0.017), regardless of maternal age, smoking, alcohol use, educational status, and history of spontaneous miscarriage.ConclusionThis report demonstrates an association between mineralocorticoid receptor gene polymorphisms, rs17484063 and rs2883929, and preterm birth, supporting a role for genetics in the association between chronic maternal stress and preterm birth. Potentially, this information may be used to predicting the risk of having a preterm delivery.

Repositioning of Memantine as a Potential Novel Therapeutic Agent against Meningitic E. coli-Induced Pathogenicities through Disease-Associated Alpha7 Cholinergic Pathway and RNA Sequencing-Based Transcriptome Analysis of Host Inflammatory Responses.

Neonatal sepsis and meningitis (NSM) remains a leading cause worldwide of mortality and morbidity in newborn infants despite the availability of antibiotics over the last several decades. E. coli is the most common gram-negative pathogen causing NSM. Our previous studies show that α7 nicotinic receptor (α7 nAChR), an essential regulator of inflammation, plays a detrimental role in the host defense against NSM. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat this disease. Using the in vitro/in vivo models of the blood-brain barrier (BBB) and RNA-seq, we undertook a drug repositioning study to identify unknown antimicrobial activities for known drugs. We have demonstrated for the first time that memantine (MEM), a FDA-approved drug for treatment of Alzheimer’s disease, could very efficiently block E. coli-caused bacteremia and meningitis in a mouse model of NSM in a manner dependent on α7 nAChR. MEM was able to synergistically enhance the antibacterial activity of ampicillin in HBMEC infected with E. coli K1 (E44) and in neonatal mice with E44-caused bacteremia and meningitis. Differential gene expression analysis of RNA-Seq data from mouse BMEC infected with E. coli K1 showed that several E44-increased inflammatory factors, including IL33, IL18rap, MMP10 and Irs1, were significantly reduced by MEM compared to the infected cells without drug treatment. MEM could also significantly up-regulate anti-inflammatory factors, including Tnfaip3, CISH, Ptgds and Zfp36. Most interestingly, these factors may positively and negatively contribute to regulation of NF-κB, which is a hallmark feature of bacterial meningitis. Furthermore, we have demonstrated that circulating BMEC (cBMEC) are the potential novel biomarkers for NSM. MEM could significantly reduce E44-increased blood level of cBMEC in mice. Taken together, our data suggest that memantine can efficiently block host inflammatory responses to bacterial infection through modulation of both inflammatory and anti-inflammatory pathways.

Cardiac Troponin Levels in Neonates Who Require ECMO for Noncardiac Indications Are Elevated in Nonsurvivors.

The aim of the study is to determine the utility of cardiac troponin (cTnI) as a marker of mortality and morbidity in newborn infants who require extracorporeal membrane oxygenation (ECMO). Retrospective medical chart analysis of term or near-term newborn infants treated with ECMO from 2002 to 2012 at a single Level III neonatal intensive care unit. Data analyzed included serial serum cTnI measurements, clinical and demographic characteristics, pre-ECMO laboratory values, and ECMO laboratory values and outcomes. Survival (27/46) was significantly related to birth weight (3,413.9 ± 662.3 vs. 2,667.7 ± 478.3 g, p < 0.001), outborn status (22/30 vs. 5/13, p = 0.0021), and the absence of a congenital diaphragmatic hernia (22/30 vs. 5/18, p = 0.0021). Mean peak cTnI did not differ between survivors and nonsurvivors but when peak cTnI was < 2.8 ng/mL, survival was 64% compared with 22% when it was > 2.8 ng/mL (p = 0.0224; odds ratio = 0.160, 95% confidence interval = 0.0292-0.8778). By multivariate analysis, peak cTnI > 2.1 was a significant risk factor for nonsurvival, p = 0.0497. The area under the curve of a receiver-operator analysis using peak cTnI > 2.1, birth weight, and birthplace was 0.89, p < 0.001. cTnI is an independent biomarker for poor outcome in neonates who receive ECMO therapy for noncardiac generations.

