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

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          Abstract

          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.

          Translated abstract

          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.

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          Bronchopulmonary dysplasia.

          Bronchopulmonary dysplasia is a chronic lung disease that affects premature babies and contributes to their morbidity and mortality. Improved survival of very immature infants has led to increased numbers of infants with this disorder. This increase puts a heavy burden on health resources since these infants need frequent re-admission to hospital in the first 2 years after birth and, even as adolescents, have lung-function abnormalities and persistent respiratory symptoms. Unlike the original description of the disease in 1967, premature infants can develop chronic oxygen dependency without severe, acute respiratory distress; this "new bronchopulmonary dysplasia" could be the result of impaired postnatal lung growth. Whether such infants subsequently have catch-up lung growth, especially if given corticosteroids postnatally, is unknown. No safe and effective preventive therapy has been identified, but promising new treatments directed either at reducing lung injury or improving lung growth are under study.
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            Neonatal infection and long-term neurodevelopmental outcome in the preterm infant.

            The relationship between infection, the inflammatory response and adverse neurodevelopmental outcome in preterm infants is slowly being elucidated. The developing brain, particularly the periventricular white matter, is vulnerable to cytotoxic and hypoxic/ischemic injury, which places these infants at increased risk for abnormal cognitive and motor functioning. This review summarizes current data evaluating associations between infection and neurodevelopmental outcome in the preterm infant. Preterm infants are at risk for intrauterine and postnatal infections. Recent studies have linked infection/inflammation associated with chorioamnionitis, sepsis and necrotizing enterocolitis with adverse neurodevelopmental outcome and impaired growth in preterm infants. Investigators have also shown associations between infection and brain injury, including severe intraventricular hemorrhage and periventricular leukomalacia. Very-low-birth-weight preterm infants are at substantial risk for neonatal infection, with associated morbidity and mortality. It is postulated that exposure of the preterm brain to inflammatory mediators during infectious episodes contributes to brain injury and poor developmental outcome. Enhanced understanding of the interaction of infection, inflammation and brain injury will be critical to developing strategies to improve neurodevelopmental outcome in preterm infants.
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              Systemic Candida infection in extremely low birth weight infants: short term morbidity and long term neurodevelopmental outcome.

              To describe mortality, morbidity at discharge and neurodevelopmental outcome at 2 years corrected age in extremely low birth weight infants with systemic Candida infection during intensive care stay. We identified all extremely low birth weight (birth weight <1000 g) infants diagnosed with Candida sepsis and/or meningoencephalitis between 1988 and mid-1996 in the tertiary neonatal intensive care centers of Toronto. The outcome of the infected infants at discharge and at 2 years corrected age was compared with a cohort of 470 extremely low birth weight infants born between 1990 and 1994. Forty-six extremely low birth weight infants with systemic Candida infection, mean (+/-SD) gestational age of 24.7 +/- 1.6 weeks and birth weight 699 +/- 135 g, were identified. Case fatality rate was 37% (17 of 46), not significantly different from the control group (35%). Data on 27 infected survivors were available at discharge. All had chronic lung disease compared with 33% in the control cases (P = 0.0001), a high incidence of periventricular leukomalacia (26% vs. 12%, P = 0.06) and an increase in severe retinopathy of prematurity (22% vs. 9%, P = 0.04); 60% had adverse neurologic outcomes at 2 years corrected age compared with 35% in the control group, and 41% vs. 12% had severe disabilities (P = 0.005). Cranial ultrasound examination was the only diagnostic modality in 5 of 13 (38%) cases with central nervous system Candida involvement. All infants with brain parenchymal lesions detected by cranial ultrasound had poor outcome. Early diagnosis and commencement of antifungal treatment favorably affected the outcome. Systemic Candida infection is associated with increased short and long term morbidity in extremely low birth weight infants. Candida infection of the central nervous system has a significant impact on long term neurodevelopmental outcome. Performance of cranial ultrasound examination is recommended as a part of the diagnostic investigation in these infants. Detection of brain parenchymal involvement might provide further information to predict outcome.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                jped
                Jornal de Pediatria
                J. Pediatr. (Rio J.)
                Sociedade Brasileira de Pediatria (Porto Alegre )
                1678-4782
                January 2014
                : 90
                : 1
                : 50-57
                Affiliations
                [1 ] Universidade Federal do Rio Grande do Sul Brazil
                [2 ] Universidade Federal do Rio Grande do Sul Brazil
                Article
                S0021-75572014000100050
                10.1016/j.jped.2013.10.002
                24148798
                daa3b297-3156-4a1c-a9c7-4154a12ec42e

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0021-7557&lng=en
                Categories
                PEDIATRICS

                Pediatrics
                Preterm,Very low birth weight,Neonatal sepsis,Mortality,Neurodevelopment,Prematuros,Muito baixo peso ao nascer,Sepse neonatal,Mortalidade,Neuro-desenvolvimento

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