Use of budesonide associated with a pulmonary surfactant to prevent bronchopulmonary dysplasia in premature newborns - A systematic review

Abstract Objective: Among the mechanisms proposed for the development of bronchopulmonary dysplasia is the increase in the pulmonary inflammatory process and oxidative stress. Thus, the control of this process may result in improvements in bronchopulmonary dysplasia-related outcomes. This study aims to analyze the current scientific evidence regarding the use of budesonide, a potent anti-inflammatory drug, associated with a pulmonary surfactant to prevent bronchopulmonary dysplasia. Methods: A systematic review of the literature was performed on the Embase and MEDLINE platforms, and studies that compared budesonide with pulmonary surfactant versus pulmonary surfactant for treating respiratory distress syndrome were included. The primary outcome was a reduction in bronchopulmonary dysplasia or death. Results: Four randomized clinical trials and two observational studies were included in this systematic review. Three of the randomized clinical trials found a reduction in bronchopulmonary dysplasia or death in the use of budesonide with the surfactant, all the other studies (1 clinical trial and 2 observational studies) found no statistical differences between the groups for the primary outcomes. The three main studies showed a reduction in the primary outcome; however, all studies showed great heterogeneity regarding the type of surfactant (poractant or beractant) and the method of administration. Conclusion: Robust clinical studies, in a heterogeneous population, using porcine surfactant associated with budesonide, with administration by a minimally invasive technique are necessary for there to be a recommendation based on scientific evidence for its widespread use.

Growth phenotypes of very low birth weight infants for prediction of neonatal outcomes from a Brazilian cohort: comparison with INTERGROWTH

Abstract Objective: To assess the predictive value of selected growth phenotypes for neonatal morbidity and mortality in preterm infants < 30 weeks and to compare them with INTERGROWTH-21st (IG21). Methods: Retrospective analysis of data from the Brazilian Neonatal Research Network (BNRN) database for very low birth weight (VLBW) at 20 public tertiary-care university hospitals. Outcome: the composite neonatal morbidity and mortality (CNMM) consisted of in-hospital death, oxygen use at 36 weeks, intraventricular hemorrhage grade 3 or 4, and Bell stage 2 or 3 necrotizing enterocolitis. Selected growth phenotypes: small-for-gestational-age (SGA) defined as being < 3rd (SGA3) or 10th (SGA10) percentiles of BW, and large-for-gestational-age (LGA) as being > 97th percentile of BW. Stunting as being < 3rd percentile of the length and wasting as being < 3rd percentile of BMI. Single and multiple log-binomial regression models were fitted to estimate the relative risks of CNMM, comparing them to IG21. Results: 4,072 infants were included. The adjusted relative risks of CNMM associated with selected growth phenotypes were (BNRN/IG21): 1.45 (0.92-2.31)/1.60 (1.27-2.02) for SGA; 0.90 (0.55-1.47)/1.05 (0.55-1.99) for LGA; 1.65 (1.08-2.51)/1.58 (1.28-1.96) for stunting; and 1.48 (1.02-2.17) for wasting. Agreement between the two references was variable. The growth phenotypes had good specificity (>95%) and positive predictive value (70-90%), with poor sensitivity and low negative predictive value. Conclusion: The BNRN phenotypes at birth differed markedly from the IG21 standard and showed poor accuracy in predicting adverse neonatal outcomes.

Growth phenotypes of very low birth weight infants for prediction of neonatal outcomes from a Brazilian cohort: comparison with INTERGROWTH.

OBJECTIVE: To assess the predictive value of selected growth phenotypes for neonatal morbidity and mortality in preterm infants < 30 weeks and to compare them with INTERGROWTH-21st (IG21). METHOD: Retrospective analysis of data from the Brazilian Neonatal Research Network (BNRN) database for very low birth weight (VLBW) at 20 public tertiary-care university hospitals. OUTCOME: the composite neonatal morbidity and mortality (CNMM) consisted of in-hospital death, oxygen use at 36 weeks, intraventricular hemorrhage grade 3 or 4, and Bell stage 2 or 3 necrotizing enterocolitis. Selected growth phenotypes: small-for-gestational-age (SGA) defined as being < 3rd (SGA3) or 10th (SGA10) percentiles of BW, and large-for-gestational-age (LGA) as being > 97th percentile of BW. Stunting as being < 3rd percentile of the length and wasting as being < 3rd percentile of BMI. Single and multiple log-binomial regression models were fitted to estimate the relative risks of CNMM, comparing them to IG21. RESULTS: 4,072 infants were included. The adjusted relative risks of CNMM associated with selected growth phenotypes were (BNRN/IG21): 1.45 (0.92-2.31)/1.60 (1.27-2.02) for SGA; 0.90 (0.55-1.47)/1.05 (0.55-1.99) for LGA; 1.65 (1.08-2.51)/1.58 (1.28-1.96) for stunting; and 1.48 (1.02-2.17) for wasting. Agreement between the two references was variable. The growth phenotypes had good specificity (>95%) and positive predictive value (70-90%), with poor sensitivity and low negative predictive value. CONCLUSION: The BNRN phenotypes at birth differed markedly from the IG21 standard and showed poor accuracy in predicting adverse neonatal outcomes.

