Publications by authors named "Niek B Achten"

18 Publications

  • Page 1 of 1

Stratification of Culture-Proven Early-Onset Sepsis Cases by the Neonatal Early-Onset Sepsis Calculator: An Individual Patient Data Meta-Analysis.

J Pediatr 2021 Feb 3. Epub 2021 Feb 3.

Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA.

Objectives: To provide a comprehensive assessment of case stratification by the Neonatal Early-Onset Sepsis (EOS) Calculator, a novel tool for reducing unnecessary antibiotic treatment.

Study Design: A systematic review with individual patient data meta-analysis was conducted, extending PROSPERO record CRD42018116188. Cochrane, PubMed/MEDLINE, EMBASE, Web of Science, Google Scholar, and major conference proceedings were searched from 2011 through May 1, 2020. Original data studies including culture-proven EOS case(s) with EOS Calculator application, independent from EOS Calculator development, and including representative birth cohorts were included. Relevant (individual patient) data were extracted from full-text and data queries. The main outcomes were the proportions of EOS cases assigned to risk categories by the EOS Calculator at initial assessment and within 12 hours. Evidence quality was assessed using Newcastle-Ottawa scale, Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies, and GRADE tools.

Results: Among 543 unique search results, 18 were included, totaling more than 459 000 newborns. Among 234 EOS cases, EOS Calculator application resulted in initial assignments to (strong consideration of) empiric antibiotic administration for 95 (40.6%; 95% CI, 34.2%-47.2%), more frequent vital signs for 36 (15.4%; 95% CI, 11.0%-20.7%), and routine care for 103 (44.0%; 95% CI, 37.6%-50.6%). By 12 hours of age, these proportions changed to 143 (61.1%; 95% CI, 54.5%-67.4%), 26 (11.1%; 95% CI, 7.4%-15.9%), and 65 (27.8%; 95% CI, 22.1%-34.0%) of 234 EOS cases, respectively.

Conclusions: EOS Calculator application assigns frequent vital signs or routine care to a substantial proportion of EOS cases. Clinical vigilance remains essential for all newborns.
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http://dx.doi.org/10.1016/j.jpeds.2021.01.065DOI Listing
February 2021

Epidemiology and Mortality of Early-Onset Neonatal Sepsis in Suriname: A 2-Year Surveillance Study.

J Pediatric Infect Dis Soc 2020 Nov 24. Epub 2020 Nov 24.

Department of Pediatrics, Tergooi Hospital, Blaricum, The Netherlands.

We conducted a nationwide surveillance study to produce reliable national estimates on incidence, etiology, and mortality of early-onset neonatal sepsis (EONS) in Suriname. The estimated national population incidence rate of EONS was 1.37 (95% CI: 0.90-1.99) per 1000 live births and in-hospital mortality was 25.9%.
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http://dx.doi.org/10.1093/jpids/piaa130DOI Listing
November 2020

Technical assessment of the neonatal early-onset sepsis risk calculator.

Lancet Infect Dis 2020 Oct 29. Epub 2020 Oct 29.

Department of Pediatrics, Tergooi Hospital, Blaricum, Netherlands; Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands; Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, Netherlands; Department of Pediatrics, Emma Children's Hospital, Amsterdam, Netherlands; Department of Pediatrics, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, Netherlands.

The use of the neonatal early-onset sepsis risk calculator, developed by Kaiser Permanente Northern California (CA, USA), is increasing for the management of late preterm and full term newborn babies at risk for early-onset sepsis. The calculator is based on a robust logistic regression model that provides quantitative individualised estimates of early-onset sepsis risk. Low sensitivity for prediction of sepsis at birth shows that standard perinatal risk factors alone are insufficient for ascertainment of neonatal early-onset sepsis. Performance is improved by the addition of physical examination findings at birth, but the sensitivity of combined findings remains limited. The present implementation of the calculator integrates risk factors and examination findings. A methodological error in adapting the regression for application in the population (rather than the development sample) and several subsequent modifications compromise the accuracy of quantitative predictions of the absolute risk of sepsis, but these factors are not expected to seriously undermine the use of the calculator for risk stratification. The calculator has served as an instrument of change away from previously recommended categorical risk ascertainment strategies, and its implementation reduces the need for diagnostic testing and empirical antibiotic treatment without apparent ill effects. However, the calculator should not be relied on to provide accurate estimates for individuals with regard to absolute risk of early-onset sepsis in newborn babies.
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http://dx.doi.org/10.1016/S1473-3099(20)30490-4DOI Listing
October 2020

C-Reactive Protein, Procalcitonin, and White Blood Count to Rule Out Neonatal Early-onset Sepsis Within 36 Hours: A Secondary Analysis of the Neonatal Procalcitonin Intervention Study.

