Comparison of mortality and survival without major morbidities of very preterm infants with very low birth weight from Japan and Brazil / Comparação entre mortalidade e sobrevida sem morbidades importantes dos recém-nascidos prematuros de muito baixo peso entre o Japão e o Brasil

Abstract Objective: This study was carried out to understand the disparities in mortality and survival without major morbidities among very premature and very low birth weight infants between participating Neonatal Intensive Care Units (NICUs) from the Brazilian Network on Neonatal Research (RBPN) and the Neonatal Research Network of Japan (NRNJ). Methods: Secondary data analysis of surveys by the RBPN and NRNJ was performed. The surveys were conducted in 2014 and 2015 and included 187 NICUs. Primary outcome was mortality or survival without any major morbidity. Logistic regression analysis adjustment for confounding factors was used. Results: The study population consisted of 6,406 infants from the NRNJ and 2,319 from the RBPN. Controlling for various confounders, infants from RBPN had 9.06 times higher adjusted odds of mortality (95%CI 7.30-11.29), and lower odds of survival without major morbidities (AOR 0.36; 95%CI 0.32-0.41) compared with those from the NRNJ. Factors associated with higher odds of mortality among Brazilian NICUs included: Air Leak Syndrome (AOR 4.73; 95%CI 1.26-15.27), Necrotizing Enterocolitis (AOR 3.25; 95%CI 1.38-7.26), and Late Onset Sepsis (LOS) (AOR 4.86; 95%CI 2.25-10.97). Conclusions: Very premature and very low birth weight infants from Brazil had significantly higher odds for mortality and lower odds for survival without major morbidities in comparison to those from Japan. Additionally, we identified the factors that increased the odds of in-hospital neonatal death in Brazil, most of which was related to LOS.

RESUMO Objetivo: Este estudo foi realizado para compreender as disparidades na mortalidade e sobrevivência sem as principais morbidades entre recém-nascidos muito prematuros e de muito baixo peso entre Unidades de Terapia Intensiva Neonatal (UTINs) participantes da Rede Brasileira de Pesquisas Neonatais (RBPN) e Rede de Pesquisa Neonatal do Japão (NRNJ). Métodos: Foi realizada uma análise dos dados secundários dos bancos de dados da RBPN e da NRNJ. As pesquisas foram realizadas em 2014 e 2015 e incluíram 187 UTINs. O desfecho primário foi mortalidade ou sobrevida sem qualquer morbidade importante. Utilizou-se a análise de regressão logística com ajuste para os fatores de confusão. Resultados: A população do estudo foi composta por 6.406 recém-nascidos do NRNJ e 2.319 do RBPN. Ajustando para diversos fatores de confusão, os prematuros da RBPN tiveram 9,06 vezes maiores chances de mortalidade (IC95% 7,30-11,29) e menores chances de sobrevivência sem morbidades importantes (AOR 0,36; IC95% 0,32-0,41) em comparação com os da NRNJ. Fatores associados a maiores chances de mortalidade entre as UTINs brasileiras incluíram: síndrome de escape de ar (AOR 4,73; IC95% 1,26-15,27), enterocolite necrosante (AOR 3,25; IC95% 1,38-7,26) e sepse de início tardio (AOR 4,86; IC95% 2,25-10,97). Conclusões: Os recém-nascidos muito prematuros e de muito baixo peso do Brasil apresentaram chances significativamente maiores de mortalidade e menores chances de sobrevivência sem as principais morbidades em comparação aos do Japão. Além disso, identificamos os fatores que aumentam as chances da morte neonatal no Brasil, sendo a maioria relacionada à sepse tardia.

Comparison of mortality and survival without major morbidities of very preterm infants with very low birth weight from Japan and Brazil.

