A significant proportion of babies that are admitted to the neonatal intensive care unit (NICU) s... more A significant proportion of babies that are admitted to the neonatal intensive care unit (NICU) suffer from late onset sepsis (LOS). In order to prevent mortality and morbidity, the early detection of LOS is of the utmost importance. Recent works have found that the use of machine learning techniques might help detect LOS at an early stage. Some works have shown that linear methods (i.e., logistic regression) display a superior performance when predicting LOS. Nevertheless, as research on this topic is still in an early phase, it has not been ruled out that non-linear machine learning (ML) techniques can improve the predictive performance. Moreover, few studies have assessed the effect of parameters other than heart rate variability (HRV). Therefore, the current study investigates the effect of non-linear methods and assesses whether other vital parameters such as respiratory rate, perfusion index, and oxygen saturation could be of added value when predicting LOS. In contrast with t...
Archives of Disease in Childhood - Fetal and Neonatal Edition
Objective Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in childre... more Objective Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. Design Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. Setting 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. Patients 660 infants born at less than 34 weeks’ gestation with platelet counts less than 50×109/L. Interventions Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×109/L (higher threshold group) or 25×109/L (lower threshold group). Main outcomes measure...
Pathogenic heterozygous NEXN variants are associated with progressive dilated cardiomyopathy (DCM... more Pathogenic heterozygous NEXN variants are associated with progressive dilated cardiomyopathy (DCM) usually presenting around 50 years of age. We describe an asymptomatic boy who had transient DCM at 3 months of age, that resolved by 4 months. Presently, at 11 years of age, he has normal cardiac function with signs of mild DCM on cardiac MRI. Genetic diagnostics revealed a paternally derived, heterozygous 1949_1951del class 4 variant in NEXN. His father had mild DCM with mildly reduced systolic function. The second patient presented with fetal hydrops at 33 weeks gestation requiring emergency caesarian delivery. Postnatally she required ventilation and continuous inotropic support for left ventricle systolic dysfunction. She died after 2 weeks when therapy was withdrawn. Homozygous c.1174C > T,p.(R392*) class 4 variants in the NEXN gene were found via WES. Microscopic investigation showed endomyocardial fibroelastosis. Her parents, both heterozygous carriers, had normal cardiac fu...
Archives of Pediatrics & Adolescent Medicine, 2006
Objectives: To use the ethanol-lock technique (in conjunction with systemic antibiotics) to salva... more Objectives: To use the ethanol-lock technique (in conjunction with systemic antibiotics) to salvage central lines from removal and to prevent persistence of catheterrelated infections among pediatric patients with longterm intravascular devices.
Archives of Disease in Childhood - Fetal and Neonatal Edition
ObjectiveTo report the parent-reported behavioural outcomes of infants included in the Systemic H... more ObjectiveTo report the parent-reported behavioural outcomes of infants included in the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants study at 2 years’ corrected age (CA).DesignRandomised placebo-controlled trial.SettingDutch and Belgian neonatal intensive care units.PatientsInfants born <30 weeks’ gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life.InterventionInfants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190).Main outcome measuresParent-reported behavioural outcomes at 2 years’ CA assessed with the Child Behavior Checklist (CBCL 1½−5).ResultsParents completed the CBCL of 183 (70% (183/262)) infants (hydrocortisone group, n=96; placebo group, n=87). Multiple imputation was used to account for missing data. Infants with critically elevated T-scores (>55) were found in 22.9%, 19.1% and 29.4% of infants for total, internalis...
Strategies to ensure high intraocular oxygen delivery to the developing retina after 32 weeks ges... more Strategies to ensure high intraocular oxygen delivery to the developing retina after 32 weeks gestational age, such as higher saturation targets and/or higher hemoglobin levels, are hypothesized to prevent ophthalmological treatment for retinopathy of prematurity (ROP). This short report summarizes the current evidence of these strategies, and discusses possibilities of future studies. A large sample size would be required and therefore the feasibility of a future randomized controlled trial is questioned.
Introduction: The brain magnetic resonance imaging (MRI) result is a major predictor for the outc... more Introduction: The brain magnetic resonance imaging (MRI) result is a major predictor for the outcome of term infants with perinatal asphyxia who underwent therapeutic hypothermia. In daily practice, no uniform method is used to assess these images. Purpose: The aim of this study was to determine which MRI-score best predicts adverse outcome at 24 months of age and has the highest inter-rater reliability. Methods: Four MRI scoring systems for term infants with perinatal asphyxia were selected: Rutherford score, Trivedi score, Weeke score, and NICHD NRN score. Experienced blinded raters retrospectively evaluated the brain MR Images of 161 infants using all four scoring systems. Long-term outcome (the composite outcome death or adverse outcome, and its separate components) were routinely assessed by standardized testing at the age of 24 months. The predictive accuracy was assessed by logistic regression analyses and expressed as area under the ROC curve (AUC). The inter-rater reliabili...
