Less invasive surfactant administration versus intubation-surfactant-extubation in the treatment of neonatal respiratory distress syndrome: a systematic review and meta-analyses

Abstract Objectives To compare LISA with INSURE technique for surfactant administration in preterm with gestational age (GA) < 36 weeks with RDS in respect to the incidence of pneumothorax, bronchopulmonary dysplasia (BPD), need for mechanical ventilation (MV), regional cerebral oxygen saturation (rSO2), peri‑intraventricular hemorrhage (PIVH) and mortality. Methods A systematic search in PubMed, Embase, Lilacs, CINAHL, SciELO databases, Brazilian Registry of Randomized Clinical Trials (ReBEC), Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. RCTs evaluating the effects of the LISA technique versus INSURE in preterm infants with gestational age < 36 weeks and that had as outcomes evaluation of the rates of pneumothorax, BPD, need for MV, rSO2, PIVH, and mortality were included in the meta-analysis. Random effects and hazard ratio models were used to combine all study results. Inter-study heterogeneity was assessed using Cochrane Q statistics and Higgin's I2 statistics. Results Sixteen RCTs published between 2012 and 2020 met the inclusion criteria, a total of 1,944 preterms. Eleven studies showed a shorter duration of MV and CPAP in the LISA group than in INSURE group. Two studies evaluated rSO2 and suggested that LISA and INSURE transiently affect brain autoregulation during surfactant administration. INSURE group had a higher risk for MV in the first 72 h of life, pneumothorax, PIVH and mortality in comparison to the LISA group. Conclusion This systematic review and meta-analyses provided evidence for the benefits of the LISA technique in the treatment of RDS, decreasing CPAP time, need for MV, BPD, pneumothorax, PIVH, and mortality when compared to INSURE.

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.

Autopsy in a Neonatal Intensive Care Unit: pathological and clinical agreement

Abstract Objectives To evaluate neonatal autopsy rates at a tertiary hospital in southern Brazil ascertain the level of agreement between premortem and postmortem diagnosis. Methods The authors reviewed all neonatal autopsies performed over a 10-year period and described the percentage of neonates who died and underwent autopsy. The authors tested for agreement between autopsy findings and the cause of death as defined by the neonatologist. Agreement between clinical diagnosis and autopsy findings was classified using the modified Goldman criteria. Additional findings at autopsy were grouped by organ system. Linear regression and multiple comparisons were used for statistical analyses. Results During the study period, 382 neonates died at the Neonatal Intensive Care Unit (NICU). Consent to perform an autopsy was obtained for 73 (19.1%). The complete agreement between autopsy findings and the neonatologist's premortem diagnosis was found in 48 patients (65.8%). Additional findings were obtained at autopsy in 25 cases (34.2%). In 5 cases (6.9%), the autopsy findings contributed to subsequent genetic counseling. Seven autopsies (9.6%) revealed a diagnosis that would have changed patient management if established premortem. The autopsy rate increased by an average of 1.87% each year. Conclusion Despite a high level of agreement between clinical diagnosis and pathological findings, autopsies provided relevant data regarding the cause of death, providing additional clinical information to neonatologists and allowing genetic counseling of family members.

Does ADHD worsen inhibitory control in preschool children born very premature and/or with very low birth weight?

Abstract Introduction Deficits in executive functioning, especially in inhibitory control, are present in children born very premature and/or with very low birth weight (VP/VLBW) and in children with attention-deficit/hyperactivity disorder (ADHD). Objective To evaluate whether ADHD imposes additional inhibitory control (IC) deficits in preschoolers born VP/VLBW. Methods 79 VP/VLBW (4 to 7 years) children were assessed for ADHD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children - Present and Lifetime Version (K-SADS-PL). IC was measured with Conners' Kiddie Continuous Performance Test (K-CPT 2) and the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P).Results: No significant differences were found between ADHD (n = 24) and non-ADHD children (n = 55) for any of the measures (p = 0.062 to p = 0.903). Both groups had deficits in most K-CPT 2 scores compared to normative samples, indicating poor IC and inconsistent reaction times. Conclusions ADHD does not aggravate IC deficits in VP/VLBW children. Either neuropsychological tasks and parent reports of executive functions (EFs) may not be sensitive enough to differentiate VP/VLBW preschoolers with and without ADHD, or these children's EFs are already so impaired that there is not much room for additional impairments imposed by ADHD.

The challenges of neonatal sepsis management / Os desafios no manejo da sepse neonatal

Abstract Objectives To present current evidence on the etiology, risk factors, diagnosis, and management of early and late neonatal sepsis. Source of data Non-systematic review of the Medline (PubMed), Scopus, Web of Science, Cochrane, and Google Scholar databases regarding the following terms: neonatal sepsis, early neonatal sepsis, late neonatal sepsis, empirical antibiotic therapy, sepsis calculator, vancomycin, newborn, preterm newborn. Data synthesis Neonatal sepsis is a frequent cause of neonatal morbidity and mortality. Its diagnosis is difficult. Continuous observation of the patient is critical to diagnostic suspicion. When neonatal sepsis is suspected, bacteriological tests should be collected. Vancomycin should not be routinely using in the empirical antibiotic regimen in late neonatal sepsis, and the main protective mechanisms against neonatal sepsis are handwashing and the use of breast milk. Conclusions Newborns constitute a group that is more vulnerable to sepsis. Knowledge of risk factors and etiological agents allows a better approach to the newborn with sepsis.