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..

Orofacial characteristics of the very low-birth-weight preterm infants.

OBJECTIVE: To evaluate the orofacial characteristics of very low-birth-weight preterm infants through anthropometric facial measures, orofacial anteroposterior analysis and the relationship between the gum pads. METHOD: Orofacial examinations was performed in 154 infants, classified into two groups: Group A comprised 54 very low-birth-weight infants who were examined after clinical stabilization and before hospital discharge, and Group B comprised 100 full-term infants. RESULTS: The average anthropometricmeasurements in millimetres for Group A and Group B were as follows: upper third:30.2 and 31.1; middle third: 24.2 and 25.9; lower third: 27.6 and 29.9; facial width: 64.8and 81.4. Regarding the orofacial anteroposterior analysis, the results showed that in99% of these infants, the mandible was in a retrognathic position relative to the maxilla.Group A and Group B had the following distributions of the relationship between thegum pads: overbite-overjet: 43% and 77%; overjet: 39% and 17%; open bite: 15% and3%; end-to-end: 2% and 1%; overbite: both 2%. CONCLUSION: The very low-birth-weight preterm infants showed the upper third with the highest values in the facialharmony analysis, followed by the lower third and the middle third; and exhibited themandible in a retrognathic position relative to the maxilla, and with overbite-overjet themost prevalent type of gum pad relationship. The study emphasizes the importance of orofacial examination during neonatal hospitalization and the investigation of birth weight and gestational age in a multidisciplinary therapeutic approach that includes orofacial neonatal evaluation and actions that promote oral health, besides foster follow-up studies.

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.

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.

Assessment of oxidative damage and enzymatic antioxidant system activity on the umbilical cord blood and saliva from preterm newborns with risk factors for early-onset neonatal sepsis.

BACKGROUND: To determine the concentration of the Lipid Peroxidation Marker: Malondialdehyde (MDA), and Antioxidant Markers: Superoxide Dismutase (SOD), Glutathione Peroxidase (GPX), Catalase (CAL) in umbilical cord blood and in unstimulated saliva in the first 24 and 48 hours of life in the PTNB of mothers with and without risk factors for early-onset neonatal sepsis. METHODS: Cross-sectional study with the signing of informed consent by the pregnant women and application of a standard questionnaire classifying the PTNB in Group 1 or 2. RESULTS: Twenty-one PTNB were studied. Regarding gender, birth weight, need for oxygen, use of phototherapy, diagnosis of assumed sepsis, presence of fetal distress, number of pregnancies, type of delivery, use of corticosteroids, premature rupture of membranes, maternal fever, chorioamnionitis, APGAR at the 5th and 10th minute of life. Statistical analysis was performed with the Mann-Whitney test (p = 0.019) on the GPX variable of umbilical cord blood in the group of mothers with risk factors for early-onset neonatal sepsis. There was no statistical difference in the MDA, SOD, and CAT variables of the group with risk factors and in any variable of the group without risk factors. CONCLUSION: There was an increase of the GPX concentration in the blood from the umbilical vein in the group with risk factors for early-onset neonatal sepsis. There was no statistical significance in the comparison of saliva and umbilical cord blood. There was no statistically significant difference in MDA, SOD, CAT.

