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Randomized controlled trials evaluating low-target oxygen saturation (SpO2:85% to 89%) vs high-target SpO2 (91% to 95%) have shown variable results regarding mortality and morbidity in extremely preterm infants. Because of the variation inherent to the accuracy of pulse oximeters, the unspecified location of probe placement, the intrinsic relationship between SpO2 and arterial oxygen saturation (SaO2) and between SaO2 and partial pressure of oxygen (PaO2) (differences in oxygen dissociation curves for fetal and adult hemoglobin), the two comparison groups could have been more similar than dissimilar. The SpO2 values were in the target range for a shorter period of time than intended due to practical and methodological constraints. So the studies did not truly compare 'target SpO2 ranges'. In spite of this overlap, some of the studies did find significant differences in mortality prior to discharge, necrotizing enterocolitis and severe retinopathy of prematurity. These differences could potentially be secondary to time spent beyond the target range (SpO2 95%) and could be avoided with an intermediate but wider target SpO2 range (87% to 93%). In conclusion, significant uncertainty persists about the desired target range of SpO2 in extremely preterm infants. Further studies should focus on studying newer methods of assessing oxygenation and strategies to limit hypoxemia (95% SpO2).

OBJECTIVE: There is concern about an increasing incidence of kernicterus in healthy term neonates in the United States. Although the incidence of kernicterus is unknown, several potential strategies that are intended to prevent kernicterus have been proposed by experts. It is necessary to assess the costs, benefits, and risks of such strategies before widespread policy changes are made. The objective of this study was to determine the direct costs to prevent a case of kernicterus with the following 3 strategies: (1) universal follow-up in the office or at home within 1 to 2 days of early newborn discharge, (2) routine predischarge serum bilirubin with selective follow-up and laboratory testing, and (3) routine predischarge transcutaneous bilirubin with selective follow-up and laboratory testing. METHODS: We performed an incremental cost-effectiveness analysis of the 3 strategies compared with current practice. We used a decision analytic model and a spreadsheet to estimate the direct costs and outcomes, including the savings resulting from prevented kernicterus, for an annual cohort of 2,800000 healthy term newborns who are eligible for early discharge. We used a modified societal perspective and 2002 US dollars. With each strategy, the test and treatment thresholds for hyperbilirubinemia are lowered compared with current practice. RESULTS: With the base-case assumptions (current incidence of kernicterus 1:100 000 and a relative risk reduction [RRR] of 0.7 with each strategy), the cost to prevent 1 case of kernicterus was 10,321463 dollars, 5,743905 dollars, and 9,191352 dollars respectively for strategies 1, 2, and 3 listed above. The total annual incremental costs for the cohort were, respectively, 202,300671 dollars, 112,580535 dollars, and 180,150494 dollars. Sensitivity analyses showed that the cost per case is highly dependent on the population incidence of kernicterus and the RRR with each strategy, both of which are currently unknown. In our model, annual cost savings of 46,179465 dollars for the cohort would result with strategy 2, if the incidence of kernicterus is high (1:10,000 births or higher) and the RRR is high (> or =0.7). If the incidence is lower or the RRR is lower, then the cost per case prevented ranged from 4,145676 dollars to as high as 77,650240 dollars. CONCLUSIONS: Widespread implementation of these strategies is likely to increase health care costs significantly with uncertain benefits. It is premature to implement routine predischarge serum or transcutaneous bilirubin screening on a large scale. However, universal follow-up may have benefits beyond kernicterus prevention, which we did not include in our model. Research is required to determine the epidemiology, risk factors, and causes of kernicterus; to evaluate the effectiveness of strategies intended to prevent kernicterus; and to determine the cost per quality-adjusted life year with any proposed preventive strategy. [ABSTRACT FROM AUTHOR]

Objective: We aimed to identify differences in morbidity and mortality between inborn versus outborn extremely low birth weight (ELBW) infants admitted to the Texas Children's Hospital neonatal intensive care unit (NICU)., Study Design: Vermont Oxford Network data were analyzed between January 2014 and December 2017. Inborn versus outborn outcomes were compared., Result: Of 533 ELBW infants, 402 were inborn, and 131 were outborn. Gestational age and birth weight (BW) were similar. After adjusting outcomes to control for maternal steroids, maternal hypertension, maternal prenatal care, and temperature below 36 °C at admission, no outcomes were significantly different except inborn patients had decreased odds of late onset sepsis (adjusted odds ratio = 0.606, 95% confidence interval: 0.377-0.973, p = 0.038)., Conclusion: In this study, outborn ELBW patients had increased odds of late onset sepsis compared with inborn ELBW patients after controlling for covariates that differed significantly between these two cohorts.