Resumo Objetivos Apresentar evidências atuais na etiologia, fatores de risco, diagnóstico e manejo da sepse neonatal precoce e tardia. Fontes de dados Revisão não sistemática feita nas bases de dados Medline (PubMed), Scopus, Web of Science, Cochrane, Google Scholar sobre os temas sepse neonatal, sepse neonatal precoce, sepse neonatal tardia, antibioticoterapia empírica, sepsis calculator, vancomicina, recém-nascido, recém-nascido pré-termo. Síntese de dados A sepse neonatal é uma causa frequente de morbimortalidade neonatal. O seu diagnóstico é difícil. A observação contínua do paciente é fundamental para uma suspeição diagnóstica. Ao se suspeitar de sepse neonatal devem-se coletar exames bacteriológicos. Não usar, rotineiramente, vancomicina no esquema empírico de antibiótico na sepse neonatal tardia. Os principais mecanismos protetores da sepse neonatal são a lavagem de mãos e o uso do leite materno. Conclusões Os recém-nascidos constituem um grupo mais vulnerável à sepse. O conhecimento dos fatores de risco e dos agentes etiológicos permite uma melhor abordagem do recém-nascido séptico.

Prevalence of metabolic syndrome-like in the follow-up of very low birth weight preterm infants and associated factors / Prevalência de síndrome metabólica "like" aos dois anos de idade corrigida em prematuros de muito baixo peso e fatores associados

Abstract Objective: To assess the prevalence of metabolic syndrome-like symptoms in a population of preterm infants with very low birth weight (<1500 g) at 2 years of corrected age and identify the occurrence of associated risk factors. Methods: Cross-sectional study during a five-year period, including preterm infants born with very low birth weight evaluated at 2 years of corrected age. Metabolic syndrome-like symptoms was defined by the presence of three or more of these criteria: abdominal circumference ≥ 90th percentile, fasting blood glucose ≥ 100 mg/dL, triglycerides ≥ 110 mg/dL, HDL cholesterol ≤ 40 mg/dL, and blood pressure ≥ 90th percentile. Results: A total of 214 preterm infants with birth weight < 1500 g were evaluated. The prevalence of metabolic syndrome-like symptoms at 2 years of corrected age was 15.1%. Arterial hypertension was present in 57.5%, HDL ≤ 40 mg/dL in 29.2%, hypertriglyceridemia in 22.6%, and abdominal circumference above the 90th percentile in 18.8%. Only 3.7% had hyperglycemia. The presence of periventricular leukomalacia was an independent risk factor for arterial hypertension at this age (OR 2.34, 95% CI: 0.079-0.69, p = 0.008). Overweight and obesity at 2 years of corrected age were independently associated with metabolic syndrome-like symptoms (OR 2.75, 95% CI: 1.19-6.36, p = 0.018). Conclusion: Metabolic syndrome-like symptoms can be observed in very low birth weight preterm infants as early as 2 years of corrected age. Overweight and early-onset obesity are significant risk factors for metabolic syndrome-like symptoms, which deserves appropriate intervention for this high-risk population.

Resumo Objetivo: Avaliar a prevalência de síndrome metabólica "like" em população de crianças prematuras com muito baixo peso de nascimento (< 1500 gramas) aos dois anos de idade corrigida e identificar a ocorrência de fatores de risco associados. Métodos: Estudo transversal que incluiu prematuros nascidos durante um período de cinco anos com muito baixo peso de nascimento, avaliados aos dois anos de idade corrigida. A síndrome metabólica "like" foi definida pela presença de três ou mais desses critérios: circunferência abdominal ≥ percentil 90, glicemia de jejum ≥ 100 mg/dL, triglicerídeos ≥ 110 mg/dL, colesterol HDL ≤ 40 mg/dL e pressão arterial ≥ percentil 90. Resultados: Foram avaliados 214 prematuros abaixo de 1.500 gramas. A prevalência de síndrome metabólica "like" aos dois anos de idade corrigida foi 15,1%. Hipertensão arterial esteve presente em 57,5%, HDL ≤ 40 mg/dL em 29,2%, hipertrigliceridemia em 22,6% e aumento da circunferência abdominal acima do percentil 90 em 18,8%. Apenas 3,7% apresentaram hiperglicemia. A presença de leucomalácia periventricular foi um fator de risco independente para hipertensão arterial nessa idade (OR 2,34; IC 95% 0,079-0,69; p = 0,008); sobrepeso e obesidade aos dois anos de idade corrigida foram independentemente associados com síndrome metabólica "like" (OR 2,75, IC 95% CI 1,19-6,36; p = 0,018). Conclusão: Síndrome metabólica "like" ocorre em prematuros de muito baixo peso tão precocemente quanto dois anos de idade corrigida. Sobrepeso e obesidade de início precoce são fatores de risco significativos para síndrome metabólica "like", merecem intervenção apropriada para essa população de alto risco.

Preterm newborn's postnatal growth patterns: how to evaluate them / Padrões de crescimento pós-natal do recém-nascido prematuro: como avaliar

Abstract Objectives: There are several factors that influence the postnatal growth of preterm infants. It is crucial to define how to evaluate the growth rate of each preterm child and its individual trajectory, the type of growth curve, either with parameters of prescriptive curves for healthy preterm infants with no morbidities or, in the case of preterm infants and their "bundle of vulnerabilities", growth curves that may represent how they are actually growing, with the aim of directing appropriate nutritional care to each gestational age range. Data sources: The main studies with growth curves for growth monitoring and the appropriate nutritional adjustments that prioritized the individual trajectory of postnatal growth rate were reviewed. PubMed and Google Scholar were searched. Data synthesis: The use of longitudinal neonatal data with different gestational ages and considering high and medium-risk pregnancies will probably be essential to evaluate the optimal growth pattern. Conclusions: Prioritizing and knowing the individual growth trajectory of each preterm child is an alternative for preterm infants with less than 33 weeks of gestational age. For larger preterm infants born at gestational age >33 weeks, the Intergrowth 21st curves are adequate.