Assessment of oxidative damage and enzymatic antioxidant system activity on the umbilical cord blood and saliva from preterm newborns with risk factors for early-onset neonatal sepsis

SUMMARY BACKGROUND: To determine the concentration of the Lipid Peroxidation Marker: Malondialdehyde (MDA), and Antioxidant Markers: Superoxide Dismutase (SOD), Glutathione Peroxidase (GPX), Catalase (CAL) in umbilical cord blood and in unstimulated saliva in the first 24 and 48 hours of life in the PTNB of mothers with and without risk factors for early-onset neonatal sepsis. METHODS: Cross-sectional study with the signing of informed consent by the pregnant women and application of a standard questionnaire classifying the PTNB in Group 1 or 2. RESULTS: Twenty-one PTNB were studied. Regarding gender, birth weight, need for oxygen, use of phototherapy, diagnosis of assumed sepsis, presence of fetal distress, number of pregnancies, type of delivery, use of corticosteroids, premature rupture of membranes, maternal fever, chorioamnionitis, APGAR at the 5th and 10th minute of life. Statistical analysis was performed with the Mann-Whitney test (p = 0.019) on the GPX variable of umbilical cord blood in the group of mothers with risk factors for early-onset neonatal sepsis. There was no statistical difference in the MDA, SOD, and CAT variables of the group with risk factors and in any variable of the group without risk factors. CONCLUSION: There was an increase of the GPX concentration in the blood from the umbilical vein in the group with risk factors for early-onset neonatal sepsis. There was no statistical significance in the comparison of saliva and umbilical cord blood. There was no statistically significant difference in MDA, SOD, CAT.

RESUMO OBJETIVOS: Determinar a concentração do marcador de peroxidação lipídica: Malondialdeído (MDA) e dos marcadores antioxidantes: Superóxido Dismutase (SOD), Glutationa Peroxidase (GPX), Catalase (CAL) no sangue do cordão umbilical e na saliva não estimulada nas primeiras 24 e 48 horas de vida nos RNPT de mães com e sem fatores de risco para sepse neonatal precoce. METODOLOGIA: Estudo transversal com a assinatura do termo de consentimento livre esclarecido pela gestante e aplicação de um questionário padrão classificando o RNPT no Grupo 1 ou 2. RESULTADOS: Foram estudados 21 RNPT. Quanto ao gênero, peso ao nascimento, necessidade de oxigênio, uso de fototerapia, diagnóstico de sepse presumida, presença de sofrimento fetal, número de gestações, tipo de parto, uso de corticoide, rotura prematura de membranas, a presença de febre materna, a presença de corioamnionite, Apgar no 50 e 100 minuto de vida, a análise estatística foi feita com o teste de Mann-Whitney (p=0,019) na váriável GPX do sangue do cordão umbilical no grupo das mães com fatores de risco para sepse neonatal precoce. Não houve diferença estatística nas outras variáveis MDA, SOD, CAT do grupo com fatores de risco e em nenhuma variável do grupo sem fatores de risco. CONCLUSÃO: O aumento de duas vezes a concentração da GPX no sangue da veia umbilical dos RNPT do grupo das mães com fatores de risco para sepse neonatal precoce. Sem significância estatística na comparação entre a saliva e o sangue do cordão umbilical. Não houve diferença estatisticamente significante nas variáveis MDA, SOD e CAT.

Simultaneous accelerated solvent extraction and hydrolysis of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide in meconium samples for gas chromatography-mass spectrometry analysis.

Cannabis misuse during pregnancy is associated with severe impacts on the mother and baby health, such as newborn low birth weight, growth restriction, pre-term birth, neurobehavioral and developmental deficits. In most of the cases, drug abuse is omitted or denied by the mothers. Thus, toxicological analyzes using maternal-fetal matrices takes place as a suitable tool to assess drug use. Herein, meconium was the chosen matrix to evaluate cannabis exposure through identification and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic (THCCOOH). Accelerated solvent extraction (ASE) was applied for sample preparation technique to simultaneously extract and hydrolyze conjugated THCCOOH from meconium, followed by a solid-phase extraction (SPE) procedure. The method was developed and validated for gas chromatography-mass spectrometry (GC-MS), reaching hydrolysis efficiency of 98%. Limits of detection (LOD) and quantification (LOQ) were, respectively, 5 and 10 ng/g. The range of linearity was LOQ to 500 ng/g. Inter and intra-batch coefficients of variation were <8.4% for all concentration levels. Accuracy was in 101.7-108.9% range. Recovery was on average 60.3%. Carryover effect was not observed. The procedure was applied in six meconium samples from babies whose mothers were drug users and showed satisfactory performance to confirm fetal cannabis exposure.

