Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28 weeks. No causal ...relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking.
This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA < 28 weeks) with an echocardiographic-confirmed PDA with a transductal diameter > 1.5 mm. Early treatment (between 24 and 72 h postnatal age) with the cyclooxygenase inhibitor (COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36 weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis.
As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28 weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36 weeks.
This trial is registered with the Dutch Trial Register NTR5479 (registered on 19 October 2015), the registry sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28 .
Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional ...lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes. Such consensus is needed to compare, understand and reproduce study findings from and among different research groups, to enable large clinical trials and, ultimately, routine clinical use. Recommendations of how EIT findings can be applied to generate diagnoses and impact clinical decision-making and therapy planning are required. This consensus paper was prepared by an international working group, collaborating on the clinical promotion of EIT called TRanslational EIT developmeNt stuDy group. It addresses the stated needs by providing (1) a new classification of core processes involved in chest EIT examinations and data analysis, (2) focus on clinical applications with structured reviews and outlooks (separately for adult and neonatal/paediatric patients), (3) a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles, (4) consensus, unified terminology with clinical user-friendly definitions and explanations, (5) a review of all major work in thoracic EIT and (6) recommendations for future development (193 pages of online supplements systematically linked with the chief sections of the main document). We expect this information to be useful for clinicians and researchers working with EIT, as well as for industry producers of this technology.
Aim
To investigate the magnitude of executive function deficits and their dependency on gestational age, sex, age at assessment, and year of birth for children born preterm and/or at low birthweight.
...Method
PubMed, PsychINFO, Web of Science, and ERIC were searched for studies reporting on executive functions in children born preterm/low birthweight and term controls born in 1990 and later, assessed at a mean age of 4 years or higher. Studies were included if five or more studies reported on the same executive function measures.
Results
Thirty‐five studies (3360 children born preterm/low birthweight, 2812 controls) were included. Children born preterm/low birthweight performed 0.5 standardized mean difference (SMD) lower on working memory and cognitive flexibility and 0.4 SMD lower on inhibition. SMDs for these executive functions did not significantly differ from each other. Meta‐regression showed that heterogeneity in SMDs for working memory and inhibition could not be explained by study differences in gestational age, sex, age at assessment, or year of birth.
Interpretation
Children born preterm/low birthweight since 1990 perform half a SMD below term‐born peers on executive function, which does not seem to improve with more recent advances in medical care or with increasing age.
What this paper adds
Children born preterm/low birthweight perform below term‐born children on core executive functions.
Lower gestational age or male sex are not risk factors for poorer executive functions.
Executive function difficulties in children born preterm/low birthweight remain stable across childhood.
Executive function difficulties are similar for children born recently and children born in earlier eras.
Resumen
Déficit en funciones ejecutivas en niños nacidos pretérmino o con bajo peso al nacer: un metaanálisis
Objetivo
Investigar la magnitud del déficit de funciones ejecutivas y su dependencia de la edad gestacional, sexo, edad a la evaluación y año de nacimiento de los niños nacidos pretérmino y/o bajo peso al nacer.
Metodo
Se buscaron en PubMed, PsychINFO, Web of Science y ERIC estudios que reportaran las funciones ejecutivas de los niños nacidos pretérmino y/o bajo peso al nacer y en niños nacidos de término como controles nacidos en 1990 y posterior, evaluados a una edad media de 4 años o más. Los estudios se incluyeron si 5 o más estudios informaban sobre las mismas medidas de la función ejecutiva.
Resultados
Se incluyeron 35 estudios (3360 niños nacidos pretérmino y/o bajo peso al nacer, 2812 controles). Estos niños tuvieron una diferencia media estandarizada (DME) de 0.5 en la memoria de trabajo y la flexibilidad cognitiva y 0.4 en la inhibición de la DME. La DMEs en funciones ejecutivas no tuvieron diferencias significativas entre ellos. La meta‐regresión mostró que la heterogeneidad de las DMEs para el trabajo de memoria y la inhibición no podría explicarse por la diferencia en la edad gestacional, sexo, edad a la evaluación o año de nacimiento.
