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.

Translating Neonatal Resuscitation Guidelines Into Practice in Brazil.

BACKGROUND AND OBJECTIVES: The Brazilian Neonatal Resuscitation Program releases guidelines based on local interpretation of international consensus on science and treatment recommendations. We aimed to analyze whether guidelines for preterm newborns were applied to practice in the 20 Brazilian Network on Neonatal Research centers of this middle-income country. METHODS: Prospectively collected data from 2014 to 2020 were analyzed for 8514 infants born at 230/7 to 316/7 weeks' gestation. The frequency of procedures was evaluated by gestational age (GA) category, including use of a thermal care bundle, positive pressure ventilation (PPV), PPV with a T-piece resuscitator, maximum fraction of inspired oxygen (Fio2) concentration during PPV, tracheal intubation, chest compressions and medications, and use of continuous positive airway pressure in the delivery room. Logistic regression, adjusted by center and year, was used to estimate the probability of receiving recommended treatment. RESULTS: For 3644 infants 23 to 27 weeks' GA and 4870 infants 28 to 31 weeks' GA, respectively, the probability of receiving care consistent with guidelines per year increased, including thermal care (odds ratio [OR], 1.52 [95% confidence interval (CI) 1.44-1.61] and 1.45 [1.38-1.52]) and PPV with a T-piece (OR, 1.45 [95% CI 1.37-1.55] and 1.41 [1.32-1.51]). The probability of receiving PPV with Fio2 1.00 decreased equally in both GA groups (OR, 0.89; 95% CI, 0.86-0.93). CONCLUSIONS: Between 2014 and 2020, the resuscitation guidelines for newborns <32 weeks' GA on thermal care, PPV with a T-piece resuscitator, and decreased use of Fio2 1.00 were translated into clinical practice.

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..

Radiographic predictors determined with an objective assessment tool for neonatal patients with necrotizing enterocolitis / Preditores radiográficos determinados com uso de ferramenta de avaliação objetiva para pacientes neonatais com enterocolite necrotizante

ABSTRACT Objective: The objective of this study was to develop and validate a computational tool to assist radiological decisions on necrotizing enterocolitis. Methodology: Patients that exhibited clinical signs and radiographic evidence of Bell's stage 2 or higher were included in the study, resulting in 64 exams. The tool was used to classify localized bowel wall thickening and intestinal pneumatosis using full-width at half-maximum measurements and texture analyses based on wavelet energy decomposition. Radiological findings of suspicious bowel wall thickening and intestinal pneumatosis loops were confirmed by both patient surgery and histopathological analysis. Two experienced radiologists selected an involved bowel and a normal bowel in the same radiography. The full-width at half-maximum and wavelet-based texture feature were then calculated and compared using the Mann-Whitney U test. Specificity, sensibility, positive and negative predictive values were calculated. Results: The full-width at half-maximum results were significantly different between normal and distended loops (median of 10.30 and 15.13, respectively). Horizontal, vertical, and diagonal wavelet energy measurements were evaluated at eight levels of decomposition. Levels 7 and 8 in the horizontal direction presented significant differences. For level 7, median was 0.034 and 0.088 for normal and intestinal pneumatosis groups, respectively, and for level 8 median was 0.19 and 0.34, respectively. Conclusions: The developed tool could detect differences in radiographic findings of bowel wall thickening and IP that are difficult to diagnose, demonstrating the its potential in clinical routine. The tool that was developed in the present study may help physicians to investigate suspicious bowel loops, thereby considerably improving diagnosis and clinical decisions.

