Nicole Boluyt

Neurodevelopment After Neonatal Hypoglycemia: A Systematic Review and Design of an Optimal Future Study

OBJECTIVE. Our goal was to assess the effect of episodes of neonatal hypoglycemia on subsequent neurodevelopment. METHODS. We searched Medline and Embase for cohort studies on subsequent neurodevelopment after episodes of hypoglycemia in the first week of life. Reference lists of available studies were reviewed, and content experts were contacted for additional studies. Included studies were selected and appraised for methodologic quality by 2 reviewers. Methodologic quality was assessed according to well-accepted criteria for prognostic studies. Eventually, all studies were given an overall quality score: poor, moderate, or high quality. Studies in the latter 2 categories were considered for quantitative data analysis. RESULTS. Eighteen eligible studies were identified. The overall methodologic quality of the included studies was considered poor in 16 studies and high in 2 studies. Pooling of results of the 2 high-quality studies was deemed inappropriate because of major clinical and methodologic heterogeneity. None of the studies provided a valid estimate of the effect of neonatal hypoglycemia on neurodevelopment. Building on the strengths and weaknesses of existing studies, we developed a proposal for an “optimal” future study design. CONCLUSIONS. Recommendations for clinical practice cannot be based on valid scientific evidence in this field. To assess the effect of neonatal hypoglycemia on subsequent neurodevelopment, a well-designed prospective study should be undertaken. We submit a design for a study that may answer the still-open questions.

Usefulness of Systematic Review Search Strategies in Finding Child Health Systematic Reviews in MEDLINE

OBJECTIVE To determine the sensitivity and precision of existing search strategies for retrieving child health systematic reviews in MEDLINE using PubMed. DESIGN Filter (diagnostic) accuracy study. We identified existing search strategies for systematic reviews, combined them with a filter that identifies articles relevant to child health, and applied the combination in MEDLINE to a reference set of child health systematic reviews. MAIN OUTCOME MEASURES Total number of records retrieved, sensitivity, and precision. RESULTS We tested 9 search filters. Sensitivity of the systematic review filters combined with the child filter ranged from 68% to 96%; sensitivity of the child filter alone was 98%. The number of records retrieved with PubMed (limited to January 1990-January 2006) by the systematic review filters combined with the child filter ranged from 7861 to 618 053. Precision for the combined filters ranged from 2% to 52%. Because of poor reporting of specific systematic review criteria in both titles and abstracts, in 25% of the records screened we were unsure whether the article concerned a systematic review according to our definition. CONCLUSIONS The high numbers of records yielded by sensitive search strategies and the low precision threaten the use of systematic reviews for clinical decision making and guideline development. Reporting of specific systematic review criteria in titles and abstracts is poor, and reporting recommendations given by Quality of Reporting of Meta-analyses (QUOROM) should be used more strictly. To make identification using MEDLINE easier, there is an urgent need to set minimal criteria that any review should fulfill for it to be indexed as a systematic review.

Quality of Evidence-Based Pediatric Guidelines

Objective. To identify evidence-based pediatric guidelines and to assess their quality. Methods. We searched Medline, Embase, and relevant Web sites of guideline development programs and national pediatric societies to identify evidence-based pediatric guidelines. A list with titles of identified guidelines was sent to 51 leading pediatricians in the Netherlands, who were asked to select the 5 most urgent topics for guideline development. Three pediatrician reviewers appraised the available guidelines on the 10 most frequently mentioned topics with the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. Results. A total of 215 evidence-based pediatric guidelines were identified; of these, 17 guidelines on the 10 most frequently mentioned topics were appraised. The AGREE instrument rates guidelines among 6 domains. For the scope and purpose domain, the mean score was 84% of the maximal mark. For stakeholder involvement, the mean score was 42%, with 12 guidelines (71%) scoring <50%. For rigor of development, the mean score was 54%, with 5 guidelines (29%) scoring <50%. For clarity and presentation, the mean score was 78%, with 4 guidelines (24%) scoring <50%. For applicability and editorial independence, performance was poor, with mean scores of 19% and 40%, respectively. Low scores were partly attributable to poor reporting. After considering all domain scores, the reviewers recommended 14 of 17 guidelines (82%) to be used in local practice. Conclusions. The current volume of pediatric guidelines categorized as evidence based in popular databases is large. Overall, these guidelines scored well, compared with other studies on guideline quality in fields outside pediatrics, when assessed for quality with the AGREE instrument. This holds especially for guidelines published or endorsed by the American Academy of Pediatrics or registered in the National Guideline Clearinghouse.