T-piece versus self-inflating bag ventilation in preterm neonates at birth.

OBJECTIVE: To verify whether the use of the T-piece resuscitator compared with the self-inflating bag in preterm infants ventilated at birth modifies survival to hospital discharge without major morbidities. DESIGN: Pragmatic prospective cohort study. SETTING: 20 Brazilian university hospitals of Brazilian Network on Neonatal Research. Patients were 1962 inborn infants in 2014-2015 ventilated at birth with 23-33' weeks gestation and birth weight 400-1499 g without malformations. Patients transferred until the 27th day after birth were excluded. INTERVENTIONS: Positive pressure ventilation at birth with T-piece resuscitator or self-inflating bag without positive end expiratory pressure valve. Intervention with ventilation followed the Brazilian Society of Pediatrics guidelines. The choice of the equipment was at the neonatologist's discretion in each delivery. The main outcome measures were survival to hospital discharge without bronchopulmonary dysplasia, severe peri-intraventricular haemorrhage and periventricular leucomalacia. Logistic regression adjusted for confounding variables was applied for main outcome. RESULTS: 1456 (74%) were only ventilated with T-piece resuscitator and 506 (26%) with the self-inflating bag. The characteristics of those ventilated with T-Piece resuscitator versus self-inflating bag were birth weight 969 ± 277 vs 941 ± 279 g, gestational age 28.2±2.5 vs 27.8±2.7 weeks and survival to hospital discharge without major morbidities 47% vs 35%. Logistic regression adjusted for maternal characteristics, obstetric and neonatal morbidities showed that the T-piece resuscitator increased the chance of survival to hospital discharge without major morbidities (OR=1.38; 95% CI 1.06 to 1.80; Hosmer-Lemeshow goodness of fit: 0.695). CONCLUSION: This study is the first that highlights the effectiveness of T-piece resuscitator ventilation in improving relevant outcomes in preterm neonates.

Time to change focus? Transitioning from higher neonatal to higher stillbirth mortality in São Paulo State, Brazil.

BACKGROUND: Differential trends in mortality suggest that stillbirths may dominate neonatal mortality in the medium to long run. Brazil has made major efforts to improve data collection on health indicators at granular geographic levels, and provides an ideal environment to test this hypothesis. Our goals were to examine levels and trends in stillbirths and neonatal deaths and the extent to which the mortality burden caused by stillbirths dominates neonatal mortality at the municipality- and state-level. METHODS: We used data from the Brazilian Ministry of Health's repository on births, fetal, and neonatal deaths (2010-2014) to calculate stillbirth and neonatal mortality rates for São Paulo state's 645 municipalities. RESULTS: At the state level, 7.9 per 1000 pregnancies ended in stillbirth (fetal death >22 weeks gestation or fetal weight >500g), but this varied from 0.0 to 28.4 per 1000 across municipalities. 7.9 per 1000 live births also died within the first 28 days. 42% of municipalities had a higher stillbirth rate than neonatal mortality rate, and in 61% of areas with low neonatal mortality (<8.0 per 1000), stillbirth rates exceeded neonatal mortality rates. CONCLUSIONS: This analysis suggests large variability and inequality in mortality outcomes at the sub-national level. The results also imply that stillbirth mortality may exceed neonatal mortality in Brazil and similar settings in the next few decades, which suggests a need for a shift in policy. This work further underscores the importance of continued research into causes and prevention of stillbirth.

Thyroid abnormalities in term infants with fungal sepsis.

OBJECTIVE:: To describe thyroid alterations in term newborns (TNB) with fungal sepsis during NICU hospitalization. METHOD:: The study included six TNB that during the clinical and laboratory manifestations of sepsis with positive cultures for fungus showed changes in thyroid hormones, called low T3 syndrome and low T3-T4 syndrome. TNB that could present hormonal changes caused by disease as those born to mothers with thyroid disease, or who had perinatal asphyxia and major surgeries were excluded. RESULTS:: Of six TNB with fungal sepsis, five had positive culture for Candida albicans and one had positive culture for Candida tropicalis. Low T3 syndrome was observed in two TNB (50%), while T3-T4 syndrome was observed in other two (100%). The four children progressed to septic shock. CONCLUSION:: Fungal sepsis is becoming more common among newborns admitted to NICU. Thyroid insufficiency could be a marker of disease severity with possible need for hormone supplementation.

