Prevalence and Outcomes of Congenital Heart Disease in Very Low Birth Weight Preterm Infants: An Observational Study From the Brazilian Neonatal Network Database.

OBJECTIVES: To evaluate the prevalence of congenital heart disease and their outcomes in a Brazilian cohort of very low birth weight preterm infants. DESIGN: Post hoc analysis of data from the Brazilian Neonatal Network database, complemented by retrospective data from medical charts and a cross-sectional survey. SETTING: Twenty public tertiary-care university hospitals. PATIENTS: A total of 13,955 newborns weighing from 401 to 1,499 g and between 22 and 36 weeks of gestational age, born from 2010 to 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of congenital heart disease was 2.45% (95% CI, 2.20-2.72%). In a multivariate regression analysis, risk factors associated with congenital heart disease were maternal diabetes (relative risk, 1.55; 95% CI, 1.11-2.20) and maternal age above 35 years (relative risk, 2.09; 95% CI, 1.73-2.51), whereas the protection factors were maternal hypertension (relative risk, 0.54; 95% CI, 0.43-0.69), congenital infection (relative risk, 0.45; 95% CI, 0.21-0.94), and multiple gestation (relative risk, 0.73; 95% CI, 0.55-0.97). The pooled standardized mortality ratio in patients with congenital heart disease was 2.48 (95% CI, 2.22-2.80), which was significantly higher than in patients without congenital heart disease (2.08; 95% CI, 2.03-2.13). However, in multiple log-binomial regression analyses, only the presence of major congenital anomaly, gestational age (< 29 wk; relative risk, 2.32; 95% CI, 2.13-2.52), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20; relative risk, 3.76; 95% CI, 3.41-4.14) were independently associated with death, whereas the effect of congenital heart disease was spotted only when a conditional inference tree approach was used. CONCLUSIONS: The overall prevalence of congenital heart disease in this cohort of very low birth weight infants was higher and with higher mortality than in the general population of live births. The occurrence of a major congenital anomaly, gestational age (< 29 wk), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20) were significantly and independently associated with death, whereas the association of congenital heart disease and death was only evident when a major congenital anomaly was present.

Cefazolin pharmacokinetics in premature infants.

OBJECTIVE: Pharmacokinetic (PK) data to guide cefazolin dosing in premature infants are virtually non-existent. Therefore, we aimed to characterize cefazolin PK in infants aged ≤32 weeks of gestation at birth. STUDY DESIGN: We conducted a prospective, open-label PK and safety study of cefazolin in infants ≤32 weeks gestation from a University Medical Center. We administered intravenous cefazolin and collected both timed and scavenged blood samples. We analyzed data using non-linear mixed effect modeling and simulated several dosage regimens to achieve target concentrations against methicillin-susceptible Staphylococcus aureus. RESULTS: We analyzed 40 samples from nine infants and observed that premature infants had lower clearance and greater volume of distribution for cefazolin compared to older children. The median (range) individual Bayesian estimates were 0.03 L/h/kg (0.01-0.08) for clearance and 0.39 L/kg (0.31-0.52) for volume. CONCLUSION: Simulations suggested reduced cefazolin dosing based on postmenstrual age achieve target concentrations and potentially reduce unnecessary exposure.

Evaluation of usability of a neonatal health information system according to the user's perception / Avaliação da usabilidade de um sistema de informação em saúde neonatal segundo a percepção do usuário

ABSTRACT Objective: To measure the level of satisfaction regarding the usability of a neonatal health information system and identify if demographic factors can influence the usability of a health information system. Methods: A cross-sectional, exploratory study was carried out with a convenience sample of 50 users of the Brazilian Neonatal Research Network. The instrument chosen for the usability evaluation was the System Usability Scale between February and March 2017. The statistical analysis of the collected variables was carried out in order to describe the sample, to quantify the level of satisfaction of the users and to identify the variables associated with the level of satisfaction. Results: The female gender represented 75% of the sample. The mean age was 52.8 years; 58% had a doctoral degree, average time of graduation was 17 years, with area of practice in medicine (neonatology), with intermediate knowledge in computer science (74%) and mean system use time of 52 months. Regarding usability, 94% rated the system as "good", "excellent" or "better than imaginable". The usability of the system was not associated with age, gender, education, profession, area of practice, knowledge in computer science and time of system use. Conclusion: The level of satisfaction of the computerized health system user was considered good. No demographic factors were associated with the satisfaction of the users.