Interpretacion
Los niños nacidos pretérmino y/o bajo peso al nacer desde 1990 realizan la mitad de un SMD por debajo de sus pares nacidos a término en la función ejecutiva, que no parece mejorar con los avances más recientes en la atención médica o con el aumento de la edad.
Resumo
Deficits da função executiva em crianças nascidas pré‐termo ou com baixo peso ao nascer: uma metanálise
Objetivo
Investigar a magnitude dos déficits da função executiva e sua dependência da idade gestacional, sexo, idade no momento da avaliação e ano de nascimento de crianças pré‐termo e / ou baixo peso ao nascer.
Método
PubMed, PsychINFO, Web of Science e ERIC foram pesquisados para estudos sobre funções executivas em crianças nascidas prematuras / com baixo peso ao nascer e controles a termo, nascidos em 1990 e anos posteriores, avaliados em uma idade média de 4 anos ou mais. Os estudos foram incluídos se 5 ou mais estudos relatassem as mesmas medidas de função executiva.
Resultados
Trinta e cinco estudos (3360 crianças nascidas pré‐termo / baixo peso ao nascer, 2812 controles) foram incluídos. As crianças nascidas pré‐termo / baixo peso ao nascer apresentaram uma diferença média padronizada (DMP) 0,5 menor na memória operacional e na flexibilidade cognitiva e DMP 0,4 menor na inibição. DMPs para essas funções executivas não diferiram significativamente entre si. Meta‐regressão mostrou que a heterogeneidade em DMPs para memória de trabalho e inibição não pode ser explicada pelas diferenças de estudo em idade gestacional, sexo, idade na avaliação ou ano de nascimento.
Interpretação
Crianças nascidas pré‐termo / baixo peso ao nascer desde 1990 realizam metade de um DMP abaixo de pares nascidos a termo em função executiva, o que não parece melhorar com os avanços mais recentes nos cuidados médicos ou com o aumento da idade.
What this paper adds
Children born preterm/low birthweight perform below term‐born children on core executive functions.
Lower gestational age or male sex are not risk factors for poorer executive functions.
Executive function difficulties in children born preterm/low birthweight remain stable across childhood.
Executive function difficulties are similar for children born recently and children born in earlier eras.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Neonatal respiratory failure is a common and serious clinical problem which in a considerable proportion of infants requires invasive mechanical ventilation. The basic goal of mechanical ventilation ...is to restore lung function while limiting ventilator-induced lung injury, which is considered an important risk factor in the development of bronchopulmonary dysplasia (BPD). Over the last decades, new conventional mechanical ventilation (CMV) modalities have been introduced in clinical practice, aiming to assist clinicians in providing lung protective ventilation strategies. These modalities use more sophisticated techniques to improve patient-ventilator interaction and transfer control of ventilation from the operator to the patient. Knowledge on how these new modalities work and how they interact with lung physiology is essential for optimal and safe use. In this review, we will discuss some important basic lung physiological aspects for applying CMV, the basic principles of the old and new CMV modalities, and the evidence to support their use in daily clinical practice.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective To determine the effect of caffeine on diaphragmatic activity, tidal volume (Vt ), and end-expiratory lung volume (EELV) in preterm infants. Study design Using transcutaneous ...electromyography of the diaphragm (dEMG), we measured diaphragmatic activity from 30 minutes before (baseline) to 3 hours after administration of an intravenous caffeine-base loading dose in 30 spontaneously breathing preterm infants (mean gestational age, 29.1 ± 1.3 weeks), most of whom were on noninvasive respiratory support. Diaphragmatic activity was expressed as the percentage change in dEMG amplitude, area under the curve, respiratory rate, and inspiratory and expiratory times. Using respiratory inductive plethysmography, we measured changes in Vt and EELV from baseline. These outcome variables were calculated at 8 fixed time points after caffeine administration (5, 15, 30, 60, 90, 120, 150, and 180 