Creation and Validation of the Singapore Birth Nomograms for Birth Weight, Length and Head Circumference Based on a 12-year Birth Cohort

Both gestation and birth weight have significant impact on mortality and morbidity in newborn infants. Nomograms at birth allow classification of infants into small for gestational age (SGA) and large for gestational age (LGA) categories, for risk stratification and more intensive monitoring. To date, the growth charts for preterm newborn infants in Singapore are based on the Fenton growth charts, which are constructed based on combining data from various Western growth cohorts. Hence, we aim to create Singapore nomograms for birth weight, length and head circumference at birth, which would reflect the norms and challenges faced by local infants. Growth parameters of all babies born or admitted to our unit from 2001 to 2012 were retrieved. Following exclusion of outliers, nomograms for 3 percentiles of 10th, 50th, and 90th were generated for the gestational age (GA) ranges of 25 to 42 weeks using quantile regression (QR) combined with the use of restricted cubic splines. Various polynomial models (second to third degrees) were investigated for suitability of fit. The optimum QR model was found to be a third degree polynomial with a single knotted cubic spline in the mid-point of the GA range, at 33.5 weeks. Check for goodness of fit was done by visual inspection first. Next, check was performed to ensure the correct proportion: 10% of all cases fall above the upper 90th percentile and 10% fall below the lower 10th percentile. Furthermore, an alternative formula-based method of nomogram construction, using mean, standard deviation (SD) and assumption of normality at each gestational age, was used for counterchecking. A total of 13,403 newborns were included in the analysis. The new infant-foetal growth charts with respect to birth weight, heel-crown length and occipitofrontal circumference from 25 to 42 weeks gestations with the 10th, 50th and 90th were presented. Nomograms for birth weight, length and head circumference at birth had significant impact on neonatal practice and validation of the Singapore birth nomograms against Fenton growth charts showed better sensitivity and comparable specificity, positive and negative predictive values.

Decreased pulmonary c-Cbl expression and tyrosine phosphorylation in the nitrofen-induced rat model of congenital diaphragmatic hernia

The high morbidity of newborn infants with congenital diaphragmatic hernia (CDH) is attributed to pulmonary hypoplasia (PH), which is characterized by a failure of alveolar development. The nitrofen-induced CDH model has been widely used to investigate the pathogenesis of PH in CDH. It has previously been shown that the fibroblast growth factor receptor (FGFR) pathway, which is essential for a proper lung development, is disrupted during late gestation of nitrofen-induced CDH. Casitas B-lineage lymphoma (c-Cbl) proteins are known regulators of signal transduction through FGFRs, indicating their important role during alveolarization in developing lungs. Furthermore, it has been demonstrated that tyrosine phosphorylation of c-Cbl proteins has a pivotal role for their physiological function and activity during fetal lung development. We designed this study to test the hypothesis that pulmonary c-Cbl expression and tyrosine phosphorylation status are decreased in the nitrofen-induced CDH model. Timed-pregnant rats received either 100mg nitrofen or vehicle on gestation day 9 (D9). Fetuses were harvested on D18 and D21, and lungs were divided into two groups: control and hypoplastic lungs with CDH (CDH(+)) (n=10 at each time-point, respectively). Pulmonary gene expression levels of c-Cbl were analyzed by quantitative real-time polymerase chain reaction. Western blotting combined with densitometry analysis was used for semi-quantification of protein levels of pulmonary c-Cbl and tyrosine phosphorylation status. Confocal-immunofluorescence staining was performed to evaluate c-Cbl protein expression and distribution. Relative mRNA expression levels of pulmonary c-Cbl were significantly decreased in CDH(+) on D18 and D21 compared to controls. Western blotting showed markedly decreased protein levels of pulmonary c-Cbl and tyrosine phosphorylation status in CDH(+) on D18 and D21. Confocal-immunofluorescence analysis confirmed decreased c-Cbl expression in CDH(+) on D18 and D21 mainly in the distal alveolar epithelium compared to controls. Decreased pulmonary c-Cbl gene and protein expression accompanied by a decreased tyrosine phosphorylation status during the late stages of fetal lung development may result in reduced c-Cbl activity, and thus interfere with the FGFR-mediated alveolarization in the nitrofen-induced CDH model.

200 Circulating Pro-Endothelin-1 (CT-proET-1) and Pulmonary Morbidity in Newborn Infants

Background and aimsPlasma concentrations of endothelin-1 (ET-1), a potent pulmonary vasoconstrictor with a short serum half-life, can be estimated by measuring its stable by-product, C-terminal pro-Endothelin-1 (CT-proET-1). To investigate the...

Allopurinol for preventing mortality and morbidity in newborn infants with hypoxic-ischaemic encephalopathy.