Clin Infect Dis 2020 Sep 3. Epub 2020 Sep 3.

Department of Paediatrics, Division of Paediatric Infectious Diseases & Immunology, Erasmus Medical Centre, University Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands.

Background: Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful.

Methods: We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis).

Results: We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis.

Conclusions: Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.
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http://dx.doi.org/10.1093/cid/ciaa876DOI Listing
September 2020

Multicentre study found that adherence to national antibiotic recommendations for neonatal early-onset sepsis was low.

Acta Paediatr 2021 Mar 10;110(3):791-798. Epub 2020 Aug 10.

Department of Paediatrics, Tergooi Hospital, Blaricum, The Netherlands.

Aim: Our aim was to evaluate adherence to the Dutch neonatal early-onset sepsis (EOS) guidelines, adapted from UK guidance. We also looked at the effect on antibiotic recommendations and duration.

Method: This was a multicentre, prospective observational cross-sectional study carried out in seven hospitals in the Netherlands between 1 September 2018 and 1 November 2019. We enrolled 1024 neonates born at 32 weeks of gestation or later if they demonstrated at least one EOS risk factor or clinical signs of infection.

Results: The Dutch guidelines recommended antibiotic treatment for 438/1024 (42.8%) of the neonates designated at risk, but only 186/438 (42.5%) received antibiotics. The guidelines advised withholding antibiotics for 586/1024 (57.2%) of neonates and in 570/586 (97.3%) cases the clinicians adhered to this recommendation. Blood cultures were obtained for 182/186 (97.8%) infants who started antibiotics and only four were positive, for group B streptococci. Antibiotic treatment was continued for more than 3 days in 56/178 (31.5%) neonates, despite a negative blood culture.

Conclusion: Low adherence to the Dutch guidelines meant that the majority of neonates did not receive the antibiotic treatment that was recommended, while some antibiotic use was prolonged despite negative blood cultures. The guidelines need to be revised.
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http://dx.doi.org/10.1111/apa.15488DOI Listing
March 2021

Risk-based maternal group B Streptococcus screening strategy is compatible with the implementation of neonatal early-onset sepsis calculator.

Clin Exp Pediatr 2020 Oct 16;63(10):406-410. Epub 2020 Apr 16.

Department of Paediatrics, Tergooi Hospitals, Blaricum, The Netherlands.

Background: The early-onset sepsis (EOS) calculator was developed and validated in a setting with routine-based group B Streptococcus (GBS) screening.

Purpose: The study aimed to evaluate the extent of influence exerted by risk-based GBS screening on management recommendations by the EOS calculator.

Methods: All newborns with a gestational age greater than 35 weeks were screened for EOS risk factors in a Dutch regional teaching hospital using a risk-based GBS screening strategy. We calculated the EOS risk at birth and stratified the infants into the following 3 risk levels with corresponding management recommendations: low, <0.65; intermediate, 0.65-1.54; and high, >1.54 per 1000 live newborns. Thereafter, we recalculated the EOS risk and recommendation for the newborn infants without available maternal GBS screening results at birth.

Results: In one year, 1,877 eligible births occurred; of them, 206 infants were included. Maternal GBS status was available for 28 of 206 infants (14%) at birth, while a definitive GBS status was later available for 162 of 206 infants (79%). Median EOS risk was slightly lower after definitive GBS status was determined (0.41 vs. 0.46 per 1,000 live births, P=0.004). In 199 of 206 newborn infants (97%), the EOS calculator recommendation remained unchanged after the GBS results unavailable at birth were updated to definitive GBS status. Use of GBS status at birth versus definitive GBS status did not result in the withholding of antibiotic treatment of the newborn infants included in this study.

Conclusion: Risk-based GBS screening is compatible with EOS calculator recommendations. Larger studies are needed to develop the best strategy for combining GBS screening and EOS calculator recommendations.
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http://dx.doi.org/10.3345/cep.2020.00094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568949PMC
October 2020

Infant respiratory syncytial virus prophylaxis and nasopharyngeal microbiota until 6 years of life: a subanalysis of the MAKI randomised controlled trial.

Lancet Respir Med 2020 10 20;8(10):1022-1031. Epub 2020 Mar 20.

Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands; Medical Research Council-University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK. Electronic address:

Background: Respiratory syncytial virus (RSV) infection during infancy is suggested to cause long-term wheeze. In turn, wheeze has been associated with bacterial dysbiosis of the respiratory tract. We investigated the effects of RSV prophylaxis with palivizumab in otherwise healthy preterm infants on respiratory microbiota composition at 1 year and 6 years of age.

Methods: In a multicentre, single-blind, randomised, placebo-controlled trial (the MAKI trial), infants born between 32-35 weeks of gestation, in one university and in 15 regional hospitals in the the Netherlands, were randomly assigned (1:1) to receive palivizumab or placebo during the RSV season of their first year of life. Intramuscular injections of palivizumab 15 mg/kg or placebo were given during one RSV season: either from Oct 1, or from discharge from the neonatal unit until March 10 (minimun of 2 and maximum of 5 injections were given). Children were 6 months old or younger at the start of the RSV season; exclusion criteria included congenital heart disease, bronchopulmonary dysplasia, Down's syndrome, or other serious congenital disorders, use of mechanical ventilation at birth, treatment with surfactant, or physician-diagnosed wheeze before the start of the RSV season. Children were followed up for clinical symptoms until 6 years of age. For this subanalysis, we obtained nasopharyngeal swabs from children aged 1 year and 6 years and analysed them using 16S-rRNA sequencing. At 6 years we also measured reversible airway obstruction. The primary outcome was the effect of palivizumab during infancy on the respiratory microbiota composition at age 1 year and 6 years (intention-to-treat analysis). The trial is registered in the ISRCTN registry, number ISRCTN73641710.

Findings: From April 1, 2008, to Dec 31, 2010, 429 infants were enrolled in the MAKI trial (n=214 to the palivizumab group; n=215 to the placebo group). At 1 year, we collected swabs and sequenced DNA from 170 (40%) of 429 children, of which 145 (85%) samples had high-quality DNA. The overall microbiota composition was significantly different (R 1·3%; p=0·0185) between the palivizumab group and the placebo group at 1 year of life; children in the palivizumab group had a significantly lower abundance of the Staphylococcus-dominated cluster (odds ratio 0·28 [95% CI 0·11-0·68]; p=0·00394), an increased abundance of biomarker species, such as Klebsiella, and a more diverse set of oral taxa, including Streptococcus spp, compared with children in the placebo group. At 6 years, we collected swabs and sequenced DNA from 349 (88%) of 395 children who completed follow-up, of which 342 (98%) samples had high-quality DNA. The overall microbiota composition was not significantly different between groups at 6 years (R 0·6%; p=0·0575); however, children in the palivizumab group had a significantly increased abundance of Haemophilus spp and lower abundance of Moraxella and Neisseriaceae spp compared with children in the placebo group. Absence of PCR-confirmed RSV infection at 1 year was significantly associated with a higher abundance of Haemophilus spp at age 6 years and a significantly lower abundance of Moraxella and Neisseriaceae than children with RSV infection at 1 year. Reversible airway obstruction at 6 years was also positively associated with Haemophilus abundance and negatively associated with the abundance of health-associated taxa, such as Moraxella, Corynebacterium, Dolosigranulum, and Staphylococcus, even after correction for RSV immunoprophylaxis (all: p<0·05). Additionally, reversible airway instruction was associated with significantly higher Streptococcus pneumoniae abundance.

Interpretation: Palivizumab in infancy in otherwise healthy preterm infants is associated with persistent effects on the abundance of specific, potentially pathogenic, microbial taxa in the respiratory tract. Several of the palivizumab-associated biomarker species were associated with reversible airway obstruction at age 6 years. These results warrant further studies to establish the long-term ecological effects and health consequences of palivizumab in infancy.

Funding: MedImmune.
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http://dx.doi.org/10.1016/S2213-2600(19)30470-9DOI Listing
October 2020

Neonatal Early-Onset Sepsis Calculator and Antibiotic Therapy-Reply.

JAMA Pediatr 2020 May;174(5):508-509

Department of Pediatrics, Tergooi Hospital, Blaricum, the Netherlands.

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http://dx.doi.org/10.1001/jamapediatrics.2019.6269DOI Listing
May 2020

Finding a role for the neonatal early-onset sepsis risk calculator.

EClinicalMedicine 2020 Feb 26;19:100255. Epub 2020 Jan 26.

Department of Pediatrics, Tergooi Hospital, Blaricum, the Netherlands.