Background: Guidelines exist for counseling expectant families of infants at periviable gestational ages (22-25 weeks), but it is much more common for neonatologists to counsel families at gestational ages beyond the threshold of viability when several aspects of these guidelines do not apply. We aimed to develop an understanding of what information is shared with mothers at risk of preterm delivery beyond periviability and to evaluate communication skills of our participants., Methods: We developed a checklist of elements to include in counseling based on a comprehensive literature review. The checklist was divided into an information sharing section and a connect score. The information sharing list was sub-divided into general information and specific complications. Neonatologists engaged in a simulated prenatal counseling session with a standardized patient. Videotaped encounters were then analyzed for checklist elements., Results: Neonatologists all scored well in communication using our tool and two other validated communication tools - the SEGUE and the analytic global OSCE. There was no difference in scoring based on years of experience or level of training. Information sharing from neonatologists more often discussed general information over specific. Neonatologists also focused more on early outcomes over long-term outcomes. Only 12% of neonatologists quoted the correct survival rate for the case., Conclusions: Neonatologists generally communicate well but share less information specific to prematurity and the long-term sequelae of prematurity. Our tool may be used to test if other interventions improve information sharing or communication.

Communication around high-risk deliveries is critical to ensure patient safety. A hospital-wide system change in paging the neonatal resuscitation team (NRT) to deliveries was implemented but disliked. An interdisciplinary team seized the opportunity to explore opportunities for an enhanced system to improve communication. The team designed a new screen to our smart panel (responder 5 staff terminal, Rauland, Mount Prospect, Illinois) to page NRT with the location and primary indication for which they were needed at delivery. Surveys assessed user satisfaction among labor and delivery and NRT. Before and after implementation of the smart panel, we assessed number of NRT pages, frequency of NRT being paged prior to the delivery, the time between page and delivery, and use of the code button to summon help. Labor and delivery and NRT user satisfaction greatly improved with the smart panel. Frequency of NRT being paged before birth increased with fewer code pages being used to summon NRT to deliveries. A touch screen-based notification system can enhance timely notification to summon NRT to deliveries while concurrently enhancing satisfaction of providers in both the delivery room and on the NRT.

Background:  Improving communication in healthcare improves the quality of care and patient outcomes, but communication between obstetric and neonatal teams before and during a high-risk delivery is poorly studied., Study Design:  We developed a survey to study communication between obstetric and neonatal teams around the time of a high-risk delivery. We surveyed neonatologists from North America and asked them to answer questions about their institutions' communication practices., Results:  The survey answers revealed variations in communication practices between responders. Most institutions relied on nursing to communicate obstetric information to the neonatal team. Although a minority of institutions used a standardized communication process to summon neonatology team or to communicate in the delivery room, these reported higher rates of information sharing and greater satisfaction with communication between services., Conclusion:  Standardized communication procedures are an underutilized method of communication and have the potential to improve communication around high-risk deliveries., Competing Interests: Conflict of Interest: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Introduction: While evidence-based medicine (EBM) is an Accreditation Council for Graduate Medical Education core competency, EBM teaching in pediatric subspecialties is rarely reported. Therefore, we designed, implemented, and evaluated this focused EBM curriculum for trainees in neonatal-perinatal medicine., Methods: This EBM curriculum consists of seven weekly 1-hour sessions. Specific EBM skills taught in the sessions include formulating a structured clinical question, conducting an efficient literature search, critically appraising published literature in both intervention and diagnostic studies, and incorporating evidence into clinical decision-making. The course was evaluated by a neonatology-adapted Fresno test (NAFT) and neonatology case vignettes, which were administered to learners before and after the curriculum. This publication includes the needs assessment survey, PowerPoint slides for the seven sessions, the NAFT, and the scoring rubric for the test., Results: The NAFT was internally reliable, with a Cronbach's alpha of .74. The intraclass correlation coefficient of the three raters' variability in assessment of learners was excellent at .98. Mean test scores increased significantly (54 points, p < .001) in 14 learners after the EBM curriculum, indicating an increase in EBM-related knowledge and skills., Discussion: This focused EBM curriculum enhances trainees' knowledge and skills and fosters evidence-based practice. The curriculum can be easily adapted for learners in pediatrics, as well as family medicine, in order to enhance trainees' EBM skills and knowledge., Competing Interests: None to report.