OBJECTIVE: This study was carried out to understand the disparities in mortality and survival without major morbidities among very premature and very low birth weight infants between participating Neonatal Intensive Care Units (NICUs) from the Brazilian Network on Neonatal Research (RBPN) and the Neonatal Research Network of Japan (NRNJ). METHODS: Secondary data analysis of surveys by the RBPN and NRNJ was performed. The surveys were conducted in 2014 and 2015 and included 187 NICUs. Primary outcome was mortality or survival without any major morbidity. Logistic regression analysis adjustment for confounding factors was used. RESULTS: The study population consisted of 6,406 infants from the NRNJ and 2,319 from the RBPN. Controlling for various confounders, infants from RBPN had 9.06 times higher adjusted odds of mortality (95%CI 7.30-11.29), and lower odds of survival without major morbidities (AOR 0.36; 95%CI 0.32-0.41) compared with those from the NRNJ. Factors associated with higher odds of mortality among Brazilian NICUs included: Air Leak Syndrome (AOR 4.73; 95%CI 1.26-15.27), Necrotizing Enterocolitis (AOR 3.25; 95%CI 1.38-7.26), and Late Onset Sepsis (LOS) (AOR 4.86; 95%CI 2.25-10.97). CONCLUSIONS: Very premature and very low birth weight infants from Brazil had significantly higher odds for mortality and lower odds for survival without major morbidities in comparison to those from Japan. Additionally, we identified the factors that increased the odds of in-hospital neonatal death in Brazil, most of which was related to LOS.

Relationship of Patent Ductus Arteriosus Echocardiographic Markers With Descending Aorta Diastolic Flow.

OBJECTIVES: To characterize the relationship of echocardiographic markers of left heart overload and flow in peripheral major end-organ vessels (eg, celiac artery) with the presence of reversed holodiastolic flow in the descending aorta, considered a surrogate marker of an increased transductal shunt volume, in preterm patients with a patent ductus arteriosus (PDA). METHODS: This work was a retrospective study of data from echocardiography performed to investigate the hemodynamic significance of a PDA in preterm patients. We studied differences in echocardiographic markers of the PDA shunt volume according to patterns of flow in the postductal descending aorta (no PDA, PDA with antegrade diastolic flow, and PDA with reversed diastolic flow). The strength of the association between each echocardiographic marker and the presence of aortic holodiastolic flow reversal was investigated. RESULTS: We studied 137 patients with a median (interquartile range) birth weight of 850 (694-1030) g and a median gestational age of 25 (24-27) weeks. Among patients with a PDA (113), those with diastolic flow reversal in the descending aorta (44) presented had increased echocardiographic markers representative of the shunt volume (increased left ventricular output, left atrial-to-aortic ratio, pulmonary vein D wave, and shorter isovolumic relaxation time) compared to those with aortic antegrade diastolic flow. A positive, albeit weak, correlation between diastolic flow reversal and shunt volume echocardiographic markers was found. Abnormal diastolic flow in the celiac artery had the strongest correlation (R2  = 0.24). CONCLUSIONS: In preterm patients with a PDA, echocardiographic markers of the shunt volume were more abnormal in patients with reversed diastolic flow in the descending aorta. These data support the assumption that variance in these markers are related to the shunt volume, which needs consideration when adjudicating hemodynamic significance.

Analysis of the performance of 11 formulae for fetal weight estimation in preterm fetuses with abnormal doppler velocimetry - A retrospective multicenter study / Análise do desempenho de 11 fórmulas de estimativa de peso fetal em conceptos prematuros com Dopplervelocimetria alterada - um estudo retrospectivo multicêntrico

Abstract Objective To assess 11 formulae commonly used to estimate fetal weight in a population of premature fetuses who had abnormal Doppler velocimetry due to early-onset placental insufficiency. The performance of each formula was evaluated in subgroups of fetuses with expected growth and intrauterine growth restriction. Methods Data were collected fromfetuses andmothers who delivered at three Brazilian hospitals between November 2002 and December 2013.We used the following formulae: Campbell; Hadlock I, II, III, IV and V; Shepard; Warsof; Weiner I and II; and Woo III. Results We analyzed 194 fetuses. Of these, 116 (59.8%) were considered appropriate for gestational age (AGA), and 103 (53.1%) were male. The amniotic fluid volume was reduced in 87 (44.8%) fetuses, and the umbilical artery Doppler revealed absence or inversion of diastolic flow in 122 (62.9%) cases, and the analysis of the ductus venosus revealed abnormal flow in 60 (34.8%) fetuses. The Hadlock formulae using three or four fetal biometric parameters had low absolute percentage error in the estimated fetal weight among preterm fetuses with abnormal Doppler studies who were born within 5 days of the ultrasound evaluation. The results were not influenced by the clinical and ultrasound parameters often found in early-onset placental insufficiency. Conclusion In this study, the formulae with the best performance for fetal weight estimation in the analyzed population were Hadlock I and IV, which use four and three fetal biometric parameters respectively to estimate the weight of preterm fetuses with abnormal Doppler studies.