Resumo Objetivos: Inúmeros são os fatores que influenciam o crescimento pós-natal de prematuros. É fundamental a definição de como avaliar velocidade de crescimento de cada criança nascida prematura e sua trajetória individual, o tipo de curva de crescimento, seja com parâmetros de curvas prescritivas para prematuros saudáveis e sem morbidades ou no caso de um prematuro e seu "pacote de vulnerabilidades", curvas de crescimento que possam representar como eles realmente crescem, com a finalidade de direcionar o cuidado nutricional apropriado a cada faixa de idade gestacional. Fonte de dados: Foram revisados os principais estudos com curvas de crescimento na monitoração do crescimento e nos ajustes nutricionais apropriados que priorizaram a trajetória individual da velocidade de crescimento pós-natal. Foram consultados PubMed e Google Scholar. Síntese dos dados: O uso de dados neonatais longitudinais com diferentes idades gestacionais e considerando gestações de alto e médio risco provavelmente será fundamental para avaliar o padrão ótimo de crescimento. Conclusões: Priorizar e conhecer a trajetória individual de crescimento de cada criança nascida prematura é opção para prematuros com menos de 33 semanas. Para prematuros maiores, nascidos com idade gestacional acima de 33 semanas, as curvas Intergrowth 21 st são adequadas.

Motor development of preterm infants assessed by the Alberta Infant Motor Scale: systematic review article / Desenvolvimento motor de prematuros avaliados pela Alberta Infant Motor Scale: artigo de revisão sistemática

Abstract Objective: Premature newborns are considered at risk for motor development deficits, leading to the need for monitoring in early life. The aim of this study was to systematically review the literature about gross motor development of preterm infants, assessed by the Alberta Infant Motor Scale (AIMS) to identify the main outcomes in development. Data source: Systematic review of studies published from 2006 to 2015, indexed in Pubmed, Scielo, Lilacs, and Medline databases in English and Portuguese. The search strategy included the keywords: Alberta Infant Motor Scale, prematurity, preterm, motor development, postural control, and follow-up. Data summary: A total of 101 articles were identified and 23 were selected, according to the inclusion criteria. The ages of the children assessed in the studies varied, including the first 6 months up to 15 or 18 months of corrected age. The percentage variation in motor delay was identified in the motor outcome descriptions of ten studies, ranging from 4% to 53%, depending on the age when the infant was assessed. The studies show significant differences in the motor development of preterm and full-term infants, with a description of lower gross scores in the AIMS results of preterm infants. Conclusions: It is essential that the follow-up services of at-risk infants have assessment strategies and monitoring of gross motor development of preterm infants; AIMS is an assessment tool indicated to identify atypical motor development in this population.

Resumo Objetivo: Recém-nascidos prematuros são considerados de risco para déficits no desenvolvimento motor, o que ocasiona a necessidade de acompanhamento nos primeiros anos de vida. O objetivo do presente estudo é revisar de forma sistemática as publicações que abordam o desenvolvimento motor amplo de crianças nascidas prematuras, avaliadas por meio da Alberta Infant Motor Scale (AIMS), de modo a apontar os principais desfechos motores. Fontes dos dados: Revisão sistemática das publicações de 2006 a 2015, indexadas nas bases de dados Pubmed, Scielo, Lilacs e Medline, nos idiomas inglês e português. A estratégia de busca incluiu palavras-chaves: prematuro, pré-termo, prematuridade, desenvolvimento motor, controle postural, seguimento, Alberta Infant Motor Scale, prematurity, pre-term, motor development, postural control e follow-up. Síntese dos dados: Foram identificados 101 artigos e selecionados 23, conforme critérios de inclusão. As idades das crianças avaliadas nos estudos incluíram os primeiros seis meses até os 15 ou 18 meses de idade corrigida. Variado percentual de atraso motor foi identificado na descrição dos desfechos motores de 10 estudos, de 4 a 53%, dependeu da idade em que o bebê foi avaliado. Os estudos apontam diferenças significativas no desenvolvimento motor de prematuros e crianças nascidas a termo, com descrição de escores brutos mais baixos nos resultados da AIMS de crianças prematuras. Conclusões: É fundamental que os serviços de seguimento de bebês de risco apresentem estratégias de avaliação e acompanhamento do desenvolvimento motor amplo de prematuros, a AIMS é uma ferramenta de avaliação indicada para identificar comportamentos motores atípicos nessa população.

Risk factors associated with growth failure in the follow-up of very low birth weight newborns / Fatores de risco associados à falha de crescimento no seguimento de recém-nascidos de muito baixo peso

Abstract Objective: To determine risk factors during neonatal hospital stay and follow-up associated with failure to thrive in the first year of life of very low birth weight newborns. Methods: Study of preterm very low birth weight newborns followed from 2006 to 2013 in a public institutional hospital program. The study included newborns that attended at least one appointment in each of the three periods: Period I, up to 3 months of corrected age (CA); Period II, 4-6 months of CA; and Period III, 7-12 months of CA. The variables were analyzed by logistic regression with XLSTAT 2014 software (Microsoft®, WA, USA). Failure to thrive (Z-score below -2 SD) was classified as a dichotomous dependent variable (0 - failure/1 - success), while the other variables were classified as explanatory variables for the hospitalization periods and for each of the follow-up periods (I, II, and III). Results: Children born adequate for gestational age increased the chance of Z-score for weight at discharge > -2 SD (OR = 10.217; 95% CI: 1.117-93.436). Metabolic bone disease and retinopathy of prematurity in Period I, as well as hospital readmissions in Periods II and III during follow-up increased the chance of Z-score < -2 SD. Conclusion: Failure to thrive is influenced by intrauterine factors and, subsequently, by several morbidities, both in the birth and hospitalization period, as well as in the post-discharge period and thus, such variables should be prioritized in the follow-up.

