Whole genome sequencing as a first-tier diagnostic test for infants in neonatal intensive care units: A pilot study in Brazil.

In this pilot study, we aimed to evaluate the feasibility of whole genome sequencing (WGS) as a first-tier diagnostic test for infants hospitalized in neonatal intensive care units in the Brazilian healthcare system. The cohort presented here results from a joint collaboration between private and public hospitals in Brazil considering the initiative of a clinical laboratory to provide timely diagnosis for critically ill infants. We performed trio (proband and parents) WGS in 21 infants suspected of a genetic disease with an urgent need for diagnosis to guide medical care. Overall, the primary indication for genetic testing was dysmorphic syndromes (n = 14, 67%) followed by inborn errors of metabolism (n = 6, 29%) and skeletal dysplasias (n = 1, 5%). The diagnostic yield in our cohort was 57% (12/21) based on cases that received a definitive or likely definitive diagnostic result from WGS analysis. A total of 16 pathogenic/likely pathogenic variants and 10 variants of unknown significance were detected, and in most cases inherited from an unaffected parent. In addition, the reported variants were of different types, but mainly missense (58%) and associated with autosomal diseases (19/26); only three were associated with X-linked diseases, detected in hemizygosity in the proband an inherited from an unaffected mother. Notably, we identified 10 novel variants, absent from public genomic databases, in our cohort. Considering the entire diagnostic process, the average turnaround time from enrollment to medical report in our study was 53 days. Our findings demonstrate the remarkable utility of WGS as a diagnostic tool, elevating the potential of transformative impact since it outperforms conventional genetic tests. Here, we address the main challenges associated with implementing WGS in the medical care system in Brazil, as well as discuss the potential benefits and limitations of WGS as a diagnostic tool in the neonatal care setting.

Risk factors for acute kidney injury in very-low birth weight newborns: a systematic review with meta-analysis.

This study aims to analyze the main risk factors for acute kidney injury in the subgroup of very-low birth weight newborns, using the diagnosing criteria of the Kidney Disease Improving Global Outcomes (KDIGO) or the Acute Kidney Injury Network (AKIN). A systematic review of the literature was performed on the EMBASE® and PubMed® platforms. Studies that evaluated the risk factors for developing AKI in VLBW newborns were included. For the meta-analysis, we only included the risk factors that were associated with AKI in the univariate analysis of at least two studies. After an initial screening, abstract readings, and full-text readings, 10 articles were included in the systematic review and 9 in the meta-analysis. The incidence of AKI varied from 11.6 to 55.8%. All the studies have performed multivariate analysis, and the risk factors that appeared most were PDA and hemodynamic instability (use of inotropes or hypotension), sepsis, and invasive mechanical ventilation. After the meta-analysis, only cesarian delivery did not show an increased risk of AKI, all the other variables remained as important risk factors. Moreover, in our meta-analysis, we found a pooled increased risk of death in newborns with AKI almost 7 times.  Conclusion: AKI in VLBW has several risk factors and must be seen as a multifactorial disease. The most common risk factors were PDA, hemodynamic instability, sepsis, and invasive mechanical ventilation. What is known: • Acute kidney injury is associated with worst outcomes in all ages. It´s prevention can help diminish mortality. What is new: • A synthesis of the main risk factors associated with AKI in very low birth weight newborns.

Reassessing the role of milrinone in the treatment of heart failure and pulmonary hypertension in neonates and children: a systematic review and meta-analysis.