RESUMO Objetivo: O objetivo deste estudo foi desenvolver e validar uma ferramenta computacional para auxiliar as decisões radiológicas na enterocolite necrotizante. Metodologia: Pacientes que exibiam sinais clínicos e evidências radiográficas do estágio 2 ou superior de Bell foram incluídos no estudo, que resultou em 64 exames. A ferramenta foi usada para classificar o aumento localizado da espessura da parede intestinal e a pneumatose intestinal com medidas de largura total a meia altura e análises de textura baseadas na decomposição da energia wavelet. Os achados radiológicos de aumento suspeito da espessura da parede intestinal e das alças na pneumatose intestinal foram confirmados pela cirurgia e análise histopatológica do paciente. Dois radiologistas experientes selecionaram um intestino afetado e um intestino normal na mesma radiografia. A largura total a meia altura e a característica da textura baseada em wavelet foram então calculadas e comparadas com o uso do teste U de Mann-Whitney. Foram calculados a especificidade, sensibilidade, valores preditivos positivos e negativos. Resultados: Os resultados da largura total a meia altura foram significativamente diferentes entre a alça normal e a distendida (mediana de 10,30 e 15,13, respectivamente). Medidas de energia wavelet horizontal, vertical e diagonal foram avaliadas em oito níveis de decomposição. Os níveis 7 e 8 na direção horizontal apresentaram diferenças significativas. Para o nível 7, as medianas foram 0,034 e 0,088 para os grupos normal e com pneumatose intestinal, respectivamente, e para o nível 8, as medianas foram 0,19 e 0,34, respectivamente. Conclusões: A ferramenta desenvolvida pode detectar diferenças nos achados radiográficos do aumento da espessura da parede intestinal e PI de difícil diagnóstico, demonstra seu potencial na rotina clínica. A ferramenta desenvolvida no presente estudo pode ajudar os médicos a investigar alças intestinais suspeitas e melhorar consideravelmente o diagnóstico e as decisões clínicas.

Radiographic predictors determined with an objective assessment tool for neonatal patients with necrotizing enterocolitis.

OBJECTIVE: The objective of this study was to develop and validate a computational tool to assist radiological decisions on necrotizing enterocolitis. METHODOLOGY: Patients that exhibited clinical signs and radiographic evidence of Bell's stage 2 or higher were included in the study, resulting in 64 exams. The tool was used to classify localized bowel wall thickening and intestinal pneumatosis using full-width at half-maximum measurements and texture analyses based on wavelet energy decomposition. Radiological findings of suspicious bowel wall thickening and intestinal pneumatosis loops were confirmed by both patient surgery and histopathological analysis. Two experienced radiologists selected an involved bowel and a normal bowel in the same radiography. The full-width at half-maximum and wavelet-based texture feature were then calculated and compared using the Mann-Whitney U test. Specificity, sensibility, positive and negative predictive values were calculated. RESULTS: The full-width at half-maximum results were significantly different between normal and distended loops (median of 10.30 and 15.13, respectively). Horizontal, vertical, and diagonal wavelet energy measurements were evaluated at eight levels of decomposition. Levels 7 and 8 in the horizontal direction presented significant differences. For level 7, median was 0.034 and 0.088 for normal and intestinal pneumatosis groups, respectively, and for level 8 median was 0.19 and 0.34, respectively. CONCLUSIONS: The developed tool could detect differences in radiographic findings of bowel wall thickening and IP that are difficult to diagnose, demonstrating the its potential in clinical routine. The tool that was developed in the present study may help physicians to investigate suspicious bowel loops, thereby considerably improving diagnosis and clinical decisions.

The ROPScore as a Screening Algorithm for Predicting Retinopathy of Prematurity in a Brazilian Population.

OBJECTIVES: To evaluate the accuracy of the ROPScore algorithm as a predictor of retinopathy of prematurity (ROP). METHODS: A prospective cohort of 220 preterm infants with a birth weight ≤1500 g and/or gestational age ≤32 weeks was included. The ROPScore was determined in the sixth week of life in 181 infants who then survived until a corrected gestational age of 45 weeks. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of the algorithm were analyzed. RESULTS: ROP was found in 17.6% of the preterm infants. The sensitivity of this test for any stage of ROP was 87.5%, while that for severe ROP was 95.4% (21/22 cases). The PPV and NPV were 59.6% and 97%, respectively, for any stage of ROP and 44.7% and 99.25%, respectively, for severe ROP. The ROPScore could therefore hypothetically reduce the number of ophthalmologic examinations required to detect ROP by 71.8%. CONCLUSION: The ROPScore is a useful screening tool for ROP and may optimize examinations and especially the identification of severe ROP.