An important step on the roadmap to a successful quality improvement (QI) project is careful selection of topics and aims to be addressed by QI projects. Using information from a variety of data monitoring systems as well as individual events and experiences, leaders of neonatal units and QI teams should first identify quality and safety gaps in their unit. They should then use an explicit, formal process for selecting the best projects to which their limited time and resources should be allocated. Priority should be given to projects that address a quality gap of high magnitude and impact, have a high likelihood of success, have a champion, fit with the unit's state of readiness for change, have organizational support and align with organizational priorities. The scope of the project should also match the experience and expertise of the QI team.

Consistency of care and elimination of unnecessary and harmful variation are underemphasized aspects of health care quality. This article describes the prevalence and patterns of practice variation in health care and neonatology; discusses the potential role of standardization as a solution to eliminating wasteful and harmful practice variation, particularly when it is founded on principles of evidence-based medicine; and proposes ways to balance standardization and customization of practice to ultimately improve the quality of neonatal care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Our objective was to evaluate the impact of a dedicated resuscitation and stabilization (RAS) room and process changes on infant stabilization time., Study Design: A prospective quality improvement study was conducted on preterm infants in a tertiary care center. A dedicated RAS room, preresuscitation huddle, infant-isolette-ventilator pairing and improved documentation were implemented. The primary outcome was median time to stabilization and secondary outcomes were illness severity on day 1 and morbidity at discharge., Results: A sustained reduction in median time to stabilization from 90 min in the preimplementation phase to 72 min in the sustainability phase was observed. All planned and iterative process changes were integrated into the RAS team's daily routine. Time to completion of procedures decreased, illness severity and morbidity remained unchanged., Conclusion: A dedicated RAS room adjacent to the delivery suite in conjunction with process changes improves efficiency of care.

Bronchopulmonary dysplasia (BPD) is associated with significant short- and long-term morbidity in preterm infants, and it can be prevented in some infants with vitamin A prophylaxis. Vitamin A, once widely used in neonatal intensive care, was scarce for the last few years, but has become available again at a much higher price, leading to dilemmas about its routine use. In this review we discuss experimental, clinical and socioeconomic evidence related to BPD, and provide a framework for clinicians and policy-makers to evaluate the value of vitamin A treatment and make decisions about its use for prevention of BPD.

Children are vulnerable to the priorities and decision-making of adults. Usually, parents/caregivers make the difficult healthcare decisions for their children based on the recommendations from the child's healthcare providers. In global health work, healthcare team members from different countries and cultures may guide healthcare decisions by parents and children, and as a result ethical assumptions may not be shared. As a result, ethical issues in pediatric global health are numerous and complex. Here we discuss critical ethical issues in global health at an individual and organizational level in hopes this supports optimized decision-making on behalf of children worldwide., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Infrastructure for facility-based neonatal care has rapidly grown in India over last few years. Experience from developed countries indicates that different health facilities have varying clinical outcomes despite accounting for differences in illness severity of admitted neonates and random variation. Variation in quality of care provided at different neonatal units may account for variable clinical outcomes. Monitoring quality of care, comparing outcomes across different centers and conducting collaborative quality improvement projects can improve outcome of neonates in health facilities. Top priority should be given to establishing quality monitoring and improvement procedures at special care neonatal units and neonatal intensive care units of the country. This article presents an overview of methods of quality improvement. Literature reports of successful collaborative quality improvement projects in neonatal health are also reviewed.