Resumo Objetivo: Determinar fatores de risco do período de internação neonatal e do seguimento ambulatorial associados à falha de crescimento no primeiro ano de vida de recém-nascidos de muito baixo peso. Métodos: Estudo com crianças nascidas prematuras de muito baixo peso em acompanhamento de 2006 a 2013 em ambulatório de alto risco de um hospital-escola. Incluídas aquelas que fizera pelo menos uma consulta em cada um dos três períodos assim determinados: Período I - até três meses de idade corrigida (IC); Período II - entre quatro e seis meses de IC; e Período III - entre sete e 12 meses de IC. As variáveis foram analisadas por regressão logística com o programa XLStat 2014 (Microsoft®, WA, EUA). A falha de crescimento (escore z abaixo de --2 DP) foi classificada como variável dependente do tipo dicotômica (0 - falha/1 - sucesso) e as demais variáveis foram classificadas como variáveis explicativas para os períodos de internação e para cada um dos períodos de seguimento (I, II e III). Resultados: Nascer adequado para a idade gestacional aumenta a chance de apresentar escore Z do peso na alta hospitalar acima de -2 DP (OR = 10,217; IC95% 1.117-93,436). Doença metabólica óssea e retinopatia da prematuridade durante o Período I e reinternações nos Períodos II e III de seguimento aumentam a chance de escore z abaixo de -2 DP. Conclusão: A falha de crescimento é influenciada por fatores intrauterinos e posteriormente por diversas morbidades, tanto no período da internação como no pós-alta. Tais variáveis estudadas deveriam ter prioridade no seguimento.

Hipotermia terapêutica para recém-nascidos com encefalopatia hipóxico isquêmica / Hypothermia therapy for newborns with hypoxic ischemic encephalopathy

Resumo Objetivo: A hipotermia terapêutica reduz a lesão cerebral e melhora o desfecho neurológico de recém-nascidos após insulto hipóxico isquêmico. Indicada para recém-nascidos a termo ou próximo do termo com evidência de asfixia perinatal e encefalopatia hipóxico isquêmica (EHI). Fontes dos dados: Foi feita uma procura no PubMed por publicações sobre hipotermia terapêutica em recém-nascidos com asfixia perinatal e selecionadas aquelas julgadas mais relevantes pelos autores. Síntese dos dados: Há duas técnicas de resfriamento corpóreo: hipotermia seletiva da cabeça e hipotermia corpórea total. A temperatura de resfriamento deve ser 34,5 ºC para seletiva de cabeça e 33,5 ºC para corpórea total; temperaturas inferiores a 32 ºC são menos neuroprotetoras e abaixo de 30 ºC há efeitos adversos sistêmicos graves. Indica-se o início da hipotermia terapêutica até seis horas após o nascimento, pois estudos evidenciaram que essa é a janela terapêutica da agressão hipóxico e isquêmica. A hipotermia deve ser mantida por 72 horas com rigorosa monitoração da temperatura corporal do recém-nascido. A hipotermia tem sido efetiva em reduzir sequelas neurológicas, principalmente em recém-nascidos de termo ou próximo do termo com encefalopatia hipóxico isquêmica moderada e em melhorar o prognóstico em longo prazo dos recém-nascidos com EHI. Conclusão: A hipotermia terapêutica é uma técnica neuroprotetora indicada para recém-nascidos com asfixia perinatal.

Abstract Objective: Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). Sources: A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. Summary of the findings: There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 ºC for selective head cooling and 33.5 ºC for total body cooling. Temperatures lower than 32 ºC are less neuroprotective, and temperatures below 30 ºC are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6 hours after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 hours, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate HIE. Conclusion: Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and HIE.

Association of late-onset neonatal sepsis with late neurodevelopment in the first two years of life of preterm infants with very low birth weight / Associação de sepse neonatal tardia com atraso do neurodesenvolvimento nos primeiros dois anos de vida de recém-nascidos pré-termos de muito baixo peso

OBJECTIVE: To establish the influence of late-onset sepsis on neurodevelopment of preterm infants with very low birth weight (VLBW), according to the etiologic agent METHOD: This was a cohort of newborns with birth weight < 1,500 g and gestational age less than 32 weeks, admitted to the institutional intensive care unit (ICU) with up to 48 hours of life, and followed-up at the outpatient follow-up clinic for preterm infants with VLBW until 2 years of corrected age. Exclusion criteria: death within the first 72 hours of life, congenital malformations and genetic syndromes, children with congenital infection by the human immunodeficiency virus (HIV), congenital infection (STORCH), presence of early-onset spesis and cases with more than one pathogen growth in blood cultures. Septic and non-septic infants were compared regarding neonatal outcomes and mortality. Neurodevelopment was assessed using the Bayley Scale (BSDI-II) at 18 to 24 months of corrected age. RESULTS: 411 preterm infants with VLBW were eligible; the mean gestational age was 29 ± 2.2 weeks and mean birth weight was 1,041 ± 281grams. Late-onset sepsis occurred in 94 preterm infants with VLBW (22.8%). VLBW infants with Gram-positive infection showed motor deficit when compared to the non-septic group, 68.8% vs. 29.3%, respectively (OR 6; 1.6-21.8, p = 0.006); the cognitive development was similar between the groups. The overall mortality rate from infection was 26.7%; considering the pathogens, the rates were 18.7% for coagulase-negative Staphylococcus, 21.8% for Gram-positive bacteria, and 50% for Gram-negative bacteria and fungi. CONCLUSION: Neonatal sepsis has a significant influence on late neurodevelopment at 2 years of corrected age in preterm infants with VLBW, and Gram-positive infections are associated with motor deficit. .