The Ropscore as a screening algorithm for predicting retinopathy of prematurity in a brazilian population

OBJECTIVES: To evaluate the accuracy of the ROPScore algorithm as a predictor of retinopathy of prematurity (ROP). METHODS: A prospective cohort of 220 preterm infants with a birth weight ≤1500 g and/or gestational age ≤32 weeks was included. The ROPScore was determined in the sixth week of life in 181 infants who then survived until a corrected gestational age of 45 weeks. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of the algorithm were analyzed. RESULTS: ROP was found in 17.6% of the preterm infants. The sensitivity of this test for any stage of ROP was 87.5%, while that for severe ROP was 95.4% (21/22 cases). The PPV and NPV were 59.6% and 97%, respectively, for any stage of ROP and 44.7% and 99.25%, respectively, for severe ROP. The ROPScore could therefore hypothetically reduce the number of ophthalmologic examinations required to detect ROP by 71.8%. CONCLUSION: The ROPScore is a useful screening tool for ROP and may optimize examinations and especially the identification of severe ROP.

Painful procedures and analgesia in the NICU: what has changed in the medical perception and practice in a ten-year period? / Procedimentos dolorosos e analgesia em UTI Neonatal: o que mudou na opinião e na prática profissional em dez anos?

ABSTRACT OBJECTIVE: To compare the use of analgesia versus neonatologists' perception regarding analgesic use in painful procedures in the years 2001, 2006, and 2011. METHODS: This was a prospective cohort study of all newborns admitted to four university neonatal intensive care units during one month in 2001, 2006, and 2011. The frequency of analgesic prescription for painful procedures was evaluated. Of the 202 neonatologists, 188 answered a questionnaire giving their opinion on the intensity of pain during lumbar puncture, tracheal intubation, mechanical ventilation, and postoperative period using a 10-cm visual analogic scale (VAS; pain >3 cm). RESULTS: For lumbar puncture, 12% (2001), 43% (2006), and 36% (2011) were performed using analgesia. Among the neonatologists, 40-50% reported VAS >3 for lumbar puncture in all study periods. For intubation, 30% received analgesia in the study periods, and 35% (2001), 55% (2006), and 73% (2011) of the neonatologists reported VAS >3 and would prescribe analgesia for this procedure. As for mechanical ventilation, 45% (2001), 64% (2006), and 48% (2011) of patient-days were under analgesia; 56% (2001), 57% (2006), and 26% (2011) of neonatologists reported VAS >3 and said they would use analgesia during mechanical ventilation. For the first three post-operative days, 37% (2001), 78% (2006), and 89% (2011) of the patients received analgesia and more than 90% of neonatologists reported VAS >3 for major surgeries. CONCLUSIONS: Despite an increase in the medical perception of neonatal pain and in analgesic use during painful procedures, the gap between clinical practice and neonatologist perception of analgesia need did not change during the ten-year period.

RESUMO OBJETIVO: Confrontar o uso de analgesia versus a percepção de neonatologistas quanto ao emprego de analgésicos para procedimentos dolorosos em 2001, 2006 e 2011. MÉTODOS: Coorte prospectiva de todos recém-nascidos internados em quatro unidades universitárias. Avaliou-se a frequência do emprego de analgésicos para procedimentos dolorosos por um mês dos anos de estudo. Dos 202 neonatologistas atuantes nas unidades nos três períodos, 188 assinalaram em escala analógica visual de 10 cm (dor >3 cm) a intensidade da dor sentida pelo recém-nascido na punção lombar, intubação traqueal, ventilação mecânica e no pós-operatório. RESULTADOS: Para punção lombar, 12%, 43% e 36% foram feitas com analgesia em 2001, 2006 e 2011 e 40-50% dos neonatologistas referiam indicar analgésicos na punção lombar nos três períodos. Na intubação, 30% foram feitas sob analgesia nos três períodos e 35% (2001), 55% (2006) e 73% (2011) dos médicos diziam indicar analgésicos. Quanto à ventilação mecânica, 45-64% dos ventilados-dia estavam sob analgesia nos três períodos e 56% (2001), 57% (2006) e 26% (2011) dos neonatologistas diziam usar analgésicos. Dos pacientes-dia nos três primeiros dias de pós-operatório, 37% (2001), 78% (2006) e 89% (2011) receberam alguma dose de analgésico. Mais de 90% dos médicos referiam usar analgesia para essa situação. CONCLUSÕES: Entre 2001 e 2011, ocorreu aumento no uso de analgésicos para procedimentos dolorosos nas unidades neonatais e uma percepção mais acentuada por parte dos médicos de que o recém-nascido sente dor, mas o lapso entre a prática clínica e a percepção médica quanto à presença de dor persistiu.