Background: Education in Quality Improvement for Pediatric Practice (EQIPP) is an online program designed to improve evidence-based care delivery by teaching front-line clinicians quality improvement (QI) skills. Our objective was to evaluate EQIPP data to characterize 1) participant enrollment, use patterns, and demographics; 2) changes in performance in clinical QI measures from baseline to follow-up measurement; and 3) participant experience., Methods: We conducted an observational study of EQIPP participants utilizing 1 of 3 modules (asthma, immunizations, gastroesophageal reflux disease) from 2009 to 2013. Enrollment and use, demographic, and quality measure data were extracted directly from the EQIPP system; participant experience was assessed via an optional online survey., Results: Study participants (n = 3501) were diverse in their gender, age, and race; most were board certified. Significant quality gaps were observed across many of the quality measures at baseline; sizable improvements were observed across most quality measures at follow-up. Participants were generally satisfied with their experience. The most influential module elements were collecting and analyzing data, creating and implementing aim statements and improvement plans, and completing "QI Basics.", Conclusions: Online educational programs, such as EQIPP, hold promise for front-line clinicians to learn QI. The sustainability of the observed improvements in care processes and their linkage to improvements in health outcomes are unknown and are an essential topic for future study., (Copyright © 2014 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Guardianship may be necessary when inpatients lack medical decision-making capacity and are unwilling to go home to be cared for by interested proxy decision makers. Interventions, centered on a clinical pathway, were conducted at Dartmouth-Hitchcock Medical Center (DHMC; Lebanon, New Hampshire). Because guardianship occurs at the interface of clinical care and governmental bureaucracy, quality improvement efforts focused on "in-hospital" processes, while actions were taken to improve communication between clinical teams and the legal system., Methods: A multidisciplinary quality improvement team mapped the DHMC guardianship process and analyzed the causes for delays before creating the clinical pathway. Specific interventions were designed and implemented to address the identified improvement areas., Results: For the 26 guardianship patients during a two-year period (May 1, 2011-May 1, 2013), the charges incurred totaled approximately $4,000,000--for an average of more than $150,000 per patient. The medically unnecessary days of their length of hospital stay decreased from an average of 27.8 to 11.3, a statistically significant result as demonstrated by statistical process control analysis. The shorter hospitalizations of the last 13 patients amounted to 214.5 medically unnecessary hospital days saved and more than $1.2 million in charges reduced during the two-year period., Conclusions: Guardianship is a complex process that generates significant delays in appropriate care and increases in charges. The redesigned, standardized guardianship process, as defined in the clinical pathway, reduced associated medically unnecessary days of hospitalization.

A neonatologist must decide whether to revive a premature baby on the borderline of viability.

Previously considered unavoidable complications of hospital care (reflecting an "entitlement" mental model), health care-associated infections are now considered as medical errors and cause significant preventable morbidity and mortality in neonates. Prevention of such infections, particularly central line-associated bloodstream infections (CLABSI), should be an important patient safety priority for all neonatal intensive care units (NICUs). An important first step is to promote a mental model of CLABSIs as preventable complications of care. Other general strategies are (1) promoting an organizational culture of safety and empowerment of staff; (2) hand hygiene; (3) avoiding overcrowding and understaffing; (4) using breast milk for enteral feedings; and (5) involving families in infection prevention efforts. Specific strategies to prevent CLABSI are (1) insertion practices: insertion of all central vascular catheters under strict sterile conditions with the aid of a checklist; (2) maintenance practices: ensuring that entries into the lumen of the vascular catheter always occur under aseptic conditions, minimizing catheter disconnections, and replacement of intravenous infusion sets at recommended intervals; (3) removal of all central lines as soon as possible. Participation in national or statewide quality improvement collaboratives is an emerging trend in neonatology that can enhance CLABSI prevention efforts by NICUs., (Thieme Medical Publishers, Inc.)

Measurement of patient safety serves to identify opportunities to improve safety within a neonatal intensive care unit (NICU), compare the safety of care provided by different NICUs, determine changes in response to safety interventions or programs, follow safety trends over time, and potentially deny payment for specific events. The ideal patient safety measures are rates of events derived from surveillance with valid and reliable detection of numerators (errors or adverse events) and denominators (the opportunities for errors or adverse events to occur). Methods used to identify these numerators and denominators include reporting, direct observation, videotaping, chart review, trigger tools, and automated methods. However, there are significant methodological and practical (feasibility) challenges to the accurate and reliable determination of rates of errors and adverse events. These include failure to detect and document such events, surveillance bias, lack of consistent definitions, frequent requirement for judgment in identifying and classifying challenges (which introduces interrater inconsistency), and need for significant additional resources., (Thieme Medical Publishers, Inc.)