Randomized controlled trial comparing nasal intermittent positive pressure ventilation and nasal continuous positive airway pressure in premature infants after tracheal extubation.

OBJECTIVE:: To analyze the frequency of extubation failure in premature infants using conventional mechanical ventilation (MV) after extubation in groups subjected to nasal intermittent positive pressure ventilation (nIPPV) and continuous positive airway pressure (nCPAP). METHOD:: Seventy-two premature infants with respiratory failure were studied, with a gestational age (GA) ≤ 36 weeks and birth weight (BW) > 750 g, who required tracheal intubation and mechanical ventilation. The study was controlled and randomized in order to ensure that the members of the groups used in the research were chosen at random. Randomization was performed at the time of extubation using sealed envelopes. Extubation failure was defined as the need for re-intubation and mechanical ventilation during the first 72 hours after extubation. RESULTS:: Among the 36 premature infants randomized to nIPPV, six (16.6%) presented extubation failure in comparison to 11 (30.5%) of the 36 premature infants randomized to nCPAP. There was no statistical difference between the two study groups regarding BW, GA, classification of the premature infant, and MV time. The main cause of extubation failure was the occurrence of apnea. Gastrointestinal and neurological complications did not occur in the premature infants participating in the study. CONCLUSION:: We found that, despite the extubation failure of the group of premature infants submitted to nIPPV being numerically smaller than in premature infants submitted to nCPAP, there was no statistically significant difference between the two modes of ventilatory support after extubation.

Randomized controlled trial comparing nasal intermittent positive pressure ventilation and nasal continuous positive airway pressure in premature infants after tracheal extubation / Estudo controlado e randomizado entre uso de ventilação positiva intermitente e pressão positiva contínua em vias aéreas em recém-nascidos prematuros após a extubação traqueal

Summary Objective: To analyze the frequency of extubation failure in premature infants using conventional mechanical ventilation (MV) after extubation in groups subjected to nasal intermittent positive pressure ventilation (nIPPV) and continuous positive airway pressure (nCPAP). Method: Seventy-two premature infants with respiratory failure were studied, with a gestational age (GA) ≤ 36 weeks and birth weight (BW) > 750 g, who required tracheal intubation and mechanical ventilation. The study was controlled and randomized in order to ensure that the members of the groups used in the research were chosen at random. Randomization was performed at the time of extubation using sealed envelopes. Extubation failure was defined as the need for re-intubation and mechanical ventilation during the first 72 hours after extubation. Results: Among the 36 premature infants randomized to nIPPV, six (16.6%) presented extubation failure in comparison to 11 (30.5%) of the 36 premature infants randomized to nCPAP. There was no statistical difference between the two study groups regarding BW, GA, classification of the premature infant, and MV time. The main cause of extubation failure was the occurrence of apnea. Gastrointestinal and neurological complications did not occur in the premature infants participating in the study. Conclusion: We found that, despite the extubation failure of the group of premature infants submitted to nIPPV being numerically smaller than in premature infants submitted to nCPAP, there was no statistically significant difference between the two modes of ventilatory support after extubation.

Resumo Objetivo: analisar a frequência de falha da extubação em recém-nascidos pré-termo (RNPT) em uso de ventilação mecânica (VM) convencional após a extubação traqueal nos grupos submetidos à ventilação por pressão positiva intermitente por via nasal (nIPPV) e pressão positiva contínua em vias aéreas (nCPAP). Método: foram estudados 72 RNPT portadores de insuficiência respiratória, com idade gestacional (IG) ≤ 36 semanas e peso de nascimento (PN) > 750 g, que necessitaram de entubação traqueal e ventilação mecânica. O estudo foi controlado e randomizado a fim de garantir a aleatoriedade na escolha dos integrantes dos grupos. A randomização foi realizada no momento da extubação por meio de envelopes selados. Falha da extubação foi definida como necessidade de reentubação e ventilação mecânica durante as primeiras 72 horas após a extubação. Resultados: entre os 36 RN randomizados para nIPPV, seis (16,6%) apresentaram falha de extubação em comparação a 11 (30,5%) dos 36 RN randomizados para nCPAP. Não houve diferença estatística entre os dois grupos de estudo em relação a PN, IG, classificação do RN e tempo de VM. A principal causa de falha da extubação foi a ocorrência de apneia. Complicações gastrointestinais e neurológicas não ocorreram nos RNPT participantes do estudo. Conclusão: constatamos que no grupo dos RNPT submetidos à nIPPV, apesar da falha da extubação ser numericamente menor que nos RNPT submetidos à nCPAP, não houve diferença estatisticamente significante entre os dois modos de suporte ventilatório após a extubação.