OBJETIVO: Estabelecer a influência da sepse tardia no neurodesenvolvimento de prematuros de muito baixo peso (MBP) recém-nascidos (RNs) de acordo com o agente etiológico. MÉTODOS: Coorte de RN com peso de nascimento < 1.500 g e idade gestacional < 32 semanas,internados na UTI da instituição dentro de 48 horas de vida, e atendidos no ambulatório de MBP para até dois anos de idade corrigida. Foram excluídos: a morte nas primeiras 72 h de vida, malformações congênitas e síndromes genéticas, filhos de mães HIV-positivas e infecção congênita, presença de sepse precoce, e os casos com mais de um microorganismo identificado em hemoculturas. RNs sépticos e não sépticos foram comparados quanto resultados neonatais, mortalidade e neurodesenvolvimento avaliados através das escalas Bayley (BSDI-II) aos 18-24 meses de idade corrigida. RESULTADOS: Um total de 411 RNs prematuros de muito baixo peso eram elegíveis, com idade gestacional = 29 ± 2,2 semanas e peso de nascimento = 1.041 ± 281 g. Sepse tardia ocorreu em 94 casos (22,8%). MBP RN com infecção causada por microrganismos Gram-positivos apresentaram atraso motor, quando comparado com o grupo sem sépsis - 68,8% vs 29,3% (OR 6; 1,6-21,8,p = 0,006), e atraso cognitivo, foi semelhante. Taxa de mortalidade global de infecção foi de 26,7%, e as taxas de mortalidade por grupo microorganismo foram: Staphylococcus coagulase negativa, 18,7%; Gram-positivos, 21,8%; Gram-negativas e fungos, 50%. CONCLUSÃO: A sepse neonatal tem uma influência significativa no atraso no desenvolvi mento neuropsicomotor aos dois anos de idade corrigida em prematuros de muito baixo peso RN e as infecções por germes gram-positivos estão associadas com atraso motor. .

Lesao pulmonar induzida pela ventilacao em recem-nascidos prematuros / Ventilator-induced lung injury in preterm infants

A necessidade de intubação e do uso de ventilação mecânica na prematuridade está relacionada à chamada lesão pulmonar induzida pela ventilação e à consequente displasia broncopulmonar. Busca-se a melhor compreensão dos mecanismos de lesão envolvendo resposta inflamatória mediada pelas citocinas para o desenvolvimento de novas estratégias protetoras. Pesquisou-se na base de dados PubMed, incluindo artigos relevantes, os unitermos "ventilator induced lung injury preterm", "continuous positive airway pressure", "preterm" e "bronchopulmonary dysplasia". Dados e informações significativas foram compilados em tópicos, com o objetivo de formar uma visão crítica e plena acerca da lesão induzida pela ventilação e de suas consequências ao prematuro. Foi revisado o papel das citocinas pró-inflamatórias como mediadores da lesão, especialmente interleucinas 6 e 8, e fator de necrose tumoral alfa. Foram apresentadas evidências em estudos com animais e também em humanos, mostrando que breves períodos de ventilação mecânica são suficientes para a liberação dessas interleucinas inflamatórias. Também foram revisadas outras formas de ventilação mecânica e de ventilação não invasiva, como alternativas protetoras aos modos convencionais. Concluiu-se que o uso de ventilação não invasiva, a intubação com administração precoce de surfactante e a extubação rápida para CPAP nasal, além de estratégias que regulam o volume corrente evitando o volutrauma (como a ventilação com volume garantido), são medidas protetoras da lesão pulmonar induzida pela ventilação mecânica no prematuro.

In preterm infants, the need for intubation and mechanical ventilation is associated with ventilator-induced lung injuries and subsequent bronchopulmonary dysplasia. The aim of the present review was to improve the understanding of the mechanisms of injury that involve cytokine-mediated inflammation to contribute to the development of new preventive strategies. Relevant articles were retrieved from the PubMed database using the search terms "ventilator-induced lung injury preterm", "continuous positive airway pressure", "preterm", and "bronchopulmonary dysplasia". The resulting data and other relevant information were divided into several topics to ensure a thorough, critical view of ventilation-induced lung injury and its consequences in preterm infants. The role of pro-inflammatory cytokines (particularly interleukins 6 and 8 and tumor necrosis factor alpha) as mediators of lung injury was assessed. Evidence from studies conducted with animals and human newborns is described. This evidence shows that brief periods of mechanical ventilation is sufficient to induce the release of pro-inflammatory cytokines. Other forms of mechanical and non-invasive ventilation were also analyzed as protective alternatives to conventional mechanical ventilation. It was concluded that non-invasive ventilation, intubation followed by early surfactant administration and quick extubation for nasal continuous positive airway pressure, and strategies that regulate tidal volume and avoid volutrauma (such as volume guarantee ventilation) protect against ventilator-induced lung injury in preterm infants.