The easiest way to order: w w w.karger.com/pape Algorithms provide a logical, concise and cost-ef... more The easiest way to order: w w w.karger.com/pape Algorithms provide a logical, concise and cost-effective approach to medical reasoning: utilizing a concise, step-by-step approach based upon clues from the history, physical examination and laboratory studies, algorithms help avoid excessive unnecessary procedures and testing. The 3rd, revised edition of Practical Algorithms in Pediatric Endocrinology deals with practical issues of child growth, puberty, diseases of the endocrine glands, sexual differentiation, as well as aberrations of water, electrolyte, mineral and carbohydrate metabolism. Fifty-six clinical issues are covered by an algorithmic approach, breaking down long lists and tables of differential diagnosis into smaller, more manageable ones. Common clinical symptoms, signs and laboratory abnormalities are classified as they present themselves at the patient's bedside. This book is aimed at general practitioners and pediatricians, in particular those who are not exposed to pediatric endocrine problems on a daily basis, and at trainees in endocrinology and pediatric endocrinology as they acquire familiarity with clinical problem solving to make rational choices when facing clinical dilemmas.
Peripheral blood culture (PBC) is considered the gold standard for diagnosis of neonatal early-on... more Peripheral 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. A 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. A 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. This 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. This 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. This 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.
Bronchopulmonary dysplasia (BPD) is the most common morbidity of preterm infants, and its inciden... more Bronchopulmonary dysplasia (BPD) is the most common morbidity of preterm infants, and its incidence has not responded to research and intervention efforts to the same degree as other major morbidities associated with prematurity. The complexity of neonatal respiratory care as well as persistent inter-institutional variability in BPD rates suggest that BPD may be amenable to quality improvement (QI) efforts. We present a systematic review of QI for BPD in preterm infants. We identified 22 reports from single centers and seven from collaborative efforts published over the past two decades. In almost all of the reports, respiratory QI interventions successfully reduced BPD or other key respiratory measures, particularly for infants with birth weight over 1000 g. Several themes and lessons from existing reports may help inform future efforts in both research and QI to impact the burden of BPD.
Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evide... more Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evidence supports this practice, and only 10% develop major bleeding. In a recent randomized trial, platelet transfusions given at a threshold of 50x10 9 /L compared to a threshold of 25x10 9 /L were associated with increased risk of major bleeding or mortality. Of 640 included neonates, 71 (11%) developed major bleeding. We included the variables gestational age, postnatal age, intra-uterine growth restriction, necrotizing enterocolitis, sepsis, platelet count and mechanical ventilation in the model. The median cross-validated c-index was 0.74 (IQR 0.69-0.82). This is a promising dynamic prediction model for bleeding in this population that should be explored further in clinical studies as a potential clinical decision support tool. The study was registered at www.clinicaltrials.gov (NCT03110887). The study protocol was published online on www.clinicaltrials.gov (NCT03110887). The institutional review 3 board of the Academic Medical Center Amsterdam approved the study and waived the need for informed 4 consent, since the study involves retrospective datacollection. The study was conducted in accordance with the 5 Declaration of Helsinki and reported according to The Transparent Reporting of a Multivariable Prediction 6 Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines. 2 7 Population 8 We performed a cohort study among consecutive preterm neonates with thrombocytopenia admitted to any one 9
Aim: Though caffeine is a consolidated treatment in preterm infants, the efficacy and safety of a... more Aim: Though caffeine is a consolidated treatment in preterm infants, the efficacy and safety of a higher dose have not been systematically appraised. Methods: A systematic review was conducted to compare high (loading dose >20 mg/kg and maintenance >10 mg/kg/day) versus low dose of caffeine. MEDLINE, EMBASE, Central, and conference proceedings for randomized controlled trials (RCTs) and quasi-RCTs were searched. Two authors independently screened the records, extracted the data and assessed the risk of bias. Results: As only six RCTs enrolling a total of 816 preterm infants were included, the required information size was not reached. The loading and maintenance doses varied between 20-80 mg/kg/day and 3-20 mg/kg/day, respectively. The use of high dose had no impact on mortality (RR: 0.85; 95% CI: 0.53-1.38; RCTs = 4) or bronchopulmonary dysplasia (RR: 0.93; 95% CI: 0.72-1.20; studies = 4), however it resulted in fewer cases of extubation failure and apneas and shorter duration of mechanical ventilation. The quality of the evidence was low due (imprecision of the estimates). Conclusion: Due to imprecision it is not possible to determine whether high dose caffeine is more effective and safe than a low dose. High dose might improve short-term respiratory function without reducing bronchopulmonary dysplasia.