minutes) and compared with baseline. Results Caffeine administration resulted in rapid (within 5 minutes) increases in dEMG amplitude (median, 43%; IQR, 24%-63%; P < .001) and area under the curve (median, 28%; IQR, 14%-48%; P < .001). Vt also increased by a median of 30% (IQR, 7%-48%), and this change was significantly correlated with the change in dEMG amplitude ( r = 0.67; P < .001). These effects were relatively stable until 120 minutes after caffeine administration. Caffeine did not consistently impact EELV, respiratory rate, or inspiratory and expiratory times. Conclusion Caffeine treatment results in a rapid and sustained increase in diaphragmatic activity and Vt in preterm infants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BackgroundPeripheral blood culture (PBC) is considered the gold standard for diagnosis of neonatal early-onset sepsis (EOS), but its diagnostic value can be questioned. We aimed to systematically ...asses the diagnostic test accuracy (DTA) of umbilical cord blood culture (UCBC) for EOS.MethodsA systematic literature search was performed in PubMed, Embase, Web of Science, and the Cochrane Library. Studies performing UCBC for the diagnosis of EOS were included.ResultsA total of 1908 articles were screened of which 17 were included. Incidences of positive PBC and UCBC were low in all studies. There was a large heterogeneity in the consistency between positive PBC and UCBC outcomes. PBC had a pooled sensitivity of 20.4% (95% CI 0.0–40.9) and specificity of 100.0% (95% CI 100.0–100.0) compared to 42.6% (95% CI 12.7–72.4%) and 97.8% (95% CI 93.1–100.0) of UCBC for clinical EOS, defined as clinical sepsis regardless of PBC outcomes.ConclusionsThis systematic review shows that, compared to PBC, UCBC has higher sensitivity and comparable specificity for clinical EOS and might be considered as diagnostic test for EOS. Due to the limited number of studies, low incidences of EOS cases, and the imperfect reference standards for EOS, results should be interpreted cautiously.ImpactThis is the first systematic review and meta-analysis investigating the diagnostic test accuracy of umbilical cord blood culture for neonatal early-onset sepsis.Peripheral blood culture is considered the gold standard for diagnosis of neonatal early-onset sepsis, but its value for this specific diagnosis can be questioned. Umbilical cord blood culture has higher sensitivity and comparable specificity for diagnosis of neonatal early-onset sepsis compared to peripheral blood culture, circumventing the risk for iatrogenic anemia and consequently might be used as a diagnostic tool for early-onset sepsis.Quality of evidence was regarded as low due to imperfect diagnostic methods of neonatal early-onset sepsis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives To test the hypothesis that fecal volatile organic compounds (VOCs) analysis by electronic nose (eNose) allows for early detection of necrotizing enterocolitis (NEC). Study design In 3 ...neonatal intensive care units, fecal samples of infants born at gestational age ≤30 weeks were collected daily, up to the 28th day of life. Included infants were allocated in 3 subgroups: NEC, sepsis, and matched controls. Three time windows were defined: (1) T−5,−4 (5 and 4 days before diagnosis); (2) T−3,−2 (3 and 2 days before diagnosis); and (3) T−1,0 (day before and day of diagnosis). Three subgroups were analyzed by eNose. Results Fecal VOC profiles of infants with NEC (n = 13) could significantly be discriminated from matched controls (n = 14) at T−3,−2 (area under the curve ± 95% CI, P value, sensitivity, specificity: 0.77 ± 0.21, P = .02, 83%, 75%); the accuracy increased at T−1,0 (0.99 ± 0.04, P ≤ .001, 89%, 89%). VOC profiles of infants with NEC were also significantly different from those with sepsis (n = 31) at T−3,−2 (0.80 ± 0.17, P = .004, 83%, 75%), but not at T−1,0 (0.64 ± 0.18, P = .216, 89%, 57%). Conclusions In this proof of principle study, we observed that fecal VOC profiles of infants with NEC could be discriminated from controls, from 2-3 days predating onset of clinical symptoms. Our observations suggest that VOC-profiling by eNose has potential as a noninvasive tool for the early prediction of NEC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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