To evaluate milrinone's impact on pediatric cardiac function, focusing on its specific role as an inotrope and lusitrope, while considering its systemic and pulmonary vasodilatory effects. Search of PubMed, EMBASE, and the Cochrane Library up to August 2023. We included all studies that evaluated milrinone in children under 18 years old in neonatal, pediatric, or cardiac intensive care units. We excluded case reports, studies that did not provide tabular information on milrinone's outcomes, and studies focused on non-intensive care populations. We extracted data on the research design, objectives, study sample, and results of each study, including the impact of milrinone and any associated factors. We screened a total of 9423 abstracts and 41 studies were ultimately included. Milrinone significantly improved left ventricular ejection fraction (WMD 3.41 [95% CI 0.61 - 6.21]), left ventricle shortening fraction (WMD 4.25 [95% CI 3.43 - 5.08]), cardiac index (WMD 0.50 [95% CI 0.32 to 0.68]), left ventricle output (WMD 55.81 [95% CI 4.91 to 106.72]), serum lactate (WMD -0.59 [95% CI -1.15 to -0.02]), and stroke volume index (WMD 2.95 [95% CI 0.09 - 5.82]). However, milrinone was not associated with improvements in ventricular myocardial performance index (WMD -0.01 [95% CI -0.06 to 0.04]) and ventricular longitudinal strain (WMD -2.14 [95% CI -4.56 to 0.28]). Furthermore, milrinone was not associated with isovolumetric relaxation time reduction (WMD -8.87 [95% CI -21.40 to 3.66]). CONCLUSION: Our meta-analysis suggests potential clinical benefits of milrinone by improving cardiac function, likely driven by its systemic vasodilatory effects. However, questions arise about its inotropic influence and the presence of a lusitropic effect. Moreover, milrinone's pulmonary vasodilatory effect appears relatively weaker compared to its systemic actions. Further research is needed to elucidate milrinone's precise mechanisms and refine its clinical applications in pediatric practice. WHAT IS KNOWN: • Milrinone is a phosphodiesterase III inhibitor that has been used to treat a variety of pediatric and neonatal conditions. • Milrinone is believed to exert its therapeutic effects by enhancing cardiac contractility and promoting vascular relaxation. WHAT IS NEW: • Milrinone may not have a significant inotropic effect. • Milrinone's pulmonary vasodilatory effect is less robust than its systemic vasodilatory effect.

Identifying two distinct subphenotypes of patent ductus arteriosus in preterm infants using machine learning.

To use unsupervised machine learning to identify potential subphenotypes of preterm infants with patent ductus arteriosus (PDA). The study was conducted retrospectively at a neonatal intensive care unit in Brazil. Patients with a gestational age < 28 weeks who had undergone at least one echocardiogram within the first two weeks of life and had PDA size > 1.5 or LA/AO ratio > 1.5 were included. Agglomerative hierarchical clustering on principal components was used to divide the data into different clusters based on common characteristics. Two distinct subphenotypes of preterm infants with hemodynamically significant PDA were identified: "inflamed," characterized by high leukocyte, neutrophil, and neutrophil-to-lymphocyte ratio, and "respiratory acidosis," characterized by low pH and high pCO2 levels.    Conclusions: This study suggests that there may be two distinct subphenotypes of preterm infants with hemodynamically significant PDA: "inflamed" and "respiratory acidosis." By dividing the population into different subgroups based on common characteristics, it is possible to get a more nuanced understanding of the effectiveness of PDA interventions. What is Known: • Treatment of PDA in preterm infants has been controversial. • Stratification of preterm infants with PDA into subgroups is important in order to determine the best treatment. What is New: • Unsupervised machine learning was used to identify two subphenotypes of preterm infants with hemodynamically significant PDA. • The 'inflamed' cluster was characterized by higher values of leukocyte, neutrophil, and neutrophil-to-lymphocyte ratio. The 'respiratory acidosis' cluster was characterized by lower pH values and higher pCO2 values.

Risk factors for shunting at 12 months following open fetal repair of spina bifida by mini-hysterotomy.