RESUMO Objetivo: Mensurar o grau de satisfação de profissionais de saúde quanto à usabilidade de um sistema de informação em saúde neonatal e identificar os fatores que podem influenciar na satisfação do usuário frente à usabilidade. Métodos: Estudo transversal e exploratório realizado com 50 profissionais de saúde integrantes dos centros da Rede Brasileira de Pesquisas Neonatais. Para avaliação da usabilidade foi utilizado o instrumento System Usability Scale entre fevereiro e março de 2017. Realizou-se a análise estatística descritiva e inferencial das variáveis coletadas, com a finalidade de descrever a amostra, quantificar o grau de satisfação dos usuários e identificar as variáveis associadas ao grau de satisfação do usuário em relação à usabilidade. Resultados: Da população avaliada, 75% era do sexo feminino, com idade média 52,8 anos, 58% com pós-graduação (doutorado); tempo médio da última formação de 17 anos; área de atuação em medicina (neonatologia), grau intermediário de conhecimento em informática e tempo de utilização média do sistema de 52 meses. Quanto à usabilidade, 94% avaliaram o sistema como "bom", "excelente" ou "melhor impossível". A usabilidade do sistema não foi associada a idade, sexo, escolaridade, profissão, área de atuação, nível de conhecimento em informática e tempo de uso do sistema. Conclusões: O grau de satisfação do usuário do sistema informatizado de saúde foi considerado bom. Não foram identificados fatores demográficos que influenciassem sua avaliação.

Trial Characteristics That Affect Parental Consent in Neonatal Drug Trials.

OBJECTIVE: The main purpose of this article is to determine parental consent rates in neonatal drug trials and describe trial characteristics associated with higher rates. STUDY DESIGN: We included neonatal drug trials published between 2009 and 2014 and compared parental consent rates among the following characteristics: phase type, gestational age, randomization type, drug administration route, drug dosing frequency, blood sampling, control type, length of study, funding source, and length of treatment. We compared characteristics using chi-square, Fisher's exact, one-way analysis of variance or Kruskal-Wallis tests. RESULTS: We identified 52 trials: 38 trials (73%) reported data of parental consent. Median percentage (interquartile range) of parental consent was 79% (62, 89). Higher rates were observed in studies that used active comparators (87%) and shorter study lengths (81% for studies <24 hours). CONCLUSION: Parental consent rates for neonatal drug trials varied by study characteristics. Information on proportion of parents consented is valuable to assess generalizability of trial results and for preparing trial protocols.

EVALUATION OF USABILITY OF A NEONATAL HEALTH INFORMATION SYSTEM ACCORDING TO THE USER'S PERCEPTION.

OBJECTIVE: To measure the level of satisfaction regarding the usability of a neonatal health information system and identify if demographic factors can influence the usability of a health information system. METHODS: A cross-sectional, exploratory study was carried out with a convenience sample of 50 users of the Brazilian Neonatal Research Network. The instrument chosen for the usability evaluation was the System Usability Scale between February and March 2017. The statistical analysis of the collected variables was carried out in order to describe the sample, to quantify the level of satisfaction of the users and to identify the variables associated with the level of satisfaction. RESULTS: The female gender represented 75% of the sample. The mean age was 52.8 years; 58% had a doctoral degree, average time of graduation was 17 years, with area of practice in medicine (neonatology), with intermediate knowledge in computer science (74%) and mean system use time of 52 months. Regarding usability, 94% rated the system as "good", "excellent" or "better than imaginable". The usability of the system was not associated with age, gender, education, profession, area of practice, knowledge in computer science and time of system use. CONCLUSION: The level of satisfaction of the computerized health system user was considered good. No demographic factors were associated with the satisfaction of the users.

Maintaining normothermia: Why and how?

A high incidence of postnatal hypothermia has been reported in high-as well low-resource countries and it remains an independent predictor of neonatal morbidity and mortality, especially in very preterm infants in all settings. The temperature of newly born infants should be maintained between 36.5 and 37.5 °C after birth through admission and stabilization. Interventions to achieve this may include environmental temperature 23-25 °C, use of radiant warmers, exothermic mattresses, woollen or plastic caps, plastic wraps, humidified and heated gases. Skin-to-skin contact has been used, especially in low-resource settings. The combinations of these interventions applied to quality improvement initiatives, including staff training, use of checklists, and continuous feedback with the staff involved in the management of the neonate, are key factors to prevent heat loss from delivery room to admission to the neonatal intensive care unit. The admission temperature should be recorded as a predictor of outcomes as well as a quality indicator.