Painful procedures and analgesia in the NICU: what has changed in the medical perception and practice in a ten-year period?

OBJECTIVE: To compare the use of analgesia versus neonatologists' perception regarding analgesic use in painful procedures in the years 2001, 2006, and 2011. METHODS: This was a prospective cohort study of all newborns admitted to four university neonatal intensive care units during one month in 2001, 2006, and 2011. The frequency of analgesic prescription for painful procedures was evaluated. Of the 202 neonatologists, 188 answered a questionnaire giving their opinion on the intensity of pain during lumbar puncture, tracheal intubation, mechanical ventilation, and postoperative period using a 10-cm visual analogic scale (VAS; pain >3cm). RESULTS: For lumbar puncture, 12% (2001), 43% (2006), and 36% (2011) were performed using analgesia. Among the neonatologists, 40-50% reported VAS >3 for lumbar puncture in all study periods. For intubation, 30% received analgesia in the study periods, and 35% (2001), 55% (2006), and 73% (2011) of the neonatologists reported VAS >3 and would prescribe analgesia for this procedure. As for mechanical ventilation, 45% (2001), 64% (2006), and 48% (2011) of patient-days were under analgesia; 56% (2001), 57% (2006), and 26% (2011) of neonatologists reported VAS >3 and said they would use analgesia during mechanical ventilation. For the first three post-operative days, 37% (2001), 78% (2006), and 89% (2011) of the patients received analgesia and more than 90% of neonatologists reported VAS >3 for major surgeries. CONCLUSIONS: Despite an increase in the medical perception of neonatal pain and in analgesic use during painful procedures, the gap between clinical practice and neonatologist perception of analgesia need did not change during the ten-year period.

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.

Practices related to late-onset sepsis in very low-birth weight preterm infants / Práticas relacionadas à sepse tardia em prematuros de muito baixo peso

OBJECTIVE: To understand the practices related to late-onset sepsis (LOS) in the centers of the Brazilian Neonatal Research Network, and to propose strategies to reduce the incidence of LOS. METHODS: This was a cross-sectional descriptive multicenter study approved by the Ethics Committee. Three questionnaires regarding hand hygiene, vascular catheters, and diagnosis/treatment of LOS were sent to the coordinator of each center. The center with the lowest incidence of LOS was compared with the others. RESULTS: All 16 centers answered the questionnaires. Regarding hand hygiene, 87% use chlorhexidine or 70% alcohol; alcohol gel is used in 100%; 80% use bedside dispensers (50% had one dispenser for every two beds); practical training occurs in 100% and theoretical training in 70% of the centers, and 37% train once a year. Catheters: 94% have a protocol, and 75% have a line insertion team. Diagnosis/treatment: complete blood count and blood culture are used in 100%, PCR in 87%, hematological scores in 75%; oxacillin and aminoglycosides is the empirical therapy in 50% of centers. Characteristics of the center with lowest incidence of LOS: stricter hand hygiene; catheter insertion and maintenance groups; use of blood culture, PCR, and hematological score for diagnosis; empirical therapy with oxacillin and aminoglycoside. CONCLUSION: The knowledge of the practices of each center allowed for the identification of aspects to be improved as a strategy to reduce LOS, including: alcohol gel use, hand hygiene training, implementation of catheter teams, and wise use of antibiotic therapy. .