OBJECTIVES: Open spina bifida (OSB) is the most common neural tube defect. Prenatal repair reduces the need for ventriculoperitoneal shunting (VPS) due to hydrocephalus from 80-90% to 40-50%. We aimed to determine which variables work as risk factors for VPS at 12 months of age in our population. METHODS: Thirty-nine patients underwent prenatal repair of OSB by mini-hysterotomy. The main outcome was occurrence of VPS in the first 12 months of life. Logistic regression was used to estimate the odds ratios (OR) between prenatal variables and the need for shunting. RESULTS: VPS at 12 months occurred in 34.2% of the children. Larger ventricle size before surgery (62.5% ≥15 mm; 46.2% between 12 and 15 mm; 11.8% <12 mm; p=0.008), higher lesion level (80% >L2, vs. 17.9% ≤L3; p=0.002; OR, 18.4 [2.96-114.30]), and later gestational age at surgery (25.25 ± 1.18 vs. 24.37 ± 1.06 weeks; p=0.036; OR, 2.23 [1.05-4.74]) were related to increased need for shunting. In the multivariate analysis, larger ventricle size before surgery (≥15 mm vs. <12 mm; p=0.046; OR, 1.35 [1.01-1.82]) and higher lesion level (>L2 vs. ≤L3; p=0.004; OR, 39.52 [3.25-480.69]) were risk factors for shunting. CONCLUSIONS: Larger ventricle size before surgery (≥15 mm) and higher lesion level (>L2) are independent risk factors for VPS at 12 months of age in fetuses undergoing prenatal repair of OSB by mini-hysterotomy in the studied population.

Three-Dimensional Ultrasound Evaluation of Lung Volume in Fetuses with Abdominal Wall Defect.

INTRODUCTION: Abdominal wall defects (AWDs) interfere with postnatal respiratory parameters. We aimed to evaluate lung volume (LV) in fetuses with AWD using three-dimensional (3D) ultrasound (US) and to correlate AWD with the type (omphalocele and gastroschisis) and size of the defect and neonatal morbidity and mortality. METHODS: This prospective observational study included 72 pregnant women with fetuses with AWD and a gestational age <25 weeks. The data on abdominal volume, 3D US LV, and herniated volume were acquired every 4 weeks up to 33 weeks. LV was compared with normal reference curves and correlated with abdominal and herniated volumes. RESULTS: Omphalocele (p < 0.001) and gastroschisis (p < 0.001) fetuses had smaller LV than normal fetuses. LV was positively correlated with abdominal volume (omphalocele, r = 0.86; gastroschisis, r = 0.88), whereas LV was negatively correlated with omphalocele-herniated volume/abdominal volume (p < 0.001, r = -0.51). LV was smaller in omphalocele fetuses that died (p = 0.002), were intubated (p = 0.02), or had secondary closure (p < 0.001). In gastroschisis, a smaller LV was observed in fetuses discharged using oxygen (p = 0.002). CONCLUSION: Fetuses with AWD had smaller 3D LV than normal fetuses. Fetal abdominal volume was inversely correlated with LV. In omphalocele fetuses, a smaller LV was associated with neonatal mortality and morbidity.

Association between fluid overload and mortality in newborns: a systematic review and meta-analysis.

Fluid overload (FO) is associated with higher rates of mortality and morbidity in pediatric and adult populations. The aim of this systematic review and meta-analysis was to investigate the association between FO and mortality in critically ill neonates. Systematic search of Ovid MEDLINE, EMBASE, Cochrane Library, trial registries, and gray literature from inception to January 2021. We included all studies that examined neonates admitted to neonatal intensive care units and described FO and outcomes of interest. We identified 17 observational studies with a total of 4772 critically ill neonates who met the inclusion criteria. FO was associated with higher mortality (OR, 4.95 [95% CI, 2.26-10.87]), and survivors had a lower percentage of FO compared with nonsurvivors (WMD, - 4.33 [95% CI, - 8.34 to - 0.32]). Neonates who did not develop acute kidney injury (AKI) had lower FO compared with AKI patients (WMD, - 2.29 [95% CI, - 4.47 to - 0.10]). Neonates who did not require mechanical ventilation on postnatal day 7 had lower fluid balance (WMD, - 1.54 [95% CI, - 2.21 to - 0.88]). FO is associated with higher mortality, AKI, and need for mechanical ventilation in critically ill neonates in the intensive care unit. Strict control of fluid balance to prevent FO is essential. A higher resolution version of the Graphical abstract is available as Supplementary information.

Latin American Consensus on the Management of Sepsis in Children: Sociedad Latinoamericana de Cuidados Intensivos Pediátricos [Latin American Pediatric Intensive Care Society] (SLACIP) Task Force: Executive Summary.