Early lumbar puncture and risk of intraventricular hemorrhage in very low birth weight infants.

BACKGROUND: Lumbar puncture (LP) is the gold standard for diagnosing meningitis; however it is unknown whether early LP (≤3days of life) is associated with increased risk of intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants. OBJECTIVE: To determine whether early LP in VLBW infants is associated with severe IVH. METHODS: VLBW infants from a cohort of 1,158,789 infants discharged from 382 neonatal intensive care units (1997-2015) were enrolled. EXCLUSION CRITERIA: infants with major congenital anomalies, outborns, died/transferred prior to day of life 3, and those who had an LP performed only after day of life 3. Logistic regression was used to determine the association between early LP and the incidence of severe IVH (IVH grades 3/4) by 28days of life for each day of life from day 0 (birth) to day 3, adjusting for clinical covariates. RESULTS: 106,461 infants were included: 754 received an LP on Day-0, 640 on Day-1, 559 on Day-2 and 483 on Day-3. Severe IVH occurred in 4% (4130/104,025) of the infants in the no LP group and 9% (217/2436) of the LP group. Severe IVH was higher for infants with early LP: adjusted OR (95% confidence interval)=2.64 (1.96-3.54) on Day-0; 2.21 (1.61-3.04) on Day-1; 1.55 (1.03-2.34) on Day-2; and 2.25 (1.50-3.38) on Day-3. CONCLUSIONS: Early LP was associated with severe IVH in VLBW infants by 28days of life. LP is either a surrogate for an unrecognized factor or is itself associated with an increased risk of IVH.

Early Empiric Antibiotic Use Is Associated With Delayed Feeding Tolerance in Preterm Infants: A Retrospective Analysis.

The causative factors of neonatal feeding intolerance are poorly understood, but potentially related to clinical practices such as empiric antibiotic usage. The objective of this study was to evaluate whether early empiric antibiotic exposure negatively affects preterm infants' enteral feeding tolerance. Data from infants without risk factors for sepsis, 500 to 1499 g birth weight and 24 to 34 weeks gestational age were analyzed. The primary outcomes were the empiric antibiotic exposure effects on the infants' total parenteral nutrition usage duration and prevalence of necrotizing enterocolitis (NEC). Among the 901 infants included, 67 were exposed to early empiric antibiotic. A 50% increase in parenteral nutrition usage duration and a 4-fold greater prevalence of NEC was seen in the early empiric antibiotic-exposed neonates, when compared with control infants (P < 0.01). Early empiric antibiotic exposure appears to negatively influence preterm infant feeding tolerance and possibly contributes to NEC.

Safety of histamine-2 receptor blockers in hospitalized VLBW infants.

BACKGROUND: Histamine-2 receptor (H2) blockers are often used in very low birth weight infants despite lack of population specific efficacy and safety data. AIMS: We sought to describe safety and temporal trends in histamine-2 receptor (H2) blocker use in hospitalized very low birth weight (VLBW) infants. STUDY DESIGN: We conducted a retrospective cohort study using a clinical database populated by an electronic health record shared by 348 neonatal intensive care units in the United States. SUBJECTS: We included all VLBW infants without major congenital anomalies. OUTCOME MEASURES: We used multivariable logistic regression with generalizing estimating equations to evaluate the association between days of H2 blocker exposure and risk of: 1) death or necrotizing enterocolitis (NEC); 2) death or sepsis; and 3) death, NEC, or sepsis. RESULTS: Of 127,707 infants, 20,288 (16%) were exposed to H2 blockers for a total of 6,422,352days. Median gestational age for infants exposed to H2 blockers was 27weeks (25th 75th percentile 26, 29). H2 blocker use decreased from 18% of infants in 1997 to 8% in 2012 (p<0.001). On multivariable analysis, infants were at increased risk of the combined outcome of death, NEC, or sepsis on days exposed to H2 blockers (odds ratio=1.14) (95% confidence interval 1.08, 1.19). CONCLUSIONS: H2 blocker use is associated with increased risk of the combined outcome of death, NEC, or sepsis in hospitalized VLBW infants.

Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants: A Meta-analysis Using Patient-level Data.