In this study, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of 2-substituted 5-hydroxyindole-3-carboxylate derivatives as potent 5-LOX inhibitors with IC(50) values ranging from 0.031 to 13.4 μM. Two datasets of same molecules were prepared with two different partial atomic charges; one with Gasteiger-Huckel and another with the ESPFIT charges obtained from the gaussian package. CoMFA and CoMSIA models were generated for both the datasets and the results were analysed. With regard to the non-cross validated r(2) values (r(ncv)(2)) and cross-validated q(2) values (q(cv)(2)) of the resulting QSAR models, the dataset with ESPFIT charges yielded higher values; hence it was further used in the study. The CoMFA and CoMSIA models have been further validated for their stability and robustness using group validation and bootstrapping techniques and for their predictive abilities using an external test set of ten compounds. The predictive power of the CoMSIA model was higher than the CoMFA model, the high predictive r(2) values of the test set reveals that the models prove to be useful tools for activity prediction of newly designed 5-LOX inhibitors. The ESPFIT-derived charges yielded better models than those based on charges calculated from Gasteiger-Huckel charges. We generated a homology model for human 5-LOX and identified the key residues at the binding site. The 3D-QSAR models were compared with the interactions at the active site to further elucidate the accuracy of the models. The data generated from 3D-QSAR study was used to design potential 5-LOX inhibitors., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Blastocystis is a ubiquitous enteric protistan parasite that has extensive genetic diversity and infects humans and many other animals. Distinct molecular methodologies developed to detect variation and obtain information about transmission patterns and clinical importance have resulted in a confusing array of terminologies for the identification and designation of Blastocystis subtypes. In this article, we propose a standardization of Blastocystis terminology to improve communication and correlate research results. Based primarily on published small-subunit ribosomal RNA gene analyses, we propose that all mammalian and avian isolates should be designated Blastocystis sp. and assigned to one of nine subtypes.

We describe the development of a database of quality indicators and outcomes for perinatal care as part of a multi-institutional collaborative quality improvement project, Neonatal Intensive Care Quality 2002. Important principles of developing such a database are also discussed including eligibility criteria that identify high-risk patients without burdening data collectors, clinically important and well-defined measures, development of systems within each hospital to ensure identification of all eligible patients, use of data collectors with knowledge of perinatal care, appropriate design of paper and electronic data-collection tools, multiple pilot tests, and periodic feedback of data to participating hospitals.

Background: Timely error detection including feedback to clinical staff is a prerequisite for focused improvement in patient safety. Real time auditing, the efficacy of which has been repeatedly demonstrated in industry, has not been used previously to evaluate patient safety. Methods successful at improving quality and safety in industry may provide avenues for improvement in patient safety., Objective: Pilot study to determine the feasibility and utility of real time safety auditing during routine clinical work in an intensive care unit (ICU)., Methods: A 36 item patient safety checklist was developed via a modified Delphi technique. The checklist focused on errors associated with delays in care, equipment failure, diagnostic studies, information transfer and non-compliance with hospital policy. Safety audits were performed using the checklist during and after morning work rounds thrice weekly during the 5 week study period from January to March 2003., Results: A total of 338 errors were detected; 27 (75%) of the 36 items on the checklist detected >or=1 error. Diverse error types were found including unlabeled medication at the bedside (n = 31), ID band missing or in an inappropriate location (n = 70), inappropriate pulse oximeter alarm setting (n = 22), and delay in communication/information transfer that led to a delay in appropriate care (n = 4)., Conclusions: Real time safety audits performed during routine work can detect a broad range of errors. Significant safety problems were detected promptly, leading to rapid changes in policy and practice. Staff acceptance was facilitated by fostering a blame free "culture of patient safety" involving clinical personnel in detection of remediable gaps in performance, and limiting the burden of data collection.

Clinical trials have evaluated the overall efficacy of surfactant therapy, as well as the relative efficacy of different surfactant preparations, the optimal timing of administration and the optimal dosage. Surfactant therapy leads to significant clinical improvement in infants at risk for, or having, respiratory distress syndrome (RDS). Clinical trials that compared the effects of synthetic or animal-derived surfactant preparations to placebo or no therapy demonstrate that surfactant therapy lead to rapid improvement in oxygenation, decreased ventilator support, decreased risk of pneumothorax, and mortality. Earlier treatment, prophylactic treatment of infants at high risk of developing RDS, and selective re-treatment leads to improved clinical outcome as well. Currently available animal-derived surfactants are superior to non-protein-containing synthetic surfactants. Ongoing evaluation will determine if important differences in animal-derived products are noted. Future trials will evaluate third-generation surfactant products and further refine what constitutes optimal use of surfactant.