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http://dx.doi.org/10.1016/j.eclinm.2019.100255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046501PMC
February 2020

Markers of endothelial cell activation in suspected late onset neonatal sepsis in Surinamese newborns: a pilot study.

Transl Pediatr 2019 Dec;8(5):412-418

Academic Pediatric Center Suriname, Academic Hospital Paramaribo, Paramaribo, Suriname.

Background: Serum levels of markers of endothelial cell activation are associated with bacteremia and mortality in sepsis in adults, children, and newborns with early onset sepsis. We hypothesize that levels of these markers are associated with these outcomes in hospitalized newborns with suspected late onset neonatal sepsis (LONS).

Methods: In this prospective cohort study, newborns admitted to the tertiary neonatal care facility of Suriname were included upon clinical suspicion of LONS and before start of antibiotic treatment, between April 1, 2015 and May 31, 2016. Serum concentrations of angiopoietin-1, angiopoietin-2, and soluble isoforms of P-selectin, E-selectin, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), platelet and endothelial cell adhesion molecule-1 (sPECAM-1), matrix metalloproteinase-9 (MMP-9), neutrophil elastase, and tissue-inhibitor of metalloproteinases-1 (TIMP-1) were measured.

Results: Twenty-thee newborns were included. Baseline characteristics were similar between newborns with and without bacteremia and between non-survivors and survivors. Only soluble E-selectin (sE-selectin) was higher in newborns with bacteremia versus non-bacteremia (P=0.04) and lower in non-survivors (P=0.04). No conclusions could be made for sVCAM-1 due to high serum concentrations.

Conclusions: In conclusion, the data from this pilot study indicate that serum levels of markers of endothelial cell activation are poorly associated with bacteremia and mortality.
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http://dx.doi.org/10.21037/tp.2019.11.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970123PMC
December 2019

Early onset sepsis calculator implementation is associated with reduced healthcare utilization and financial costs in late preterm and term newborns.

Eur J Pediatr 2020 May 2;179(5):727-734. Epub 2020 Jan 2.

Department of Pediatrics, Tergooi Hospitals, Rijksstraatweg 1, 1261 AN, Blaricum, The Netherlands.

The neonatal early onset sepsis (EOS) calculator is a novel tool for antibiotic stewardship in newborns, associated with a reduction of empiric antibiotic treatment for suspected EOS. We studied if implementation of the EOS calculator results in less healthcare utilization and lower financial costs of suspected EOS. For this, we compared two single-year cohorts of hospitalizations within 3 days after birth in a Dutch nonacademic teaching hospital, before and after implementation of the EOS calculator. All admitted newborns born at or after 35 weeks of gestation were eligible for inclusion. We analyzed data from 881 newborns pre-implementation and 827 newborns post-implementation. We found significant reductions in EOS-related laboratory tests performed and antibiotic days, associated with implementation of the EOS calculator. Mean length of hospital stay was shorter, and EOS-related financial costs were lower after implementation among term, but not among preterm newborns.Conclusion: In addition to the well-known positive impact on antibiotic stewardship, implementation of the EOS calculator is also clearly associated with reductions in healthcare utilization related to suspected EOS in late preterm and term newborns and with a reduction in associated financial costs among those born term.What is Known:• The early-onset sepsis (EOS) calculator is a novel tool for antibiotic stewardship in newborns, associated with a reduction in empiric antibiotic treatment for suspected EOS.What is New:• In newborns at risk for EOS, EOS calculator implementation is associated with a significant reduction in laboratory investigations related to suspected EOS and significantly shorter stay in those born term.• EOS calculator implementation in term newborns is associated with a mean reduction of €207 in costs for EOS-related care per admitted newborn.
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http://dx.doi.org/10.1007/s00431-019-03510-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160215PMC
May 2020

Association of Use of the Neonatal Early-Onset Sepsis Calculator With Reduction in Antibiotic Therapy and Safety: A Systematic Review and Meta-analysis.

JAMA Pediatr 2019 Sep 3. Epub 2019 Sep 3.

Department of Pediatrics, Tergooi Hospital, Blaricum, the Netherlands.

Importance: The neonatal early-onset sepsis (EOS) calculator is a clinical risk stratification tool increasingly used to guide the use of empirical antibiotics for newborns. Evidence on the effectiveness and safety of the EOS calculator is essential to inform clinicians considering implementation.