Resumo Objetivo Avaliar o desempenho de 11 fórmulas comumente utilizadas para estimativa de peso fetal em uma população de fetos prematuros com dopplervelocimetria alterada devido a insuficiência placentária de início precoce. O desempenho de cada fórmula foi avaliado em subgrupos de fetos com crescimento adequado e com crescimento intrauterino restrito. Métodos Foram coletados os dados de mães e fetos cujos partos foram acompanhados em 3 instituições brasileiras entre novembro de 2002 e dezembro de 2013. As fórmulas selecionadas para análise foram: Campbell; Hadlock I, II, III, IV e V; Shepard; Warsof; Weiner I e II; e Woo III. Resultados Foram analisados os pesos de 194 fetos, dos quais 116 (59,8%) foram considerados adequados para a idade gestacional, 103 (53,1%) eram do sexo masculino, em 87 (44,8%) havia redução do volume de líquido amniótico, em 122 (62,9%) o Doppler de artéria umbilical demonstrou ausência ou inversão do fluxo na diástole, e em 60 (34,8%) a análise do duto venoso indicou fluxo anormal. A média do erro percentual absoluto (EPA) demonstrou que as fórmulas de Hadlock que utilizam 3 ou 4 parâmetros biométricos fetais apresentaram o melhor desempenho. Os resultados obtidos para essas fórmulas não sofreram influência dos parâmetros clínicos e ultrassonográficos frequentemente encontrados na insuficiência placentária de início precoce. Conclusão O presente estudo demonstrou o melhor desempenho das fórmulas de Hadlock que contêm 3 ou 4 parâmetros da biometria para estimativa de peso de fetos prematuros com anormalidades ao mapeamento Doppler.

Analysis of the Performance of 11 Formulae for Fetal Weight Estimation in Preterm Fetuses with Abnormal Doppler Velocimetry - A Retrospective Multicenter Study.

OBJECTIVE: To assess 11 formulae commonly used to estimate fetal weight in a population of premature fetuses who had abnormal Doppler velocimetry due to early-onset placental insufficiency. The performance of each formula was evaluated in subgroups of fetuses with expected growth and intrauterine growth restriction. METHODS: Data were collected from fetuses and mothers who delivered at three Brazilian hospitals between November 2002 and December 2013. We used the following formulae: Campbell; Hadlock I, II, III, IV and V; Shepard; Warsof; Weiner I and II; and Woo III. RESULTS: We analyzed 194 fetuses. Of these, 116 (59.8%) were considered appropriate for gestational age (AGA), and 103 (53.1%) were male. The amniotic fluid volume was reduced in 87 (44.8%) fetuses, and the umbilical artery Doppler revealed absence or inversion of diastolic flow in 122 (62.9%) cases, and the analysis of the ductus venosus revealed abnormal flow in 60 (34.8%) fetuses. The Hadlock formulae using three or four fetal biometric parameters had low absolute percentage error in the estimated fetal weight among preterm fetuses with abnormal Doppler studies who were born within 5 days of the ultrasound evaluation. The results were not influenced by the clinical and ultrasound parameters often found in early-onset placental insufficiency. CONCLUSION: In this study, the formulae with the best performance for fetal weight estimation in the analyzed population were Hadlock I and IV, which use four and three fetal biometric parameters respectively to estimate the weight of preterm fetuses with abnormal Doppler studies.

OBJETIVO: Avaliar o desempenho de 11 fórmulas comumente utilizadas para estimativa de peso fetal em uma população de fetos prematuros com dopplervelocimetria alterada devido a insuficiência placentária de início precoce. O desempenho de cada fórmula foi avaliado em subgrupos de fetos com crescimento adequado e com crescimento intrauterino restrito. MéTODOS: Foram coletados os dados de mães e fetos cujos partos foram acompanhados em 3 instituições brasileiras entre novembro de 2002 e dezembro de 2013. As fórmulas selecionadas para análise foram: Campbell; Hadlock I, II, III, IV e V; Shepard; Warsof; Weiner I e II; e Woo III. RESULTADOS: Foram analisados os pesos de 194 fetos, dos quais 116 (59,8%) foram considerados adequados para a idade gestacional, 103 (53,1%) eram do sexo masculino, em 87 (44,8%) havia redução do volume de líquido amniótico, em 122 (62,9%) o Doppler de artéria umbilical demonstrou ausência ou inversão do fluxo na diástole, e em 60 (34,8%) a análise do duto venoso indicou fluxo anormal. A média do erro percentual absoluto (EPA) demonstrou que as fórmulas de Hadlock que utilizam 3 ou 4 parâmetros biométricos fetais apresentaram o melhor desempenho. Os resultados obtidos para essas fórmulas não sofreram influência dos parâmetros clínicos e ultrassonográficos frequentemente encontrados na insuficiência placentária de início precoce. CONCLUSãO: O presente estudo demonstrou o melhor desempenho das fórmulas de Hadlock que contêm 3 ou 4 parâmetros da biometria para estimativa de peso de fetos prematuros com anormalidades ao mapeamento Doppler.