BACKGROUND: Invasive candidiasis (IC) is an important cause of sepsis in premature infants and is associated with a high risk of death and neurodevelopmental impairment. Prevention of IC has become a major focus in very low birth weight infants, with fluconazole increasingly used as prophylaxis. METHODS: We identified all randomized, placebo-controlled trials evaluating fluconazole prophylaxis in premature infants conducted in the United States. We obtained patient-level data from the study investigators and performed an aggregated analysis. The occurrence of each endpoint in infants who received prophylaxis with fluconazole vs placebo was compared. Endpoints evaluated were IC or death, IC, death, Candida colonization, and fluconazole resistance among tested isolates. Safety endpoints evaluated included clinical and laboratory parameters. RESULTS: Fluconazole prophylaxis reduced the odds of IC or death, IC, and Candida colonization during the drug exposure period compared with infants given placebo: odds ratios of 0.48 (95% confidence interval [CI], .30-.78), 0.20 (95% CI, .08-.51), and 0.28 (95% CI, .18-.41), respectively. The incidence of clinical and laboratory adverse events was similar for infants who received fluconazole compared with placebo. There was no statistically significant difference in the proportion of tested isolates that were resistant to fluconazole between the fluconazole and placebo groups. CONCLUSIONS: Fluconazole prophylaxis is effective and safe in reducing IC and Candida colonization in premature infants, and has no impact on resistance.

Insulin, Hyperglycemia, and Severe Retinopathy of Prematurity in Extremely Low-Birth-Weight Infants.

OBJECTIVE: This study aims to determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely low-birth-weight (ELBW) infants. STUDY DESIGN: In this retrospective database study, we included all ELBW infants who were ≤ 32 weeks gestational age (GA). We excluded infants without any ophthalmology evaluation and infants who died before 28 days of life. A multivariable model was constructed to determine the association between hyperglycemia, insulin use, and severe ROP. We defined hyperglycemia as blood glucose (BG) > 180 mg/dL. Covariates were GA, small for GA status, discharge year, sex, Apgar score at 5 minutes, mechanical ventilation, oxygen use, bacteremia, and postnatal steroid exposure. We defined severe ROP as ROP requiring bevacizumab, cryotherapy, laser therapy, or vitrectomy. Sensitivity analysis using BG > 150 mg/dL and > 200 mg/dL was performed. RESULTS: A total of 24,548 infants were included; 2,547 (10%) had severe ROP. Hyperglycemia alone was not associated with severe ROP (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.66-1.17). Hyperglycemia and insulin use were not associated with severe ROP (OR, 1.43; 95% CI, 0.91-2.23). BG > 150 mg/dL and insulin use were associated with severe ROP (OR, 1.34; 95% CI, 1.02-1.76). CONCLUSIONS: Hyperglycemia alone was not associated with severe ROP in ELBW infants. However, we did observe a possible trend between the use of insulin and severe ROP.

Early Hyperglycemia in Pediatric Traumatic Brain Injury Predicts for Mortality, Prolonged Duration of Mechanical Ventilation, and Intensive Care Stay.

We aim to study the association between hyperglycemia and in-hospital outcomes among children with moderate and severe traumatic brain injury (TBI). This retrospective cohort study was conducted in a tertiary pediatric hospital between 2003 and 2013. All patients < 16 years old who presented to the Emergency Department within 24 hours of head injury with a Glasgow Coma Scale (GCS) ≤ 13 were included. Our outcomes of interest were death, 14 ventilation-free, 14 pediatric intensive care unit- (PICU-) free, and 28 hospital-free days. Hyperglycemia was defined as glucose > 200 mg/dL (11.1 mmol/L). Among the 44 patients analyzed, the median age was 8.6 years (interquartile range (IQR) 5.0-11.0). Median GCS and pediatric trauma scores were 7 (IQR 4-10) and 4 (IQR 3-6), respectively. Initial hyperglycemia was associated with death (37% in the hyperglycemia group versus 8% in the normoglycemia group, p = 0.019), reduced median PICU-free days (6 days versus 11 days, p = 0.006), and reduced median ventilation-free days (8 days versus 12 days, p = 0.008). This association was however not significant in the stratified analysis of patients with GCS ≤ 8. Conclusion. Our findings demonstrate that early hyperglycemia is associated with increased mortality, prolonged duration of mechanical ventilation, and PICU stay in children with TBI.