Objective: The aim of this study was to develop evidence-based recommendations for the diagnosis and treatment of sepsis in children in low- and middle-income countries (LMICs), more specifically in Latin America. Design: A panel was formed consisting of 27 experts with experience in the treatment of pediatric sepsis and two methodologists working in Latin American countries. The experts were organized into 10 nominal groups, each coordinated by a member. Methods: A formal consensus was formed based on the modified Delphi method, combining the opinions of nominal groups of experts with the interpretation of available scientific evidence, in a systematic process of consolidating a body of recommendations. The systematic search was performed by a specialized librarian and included specific algorithms for the Cochrane Specialized Register, PubMed, Lilacs, and Scopus, as well as for OpenGrey databases for grey literature. The GRADEpro GDT guide was used to classify each of the selected articles. Special emphasis was placed on search engines that included original research conducted in LMICs. Studies in English, Spanish, and Portuguese were covered. Through virtual meetings held between February 2020 and February 2021, the entire group of experts reviewed the recommendations and suggestions. Result: At the end of the 12 months of work, the consensus provided 62 recommendations for the diagnosis and treatment of pediatric sepsis in LMICs. Overall, 60 were strong recommendations, although 56 of these had a low level of evidence. Conclusions: These are the first consensus recommendations for the diagnosis and management of pediatric sepsis focused on LMICs, more specifically in Latin American countries. The consensus shows that, in these regions, where the burden of pediatric sepsis is greater than in high-income countries, there is little high-level evidence. Despite the limitations, this consensus is an important step forward for the diagnosis and treatment of pediatric sepsis in Latin America.

Identifying clinical phenotypes in extremely low birth weight infants-an unsupervised machine learning approach.

There is increasing evidence that patient heterogeneity significantly hinders advancement in clinical trials and individualized care. This study aimed to identify distinct phenotypes in extremely low birth weight infants. We performed an agglomerative hierarchical clustering on principal components. Cluster validation was performed by cluster stability assessment with bootstrapping method. A total of 215 newborns (median gestational age 27 (26-29) weeks) were included in the final analysis. Six clusters with different clinical and laboratory characteristics were identified: the "Mature" (Cluster 1; n = 60, 27.9%), the mechanically ventilated with "adequate ventilation" (Cluster 2; n = 40, 18.6%), the mechanically ventilated with "poor ventilation" (Cluster 3; n = 39, 18.1%), the "extremely immature" (Cluster 4; n = 39, 18.1%%), the neonates requiring "Intensive Resuscitation" in the delivery room (Cluster 5; n = 20, 9.3%), and the "Early septic" group (Cluster 6; n = 17, 7.9%). In-hospital mortality rates were 11.7%, 25%, 56.4%, 61.5%, 45%, and 52.9%, while severe intraventricular hemorrhage rates were 1.7%, 5.3%, 29.7%, 47.2%, 44.4%, and 28.6% in clusters 1, 2, 3, 4, 5, and 6, respectively (p < 0.001).Conclusion: Our cluster analysis in extremely preterm infants was able to characterize six distinct phenotypes. Future research should explore how better phenotypic characterization of neonates might improve care and prognosis. What is Known: • Patient heterogeneity is becoming more acknowledged as a cause of clinical trial failure. • Machine learning algorithms can find patterns within a heterogeneous group. What is New: • We identified six different phenotypes of extremely preterm infants who exhibited distinct clinical and laboratorial characteristics.

Electrical impedance tomography clues to detect pulmonary thrombosis in a teenager with COVID-19.

We report a case of pulmonary thrombosis in a teenager during a hypercoagulable state associated with COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). A condition rare in children and adolescents, pulmonary thrombosis underdiagnosis likely increases morbidity and mortality. A pulmonary thrombosis diagnosis requires a high level of suspicion and relies on the combination of clinical presentation, D-dimer elevation, and computed tomography (CT) pulmonary angiography or ventilation/perfusion scans, imaging techniques that are difficult to perform. Electrical impedance tomography (EIT) has gained attention, as it provides real-time ventilation distribution analysis. In addition, lung pulsatility images can be obtained through this technique using electrocardiogram gating to filter out ventilation. In this case report, the reduced EIT pulsatility corresponded to the perfusion defect found on the CT scan, information that was obtained at the bedside without radiation or contrast exposure.