Oral glucose for pain relief during examination for retinopathy of prematurity: a masked randomized clinical trial

OBJECTIVE: Ophthalmologic examination for retinopathy of prematurity is a painful procedure. Pharmacological and non-pharmacological interventions have been proposed to reduce pain during eye examinations. This study aims to evaluate the analgesic effect of 25% glucose using a validated pain scale during the first eye examination for retinopathy of prematurity in preterm infants with birth weight <1,500 g and/or gestational age <32 weeks. METHODS: A masked, randomized clinical trial for one dose of 1 ml of oral 25% glucose solution 2 minutes before the first ophthalmologic examination for retinopathy of prematurity was conducted between March 2008 and April 2010. The results were compared to those of a control group that did not receive oral glucose solution. Pain was evaluated using a Neonatal Infant Pain Scale immediately before and immediately after the ophthalmologic examination in both groups. Clinicaltrials.gov: NCT00648687 RESULTS: One hundred and twenty-four patients who were examined for the first time for retinopathy of prematurity were included. Seventy were included in the intervention group and 54 in the control group. The number of patients with pain immediately before the procedure was similar in both groups. The number of patients with pain after ophthalmologic examination was 15.7% in the intervention group and 68.5% in the control group (p<0.001). CONCLUSIONS: One ml of oral 25% glucose solution given 2 minutes before an ophthalmologic examination for retinopathy of prematurity was an effective measure for pain relief.

Uso de medicamentos off-label e não licenciados em unidade de tratamento intensivo neonatal e sua associação com escores de gravidade / Use of off-label and unlicensed drugs in the neonatal intensive care unit and its association with severity scores

OBJETIVO: Avaliar a frequência da prescrição de medicamentos de uso não licenciado (UL) e off-label (OL) em recém-nascidos internados em unidade de tratamento intensivo neonatal de hospital de nível terciário e verificar a associação do seu uso com a gravidade dos pacientes. MÉTODOS: Estudo observacional de coorte dos medicamentos prescritos no período de 6 semanas da internação de neonatos, entre julho e agosto de 2011. Os medicamentos foram classificados em UL e OL para dose, frequência, apresentação, faixa etária e indicação, de acordo com bulário eletrônico aprovado pela Food and Drug Administration. Os pacientes foram acompanhados até alta hospitalar ou 31 dias de internação, com registro diário do Neonatal Therapeutic Intervention Scoring System. RESULTADOS: Foram identificados 318 itens de prescrição para 61 pacientes (média de cinco itens/paciente) e apenas 13 pacientes com uso de medicamentos adequados (21%). Identificaram-se prevalências de 7,5% para prescrições UL e de 27,7% para OL. O uso OL mais prevalente foi para medicamentos não padronizados para faixa etária - 19,5%. Computaram-se 57 medicações - um paciente recebeu 10 fármacos UL/OL na internação. A prevalência de usos OL foi maior em prematuros < 35 semanas e nos com escores de gravidade mais elevados (p = 0,00). CONCLUSÕES: A prevalência de neonatos expostos a medicamentos UL/OL durante a internação hospitalar foi elevada, especialmente naqueles com maior escore de gravidade no Neonatal Therapeutic Intervention Scoring System. Embora haja apreciação geral de que neonatos, especialmente pré-termo, tenham alta taxa de uso de medicamentos, uma avaliação incluindo diferentes culturas e países é necessária para priorizar áreas de pesquisa futura na farmacoterapêutica dessa população vulnerável.

OBJECTIVE: To analyze the frequency of unlicensed (UL) and off-label (OL) prescriptions in neonates admitted to the neonatal intensive care unit of a tertiary care hospital and to determine their association with patients' severity. METHODS: Observational cohort study including drugs prescribed during hospitalization of neonates over a 6-week period between July and August 2011. The drugs were classified as UL and OL for dose, frequency, presentation, age group, or indication, according to an electronic list of drugs approved by the Food and Drug Administration. Patients were followed until hospital discharge or 31 days of hospitalization, with daily records of the Neonatal Therapeutic Intervention Scoring System (NTISS). RESULTS: We identified 318 prescription items for 61 patients (average of five items/patient); there were only 13 patients with appropriate use of medications (21%). A prevalence of 7.5% was identified for UL prescriptions and 27.7% for OL, and the most prevalent OL use was that related to age group - 19.5%. Fifty-seven medications were computed - one patient received 10 UL/OL drugs during hospitalization. The prevalence of OL uses was higher in preterm infants < 35 weeks and in those with higher severity scores (p = 0.00). CONCLUSIONS: The prevalence of neonates exposed to UL/OL drugs during hospitalization was high, especially for those with higher NTISS scores. Although there is general appreciation that neonates, especially preterm infants, have a high rate of drug use, an assessment including different cultures and countries is still needed to prioritize areas for future research in the pharmacotherapy of this vulnerable population.

Intraocular pressure in very low birth weight preterm infants and its association with postconceptional age

OBJECTIVE: To evaluate intraocular pressure in very low birth weight preterm infants and correlate it with postconceptional age. METHODS: The intraocular pressure in a prospective cohort of very low birth weight premature infants (defined as a birth weight <1,500 g and gestational age <32 weeks) admitted to Hospital de Clínicas de Porto Alegre , Brazil was evaluated weekly. The evaluated outcome was the variation in the intraocular pressure following changes in the postconceptional age (defined as the gestational age at birth plus the age in weeks at the time of examination) in the weeks following preterm birth. Mixed-effects models were used for the statistical analysis to determine the intraocular pressure variation according to postconceptional age, and means and 10th and 90th percentiles were calculated for the intraocular pressure values. RESULTS: Fifty preterm infants with a mean gestational age of 29.7 ± 1.6 weeks and a mean birth weight of 1,127.7 ± 222.7 g were evaluated. The mean intraocular pressure for the entire cohort considering both eyes was 14.9 ± 4.5 mmHg, and 13.5% of all recorded intraocular pressure values were greater than 20 mmHg. The analysis revealed a mean reduction in the intraocular pressure of 0.29 mmHg for each increase in postconceptional age (p = 0.047; 95% CI: -0.58 to -0.0035). The mean intraocular pressure (P10-P90) decreased from 16.3 mmHg (10.5222.16) at 26.3 weeks to 13.1 mmHg (7.28-18.92) at 37.6 weeks of postconceptional age. CONCLUSIONS: The mean intraocular pressure in very low birth weight preterm infants was 14.9 ± 4.5 mmHg. This value decreased 0.29 mmHg per week as the postconceptional age increased.