Exogenous surfactant therapy has an established role in the management of neonatal respiratory distress syndrome (RDS). This article summarises the current evidence on surfactant therapy. The use of surfactant for the treatment or prophylaxis of neonatal RDS results in a 30% to 65% relative reduction in the risk of pneumothorax and up to a 40% relative reduction in the risk of mortality. Adverse effects, of which pulmonary haemorrhage is of most concern, are infrequent and long-term follow-up studies of treated patients are reassuring. Natural surfactants have advantages over synthetic surfactants, including a lower frequency of pneumothorax and a lower mortality. Prophylactic administration of surfactant is preferred over 'rescue' administration, especially in infants of < 30 weeks' gestation, as it decreases the risk of pneumothorax, pulmonary interstitial emphysema and neonatal mortality. Prophylaxis can be administered after initial resuscitation and stabilisation. In preterm infants who do not receive prophylactic surfactant, the first dose of surfactant should be administered as early as possible--early selective treatment decreases the risk of pneumothorax, pulmonary interstitial emphysema, chronic lung disease and neonatal mortality. A regimen of using multiple doses of surfactant if required has advantages over a single dose regimen. Exogenous surfactant therapy has also been used in neonatal respiratory disorders other than RDS. In trials in severe meconium aspiration syndrome, surfactant therapy reduced the need for extracorporeal membrane oxygenation. Its role in other disorders requires testing. The development and testing of newer surfactants is in progress.

Background: Metalloporphyrins are heme analogues that inhibit heme oxygenase, the rate-limiting enzyme in the catabolism of heme to bilirubin. By preventing the formation of bilirubin, they have the potential to reduce the level of unconjugated bilirubin in neonates and thereby reduce the risk of neonatal encephalopathy and long term neurodevelopmental impairment from bilirubin toxicity to the nervous system., Objectives: 1. To determine the efficacy of metalloporphyrins in reducing bilirubin levels, reducing the need for phototherapy or exchange transfusion and reducing the incidence of bilirubin encephalopathy in neonates with unconjugated hyperbilirubinemia when compared to placebo, phototherapy or exchange transfusion. 2. To determine the nature and frequency of side effects of metalloporphyrins when used to treat unconjugated hyperbilirubinemia in neonates., Search Strategy: We searched Medline (1966 - January 2003) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (2003, issue 1). We hand-searched the articles cited in each publication obtained. We hand searched the abstracts of the Society for Pediatric Research (USA) (published in Pediatric Research) for the years 1985 - 2002., Selection Criteria: We included only randomized controlled studies, in which preterm or term neonates (age 28 days of life or less) with unconjugated hyperbilirubinemia due to any cause were randomly allocated to receive a metalloporphyrin in the treatment arm(s), and to receive a placebo or a conventional treatment (phototherapy or exchange transfusion) or no treatment for hyperbilirubinemia in the comparison arm(s). Any preparation of metalloporphyrin could be used, in any form, by any route, at any dose., Data Collection and Analysis: Two authors extracted data independently. Data were entered into Revman by one author and checked by a second author. Prespecified subgroup analyses were planned in term versus preterm infants, hemolytic versus non-hemolytic causes of jaundice and according to the type of metalloporphyrin used., Main Results: Three small studies, enrolling a total of 170 infants, were eligible for inclusion in this review. None blinded intervention or outcome assessment. In all three studies some patients were excluded after randomization. Metalloporphyrin-treated infants appeared to have short-term benefits compared to controls, including a lower maximum plasma bilirubin level in one study, a lower frequency of severe hyperbilirubinemia in one study, a decreased need for phototherapy, fewer plasma bilirubin measurements and a shorter duration of hospitalization. None of the enrolled infants required an exchange transfusion in the two studies that described this outcome. None of the studies reported on neonatal kernicterus, death, long-term neurodevelopmental outcomes or iron deficiency anemia. Though a small number of metalloporphyrin-treated as well as control infants developed a photosensitivity rash, the trials were too small to rule out an increase in the risk of photosensitivity or other adverse effects from metalloporphyrin treatment. No subgroup analyses were possible due to the small number of included trials., Reviewer's Conclusions: Treatment of neonatal unconjugated hyperbilirubinemia with metalloporphyrins may reduce neonatal bilirubin levels and decrease the need for phototherapy and hospitalization. There is no evidence to support or refute the possibility that treatment with a metalloporphyrin decreases the risk of neonatal kernicterus or of long-term neurodevelopmental impairment due to bilirubin encephalopathy. There is no evidence to support or refute the possibility that cutaneous photosensitivity is increased with metalloporphyrin treatment. Routine treatment of neonatal unconjugated hyperbilirubinemia with a metalloporphyrin cannot be recommended at present.