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.

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.

Cardiac troponin T and illness severity in the very-low-birth-weight infant.

Introduction. Respiratory distress are very common in Very-low-birth-weight (VLBW) infants and Myocardial injury may play a role in the disease outcome. Cardiac troponin T (cTnT) is the most useful marker of injury in adult population, but has not been extensively studied in this population. Aim. To study the role of cTnT in VLBW infants and its association with clinical outcomes. Methods. All VLBW infants admitted to our NICU were included in the study. Echocardiography and blood samples for cTnT determination were collected at 24 and 48 hours of life, and values >0.1 ng/mL were considered CTnT-positive values. Results. A total of 116 neonates had their blood samples collected. The median cTnT concentration within 24 hours was 0.191 (0.1-0.79) ng/mL and within 48 hours was 0.293 (0.1-1.0) ng/mL. A logistic regression analysis showed that PDA, low GA, and use of dopamine were independently associated with positive cTnT and abnormal Dopplerfluxometry and diuretics use had protective effects and was independently associated with troponin values. Conclusion. We observed a high prevalence of positivecTnT values in VLBW infants associated with illness severity. Our findings suggest that cTnT may be a useful and early marker of myocardial injury in VLBW infants.

Development of a technique for evaluating temporal parameters of sucking in breastfeeding preterm newborns.

AIMS: The aim of the current study was to developed and test the reliability of a technique for measuring temporal parameters of sucking in breastfeeding infants. METHODS: The technique was developed using a cohort of 11 term and 12 preterm infants, and subsequently evaluated using a cohort of 43 preterm infants. Measurements related to sucking pressure in the term and preterm infants were acquired. The signals were recorded for 5 min, saved on a computer, and stored for analysis. For purposes of analysis, the minute with the highest quality signal was chosen. Signal analysis was performed by two researchers, and inter- and intra-observer agreement was assessed. The newborns in the sample had different gestational ages. RESULTS: A technique was developed for the analysis of temporal parameters of sucking during breastfeeding and evaluated in 43 preterm infants with different gestational ages for the following variables: number of bursts per minute, number of sucks per burst, sucking rate, pause rate, and duration of pauses. The intra-observer agreement was 0.85 and the inter-observer agreement was 0.85. CONCLUSIONS: The technique that was developed and validated proved capable of measuring temporal parameters of sucking in breastfeeding newborns.

Red blood cell transfusions are independently associated with intra-hospital mortality in very low birth weight preterm infants.

OBJECTIVE: To test the hypothesis that red blood cell (RBC) transfusions in preterm infants are associated with increased intra-hospital mortality. STUDY DESIGN: Variables associated with death were studied with Cox regression analysis in a prospective cohort of preterm infants with birth weight <1500 g in the Brazilian Network on Neonatal Research. Intra-hospital death and death after 28 days of life were analyzed as dependent variables. Independent variables were infant demographic and clinical characteristics and RBC transfusions. RESULTS: Of 1077 infants, 574 (53.3%) received at least one RBC transfusion during the hospital stay. The mean number of transfusions per infant was 3.3 ± 3.4, with 2.1 ± 2.1 in the first 28 days of life. Intra-hospital death occurred in 299 neonates (27.8%), and 60 infants (5.6%) died after 28 days of life. After adjusting for confounders, the relative risk of death during hospital stay was 1.49 in infants who received at least one RBC transfusion in the first 28 days of life, compared with infants who did not receive a transfusion. The risk of death after 28 days of life was 1.89 times higher in infants who received more than two RBC transfusions during their hospital stay, compared with infants who received one or two transfusions. CONCLUSION: Transfusion was associated with increased death, and transfusion guidelines should consider risks and benefits of transfusion.