Nonpharmacologic Treatments for Childhood Constipation: Systematic Review

OBJECTIVE: To summarize the evidence and assess the reported quality of studies concerning nonpharmacologic treatments for childhood constipation, including fiber, fluid, physical movement, prebiotics, probiotics, behavioral therapy, multidisciplinary treatment, and forms of alternative medicine. METHODS: We systematically searched 3 major electronic databases and reference lists of existing reviews. We included systematic reviews and randomized controlled trials (RCTs) that reported on nonpharmacologic treatments. Two reviewers rated the methodologic quality independently. RESULTS: We included 9 studies with 640 children. Considerable heterogeneity across studies precluded meta-analysis. We found no RCTs for physical movement, multidisciplinary treatment, or alternative medicine. Some evidence shows that fiber may be more effective than placebo in improving both the frequency and consistency of stools and in reducing abdominal pain. Compared with normal fluid intake, we found no evidence that water intake increases or that hyperosmolar fluid treatment is more effective in increasing stool frequency or decreasing difficulty in passing stools. We found no evidence to recommend the use of prebiotics or probiotics. Behavioral therapy with laxatives is not more effective than laxatives alone. CONCLUSIONS: There is some evidence that fiber supplements are more effective than placebo. No evidence for any effect was found for fluid supplements, prebiotics, probiotics, or behavioral intervention. There is a lack of well-designed RCTs of high quality concerning nonpharmacologic treatments for children with functional constipation.

Value of Abdominal Radiography, Colonic Transit Time, and Rectal Ultrasound Scanning in the Diagnosis of Idiopathic Constipation in Children: A Systematic Review

OBJECTIVE To perform a systematic review evaluating the value of abdominal radiography, colonic transit time (CTT), and rectal ultrasound scanning in the diagnosis of idiopathic constipation in children. STUDY DESIGN Eligible studies were those assessing diagnostic accuracy of abdominal radiography, CTT, or rectal ultrasound scanning in children suspected for idiopathic constipation. Methodological quality of the included studies was assessed with the Quality Assessment of studies of Diagnostic Accuracy included in Systematic reviews checklist. RESULTS One systematic review summarized 6 studies on abdominal radiography until 2004. The additional 9 studies evaluated abdominal radiography (n = 2), CTT (n = 3), and ultrasound scanning (n = 4). All studies except two used a case-control study design, which will lead to overestimation of test accuracy. Furthermore, none of the studies interpreted the results of the abdominal radiography, ultrasound scanning, or CTT without knowledge of the clinical diagnosis of constipation. The sensitivity of abdominal radiography, as studied in 6 studies, ranged from 80% (95% CI, 65-90) to 60% (95% CI, 46-72), and its specificity ranged from 99% (95% CI, 95-100) to 43% (95% CI, 18-71). Only one study presented test characteristics of CTT, and two studies presented test characteristics of ultrasonography. CONCLUSION We found insufficient evidence for a diagnostic association between clinical symptoms of constipation and fecal loading on abdominal radiographs, CTT, and rectal diameter on ultrasound scanning in children.

Diagnostic accuracy of tests in pediatric gastroesophageal reflux disease.