Níveis plasmáticos de cafeína no cordão umbilical e apneia da prematuridade / Serum levels of caffeine in umbilical cord and apnea of prematurity

OBJETIVO: Determinar a influência da presença de cafeína no sangue de cordão umbilical na ocorrência de apneia. MÉTODOS: Estudo de coorte prospectivo de recém-nascidos pré-termo com peso de nascimento menor que 2.000 g. Os critérios de exclusão foram: mães que receberam opioides; ventilação mecânica durante os primeiros 4 dias de vida; malformações cerebrais e cardíacas maiores; asfixia perinatal; hemorragia peri-intraventricular grave; exsanguineotransfusão antes do quarto dia de vida; e uso de metilxantina antes da extubação. Os recém-nascidos foram divididos em com e sem cafeína detectável no sangue de cordão umbilical, sendo acompanhados nos primeiros 4 dias para verificar ocorrência de apneia. RESULTADOS: Oitenta e sete recém-nascidos com e 40 sem cafeína detectável no sangue de cordão umbilical foram estudados. A mediana da concentração de cafeína dos 87 pacientes com cafeína detectável no sangue de cordão umbilical foi 2,3 µg/mL (0,2-9,4 µg/mL). Não houve associação entre ocorrência de apneia e presença de cafeína no sangue de cordão umbilical. Recém-nascidos com cafeína detectável no cordão umbilical tiveram tendência a apresentar apneia mais tardiamente (66,3±4,14 horas) do que aqueles com níveis indetectáveis (54,2±6,26 horas). CONCLUSÃO: A detecção de níveis de cafeína no sangue de cordão umbilical não diminuiu a ocorrência de apneia da prematuridade, mas teve um efeito limítrofe atrasando sua ocorrência, o que sugere que mesmo um nível baixo de cafeína no sangue de cordão umbilical pode retardar a ocorrência de apneia.

OBJECTIVE: To determine the influence of presence of caffeine in umbilical cord blood on apnea occurrence. METHODS: A prospective cohort study with preterm newborns with birth weight lower than 2,000 g was undertaken. Exclusion criteria were: mothers who received opioids; mechanical ventilation during the first 4 days of life; cerebral and major cardiac malformations; perinatal asphyxia; severe periintraventricular hemorrhage; exchange transfusion before the fourth day of life; and those who received methylxantine prior to extubation. Neonates were divided into detectable and undetectable caffeine in umbilical cord blood. Newborns were followed for the first 4 days for occurrence of apnea spells. RESULTS: Eighty-seven newborns with and 40 without detectable caffeine in umbilical cord blood were studied. Median caffeine concentration of the 87 patients with detectable caffeine in umbilical blood was 2.3 µg/mL (0.2-9.4 µg/mL). There was no association between occurrence of apnea spells and presence of caffeine in umbilical cord blood. Neonates with detectable caffeine in umbilical blood had borderline later apnea (66.3±4.14 hours) than those with undetectable levels (54.2±6.26 hours). CONCLUSION: Detected levels of caffeine in umbilical cord blood did not decrease occurrence of apnea of prematurity, but it had a borderline effect delaying its occurrence, suggesting that even a low level of caffeine in umbilical cord blood might delay occurrence of apnea spells.

Ser pequeno para a idade gestacional é um fator de risco para a retinopatia da prematuridade?: estudo com 345 pré-termos de muito baixo peso / Is being small for gestational age a risk factor for retinopathy of prematurity?: a study with 345 very low birth weight preterm infants

OBJETIVO: Comparar a prevalência e os fatores de risco para a retinopatia da prematuridade entre pré-termos pequenos para a idade gestacional e pré-termos apropriados para a idade gestacional. MÉTODOS: Estudo de coorte, prospectivo, incluindo pré-termos com peso de nascimento ≤ 1.500 g e idade gestacional ≤ 32 semanas divididos em dois grupos: apropriados para a idade gestacional ou pequenos para a idade gestacional. As prevalências da retinopatia da prematuridade e os fatores de risco foram estudados nos dois grupos. Regressão logística foi utilizada após análise univariada. RESULTADOS: Foram examinados um total de 345 pacientes: 199 no grupo apropriados para a idade gestacional e 146 no grupo pequenos para a idade gestacional. As médias do peso de nascimento e da idade gestacional na coorte de 345 pacientes foram 1.128,12 g (±239,9) e 29,7 semanas (±1,9), respectivamente. A prevalência da retinopatia da prematuridade em qualquer estadiamento e da retinopatia da prematuridade severa (necessitando tratamento) foi 29,6 e 7 por cento, respectivamente. A retinopatia da prematuridade em qualquer estadiamento ocorreu em 66 apropriados para a idade gestacional (33,2 por cento) e em 36 pequenos para a idade gestacional (24,7 por cento) (p = 0,111). A retinopatia da prematuridade severa ocorreu em 15 apropriados para a idade gestacional (7,5 por cento) e em nove pequenos para a idade gestacional (6,2 por cento) (p = 0,779). Após regressão logística ajustada, o ganho ponderal do nascimento até a sexta semana de vida e a necessidade de transfusões sanguíneas foram fatores de risco significativos para a retinopatia da prematuridade nos dois grupos. CONCLUSÕES: Este estudo mostrou que ser pequenos para a idade gestacional não foi um fator de risco significativo para o surgimento da retinopatia da prematuridade e que os fatores de risco para a retinopatia da prematuridade são semelhantes em pré-termos pequenos para a idade gestacional...