Background Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstru... more Background Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative. Objectives To determine if administration of inhalation corticosteroids after the first week of life until 36 weeks PMA to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes.
Background Randomized controlled trials have shown that treatment of chronically ventilated prete... more Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortal...
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2019
ObjectiveTo investigate the association between invasive mechanical ventilation (IMV) duration an... more ObjectiveTo investigate the association between invasive mechanical ventilation (IMV) duration and long-term neurodevelopmental outcomes in preterm infants in an era of restricted IMV.DesignRetrospective cohort study.SettingSingle neonatal intensive care unit in Amsterdam.PatientsAll ventilated patients with a gestational age between 24 and 30 weeks born between 2010 and 2015.Main outcome measuresNeurodevelopmental impairment (NDI) at 24 months corrected age (CA). Data on patient characteristics, respiratory management, neonatal morbidities, mortality and bronchopulmonary dysplasia were collected. The relationship between IMV duration and NDI was determined by multivariate logistic regression analysis.ResultsDuring the study period, 368 admitted infants received IMV for a median duration of 2 days. Moderate and severe bronchopulmonary dysplasia was diagnosed in 33% of the infant. Multivariate regression analysis with adjustment for gestational age, small for gestational age and soci...
Determination when patients with short bowel syndrome grow independently of parenteral nutrition ... more Determination when patients with short bowel syndrome grow independently of parenteral nutrition remains a large clinical problem. A possible parameter with positive predictive value for enteric function could be plasma citrulline. Citrulline is a non-protein amino acid, produced by the enterocyte. To support this hypothesis, we report of two patients with short bowel syndrome in whom this marker has been determined during the course of their disease.
A significant proportion of babies that are admitted to the neonatal intensive care unit (NICU) s... more A significant proportion of babies that are admitted to the neonatal intensive care unit (NICU) suffer from late onset sepsis (LOS). In order to prevent mortality and morbidity, the early detection of LOS is of the utmost importance. Recent works have found that the use of machine learning techniques might help detect LOS at an early stage. Some works have shown that linear methods (i.e., logistic regression) display a superior performance when predicting LOS. Nevertheless, as research on this topic is still in an early phase, it has not been ruled out that non-linear machine learning (ML) techniques can improve the predictive performance. Moreover, few studies have assessed the effect of parameters other than heart rate variability (HRV). Therefore, the current study investigates the effect of non-linear methods and assesses whether other vital parameters such as respiratory rate, perfusion index, and oxygen saturation could be of added value when predicting LOS. In contrast with t...
Archives of Disease in Childhood - Fetal and Neonatal Edition
Objective Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in childre... more Objective Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. Design Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. Setting 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. Patients 660 infants born at less than 34 weeks’ gestation with platelet counts less than 50×109/L. Interventions Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×109/L (higher threshold group) or 25×109/L (lower threshold group). Main outcomes measure...
Pathogenic heterozygous NEXN variants are associated with progressive dilated cardiomyopathy (DCM... more Pathogenic heterozygous NEXN variants are associated with progressive dilated cardiomyopathy (DCM) usually presenting around 50 years of age. We describe an asymptomatic boy who had transient DCM at 3 months of age, that resolved by 4 months. Presently, at 11 years of age, he has normal cardiac function with signs of mild DCM on cardiac MRI. Genetic diagnostics revealed a paternally derived, heterozygous 1949_1951del class 4 variant in NEXN. His father had mild DCM with mildly reduced systolic function. The second patient presented with fetal hydrops at 33 weeks gestation requiring emergency caesarian delivery. Postnatally she required ventilation and continuous inotropic support for left ventricle systolic dysfunction. She died after 2 weeks when therapy was withdrawn. Homozygous c.1174C > T,p.(R392*) class 4 variants in the NEXN gene were found via WES. Microscopic investigation showed endomyocardial fibroelastosis. Her parents, both heterozygous carriers, had normal cardiac fu...