OBJECTIVE To systematically review the literature evaluating the diagnostic accuracy of commonly used diagnostic tests over conventional history taking and physical examination in children ≤ 18 months and >18 months suspected of gastroesophageal reflux disease (GERD). STUDY DESIGN We searched Medline, Embase, and the Cochrane database for studies assessing the diagnostic accuracy of pH-metry, pH-impedance, esophagogastroscopy, barium contrast study, scintigraphy, and empirical treatment as diagnostic tools. Quality was assessed according to Quality Assessment of Studies of Diagnostic Accuracy Included in Systematic Reviews criteria. RESULTS Of the 2178 studies found, 6 studies were included, containing 408 participants (age 1 month-13.6 years) and 145 controls (age 1 month-16.9 years). Studies included children with GERD symptoms; 1 included an atypical presentation. In all the studies, the diagnostic accuracy of pH-metry was investigated, and in 2 studies esophagogastroscopy was investigated as well. Sensitivity and specificity were calculated in 3 studies. The range of reported sensitivity and specificity was broad and unreliable because of poor methodological quality according to Quality Assessment of Studies of Diagnostic Accuracy Included in Systematic Reviews criteria and inadequate study design. CONCLUSION Diagnostic accuracy of tests in children suspected of GERD remains unclear and implications for practice are hard to give. There is an urgent need of well-designed randomized controlled trials where the effect of treatment according to specific signs and symptoms will be compared with the effect of treatment based on the results of additional diagnostic tests, for patient relevant outcomes.

State of the Evidence on Acute Asthma Management in Children: A Critical Appraisal of Systematic Reviews

OBJECTIVE. Our goal was to evaluate clinical, methodologic, and reporting aspects of systematic reviews on the management of acute asthma in children. METHODS. We undertook a systematic review of systematic reviews on acute asthma management in children. We identified eligible reviews by searching the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Medline, and Embase 1990 to March 2006. Data were extracted on clinical issues, methodologic characteristics, and results of the reviews. Methodologic quality was assessed with the Overview Quality Assessment Questionnaire and with additional questions on heterogeneity. Separate reporting on children in mixed adult-pediatric population reviews was assessed. Methodologic quality of systematic reviews published in peer-reviewed journals was compared with Cochrane reviews. RESULTS. A total of 23 systematic reviews were included: 14 were published in the Cochrane Library, and 9 were published in peer-reviewed journals. Eight reviews included children only, and 15 were mixed-population reviews. The majority of reviews defined the study population as having “acute asthma” without a more precise definition, and 16 different health outcomes were reported. The overall quality according to the Overview Quality Assessment Questionnaire was good, with Cochrane reviews showing minimal flaws and journal reviews showing minor flaws (median scores: 7 vs 5). Results on children were reported separately in 8 of 15 mixed-population reviews. Clinical heterogeneity was explored in only 2 of 23 reviews, and the methods used to identify and address heterogeneity were diverse. CONCLUSIONS. The methodologic quality of both the Cochrane and journal reviews on the management of acute asthma in children seems good, with Cochrane reviews being more rigorous. However, their usefulness for clinical practice is hampered by a lack of clear definitions of included populations, clinically important health outcomes, and separate reporting on children in mixed reviews. A major threat to these reviews’ validity is the insufficient identification and handling of heterogeneity.

Assessment of Controversial Pediatric Asthma Management Options Using GRADE

OBJECTIVES: To develop explicit and transparent recommendations on controversial asthma management issues in children and to illustrate the usefulness of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach in rating the quality of evidence and strength of recommendations. METHODS: Health care questions were formulated for 3 controversies in clinical practice: what is the most effective treatment in asthma not under control with standard-dose inhaled corticosteroids (ICS; step 3), the use of leukotriene receptor antagonist for viral wheeze, and the role of extra fine particle aerosols. GRADE was used to rate the quality of evidence and strength of recommendations after performing systematic literature searches. We provide evidence profiles and considerations about benefit and harm, preferences and values, and resource use, all of which played a role in formulating final recommendations. RESULTS: By applying GRADE and focusing on outcomes that are important to patients and explicit other considerations, our recommendations differ from those in other international guidelines. We prefer to double the dose of ICS instead of adding a long-acting β-agonist in step 3; ICS instead of leukotriene receptor antagonist are the first choice in preschool wheeze, and extra fine particle ICS formulations are not first-line treatment in children with asthma. Recommendations are weak and based on low-quality evidence for critical outcomes. CONCLUSIONS: We provide systematically and transparently developed recommendations about controversial asthma management options. Using GRADE for guideline development may change recommendations, enhance guideline implementation, and define remaining research gaps.