OBJETIVO: Conhecer as práticas relacionadas a sepse tardia (ST) nos centros da Rede Brasileira de Pesquisas Neonatais (RBPN) e propor estratégias para redução da ST. MÉTODOS: Estudo transversal, multicêntrico da RBPN, aprovado pelo CEP. Três questionários sobre higienização das mãos, cateteres vasculares e diagnóstico/tratamento da ST foram elaborados e enviados aos coordenadores de cada centro. O centro com a menor incidência de ST foi comparado aos demais. RESULTADOS: Todos os 16 centros responderam aos questionários. Quanto à higienização das mãos: 87% usam chlorhexidine ou álcool 70%; 100% álcool gel; almotolia/leito em 80% (50% dispõem de um dispensador para cada dois leitos); Treinamento prático ocorre em 100%, teórico em 70% dos centros e 37% treinam uma vez/ano. Cateteres: 94% têm protocolo para passagem, 75% grupo de inserção. Diagnóstico/tratamento: hemograma e hemocultura são usados em 100% dos centros; PCR em 87%; 75% usam escores hematológicos; oxacilina e aminoglicosídeo são usados como terapia empírica em 50% dos centros. Características do centro com menor incidência de ST: rigorosa higienização das mãos; grupos de inserção e manutenção de cateteres; uso de hemocultura, PCR e escores hematológicos para diagnóstico da ST; tratamento empírico com oxacilina e aminoglicosídeo. CONCLUSÕES: O conhecimento das práticas de cada centro permitiu identificar aspectos a serem aprimorados como estratégia para a redução da ST incluindo: uso de álcool gel, treinamento em higienização das mãos, implantação de grupos de cateteres e uso racional de antibióticos. .

Practices related to late-onset sepsis in very low-birth weight preterm infants.

OBJECTIVE: To understand the practices related to late-onset sepsis (LOS) in the centers of the Brazilian Neonatal Research Network, and to propose strategies to reduce the incidence of LOS. METHODS: This was a cross-sectional descriptive multicenter study approved by the Ethics Committee. Three questionnaires regarding hand hygiene, vascular catheters, and diagnosis/treatment of LOS were sent to the coordinator of each center. The center with the lowest incidence of LOS was compared with the others. RESULTS: All 16 centers answered the questionnaires. Regarding hand hygiene, 87% use chlorhexidine or 70% alcohol; alcohol gel is used in 100%; 80% use bedside dispensers (50% had one dispenser for every two beds); practical training occurs in 100% and theoretical training in 70% of the centers, and 37% train once a year. Catheters: 94% have a protocol, and 75% have a line insertion team. Diagnosis/treatment: complete blood count and blood culture are used in 100%, PCR in 87%, hematological scores in 75%; oxacillin and aminoglycosides is the empirical therapy in 50% of centers. Characteristics of the center with lowest incidence of LOS: stricter hand hygiene; catheter insertion and maintenance groups; use of blood culture, PCR, and hematological score for diagnosis; empirical therapy with oxacillin and aminoglycoside. CONCLUSION: The knowledge of the practices of each center allowed for the identification of aspects to be improved as a strategy to reduce LOS, including: alcohol gel use, hand hygiene training, implementation of catheter teams, and wise use of antibiotic therapy.

There is no difference in nitric oxide metabolites and neonatal outcome between premature infants born to pre-eclamptic and those born to normotensive women.

BACKGROUND: The pathophysiology of pre-eclampsia (PE) is complex, and nitric oxide (NO) may be a factor. The neonatal outcome in pregnancies complicated by PE is controversial, and the PE/NO/neonatal diseases relationship has not been well established. AIMS: To measure nitrate and nitrite levels in the placenta, umbilical cord blood, blood and urine of preterm neonates born to pre-eclamptic and normotensive women and to investigate the relationship between placental, fetal and neonatal NO metabolites and neonatal outcome. METHODS: A prospective study was undertaken of 30 preterm infants <34 weeks of gestation, born to pre-eclamptic mothers and matched by gestational age with 30 infants born to normotensive mothers. Samples from the placental tissue, venous cord blood and the newborns' blood on day 4 and urine on days 1 and 4 were assayed for NO metabolites (nitrate and nitrite). Clinical variables and NO metabolites were compared between the groups. Generalised linear models were fitted to associate NO metabolites levels with adverse neonatal outcomes. RESULTS: There were no differences in NO metabolites and neonatal outcomes between the two groups. Increased levels of NO metabolites were found in the placenta and cord blood of small-for-gestational-age infants, and in the cord blood of newborns with necrotising enterocolitis and those who died. CONCLUSION: NO metabolite levels in the placenta and fetal and neonatal circulation were not associated with PE; however, cord blood levels of NO metabolites differed according to fetal growth and neonatal outcome.