Pediatric post-marketing safety systems in North America: assessment of the current status.

PURPOSE: It is critical to have pediatric post-marketing safety systems that contain enough clinical and epidemiological detail to draw regulatory, public health, and clinical conclusions. The pediatric safety surveillance workshop (PSSW), coordinated by the Food and Drug Administration (FDA), identified these pediatric systems as of 2010. This manuscript aims to update the information from the PSSW and look critically at the systems currently in use. METHODS: We reviewed North American pediatric post-marketing safety systems such as databases, networks, and research consortiums found in peer-reviewed journals and other online sources. We detail clinical examples from three systems that FDA used to assess pediatric medical product safety. RESULTS: Of the 59 systems reviewed for pediatric content, only nine were pediatric-focused and met the inclusion criteria. Brief descriptions are provided for these nine. The strengths and weaknesses of three systems (two of the nine pediatric-focused and one including both children and adults) are illustrated with clinical examples. CONCLUSIONS: Systems reviewed in this manuscript have strengths such as clinical detail, a large enough sample size to capture rare adverse events, and/or a patient denominator internal to the database. Few systems include all of these attributes. Pediatric drug safety would be better informed by utilizing multiple systems to take advantage of their individual characteristics.

Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review.

IMPORTANCE: Obesity affects nearly one-sixth of US children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxic side effects. The depth of available literature regarding obesity's effect on drug safety, pharmacokinetics, and dosing in obese children is unknown. OBJECTIVE: To perform a systematic literature review describing the current evidence of the effect of obesity on drug disposition in children. EVIDENCE REVIEW: We searched the MEDLINE, Cochrane, and EMBASE databases (January 1, 1970-December 31, 2012) and included studies if they contained data on drug clearance, volume of distribution, or drug concentration in obese children (aged ≤18 years). We compared exposure and weight-normalized volume of distribution and clearance between obese and nonobese children. We explored the association between drug physicochemical properties and clearance and volume of distribution. FINDINGS: Twenty studies met the inclusion criteria and contained pharmacokinetic data for 21 drugs. The median number of obese children studied per drug was 10 (range, 1-112) and ages ranged from newborn to 29 years (1 study described pharmacokinetics in children and adults together). Dosing schema varied and were either a fixed dose (6 [29%]) or based on body weight (10 [48%]) and body surface area (4 [19%]). Clinically significant pharmacokinetic alterations were observed in obese children for 65% (11 of 17) of the studied drugs. Pharmacokinetic alterations resulted in substantial differences in exposure between obese and nonobese children for 38% (5 of 13) of the drugs. We found no association between drug lipophilicity or Biopharmaceutical Drug Disposition Classification System class and changes in volume of distribution or clearance due to obesity. CONCLUSIONS AND RELEVANCE: Consensus is lacking on the most appropriate weight-based dosing strategy for obese children. Prospective pharmacokinetic trials in obese children are needed to ensure therapeutic efficacy and enhance drug safety.

Safety of octreotide in hospitalized infants.

BACKGROUND: Octreotide is used off-label in infants for treatment of chylothorax, congenital hyperinsulinism, and gastrointestinal bleeding. The safety profile of octreotide in hospitalized infants has not been described; we sought to fill this information gap. METHODS: We identified all infants exposed to at least 1 dose of octreotide from a cohort of 887,855 infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012. We collected laboratory and clinical information while infants were exposed to octreotide and described the frequency of baseline diagnoses, laboratory abnormalities, and clinical adverse events (AEs). RESULTS: A total of 428 infants received 490 courses of octreotide. The diagnoses most commonly associated with octreotide use were chylothorax (50%), pleural effusion (32%), and hypoglycemia (22%). The most common laboratory AEs that occurred during exposure to octreotide were thrombocytopenia (47/1000 infant-days), hyperkalemia (21/1000 infant-days), and leukocytosis (20/1000 infant-days). Hyperglycemia occurred in 1/1000 infant-days and hypoglycemia in 3/1000 infant-days. Hypotension requiring pressors (12%) was the most common clinical AE that occurred during exposure to octreotide. Necrotizing enterocolitis was observed in 9/490 (2%) courses, and death occurred in 11 (3%) infants during octreotide administration. CONCLUSION: Relatively few AEs occurred during off-label use of octreotide in this cohort of infants. Additional studies are needed to further evaluate the safety, dosing, and efficacy of this medication in infants.