OBJECTIVE: To analyze prevalence and risk factors for retinopathy of prematurity (ROP) among preterm infants born small for gestational age (SGA) and appropriate for gestational age (AGA). METHODS: A prospective cohort study included preterm infants with birth weight (BW) ≤ 1,500 grams and gestational age (GA) ≤ 32 weeks, divided into two groups: AGA or SGA. Prevalences and risk factors for ROP were determined in both groups. Logistic regression was used for the significant variables after univariate analysis. RESULTS: A total of 345 patients were examined: 199 included in the AGA group and 146 in the SGA. Mean BW and GA in the whole cohort (345 patients) were 1,128.12 grams (±239.9) and 29.7 weeks (±1.9), respectively. The prevalence of any stage ROP and severe ROP (needing treatment) was 29.6 and 7.0 percent, respectively. ROP in any evolutive stage developed in 66 AGA (33.2 percent) and in 36 SGA (24.7 percent) (p = 0.111). Severe ROP occurred in 15 AGA (7.5 percent) and in nine SGA (6.2 percent) (p = 0.779). After adjusted logistic regression, weight gain from birth to sixth week of life and need for blood transfusions were found to be significant risk factors for ROP in both groups. CONCLUSIONS: This study has shown that being SGA was not a significant risk factor for any stage ROP or for severe ROP in this cohort and, also, that the risk factors for ROP were similar among SGA and AGA very-low-birth-weight preterm babies.

Sepse neonatal como fator de risco para leucomalácia periventricular em pré-termos de muito baixo peso / Periventricular leukomalacia in very low birth weight preterm neonates with high risk for neonatal sepsis

OBJETIVO: Verificar a associação de leucomalácia periventricular (LPV) e sepse neonatal em recém-nascidos de muito baixo peso (RNMBP). MÉTODOS: Foram incluídos RNMBP com suspeita clínica de infecção nascidos na instituição de 01/08/2005 a 31/07/2007. Foram excluídos óbitos antes dos 14 dias, malformações do sistema nervoso central e infecções congênitas. Foi realizado ultra-som cerebral no terceiro dia e semanalmente até a sexta semana de vida ou alta. LPV foi diagnosticada por hiperecogenicidade difusa periventricular persistente por mais de 7 dias, ou por cistos periventriculares. RNMBP foram divididos em grupos com e sem LPV. Sepse foi definida por manifestação clínica com cultura positiva. Os testes t, Mann-Whitney, qui-quadrado e regressão logística foram usados. RESULTADOS: Foram incluídos 88 RNMBP, sendo que 62 (70,5 por cento) sobreviveram e 51 (57,8 por cento) tiveram LPV. Os grupos foram semelhantes no peso de nascimento, idade gestacional, escore de Apgar, tipo de parto, SNAPPE-II, presenças de enterocolite necrosante, persistência de canal arterial e óbitos. Sepse e ventilação mecânica foram mais freqüentes no grupo com LPV (23,5 e 2,7 por cento, p = 0,005; 86 e 59 por cento, p = 0,004, respectivamente). Na regressão logística, ambos foram fatores de risco independentes para LPV (p = 0,027 e 0,015, respectivamente). CONCLUSÃO: Corioamnionite é fator de risco definido para LPV. Demonstramos que sepse neonatal também é fator de risco importante. Acreditamos que a resposta inflamatória sistêmica seja o principal fator envolvido na etiopatogenia da LPV em RNMBP.

OBJECTIVE: To investigate the association between periventricular leukomalacia (PVL) and neonatal sepsis in very low birth weight infants (VLBWI). METHODS: We studied VLBWI with a clinical suspicion of infection who had been born at our institution between the 1st of August, 2005 and the 31st of July, 2007. Children were excluded if they died before reaching 14 days, had malformations of the central nervous system or congenital infections. Ultrasound brain scans were carried out on the third day and weekly up until the sixth week of life or discharge. Periventricular leukomalacia was diagnosed by persistent diffuse periventricular hyperechogenecity for more than 7 days, or by periventricular cysts. The VLBWI were separated into two groups on the basis of the presence or absence of PVL. Sepsis was defined as clinical manifestation plus a positive culture. The Mann-Whitney, chi-square and t tests were applied followed by logistic regression. RESULTS: A total of 88 VLBWI were studied. Of these, 62 (70.5 percent) survived and 51 (57.8 percent) had PVL. Both groups were similar in terms of birth weight, gestational age, Apgar score, type of delivery, SNAPPE-II score, presence of necrotizing enterocolitis, persistent ductus arteriosus and deaths. Sepsis and mechanical ventilation were more common in the group with PVL (23.5 and 2.7 percent, p = 0.005; 86 and 59 percent, p = 0.004, respectively). Both of these were identified as, independent risk factors for PVL by logistic regression (p = 0.027 and 0.015, respectively). CONCLUSIONS: Chorioamnionitis has been defined as a risk factor for PVL. We have demonstrated that neonatal sepsis is also an important risk factor. We believe that the systemic inflammatory response is the principal factor involved in the etiopathogenesis of PVL among VLBWI.