Objective: To assess the association between management of neonatal EOS guided by the neonatal EOS calculator (compared with conventional management strategies) and reduction in antibiotic therapy for newborns.

Data Sources: Electronic searches in MEDLINE, Embase, Web of Science, and Google Scholar were conducted from 2011 (introduction of the EOS calculator model) through January 31, 2019.

Study Selection: All studies with original data that compared management guided by the EOS calculator with conventional management strategies for allocating antibiotic therapy to newborns suspected to have EOS were included.

Data Extraction And Synthesis: Following PRISMA-P guidelines, relevant data were extracted from full-text articles and supplements. CHARMS (Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) tools were used to assess the risk of bias and quality of evidence. Meta-analysis using a random-effects model was conducted for studies with separate cohorts for EOS calculator and conventional management strategies.

Main Outcomes And Measures: The difference in percentage of newborns treated with empirical antibiotics for suspected or proven EOS between management guided by the EOS calculator and conventional management strategies. Safety-related outcomes involved missed cases of EOS, readmissions, treatment delay, morbidity, and mortality.

Results: Thirteen relevant studies analyzing a total of 175 752 newborns were included. All studies found a substantially lower relative risk (range, 3%-60%) for empirical antibiotic therapy, favoring the EOS calculator. Meta-analysis revealed a relative risk of antibiotic use of 56% (95% CI, 53%-59%) in before-after studies including newborns regardless of exposure to chorioamnionitis. Evidence on safety was limited, but proportions of missed cases of EOS were comparable between management guided by the EOS calculator (5 of 18 [28%]) and conventional management strategies (8 of 28 [29%]) (pooled odds ratio, 0.96; 95% CI, 0.26-3.52; P = .95).

Conclusions And Relevance: Use of the neonatal EOS calculator is associated with a substantial reduction in the use of empirical antibiotics for suspected EOS. Available evidence regarding safety of the use of the EOS calculator is limited, but shows no indication of inferiority compared with conventional management strategies.
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http://dx.doi.org/10.1001/jamapediatrics.2019.2825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724419PMC
September 2019

Sepsis calculator implementation reduces empiric antibiotics for suspected early-onset sepsis.

Eur J Pediatr 2018 May 18;177(5):741-746. Epub 2018 Feb 18.

Department of Paediatrics, Tergooi hospitals, Rijksstraatweg 1, 1261 AN, Blaricum, The Netherlands.

Significant overtreatment with antibiotics for suspected early onset sepsis (EOS) constitutes a persisting clinical problem, generating unnecessary risks, harms, and costs for many newborns. We aimed to study feasibility and impact of a sepsis calculator to help guide antibiotic for suspected EOS in a European setting. In this single-center study, the sepsis calculator was implemented as an addition to and in accordance with existing protocols. One thousand eight hundred seventy-seven newborns ≥ 35 weeks of gestational age were prospectively evaluated; an analogous retrospective control group (n = 2076) was used for impact analysis. We found that empirical treatment with intravenous antibiotics for suspected EOS was reduced from 4.8 to 2.7% after sepsis calculator implementation (relative risk reduction 44% (95% confidence interval 21.4-59.5%)). No evidence for changes in time to treatment start, treatment duration, or proven sepsis rates was found. Adherence to sepsis calculator recommendation was 91%.

Conclusion: Pragmatic and feasible implementation of the sepsis calculator yields a 44% reduction of empirical use of antibiotics for EOS, without signs of delay or prolongation of treatment. These findings warrant a multicenter, nation-wide, randomized study evaluating systematic use of the sepsis calculator prediction model and its effects in clinical practice outside of the USA. What is known: • Significant overtreatment with antibiotics for suspected early-onset sepsis results in unnecessary costs, risks, and harms. • Implementation of the sepsis calculator in the USA has resulted in a significant decrease in empirical antibiotic treatment, without apparent adverse events. What is new: • Implementation of the sepsis calculator in daily clinical decision-making in a Dutch teaching hospital is feasible in conjunction with existing protocols, with high adherence. • Antibiotic therapy for suspected early-onset sepsis was reduced by 44% following implementation of the calculator.
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http://dx.doi.org/10.1007/s00431-018-3113-2DOI Listing
May 2018

Interference Between Respiratory Syncytial Virus and Human Rhinovirus Infection in Infancy.

J Infect Dis 2017 Apr;215(7):1102-1106

Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine.

Background: Respiratory syncytial virus (RSV) and human rhinovirus (HRV) are the most common viruses associated with acute respiratory tract infections in infancy. Viral interference is important in understanding respiratory viral circulation and the impact of vaccines.