Thyroid abnormalities in term infants with fungal sepsis / Alterações tireoidianas no recém-nascido de termo com sepse fúngica

Summary Objective: To describe thyroid alterations in term newborns (TNB) with fungal sepsis during NICU hospitalization. Method: The study included six TNB that during the clinical and laboratory manifestations of sepsis with positive cultures for fungus showed changes in thyroid hormones, called low T3 syndrome and low T3-T4 syndrome. TNB that could present hormonal changes caused by disease as those born to mothers with thyroid disease, or who had perinatal asphyxia and major surgeries were excluded. Results: Of six TNB with fungal sepsis, five had positive culture for Candida albicans and one had positive culture for Candida tropicalis. Low T3 syndrome was observed in two TNB (50%), while T3-T4 syndrome was observed in other two (100%). The four children progressed to septic shock. Conclusion: Fungal sepsis is becoming more common among newborns admitted to NICU. Thyroid insufficiency could be a marker of disease severity with possible need for hormone supplementation.

Resumo Objetivo: descrever as alterações tireoidianas em recém-nascidos de termo (RNT) que apresentaram sepse fúngica durante internação na UTI neonatal. Método: foram incluídos seis RNT que, durante as manifestações clínicas e laboratoriais de sepse, com culturas positivas para fungo, apresentaram alterações dos hormônios tireoidianos, denominadas síndrome do T3 baixo e síndrome do T3 e T4 baixo. Foram excluídos RNT que apresentaram alteração hormonal por doença, como RNT filhos de mães com doença tireoidiana, asfixia perinatal e cirurgias de grande porte. Resultados: dos seis RNT com sepse fúngica, cinco apresentavam cultura positiva para Candida albicans e um para C. tropicalis. A síndrome do T3 baixo foi observada em duas crianças (50%) e a do T3 e T4 baixo em dois RN (100%). As quatro crianças evoluíram com choque séptico. Conclusão: a sepse fúngica é cada vez mais frequente nos recém-nascidos internados em UTI neonatal. A insuficiência tireoidiana pode vir a ser marcadora de gravidade da doença, e a suplementação hormonal pode ser necessária.

Death or survival with major morbidity in VLBW infants born at Brazilian neonatal research network centers.

OBJECTIVE: To analyze unfavorable outcomes at hospital discharge of preterm infants born at Brazilian public university centers. METHODS: Prospective cohort of 2646 inborn infants with gestational age 23-33 weeks and birth weight 400-1499 g, without malformations, born at 20 centers in 2012-2013. Unfavorable outcome was defined as in-hospital death or survival at hospital discharge with ≥1 major morbidities: bronchopulmonary dysplasia (BPD) at 36 corrected weeks, intraventricular hemorrhage (IVH) grades 3-4, periventricular leukomalacia (PVL) or surgically treated retinopathy of prematurity (ROP). RESULTS: Among 2646 infants, 1390 (53%) either died or survived with major morbidities: 793 (30%) died; 497 (19%) had BPD; 358 (13%) had IVH 3-4 or PVL; and 84 (3%) had ROP. Logistic regression adjusted by center showed association of unfavorable outcome with: antenatal steroids (OR 0.70; 95%CI 0.55-0.88), C-section (0.72; 0.58-0.90), gestational age <30 (4.00; 3.16-5.07), being male (1.44; 1.19-1.75), small for gestational age (2.19; 1.72-2.78), 5th-min Apgar <7 (3.89; 2.88-5.26), temperature at NICU admission <36.0 °C (1.42; 1.15-1.76), respiratory distress syndrome (3.87; 2.99-5.01), proven late sepsis (1.33; 1.05-1.69), necrotizing enterocolitis (3.10; 2.09-4.60) and patent ductus arteriosus (1.69; 1.37-2.09). CONCLUSIONS: More than half of the VLBW infants born at public university level 3 Brazilian hospitals either die or survive with major morbidities.

Nonthyroidal illnesses syndrome in full-term newborns with sepsis.