Exogenous surfactant therapy is widely used in the management of neonatal respiratory distress syndrome. Two types of surfactants are available: synthetic surfactants, and those derived from animal sources ("natural" surfactants). Both of these surfactants have been shown to be effective. In this article, we review the evidence to compare the two types of surfactants in terms of their physical properties, physiologic effects, and clinical outcomes. Natural surfactants have been shown to have advantages over synthetic surfactants in their physical properties and physiologic effects in animals, as well as in humans. A systematic review of 11 randomized clinical trials comparing natural and synthetic surfactants demonstrated that the use of natural surfactant preparations results in greater clinical benefits compared with synthetic surfactants. These benefits include a more rapid improvement in oxygenation and lung compliance after surfactant therapy, a decrease in the risk of mortality (typical relative risk 0.87; typical risk difference -0.02), and a decrease in the risk of pneumothorax (typical relative risk 0.63; typical risk difference -0.04). Although the use of natural surfactants results in a slightly increased risk of intraventricular hemorrhage (typical relative risk 1.09; typical risk difference 0.03), there is no increase in the risk of grade 3 or 4 intraventricular hemorrhage. There are theoretical but unproven risks of natural surfactants, such as transmission of infectious agents, immunogenicity and impurities in composition. The use of natural surfactants is preferred in most situations. In addition, clinicians should determine the costs of different types of surfactants in their individual practice settings and use this information in decision-making.

Exogenous surfactant therapy has been a significant advance in the management of preterm infants with RDS. It has become established as a standard part of the management of such infants. Both natural and synthetic surfactants lead to clinical improvement and decreased mortality, with natural surfactants having additional advantages over currently available synthetic surfactants. The use of prophylactic surfactant administered after initial stabilization at birth to infants at risk for RDS has benefits compared with rescue surfactant given to treat infants with established RDS. In infants who do not receive prophylaxis, earlier treatment (before 2 hours) has benefits over later treatment. The use of multiple doses of surfactant is a superior strategy to the use of a single dose, whereas the use of a higher threshold for retreatment seems to be as effective as a low threshold. Adverse effects of surfactant therapy are infrequent and usually not serious. Long-term follow-up of infants treated with surfactant in the neonatal period is reassuring. In the future we are likely to see the development of new types of surfactants. Further research is required to determine the optimal use of surfactant in conjunction with other respiratory interventions.

Objective: To study the frequency and types of major birth defects in very low birth weight (VLBW) infants and their impact on mortality and resource use., Study Design: Analysis of data from the Vermont Oxford Network Database from 1994 and 1995 on infants with birth weights of 501 to 1500 g. Major birth defects were reported from a list of 40 defined major defects or if they were considered lethal or life-threatening. Mortality and length of stay were determined., Results: Major birth defects were present in 823 (4.3%) of 19,228 VLBW infants from 147 hospitals. The most common categories were chromosomal anomalies (20%); named syndromes, sequences, and associations (19%); and gastrointestinal (14%), cardiovascular (11%), and nervous system (10%) anomalies. Infants with major birth defects had a higher mortality rate (58% vs 13%, P <.001) and a higher rate of major surgery (29% vs 5%, P <.001) than infants without such defects. Infants with major birth defects accounted for 16.3% of deaths and 18.9% of major surgical procedures but only for 2.9% of total hospital days., Conclusions: Major birth defects accounted for 16% of all deaths in VLBW infants. However, they accounted for a low proportion of total hospital days.