Archives of Pediatrics & Adolescent Medicine, 2006
Objectives: To use the ethanol-lock technique (in conjunction with systemic antibiotics) to salva... more Objectives: To use the ethanol-lock technique (in conjunction with systemic antibiotics) to salvage central lines from removal and to prevent persistence of catheterrelated infections among pediatric patients with longterm intravascular devices.
Archives of Disease in Childhood - Fetal and Neonatal Edition
ObjectiveTo report the parent-reported behavioural outcomes of infants included in the Systemic H... more ObjectiveTo report the parent-reported behavioural outcomes of infants included in the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants study at 2 years’ corrected age (CA).DesignRandomised placebo-controlled trial.SettingDutch and Belgian neonatal intensive care units.PatientsInfants born <30 weeks’ gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life.InterventionInfants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190).Main outcome measuresParent-reported behavioural outcomes at 2 years’ CA assessed with the Child Behavior Checklist (CBCL 1½−5).ResultsParents completed the CBCL of 183 (70% (183/262)) infants (hydrocortisone group, n=96; placebo group, n=87). Multiple imputation was used to account for missing data. Infants with critically elevated T-scores (>55) were found in 22.9%, 19.1% and 29.4% of infants for total, internalis...
Strategies to ensure high intraocular oxygen delivery to the developing retina after 32 weeks ges... more Strategies to ensure high intraocular oxygen delivery to the developing retina after 32 weeks gestational age, such as higher saturation targets and/or higher hemoglobin levels, are hypothesized to prevent ophthalmological treatment for retinopathy of prematurity (ROP). This short report summarizes the current evidence of these strategies, and discusses possibilities of future studies. A large sample size would be required and therefore the feasibility of a future randomized controlled trial is questioned.
Introduction: The brain magnetic resonance imaging (MRI) result is a major predictor for the outc... more Introduction: The brain magnetic resonance imaging (MRI) result is a major predictor for the outcome of term infants with perinatal asphyxia who underwent therapeutic hypothermia. In daily practice, no uniform method is used to assess these images. Purpose: The aim of this study was to determine which MRI-score best predicts adverse outcome at 24 months of age and has the highest inter-rater reliability. Methods: Four MRI scoring systems for term infants with perinatal asphyxia were selected: Rutherford score, Trivedi score, Weeke score, and NICHD NRN score. Experienced blinded raters retrospectively evaluated the brain MR Images of 161 infants using all four scoring systems. Long-term outcome (the composite outcome death or adverse outcome, and its separate components) were routinely assessed by standardized testing at the age of 24 months. The predictive accuracy was assessed by logistic regression analyses and expressed as area under the ROC curve (AUC). The inter-rater reliabili...
The easiest way to order: w w w.karger.com/pape Algorithms provide a logical, concise and cost-ef... more The easiest way to order: w w w.karger.com/pape Algorithms provide a logical, concise and cost-effective approach to medical reasoning: utilizing a concise, step-by-step approach based upon clues from the history, physical examination and laboratory studies, algorithms help avoid excessive unnecessary procedures and testing. The 3rd, revised edition of Practical Algorithms in Pediatric Endocrinology deals with practical issues of child growth, puberty, diseases of the endocrine glands, sexual differentiation, as well as aberrations of water, electrolyte, mineral and carbohydrate metabolism. Fifty-six clinical issues are covered by an algorithmic approach, breaking down long lists and tables of differential diagnosis into smaller, more manageable ones. Common clinical symptoms, signs and laboratory abnormalities are classified as they present themselves at the patient's bedside. This book is aimed at general practitioners and pediatricians, in particular those who are not exposed to pediatric endocrine problems on a daily basis, and at trainees in endocrinology and pediatric endocrinology as they acquire familiarity with clinical problem solving to make rational choices when facing clinical dilemmas.
Peripheral blood culture (PBC) is considered the gold standard for diagnosis of neonatal early-on... more Peripheral 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. A 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. A 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. This 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. This 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. This 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.
Bronchopulmonary dysplasia (BPD) is the most common morbidity of preterm infants, and its inciden... more Bronchopulmonary dysplasia (BPD) is the most common morbidity of preterm infants, and its incidence has not responded to research and intervention efforts to the same degree as other major morbidities associated with prematurity. The complexity of neonatal respiratory care as well as persistent inter-institutional variability in BPD rates suggest that BPD may be amenable to quality improvement (QI) efforts. We present a systematic review of QI for BPD in preterm infants. We identified 22 reports from single centers and seven from collaborative efforts published over the past two decades. In almost all of the reports, respiratory QI interventions successfully reduced BPD or other key respiratory measures, particularly for infants with birth weight over 1000 g. Several themes and lessons from existing reports may help inform future efforts in both research and QI to impact the burden of BPD.
Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evide... more Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evidence supports this practice, and only 10% develop major bleeding. In a recent randomized trial, platelet transfusions given at a threshold of 50x10 9 /L compared to a threshold of 25x10 9 /L were associated with increased risk of major bleeding or mortality. Of 640 included neonates, 71 (11%) developed major bleeding. We included the variables gestational age, postnatal age, intra-uterine growth restriction, necrotizing enterocolitis, sepsis, platelet count and mechanical ventilation in the model. The median cross-validated c-index was 0.74 (IQR 0.69-0.82). This is a promising dynamic prediction model for bleeding in this population that should be explored further in clinical studies as a potential clinical decision support tool. The study was registered at www.clinicaltrials.gov (NCT03110887). The study protocol was published online on www.clinicaltrials.gov (NCT03110887). The institutional review 3 board of the Academic Medical Center Amsterdam approved the study and waived the need for informed 4 consent, since the study involves retrospective datacollection. The study was conducted in accordance with the 5 Declaration of Helsinki and reported according to The Transparent Reporting of a Multivariable Prediction 6 Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines. 2 7 Population 8 We performed a cohort study among consecutive preterm neonates with thrombocytopenia admitted to any one 9
Aim: Though caffeine is a consolidated treatment in preterm infants, the efficacy and safety of a... more Aim: Though caffeine is a consolidated treatment in preterm infants, the efficacy and safety of a higher dose have not been systematically appraised. Methods: A systematic review was conducted to compare high (loading dose >20 mg/kg and maintenance >10 mg/kg/day) versus low dose of caffeine. MEDLINE, EMBASE, Central, and conference proceedings for randomized controlled trials (RCTs) and quasi-RCTs were searched. Two authors independently screened the records, extracted the data and assessed the risk of bias. Results: As only six RCTs enrolling a total of 816 preterm infants were included, the required information size was not reached. The loading and maintenance doses varied between 20-80 mg/kg/day and 3-20 mg/kg/day, respectively. The use of high dose had no impact on mortality (RR: 0.85; 95% CI: 0.53-1.38; RCTs = 4) or bronchopulmonary dysplasia (RR: 0.93; 95% CI: 0.72-1.20; studies = 4), however it resulted in fewer cases of extubation failure and apneas and shorter duration of mechanical ventilation. The quality of the evidence was low due (imprecision of the estimates). Conclusion: Due to imprecision it is not possible to determine whether high dose caffeine is more effective and safe than a low dose. High dose might improve short-term respiratory function without reducing bronchopulmonary dysplasia.
Background Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstru... more Background Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative. Objectives To determine if administration of inhalation corticosteroids after the first week of life until 36 weeks PMA to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes.
Background Randomized controlled trials have shown that treatment of chronically ventilated prete... more Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortal...
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2019
ObjectiveTo investigate the association between invasive mechanical ventilation (IMV) duration an... more ObjectiveTo investigate the association between invasive mechanical ventilation (IMV) duration and long-term neurodevelopmental outcomes in preterm infants in an era of restricted IMV.DesignRetrospective cohort study.SettingSingle neonatal intensive care unit in Amsterdam.PatientsAll ventilated patients with a gestational age between 24 and 30 weeks born between 2010 and 2015.Main outcome measuresNeurodevelopmental impairment (NDI) at 24 months corrected age (CA). Data on patient characteristics, respiratory management, neonatal morbidities, mortality and bronchopulmonary dysplasia were collected. The relationship between IMV duration and NDI was determined by multivariate logistic regression analysis.ResultsDuring the study period, 368 admitted infants received IMV for a median duration of 2 days. Moderate and severe bronchopulmonary dysplasia was diagnosed in 33% of the infant. Multivariate regression analysis with adjustment for gestational age, small for gestational age and soci...
Determination when patients with short bowel syndrome grow independently of parenteral nutrition ... more Determination when patients with short bowel syndrome grow independently of parenteral nutrition remains a large clinical problem. A possible parameter with positive predictive value for enteric function could be plasma citrulline. Citrulline is a non-protein amino acid, produced by the enterocyte. To support this hypothesis, we report of two patients with short bowel syndrome in whom this marker has been determined during the course of their disease.
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