OBJECTIVE: To assess hormonal changes in nonthyroidal illness syndrome (NTIS) in full-term newborns (NT) with sepsis. MATERIALS AND METHODS: We included 28 NT with sepsis divided into 2 groups according to the time of normalization of serum and clinical indicators of infection: group A(A), 16 NT with improvement in up to 8 days; and group B(B), 12 NT improvement after 8 days. Among the 28 NT, 15 NT progressed to septic shock, with 5 NT group A and 10 NT in group B. NT were excluded when they showed severe sepsis and asphyxia, and congenital malformations, as well as those whose mothers had thyroid disease and IUGR. RESULTS: 17 NT (60.7%) presented NTIS. Low T3 was observed in NTIS in 10 NT (58.8%), and low T4 and T3 in 5 NT (29.5%), all of them with septic shock. Two NT showed mixed changes (11.7%). After sepsis was cured, there was no hormonal change, except in 3 NT. Administration of dopamine, furosemide, and corticosteroids did not affect the results. CONCLUSIONS: This study indicates that nonthyroidal illness syndrome may be transiently present during sepsis in full-term newborns, especially in cases of prolonged sepsis. Low T3 can occur without changes in reverse T3 (different from adults), and low T4 and T3 occur mainly in patients with septic shock.

Nonthyroidal illnesses syndrome in full-term newborns with sepsis

ABSTRACT Objective To assess hormonal changes in nonthyroidal illness syndrome (NTIS) in full-term newborns (NT) with sepsis. Materials and methods We included 28 NT with sepsis divided into 2 groups according to the time of normalization of serum and clinical indicators of infection: group A(A), 16 NT with improvement in up to 8 days; and group B(B), 12 NT improvement after 8 days. Among the 28 NT, 15 NT progressed to septic shock, with 5 NT group A and 10 NT in group B. NT were excluded when they showed severe sepsis and asphyxia, and congenital malformations, as well as those whose mothers had thyroid disease and IUGR. Results 17 NT (60.7%) presented NTIS. Low T3 was observed in NTIS in 10 NT (58.8%), and low T4 and T3 in 5 NT (29.5%), all of them with septic shock. Two NT showed mixed changes (11.7%). After sepsis was cured, there was no hormonal change, except in 3 NT. Administration of dopamine, furosemide, and corticosteroids did not affect the results. Conclusions This study indicates that nonthyroidal illness syndrome may be transiently present during sepsis in full-term newborns, especially in cases of prolonged sepsis. Low T3 can occur without changes in reverse T3 (different from adults), and low T4 and T3 occur mainly in patients with septic shock. Arch Endocrinol Metab. 2015;59(6):528-34.

Development and practical application of accelerated solvent extraction for the isolation of cocaine/crack biomarkers in meconium samples.

A method using accelerated solvent extraction (ASE) for the isolation of cocaine/crack biomarkers in meconium samples, followed by solid phase extraction (SPE) and the simultaneous quantification by gas chromatography-mass spectrometry (GC-MS) was developed and validated. Initially, meconium samples were submitted to an ASE procedure, which was followed by SPE with Bond Elut Certify I cartridges. The analytes were derivatizated with PFP/PFPA and analyzed by GC-MS. The limits of detection (LOD) were between 11 and 17ng/g for all analytes. The limits of quantification (LOQ) were 30ng/g for anhydroecgonine methyl ester, and 20ng/g for cocaine, benzoylecgonine, ecgonine methyl ester and cocaethylene. Linearity ranged from the LOQ to 1500ng/g for all analytes, with a coefficients of determination greater than 0.991, except for m-hydroxybenzoylecgonine, which was only qualitatively detected. Precision and accuracy were evaluated at three concentration levels. For all analytes, inter-assay precision ranged from 3.2 to 18.1%, and intra-assay precision did not exceed 12.7%. The accuracy results were between 84.5 and 114.2% and the average recovery ranged from 17 to 84%. The method was applied to 342 meconium samples randomly collected in the University Hospital-University of São Paulo (HU-USP), Brazil. Cocaine biomarkers were detected in 19 samples, which represent 5.6% of exposure prevalence. Significantly lower birth weight, length and head circumference were found for the exposed newborns compared with the non-exposed group. This is the first report in which ASE was used as a sample preparation technique to extract cocaine biomarkers from a complex biological matrix such as meconium samples. The advantages of the developed method are the smaller demand for organic solvents and the minor sample handling, which allows a faster and accurate procedure, appropriate to confirm fetal exposure to cocaine/crack.