Background: Free oxygen radicals have been implicated in the pathogenesis of chronic lung disease in preterm infants. Superoxide dismutase is a naturally occurring enzyme which provides a defence against such oxidant injury. Exogenously administered superoxide dismutase has been tested in clinical trials to prevent chronic lung disease in preterm infants., Objectives: To determine if exogenously administered superoxide dismutase is efficacious in the prevention of chronic lung disease in preterm infants who are mechanically ventilated, and efficacious in decreasing the following outcomes: bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus and mortality. To determine the frequency and nature of adverse effects of superoxide dismutase., Search Strategy: We searched Medline (1966 - 2000) and the Cochrane Controlled Trials Register (CCTR) using the following keywords: [bronchopulmonary dysplasia OR chronic lung disease] AND superoxide dismutase, limited to human studies in newborn infants (infant, newborn). We hand searched the reference lists of articles located and the abstracts of the Society for Pediatric Research (USA) (published in Pediatric Research) from 1980 - 2000., Selection Criteria: Randomized controlled trials where subjects were preterm infants who had developed or were at risk of developing respiratory distress syndrome requiring assisted ventilation and who were randomly allocated to receive either superoxide dismutase (in any form, by any route) or placebo or no treatment. We included studies which reported any of the following outcomes: chronic lung disease, bronchopulmonary dysplasia, any intraventricular hemorrhage, intraventricular hemorrhage grades III/IV, patent ductus arteriosus, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, neonatal mortality, death prior to discharge and neurodevelopmental outcome., Data Collection and Analysis: We extracted and assessed separately all data for each study and entered final data into RevMan. We did not perform subgroup analyses (which were originally planned) because only two studies were eligible for inclusion. We assessed the methodological quality of the studies by assessing the risk for bias. We pooled the outcomes of infants who had developed bronchopulmonary dysplasia at 28 days with those who had died at 28 days to derive the combined outcome of bronchopulmonary dysplasia or death at 28 days. Similarly we pooled the outcomes of infants who had respiratory problems after discharge with those who had died prior to discharge to derive the combined outcome of respiratory problems after discharge or death. We used the standard method of the Cochrane Neonatal Review Group for statistical analysis, using a fixed effect model., Main Results: Two randomized controlled trials were included for analysis. No differences were found in either study or in the pooled data in death prior to discharge, oxygen dependency at 36 weeks corrected age, oxygen dependency at 28 days of life or in other outcomes. In one study (Rosenfeld 1984), survivors who had been treated with superoxide dismutase had a shorter duration of continuous positive airway pressure (4.9 vs 9.7 days), a lower frequency of respiratory problems after discharge (relative risk 0.33, 95% confidence limits 0.11, 0.96) and a lower frequency of chest radiograph abnormalities (relative risk 0.30, 95% confidence limits 0.11, 0.87) compared to survivors who received placebo. A third study was available only in abstract form and will be evaluated for inclusion after publication., Reviewer's Conclusions: Based on currently available published trials, there is insufficient evidence to draw firm conclusions about the efficacy of superoxide dismutase in preventing chronic lung disease of prematurity. Data from a small number of treated infants suggest that it is well tolerated and has no serious adverse effects.

A total of 3472 deliveries were studied over a year to evaluate (i) the importance of thin meconium stained liquor (MSL) in the causation of meconium aspiration syndrome (MAS), and (ii) the efficacy of intrapartum plus endotracheal suction at birth in the prevention of MAS due to thin meconium. Two hundred and ninety four (8.5%) of deliveries had meconium stained liquor of which thin MSL was present in 101. MAS occurred in 98 babies. Thin MSL was responsible for 19.4% of cases of MAS. Inspite of intrapartum suction, a high proportion (55-78%) of infants had meconium in the trachea, though thin meconium was found in the trachea significantly less often than thick meconium. Combined intrapartum and endotracheal suction reduced the incidence of MAS due to thin meconium from 26% to 16%. MAS due to thin meconium occurred in asphyxiated as well as vigorous babies inspite of combined suction. Thin meconium accounts for a significant proportion of deliveries with MSL and causes a considerable number of cases of MAS. To prevent meconium aspiration syndrome caused by thin meconium, all neonates born through thin MSL, whether they are asphyxiated or not should undergo intrapartum suction followed by immediate endotracheal suction at birth.