Late-onset sepsis in very low birth weight infants: a Brazilian Neonatal Research Network Study.

BACKGROUND: Late-onset sepsis (LOS) is an important cause of morbidity and mortality in very low birth weight (VLBW) infants. AIM: To determine the incidence, risk factors and etiology of LOS. METHODS: LOS was investigated in a multicenter prospective cohort of infants at eight public university neonatal intensive care units (NICUs). Inclusion criteria included inborn, 23-33 weeks of gestational age, 400-1499 g birth weight, who survived >3 days. RESULTS: Of 1507 infants, 357 (24%) had proven LOS and 345 (23%) had clinical LOS. Infants with LOS were more likely to die. The majority of infections (76%) were caused by Gram-positive organisms. Independent risk factors for proven LOS were use of central venous catheter and mechanical ventilation, age at the first feeding and number of days on parenteral nutrition and on mechanical ventilation. CONCLUSION: LOS incidence and mortality are high in Brazilian VLBW infants. Most risk factors are associated with routine practices at NICU.

Diagnostic accuracy of semi-quantitative and quantitative culture techniques for the diagnosis of catheter-related infections in newborns and molecular typing of isolated microorganisms.

BACKGROUND: Catheter-related bloodstream infections (CR-BSIs) have become the most common cause of healthcare-associated bloodstream infections in neonatal intensive care units (ICUs). Microbiological evidence implicating catheters as the source of bloodstream infection is necessary to establish the diagnosis of CR-BSIs. Semi-quantitative culture is used to determine the presence of microorganisms on the external catheter surface, whereas quantitative culture also isolates microorganisms present inside the catheter. The main objective of this study was to determine the sensitivity and specificity of these two techniques for the diagnosis of CR-BSIs in newborns from a neonatal ICU. In addition, PFGE was used for similarity analysis of the microorganisms isolated from catheters and blood cultures. METHODS: Semi-quantitative and quantitative methods were used for the culture of catheter tips obtained from newborns. Strains isolated from catheter tips and blood cultures which exhibited the same antimicrobial susceptibility profile were included in the study as positive cases of CR-BSI. PFGE of the microorganisms isolated from catheters and blood cultures was performed for similarity analysis and detection of clones in the ICU. RESULTS: A total of 584 catheter tips from 399 patients seen between November 2005 and June 2012 were analyzed. Twenty-nine cases of CR-BSI were confirmed. Coagulase-negative staphylococci (CoNS) were the most frequently isolated microorganisms, including S. epidermidis as the most prevalent species (65.5%), followed by S. haemolyticus (10.3%), yeasts (10.3%), K. pneumoniae (6.9%), S. aureus (3.4%), and E. coli (3.4%). The sensitivity of the semi-quantitative and quantitative techniques was 72.7% and 59.3%, respectively, and specificity was 95.7% and 94.4%. The diagnosis of CR-BSIs based on PFGE analysis of similarity between strains isolated from catheter tips and blood cultures showed 82.6% sensitivity and 100% specificity. CONCLUSION: The semi-quantitative culture method showed higher sensitivity and specificity for the diagnosis of CR-BSIs in newborns when compared to the quantitative technique. In addition, this method is easier to perform and shows better agreement with the gold standard, and should therefore be recommended for routine clinical laboratory use. PFGE may contribute to the control of CR-BSIs by identifying clusters of microorganisms in neonatal ICUs, providing a means of determining potential cross-infection between patients.

Cord blood cytokine levels in focal early-onset neonatal infection after preterm premature rupture of membranes.