Delayed neuronal death following a perinatal hypoxic insult is due partly to xanthine oxidase-mediated production of cytotoxic free radicals. Evidence exists that allopurinol, a xanthine-oxidase inhibitor, reduces delayed cell death in experimental models of perinatal asphyxia and in people with organ reperfusion injury. To determine the effect of allopurinol on mortality and morbidity in newborn infants with hypoxic-ischaemic encephalopathy. We used the standard search strategy of the Cochrane Neonatal Group. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012, Issue 1), MEDLINE (1966 to March 2012), EMBASE (1980 to March 2012), CINAHL (1982 to March 2012), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials that compared allopurinol administration versus placebo or no drug in newborn infants with hypoxic-ischaemic encephalopathy. We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors. We included three trials in which a total of 114 infants participated. In one trial, participants were exclusively infants with severe encephalopathy. The other trials also included infants with mild and moderately severe encephalopathy. These studies were generally of good methodological quality, but were too small to exclude clinically important effects of allopurinol on mortality and morbidity. Meta-analysis did not reveal a statistically significant difference in the risk of death (typical risk ratio 0.88; 95% confidence interval (95% CI) 0.56 to 1.38; risk difference -0.04; 95% CI -0.18 to 0.10) or a composite of death or severe neurodevelopmental disability (typical risk ratio 0.78; 95% CI 0.56 to 1.08; risk difference -0.14; 95% CI -0.31 to 0.04). The available data are not sufficient to determine whether allopurinol has clinically important benefits for newborn infants with hypoxic-ischaemic encephalopathy. Much larger trials are needed. Such trials could assess allopurinol as an adjunct to therapeutic hypothermia in infants with moderate and severe encephalopathy and should be designed to exclude important effects on mortality and adverse long-term neurodevelopmental outcomes.

Antifungal therapy for newborn infants with invasive fungal infection

A variety of antifungal drugs, drug preparations and drug combinations are available to treat newborn infants with suspected or confirmed invasive fungal infection. There is a need to assess their relative merits. To assess the effect of treatment with different antifungal drugs, drug preparations or drug combinations on mortality and morbidity in newborn infants with suspected or confirmed invasive fungal infection. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2012, Issue 2), MEDLINE, EMBASE, CINAHL (to March 2012), conference proceedings and previous reviews. Randomised and quasi-randomised control trials comparing one antifungal agent or combination of agents with another in newborn infants with suspected or confirmed invasive fungal infection. We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and synthesis of data using risk ratio and risk difference. We identified only one small trial in which 24 newborn infants participated. This trial compared the use of fluconazole versus amphotericin B (plus 5-fluorocytosine if fungal meningitis present). The trial did not detect a statistically significant effect on mortality (risk ratio 0.73; 95% confidence interval 0.26 to 2.05). There are insufficient data to inform practice. Large randomised controlled trials are required to compare antifungal drugs, drug preparations or drug combinations for treating newborn infants with invasive fungal infection.

Respiratory function monitoring to reduce mortality and morbidity in newborn infants receiving resuscitation

Respiratory function monitoring to reduce mortality and morbidity in newborn infants receiving resuscitation

Respiratory function monitoring to reduce mortality and morbidity in newborn infants receiving resuscitation

A respiratory function monitor is routinely used in neonatal intensive care units to continuously measure and display airway pressures, tidal volume and leak during ventilation. During positive pressure ventilation in the delivery room, clinical signs are used to monitor the effectiveness of ventilation. The additional use of a respiratory function monitor during positive pressure ventilation in the delivery room might help to improve the effectiveness of ventilation. To determine whether the use of a respiratory function monitor in addition to clinical assessment compared to clinical assessment alone in newborn infants resuscitated with positive pressure ventilation reduces mortality and morbidity. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2010), MEDLINE (January 1996 to March 2010), EMBASE (January 1980 to March 2010) and CINAHL (January 1982 to March 2010). Clinical trials registers and the abstracts of the Society for Pediatric Research and the European Society for Pediatric Research were searched from 2004 to 2009. No language restrictions were applied. We planned to include randomised and quasi-randomised controlled trials and cluster trials that compared the use of a respiratory function monitor in addition to clinical assessment, compared to clinical assessment alone, in newborn infants resuscitated with positive pressure ventilation. Two review authors independently evaluated the search results against the selection criteria. Data extraction and risk of bias assessment were not performed because there were no studies that met our inclusion criteria. No studies were found meeting the criteria for inclusion in this review There is insufficient evidence to determine the efficacy and safety of a respiratory function monitor in addition to clinical assessment during positive pressure ventilation at neonatal resuscitation. Randomised clinical trials comparing positive pressure ventilation with and without a respiratory function monitor in addition to clinical assessment at neonatal resuscitation are warranted.