Methods: To study viral interference, we evaluated cases of RSV and HRV codetection by polymerase chain reaction in 2 prospective birth cohort studies (the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure [INSPIRE] study and the Tennessee Children's Respiratory Initiative [TCRI]) and a double-blinded, randomized, controlled trial (MAKI), using adjusted multivariable regression analyses.

Results: Among 3263 respiratory tract samples, 24.5% (798) and 37.3% (1216) were RSV and HRV positive, respectively. The odds of HRV infection were significantly lower in RSV-infected infants in all cohorts, with adjusted odds ratios of 0.30 (95% confidence interval [CI], .22-.40 in the INSPIRE study, 0.18 (95% CI, .11-.28) in the TCRI (adjusted for disease severity), and 0.34 (95% CI, .16-.72) in the MAKI trial. HRV infection was significantly more common among infants administered RSV immunoprophylaxis, compared with infants who did not receive immunoprophylaxis (OR, 1.65; 95% CI, 1.65-2.39).

Conclusions: A negative association of RSV on HRV codetection was consistently observed across populations, seasons, disease severity, and geographical regions. Suppressing RSV infection by RSV immunoprophylaxis might increase the risk of having HRV infection.
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http://dx.doi.org/10.1093/infdis/jix031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426371PMC
April 2017

Population-Attributable Risk of Risk Factors for Recurrent Wheezing in Moderate Preterm Infants During the First Year of Life.

Paediatr Perinat Epidemiol 2016 07 16;30(4):376-85. Epub 2016 May 16.

Division of Pediatric Immunology and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.

Background: Recurrent wheezing in young infants has a high prevalence, influences quality of life, and generates substantial health care costs. We previously showed that respiratory syncytial virus infection is an important mechanism of recurrent wheezing in moderate preterm infants. We aimed to provide population-attributable risks (PAR) of risk factors for recurrent wheezing during the first year of life in otherwise healthy moderate preterm infants.

Methods: RISK is a multicentre prospective birth cohort study of 4424 moderate preterm infants born at 32-35 weeks gestation. We estimated PAR of risk factors for recurrent wheezing, which was defined as three or more parent-reported wheezing episodes during the first year of life.

Results: We evaluated 3952 (89%) children at 1 year of age, of whom 705 infants (18%) developed recurrent wheezing. Fourteen variables were independently associated with recurrent wheezing. Hospitalisation for respiratory syncytial virus bronchiolitis had a strong relationship with recurrent wheezing (RR 2.6; 95% confidence interval, CI, 2.2, 3.1), but a relative modest PAR (8%; 95% CI 6, 11%) which can be explained by a low prevalence (13%). Day-care attendance showed a strong relationship with recurrent wheezing (RR 1.9; 95% CI 1.7, 2.2) and the highest PAR (32%; 95% CI 23, 37%) due to a high prevalence (67%). The combined adjusted PAR for the 14 risk factors associated with recurrent wheezing was 49% (95% CI 46, 52%).

Conclusions: In moderate preterm infants, day-care attendance has the largest PAR for recurrent wheezing. Trial evidence is needed to determine the potential benefit of delayed day-care attendance in this population.
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http://dx.doi.org/10.1111/ppe.12295DOI Listing
July 2016

Cesarean section and hospitalization for respiratory syncytial virus infection.

Pediatr Infect Dis J 2015 Feb;34(2):227

Department of Pediatric Immunology and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.

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http://dx.doi.org/10.1097/INF.0000000000000612DOI Listing
February 2015

An infected urachal cyst--a rare diagnosis in a child with acute abdominal pain.

Eur J Pediatr 2012 Mar 12;171(3):587-8. Epub 2011 Nov 12.

Department of Paediatrics, Meander Medical Centre, Postbus 1502, 3800 BM, Amersfoort, The Netherlands.

Unlabelled: A 2-year-old girl who presented with acute abdominal pain and spiking fever was diagnosed with an infected urachal cyst. Ultrasonography aided the diagnosis and the urachal remnant was removed successfully through a single laparoscopic procedure. Treatment is through removal of the complete structure, to prevent malignant degeneration in adulthood.

Conclusion: Urachal cysts may cause abdominal complaints when infected. Although rare, they should be added to the differential diagnosis of acute abdominal pain in the paediatric patient, as this case illustrates.
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http://dx.doi.org/10.1007/s00431-011-1622-3DOI Listing
March 2012