This study aimed to evaluate the levels of pro- and anti-inflammatory cytokines in umbilical cord blood of preterm neonates who developed focal early-onset infection (EOI) after preterm premature rupture of membranes (PPROM). This is a prospective study conducted on 46 preterm infants from mothers with PPROM. The cytokines were measure by flow cytometry. Newborns were classified into two groups as focal EOI (n=19) and non-infected (n=27). Interleukin (IL)-6 and IL-8 levels were higher, whereas IL-10 and IL-12 p70 levels were lower in the EOI when compared to the non-infected group. The best combination of cytokines was IL-6+IL-8, with a diagnostic accuracy of 0.97. Focal EOI after PPROM is associated with increased levels of IL-6 and IL-8 and diminished IL-10 and IL-12 in the cord blood of preterm infants. Combined assessment of IL-6 and IL-8 in cord blood may provide an additional tool for identifying preterm infants who develop EOI after PPROM.

Neonatal meningitis according to the microbiological diagnosis: a decade of experience in a tertiary center / Meningite neonatal de acordo com diagnóstico microbiológico: uma década de experiência em centro terciário

The aim of this study was to evaluate the incidence of and mortality due to meningitis and compare data according to microbiological diagnosis. This was a ten-year retrospective study conducted at a neonatal intensive care unit (NICU). Newborns with meningitis confirmed by positive CSF culture were included; those with congenital infection or malformations that made lumbar puncture impossible were excluded. The variables investigated were birth weight, gestational and postnatal age, procedures, hematological and CSF parameters, and complications. Parametric and non-parametric tests were used (statistical value p<0.05). The incidence of meningitis was 0.6 percent and mortality was 27 percent. Of the 22 cases, 59 percent involved Gram-negative bacteria; 36 percent Gram-positive and 5 percent fungi. The groups did not differ in relation to birth weight, gestational and postnatal age, procedures or hematological and CSF parameters. Sepsis, convulsions and deaths were frequent in both groups, without statistical difference. Gram-negative cases showed abscesses and higher frequency of ventriculitis and hydrocephaly. Meningitis was infrequent, but presented high mortality and frequent complications.

O objetivo do estudo foi avaliar incidência e mortalidade da meningite e comparar dados de acordo com o diagnóstico microbiológico. Estudo retrospectivo, de 10 anos, em UTI Neonatal. Incluídos RNs com meningite confirmada por cultura de líquor positiva; RN com infecção congênita ou malformações que impedem punção lombar foram excluídos. Variáveis: peso ao nascimento, idades gestacional e pós natal, procedimentos, parâmetros hematológicos e liquóricos, complicações. Testes paramétricos e não paramétricos foram utilizados (valor estatístico p<0,05). A incidência de meningite foi de 0,6 por cento e mortalidade de 27 por cento. Dos 22 casos, 59 por cento foram por bactérias Gram-negativas; 36 por cento por bactérias Gram-positivas e 5 por cento por fungos. Grupos não diferiram quanto ao peso ao nascimento, idades gestacional e pós-natal, procedimentos e por parâmetros hematológicos e liquóricos. Sepse, convulsões e óbitos foram frequentes e não diferiram entre os grupos. Gram-negativos causaram abscessos e mais frequentemente ventriculite e hidrocefalia. Meningite não foi freqüente, mas apresentou alta mortalidade e complicações.

Neonatal meningitis according to the microbiological diagnosis: a decade of experience in a tertiary center.

The aim of this study was to evaluate the incidence of and mortality due to meningitis and compare data according to microbiological diagnosis. This was a ten-year retrospective study conducted at a neonatal intensive care unit (NICU). Newborns with meningitis confirmed by positive CSF culture were included; those with congenital infection or malformations that made lumbar puncture impossible were excluded. The variables investigated were birth weight, gestational and postnatal age, procedures, hematological and CSF parameters, and complications. Parametric and non-parametric tests were used (statistical value p<0.05). The incidence of meningitis was 0.6% and mortality was 27%. Of the 22 cases, 59% involved Gram-negative bacteria; 36% Gram-positive and 5% fungi. The groups did not differ in relation to birth weight, gestational and postnatal age, procedures or hematological and CSF parameters. Sepsis, convulsions and deaths were frequent in both groups, without statistical difference. Gram-negative cases showed abscesses and higher frequency of ventriculitis and hydrocephaly. Meningitis was infrequent, but presented high mortality and frequent complications.