Management Practice and Mortality for Infants with Congenital Diaphragmatic Hernia.

OBJECTIVE: Congenital diaphragmatic hernia (CDH) is fatal in 20 to 40% of cases, largely due to pulmonary dysmaturity, lung hypoplasia, and persistent pulmonary hypertension. Evidence for survival benefit of inhaled nitric oxide (iNO), extracorporeal membrane oxygenation (ECMO), and other medical interventions targeting pulmonary hypertension is lacking. We assessed medical interventions and mortality over time in a large multicenter cohort of infants with CDH. STUDY DESIGN: We identified all infants ≥ 34 weeks' gestation with CDH discharged from 29 neonatal intensive care units between 1999 and 2012 with an average of ≥ 2 CDH admissions per year. We examined mortality and the proportion of infants exposed to medical interventions, comparing four periods of time: 1999-2001, 2002-2004, 2005-2007, and 2008-2012. RESULTS: We identified 760 infants with CDH. From 1999-2001 to 2008-2012, use of iNO increased from 20% of infants to 50%, sildenafil use increased from 0 to 14%, and milrinone use increased from 0 to 22% (p < 0.001). Overall mortality (28%) did not significantly change over time compared with the earliest time period. CONCLUSION: Despite changing use of iNO, sildenafil, and milrinone, CDH mortality has not significantly decreased in this population of infants.

Epidemiology of pediatric acute respiratory distress syndrome in singapore: risk factors and predictive respiratory indices for mortality.

AIM: Acute respiratory distress syndrome (ARDS) represents the most severe form of acute lung injury. The aim of our study is to describe the epidemiology of pediatric ARDS in Singapore and compare the outcomes of ARDS using the following respiratory indices: PaO2/FiO2 ratio (P/F ratio), SpO2/FiO2 ratio (S/F ratio), oxygenation index (OI), and oxygen saturation index (OSI). METHODS: We examined medical records of patients admitted to the Children's Intensive Care Unit in KK Women's and Children's Hospital from 2009 to 2012. Those who fulfilled criteria for the American-European Consensus Conference definition for ARDS were identified. Demographic, clinical, and radiographic information were extracted and analyzed. RESULTS: We identified 70 patients with ARDS. Median age (interquartile range) was 6.2 (1.4, 10.4) years. The most common risk factor was pneumonia [50 (71%)]. Overall mortality was 44 (63%) patients. Thirty-two (56%) patients had an underlying chronic comorbidity; 18 (46%) were hematology-oncology conditions. Fifty-six (80%) patients had multiorgan dysfunction. Adjunct therapies used in our patients included inhaled nitric oxide [5 (7%)], prone position [22 (31%)], steroids [26 (37%)], and neuromuscular blockade [26 (37%)]. A high OI and low PF ratio after 24 h of diagnosis of ARDS were associated with mortality. From day 3 onward, all four respiratory indices appropriately differentiated survivors from non-survivors. Severity based on the S/F ratio and OSI demonstrated association with decreased ventilator free days and ICU free days. CONCLUSION: Risk factors for mortality included having an underlying comorbidity, multiorgan dysfunction, a low PF ratio, and high OI at 24 h of ARDS. Abnormal SpO2-based measurements were reliable markers of poor outcomes in pediatric ARDS.

Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trial.