Risk Perception and Decision Making about Early-Onset Sepsis among Neonatologists: A National Survey.

OBJECTIVE: Many newborns are investigated and empirically treated for suspected early-onset sepsis (EOS). This study aimed to describe neonatologists' self-identified risk thresholds for investigating and treating EOS and assess the consistency of these thresholds with clinical decisions. STUDY DESIGN: Voluntary online survey, available in two randomized versions, sent to neonatologists from 20 centers of the Brazilian Network on Neonatal Research. The surveys included questions about thresholds for investigating and treating EOS and presented four clinical scenarios with varying calculated risks. In survey version A, only the scenarios were presented, and participants were asked if they would order a blood test or start antibiotics. Survey version B presented the same scenarios and the risk of sepsis. Clinical decisions were compared between survey versions using chi-square tests and agreement between thresholds and clinical decisions were investigated using Kappa coefficients. RESULTS: In total, 293 surveys were completed (145 survey version A and 148 survey version B). The median risk thresholds for blood test and antibiotic treatment were 1:100 and 1:25, respectively. In the high-risk scenario, there was no difference in the proportion choosing antibiotic therapy between the groups. In the moderate-risk scenarios, both tests and antibiotics were chosen more frequently when the calculated risks were included (survey version B). In the low-risk scenario, there was no difference between survey versions. There was poor agreement between the self-described thresholds and clinical decisions. CONCLUSION: Neonatologists overestimate the risk of EOS and underestimate their risk thresholds. Knowledge of calculated risk may increase laboratory investigation and antibiotic use in infants at moderate risk for EOS. KEY POINTS: · Neonatologists overestimate the risk of EOS.. · There is wide variation in diagnostic/treatment thresholds for EOS.. · Clinical decision on EOS is not consistent with risk thresholds.. · Knowledge of risk may increase investigation and treatment of EOS..

Vertical transmission of SARS-CoV2 during pregnancy: A high-risk cohort.

OBJECTIVE: Identify the potential for and risk factors of SARS-CoV-2 vertical transmission. METHODS: Symptomatic pregnant women with COVID-19 diagnosis in whom PCR for SARS-CoV-2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS-CoV-2 positivity in AF and/or CB on neonatal outcomes were investigated. RESULTS: Overall 73.4% (80/109) were admitted in hospital due to COVID-19, 22.9% needed intensive care and there were four maternal deaths. Positive RT-PCR for SARS-CoV-2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID-19 symptoms and delivery was inversely associated with SARS-CoV-2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS-CoV-2 in AF and/or CB (p = 0.001). SARS-CoV-2 positivity in the compartments was not associated with neonatal outcomes. CONCLUSION: Vertical transmission is possible in pregnant women with COVID-19 and a shorter interval between maternal symptoms and delivery is an influencing factor.

Early fluid overload is associated with mortality and prolonged mechanical ventilation in extremely low birth weight infants.

Recent studies revealed that fluid overload is associated with higher mortality in critically ill children and adults. This study aimed to evaluate the association between fluid overload in the first 3 days of life and mortality in extremely low birth weight infants. This single-center retrospective cohort study included two hundred nineteen newborns with birth weight less than 1000 g who were admitted to the neonatal intensive care between January 2012 and December 2017. Overall mortality was 32.4%, the median gestational age was 27.3 (26.1-29.4) weeks, and birth weight was 770 (610-900) grams. In the group with severe fluid overload, we found a higher rate of deaths (72.2%); mean airway pressure was significantly higher and with longer invasive mechanical ventilation necessity.Conclusion: Early fluid overload in extremely low birth weight infants is associated with higher mortality rate, higher mean airway pressure in invasive mechanically ventilated patients, and longer mechanical ventilation duration in the first 7 days of life. What is Known: • Fluid overload is associated with a higher mortality rate and prolonged mechanical ventilation in children and adults. What is New: • Fluid overload in the first 72 h of life in an extremely premature infant is associated with higher mortality rate, higher mean airway pressure in invasive mechanically ventilated patients, and longer mechanical ventilation duration the first 7 days of life.

First-year profile of biomarkers for early detection of renal injury in infants with congenital urinary tract obstruction.