Stressful Life Events in Children With Functional Defecation Disorders.

Objectives: The aim of the study was to determine the prevalence of stressful life events including (sexual) abuse in children with functional defecation disorders by performing a systematic review. Methods: We searched MEDLINE, EMBASE, and PsycINFO for cohort, case-control and cross-sectional studies investigating the prevalence of stressful life events, including (sexual) abuse in children with functional defecation disorders. Results: The search yielded 946 articles, of which 8 were included with data from 654 children with functional constipation and 1931 children with (constipation-associated) fecal incontinence (FI). Overall, children with functional defecation disorders had been significantly more exposed to stressful life events than healthy children, with prevalence rates ranging from 1.6% to 90.9%. Being bullied, being a relational victim, interruption of toilet training, punishment by parents during toilet training, and hospitalization were significantly related to FI, whereas separation from the best friend, failure in an examination, severe illness in a close family member, loss of job by a parent, frequent punishment, and living in a war-affected area were significantly related to constipation. Only 1 study measured the prevalence of child abuse, which reported a significantly higher prevalence of child (sexual) abuse in children with FI compared with controls. Conclusions: The prevalence of stressful life events, including (sexual) abuse is significantly higher in children with functional defecation disorders compared with healthy children. To gain more insight into the true prevalence of child (sexual) abuse in children with functional defecation disorders, more studies are clearly needed.

Mo1993 The Prevalence of Stressful Life Events Including Sexual Child Abuse in Children With Functional Defecation Disorders: A Systematic Review

Background: Early life exposure to antibiotics might alter the development of the host microbiome and influence Crohns disease (CD) risk. Although this association has been suggested by a few recent studies, larger studies with longer duration of follow-up and more rigorous control of confounding are needed. We sought to further evaluate the association between antibiotic use during the first year of life and subsequent CD by performing a nationwide birth cohort study in Denmark.Methods: All children born in Denmark between 1995 and 2007 were identified in the Danish Medical Birth Registry, and followed until death, emigration, or end of study (January 1, 2011). Outpatient antibiotic use was identified using the National Prescription Registry. Cases of CD were identified using the Danish National Patient Registry; a subset was confirmed by linkage to the National Pathology Registry. As a negative control, we analyzed exposure to systemic adrenergic agents, the second most commonly prescribed class of medications in the first year of life. Relative risk was determined by Cox proportional hazards models, after adjusting for route of delivery, birth order, gender, birth year, and family history of CD.Results: The birth cohort consisted of 850,962 children followed for a mean of 8.5 years (7,206,533 person-years of follow up). Of these, 51.3% were male, 17.5% were born by c-section, 1.0% had a family history of CD and 41.1% had ≥ 1 filled antibiotic prescription in the first year of life. 291 cases of CD were observed during follow-up. A positive association between antibiotic use and CD did not reach statistical significance (adjusted HR 1.2, 95% CI 0.9-1.5). Results of a subanalysis of confirmed cases were similar (adjusted HR 1.4, 95% CI 0.9-2.2). As expected, there was a positive association with family history of CD (adjusted HR 16.4, 95% CI 8.631.1). There was no association between use of systemic adrenergic drugs and CD (adjusted HR 1.0, 95% CI 0.5-1.8).Discussion: We found a non-significant trend for the association between early-life antibiotic exposure and risk of CD. No association was observed in our negative control group. Our findings are consistent with previously observed associations between antibiotic use and CD.