IMPORTANCE: Invasive candidiasis in premature infants causes death and neurodevelopmental impairment. Fluconazole prophylaxis reduces candidiasis, but its effect on mortality and the safety of fluconazole are unknown. OBJECTIVE: To evaluate the efficacy and safety of fluconazole in preventing death or invasive candidiasis in extremely low-birth-weight infants. DESIGN, SETTING, AND PATIENTS: This study was a randomized, blinded, placebo-controlled trial of fluconazole in premature infants. Infants weighing less than 750 g at birth (N = 361) from 32 neonatal intensive care units (NICUs) in the United States were randomly assigned to receive either fluconazole or placebo twice weekly for 42 days. Surviving infants were evaluated at 18 to 22 months corrected age for neurodevelopmental outcomes. The study was conducted between November 2008 and February 2013. INTERVENTIONS: Fluconazole (6 mg/kg of body weight) or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was a composite of death or definite or probable invasive candidiasis prior to study day 49 (1 week after completion of study drug). Secondary and safety outcomes included invasive candidiasis, liver function, bacterial infection, length of stay, intracranial hemorrhage, periventricular leukomalacia, chronic lung disease, patent ductus arteriosus requiring surgery, retinopathy of prematurity requiring surgery, necrotizing enterocolitis, spontaneous intestinal perforation, and neurodevelopmental outcomes-defined as a Bayley-III cognition composite score of less than 70, blindness, deafness, or cerebral palsy at 18 to 22 months corrected age. RESULTS: Among infants receiving fluconazole, the composite primary end point of death or invasive candidiasis was 16% (95% CI, 11%-22%) vs 21% in the placebo group (95% CI, 15%-28%; odds ratio, 0.73 [95% CI, 0.43-1.23]; P = .24; treatment difference, -5% [95% CI, -13% to 3%]). Invasive candidiasis occurred less frequently in the fluconazole group (3% [95% CI, 1%-6%]) vs the placebo group (9% [95% CI, 5%-14%]; P = .02; treatment difference, -6% [95% CI, -11% to -1%]). The cumulative incidences of other secondary outcomes were not statistically different between groups. Neurodevelopmental impairment did not differ between the groups (fluconazole, 31% [95% CI, 21%-41%] vs placebo, 27% [95% CI, 18%-37%]; P = .60; treatment difference, 4% [95% CI, -10% to 17%]). CONCLUSIONS AND RELEVANCE: Among infants with a birth weight of less than 750 g, 42 days of fluconazole prophylaxis compared with placebo did not result in a lower incidence of the composite of death or invasive candidiasis. These findings do not support the universal use of prophylactic fluconazole in extremely low-birth-weight infants. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00734539.

Late-onset bloodstream infections in hospitalized term infants.

BACKGROUND: The epidemiology and incidence of late-onset blood stream infections (BSIs) in premature infants have been described, but studies describing late-onset BSI in term infants are sparse. We sought to describe the pathogens, incidence, risk factors and mortality of late-onset BSI in hospitalized term infants. METHODS: A cohort study was conducted of infants ≥37 weeks gestational age and ≤120 days of age discharged from Pediatrix Medical Group neonatal intensive care units from 1997 to 2010. We examined all cultures obtained from day of life 4-120 and used multivariable regression to assess risk factors for late-onset BSI. RESULTS: We found a total of 206,019 infants cared for between day of life 4 and 120, and the incidence of late-onset BSI was 2.7/1000 admissions. We identified Gram-positive organisms in 64% of the cultures and Gram-negative organisms in 26%. We found a decreased risk of late-onset BSI in infants with the following characteristics: small for gestational age, delivery by Cesarean, antenatal antibiotic use and discharged in the later years of the study. Late-onset BSI increased the risk of death after controlling for confounders [odds ratio 8.43 (95% confidence interval 4.42-16.07)]. CONCLUSION: Our data highlight the importance of late-onset BSI in hospitalized term infants. We identified Gram-positive organisms as the most common pathogen, and late-onset BSI was an independent risk factor for death.

Reducing central line-associated bloodstream infections in North Carolina NICUs.

OBJECTIVE: Central lines in NICUs have long dwell times. Success in reducing central line-associated bloodstream infections (CLABSIs) requires a multidisciplinary team approach to line maintenance and insertion. The Perinatal Quality Collaborative of North Carolina (PQCNC) CLABSI project supported the development of NICU teams including parents, the implementation of an action plan with unique bundle elements and a rigorous reporting schedule. The goal was to reduce CLABSI rates by 75%. METHODS: Thirteen NICUs participated in an initiative developed over 3 months and deployed over 9 months. Teams participated in monthly webinars and quarterly face-to-face learning sessions. NICUs reported on bundle compliance and National Health Surveillance Network infection rates at baseline, during the intervention, and 3 and 12 months after the intervention. Process and outcome indicators were analyzed using statistical process control methods (SPC). RESULTS: Near-daily maintenance observations were requested for all lines with a 68% response rate. SPC analysis revealed a trend to an increase in bundle compliance. We also report significant adoption of a new maintenance bundle element, central line removal when enteral feedings reached 120 ml/kg per day. The PQCNC CLABSI rate decreased 71%, from 3.94 infections per 1000 line days to 1.16 infections per 1000 line days with sustainment 1 year later (P = .01). CONCLUSIONS: A collaborative structure targeting team development, family partnership, unique bundle elements and strict reporting on line care produced the largest reduction in CLABSI rates for any multiinstitutional NICU collaborative.