BACKGROUND: Diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. Use of renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and prevention or minimization of definitive renal damage. METHODS: This longitudinal, prospective study analyzed the first-year profile of two serum renal biomarkers: creatinine (sCr) and cystatin C (sCyC); and six urinary renal biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-ß1), retinol-binding protein (RBP), cystatin C (uCyC), and microalbuminuria (µALB) in a cohort of 37 infants with UTO divided into three subgroups: 14/37 with unilateral hydro(uretero)nephrosis, 13/37 with bilateral hydro(uretero)nephrosis, and 10/37 patients with lower urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. RESULTS: All urine biomarkers showed significantly higher values at the first month of life (p ≤ 0.009), while NGAL (p = 0.005), TGF-ß1 (p < 0.001), and µALB (p < 0.001) were high since birth compared to controls. Best single biomarker performances were RBP in bilateral hydronephrosis and LUTO subgroups and KIM-1 in unilateral hydronephrosis subgroup. Best biomarker combination results for all subgroups were obtained by matching RBP with TGF-ß1 or KIM-1 and NGAL with CyC ([AUC] ≤ 0.934; sensitivity ≤ 92.4%; specificity ≤ 92.8%). CONCLUSIONS: RBP, NGAL, KIM-1, TGF-ß1, and CyC, alone and especially in combination, are relatively efficient in identifying surgically amenable congenital UTO and could be of practical use in indicating on-time surgery.

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.

Anaphylaxis Knowledge Among Pediatric Intensivists in Brazil: A Multicenter Survey.

OBJECTIVE: To assess the knowledge and practice preferences of anaphylaxis treatment among pediatric intensivists in 5 Brazilian pediatric intensive care unit (PICU) settings. STUDY DESIGN: The cohort was a cross-sectional sample from 5 PICUs; a 7-question survey was personally applied to participants regarding their professional clinical experience and the first-line drug choices when treating an anaphylaxis episode. RESULTS: Of 43 participant physicians, the majority (83.8%) correctly identified epinephrine as the treatment of choice for anaphylaxis, yet only 41.9% chooses the intramuscular route of administration. CONCLUSION: This study shows that the knowledge of anaphylaxis treatment is deficient among pediatric intensivists in Brazil. The dissemination of recent World Allergy Organization guidelines on anaphylaxis should be encouraged.

Short-term prognostic factors in myelomeningocele patients.

PURPOSE: Patients with myelomeningocele have a high mortality and neurological disabilities that are correlated with the anatomical characteristics of the defect and with the development of acquired complications. The challenge in the postnatal management of myelomeningocele (MMC) is the early recognition of cases at risk for complications in order to establish individualized treatment strategies. This study aims to identify short-term prognostic markers for newborns with MMC. Anatomical characteristics of the spinal defect and technical aspects of the neurosurgical correction were analyzed for this purpose. METHODS: A retrospective cohort study was conducted in 70 patients with MMC born between January 2007 and December 2013. Features of MMC anatomy and neurosurgical treatment were analyzed for the following outcomes: neonatal resuscitation, length of hospital stay, need for ventricular shunt, wound dehiscence, wound infection, central nervous system infection, and sepsis. RESULTS: Large MMC was associated with central nervous system (CNS) infection, wound complications, and longer hospital stay. Patients with thoracic MMC required longer hospital stay. Surgical repair performed after 48 h of life increased in 5.72 times the risk of CNS infection. Absence of antenatal hydrocephalus was a favorable prognostic marker. CONCLUSION: Extent of the spinal cord defect and the time of surgical correction influenced the short-term outcomes of patients with myelomeningocele. Extensive lesions were associated with higher rates of CNS infections, surgical wound complications, and prolonged hospital stay. Interventions performed within 48 h after birth significantly reduced occurrence of CNS infections. Absence of antenatal hydrocephalus was associated with fewer complications in the first days of life.

Intranasal dexmedetomidine for sedation for pediatric computed tomography imaging.