A Pumpless Lung Assist Device Reduces Mechanical Ventilation-Induced Lung Injury in Juvenile Piglets

Respiratory failure is a major contributor to mortality and morbidity in newborn infants. The lung assist device (LAD) is a novel gas exchange device that supplements mechanical ventilation. The objective is to test the effect of the LAD on pulmonary histopathology in juvenile piglets with acute lung injury caused by saline lung lavage (SLL) followed by intermittent mandatory ventilation (IMV). Three- to 4-wk-old piglets were randomized to no intervention (control group), SLL alone (SLL group), SLL + IMV (IMV group), or SLL + IMV + LAD (LAD group) (n = 6 per group). The carotid artery and jugular vein were cannulated and an arteriovenous circuit completed, and the LAD was inserted into this circuit. Gas exchange via the LAD was initiated by passage of 100% oxygen over the blood-carrying hollow fibers of the LAD. Hemodynamic variables were recorded. Mechanical ventilation was systematically weaned. Lung histology was scored by two observers masked to treatment group. There were no differences in hemodynamic variables between the study groups. There was a significant increase in the total lung injury score in the IMV group compared with the LAD group. The novel pumpless low-resistance LAD has shown feasibility and potential to decrease ventilator-induced lung injury in a juvenile animal model.

Congenital cytomegalovirus infection: Update on management strategies

Congenital cytomegalovirus (CMV) infections are underrecognized as a cause of serious morbidity in newborn infants. The era of therapeutic nihilism regarding these infections has come to an end, however, as useful therapies are now available that may modify the outcome. The infected fetus can be treated in utero, or the newborn infant can be treated when CMV is recognized in the neonatal period. Expanded screening of newborns for congenital CMV infection will make it even more important for clinicians to be aware of current therapeutic options. The most effective option for the treatment of life-threatening or sight-threatening CMV disease at any age is the nucleoside analog ganciclovir. For the newborn with congenital CMV infection, the value of ganciclovir appears to relate to its ability to preserve hearing; other improvements in overall neurodevelopmental status are inferred but remain to be proven. In the pregnant woman with primary CMV infection, the use of CMV-specific immune globulin, though still investigational, is garnering attention and may prove to be a valuable therapy.

The impact of Neonatal Resuscitation Program courses on mortality and morbidity of newborn infants with perinatal asphyxia

Objective. Neonatal care provided within the first few minutes of life plays a major role in the reduction of neonatal morbidity and mortality. Neonatal Resuscitation Program (NRP) courses had been held since 1996. The aim of this study was to evaluate the impact of the NRP on morbidity and mortality of newborn infants with perinatal asphyxia. Methods. This retrospective study comprised newborn infants who were born in hospitals at Trakya region of Turkey during the last 3 years and were diagnosed as perinatal asphyxia and were referred to our Neonatal Unit. Those patients who were referred before NRP course (pretraining period) were designated as Group 1, those who were referred after the first NRP course (transition period) as Group 2, and those who were referred after the second NRP course (post-training period) as Group 3. Chart review was performed with regard to gestational age, birth weight, Apgar scores, resuscitation type, stage of hypoxic ischemic encephalopathy (HIE), existence of meconium aspiration syndrome (MAS), progress of the disease, duration of hospitalization. Results. The study comprised 66 patients; 35 in Group 1, 18 in Group 2 and 13 in Group 3. The number of cases who had not been resuscitated was 10 in the pretraining period, 3 in the transition period and 1 in the post-training period which decreased significantly. The first minute Apgar scores in three groups were as follows; 2.08 ± 1.2, 2.2 ± 1.1 and 3.7 ± 1.4, and this increase was statistically significant. The fifth minute Apgar scores also increased from 5.43 ± 1.5 in the pretraining period to 6.5 ± 1.9 in the post-training period, but this increase was not statistically significant. The number of patients with Stage 1 and 2 HIE decreased more in Group 3 ( n = 11 in Stage 1 HIE, n = 17 in Stage 2 HIE) compared to those in Group 1 ( n = 7 in Stage 1 HIE, n = 5 in Stage 2 HIE) but the difference was not statistically significant. The duration of hospitalization decreased in post-training period (15.1 ± 10.3 days in pretraining period, 12.0 ± 8.9 days in transition period, 6.1 ± 1.2 days in post-training period). Conclusions. After NRP courses, the number of patients with perinatal asphyxia and with no resuscitation and also the duration of hospitalization decreased significantly, whereas the first minute Apgar scores increased significantly.