UNLABELLED: This prospective observational pilot study evaluated the aerosolized intranasal route for dexmedetomidine as a safe, effective, and efficient option for infant and pediatric sedation for computed tomography imaging. The mean time to sedation was 13.4 minutes, with excellent image quality, no failed sedations, or significant adverse events. TRIAL REGISTRATION: Registered with ClinicalTrials.gov: NCT01900405.

Risk Factors for Mortality and Outcomes in Pediatric Acute Lung Injury/Acute Respiratory Distress Syndrome.

OBJECTIVES: Children admitted to PICUs often present with or develop respiratory failure that requires mechanical ventilation. We prospectively identified children admitted to three general PICUs, with the goal of identifying risk factors for mortality. DESIGN: Prospective multicenter observational study. SETTING: Three general PICUs, two in São Paulo and one in Curitiba, Brazil. PATIENTS: Children aged between 1 month and 15 years, consecutively admitted between August 2008 and July 2010, with acute lung injury or acute respiratory distress syndrome that developed at least 12 hours after invasive or noninvasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used logistic regression models to explore the relationship between death and independent variables. Of 3,046 patients admitted to the three PICUs, 1,658 patients underwent mechanical ventilation, and 84 fulfilled the acute lung injury/acute respiratory distress syndrome inclusion criteria and were analyzed. Nearly 60% were boys, and the median age was 31 months. Pressure control/assist control was the initial mode of mechanical ventilation in 86% of cases, and the median durations of mechanical ventilation and PICU stay were 12 and 15 days, respectively. None of the eight patients with acute lung injury died, whereas 33 of 76 of the remaining patients with acute respiratory distress syndrome died, for an overall mortality rate of 39.3% (95% CI, 28.8-50.6%). In different multivariate logistic regression model, the number of organ dysfunctions at admission, peak inspiratory pressure, airway pressure gradient on day 1, and the mean airway pressure gradient over the first 7 days of mechanical ventilation were significantly associated with mortality. CONCLUSION: Mortality is high in pediatric acute lung injury/acute respiratory distress syndrome. Mechanical ventilation-associated risk factors for death among such patients are potential targets for intervention.

Colloids for the Initial Management of Severe Sepsis and Septic Shock in Pediatric Patients: A Systematic Review.

AIM: The goal of this study was to perform a systematic review of the literature assessing the use of colloids for the initial treatment of severe sepsis and septic shock in pediatric patients. DESIGN: The PICO [Patient, Intervention, Comparison, Outcome] method was used for the selection of studies, and the Cochrane Bias Tool was used to analyze the quality of the selected studies. DATA SEARCH: Relevant studies were sought using the following databases: EMBASE (1980 to March 2014), PubMed (1970 to March 2014), Cochrane (1980 to March 2014), Web of Science, and Scopus. Searches used the following key words: isotonic solution, crystalloid, saline solution, colloid, resuscitation, fluid therapy, sepsis and septic shock, starch, and gelatin. The filters children and clinical trial were used when possible. REVIEW METHOD: Study selection was performed by 1 examiner. The selected articles were analyzed by 2 examiners who validated the articles according to the Cochrane Bias Tool. Discrepancies were resolved by consensus or by a third examiner. RESULT: A total of 110 articles were selected based on the key words. Of these, 99 were excluded because they assessed postoperative follow-up, burn cases, cardiac surgery, or nutritional therapy or were review articles, guidelines, or editorials. One study was included after an analysis of previous reviews. A total of 12 articles were selected for analysis because they were reports of clinical trials conducted with prospective cohorts and they analyzed the use of crystalloids and colloids or colloids only in the initial treatment of severe sepsis or septic shock in children and adolescents. The total number of patients was 4375, and they ranged in age from 2 months to 15 years, with most patients between 5 and 15 years. Five studies assessed patients diagnosed with malaria, 5 assessed patients with dengue shock syndrome, 1 studied febrile diseases, and 1 examined the progression of patients with septic shock caused by various causes. CONCLUSIONS: The studies analyzed did not find evidence to suggest that the use of colloids is superior to crystalloids. In some studies, the fluid volume needed to achieve initial stabilization was smaller in the group given colloids. Crystalloids are the preferred therapeutic option because of their effectiveness, low cost, and wide availability. Colloids may be the first choice in cases of malaria when the central nervous system is affected.