Comparison of New Bronchopulmonary Dysplasia Definitions on Long-Term Outcomes in Preterm Infants.

OBJECTIVE: To compare the discriminative performances of the 2018 National Institutes of Health (NIH) and the 2019 Jensen definitions of bronchopulmonary dysplasia (BPD) with the 2001 NIH definition on adverse neurodevelopmental and respiratory outcomes at 2 years and 5 years corrected age. STUDY DESIGN: In this single-center retrospective cohort study, outcomes of infants born at <30 weeks of gestational age were collected. The 3 definitions of BPD were compared by adding the different definitions to the National Institute of Child Health and Human Development's outcome prediction model for neurodevelopmental impairment (NDI) or death. Discriminative performance was compared for both outcomes at 2 years and 5 years corrected age by calculating the areas under the receiver operating characteristic curve and z-statistics. RESULTS: The presence of BPD and its severity were determined in 584 infants. There were considerable shifts in BPD grading among the different definitions. At both time points, all BPD definition models had comparable discriminating power for NDI and respiratory morbidity, with one exception. Compared with the 2001 NIH definition, the 2018 NIH definition had less predictive power for the neurologic outcome at 2 years corrected age. CONCLUSIONS: Our comparison of the 3 BPD definitions shows similar discriminative performance on long term neurodevelopmental and respiratory outcomes at 2 years and 5 years corrected age.

Prucalopride is no more effective than placebo for children with functional constipation.

BACKGROUND & AIMS: Prucalopride is a selective, high-affinity agonist of the 5-hydroxytryptamine (serotonin) receptor 4 that enhances motility in the gastrointestinal tract. We performed a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of prucalopride in children (6 months to 18 years old) with functional constipation. METHODS: Children with functional constipation, based on the Rome III criteria, were given prucalopride (children ≤ 50 kg were given a 0.04 mg/kg oral solution; children >50 kg were given a 2-mg tablet) or placebo once daily for 8 weeks. The primary efficacy end point was the proportion of children with toileting skills who had a mean of ≥ 3 spontaneous bowel movements/week and ≤ 1 episode of fecal incontinence/2 weeks, from study weeks 5-8 (responders). Adverse events, clinical laboratory values, and electrocardiograms were monitored. RESULTS: Efficacy and safety were assessed in 213 children (106 prucalopride, 107 placebo). Twenty-five percent were younger than 4 years old, 50% were 4-11 years old, and 25% were 12-18 years old; 55.4% were girls. At screening, 62.3% of patients in the prucalopride group and 55.1% in the placebo group had a history of fecal incontinence; 60.4% and 55.1% in the prucalopride and placebo groups, respectively, had a mean of ≤ 1 spontaneous bowel movements/week. The proportion of responders was similar between groups (prucalopride, 17.0% and placebo, 17.8%). There were no statistically significant differences in the primary efficacy end point when patients were stratified by sex, age group, or country. The incidence of treatment-emergent adverse events was similar in the prucalopride (69.8%) and placebo (60.7%) groups. CONCLUSIONS: Prucalopride, although generally well tolerated, was not more effective than placebo in children with functional constipation. ClinicalTrials.gov Number: NCT01330381.

The value of fluoroscopic defecography in the diagnostic and therapeutic management of defecation disorders in children.

BACKGROUND: Defecography is a study to assess anorectal function during evacuation. OBJECTIVE: To investigate the value of fluoroscopic defecography in directing diagnostic and therapeutic management in children with defecation disorders. MATERIALS AND METHODS: We reviewed all fluoroscopic defecography studies performed (2003-2009) in children with defecation problems and normal anorectal motility studies. Results were classified into three groups: (1) normal pelvic floor function; (2) pelvic floor dyssynergia, including incomplete relaxation of pelvic musculature, inconsistent change in anorectal angle and incomplete voluntary evacuation; (3) structural abnormality, including excessive pelvic floor descent with an intra-rectal intussusception, rectocele or rectal prolapse. RESULTS: We included 18 patients (13 boys, median age 9.1 years). Indication for fluoroscopic defecography was chronic constipation in 56%, fecal incontinence in 22% and rectal prolapse in 22%. Defecography showed pelvic floor dyssynergia in 9 children (50%), a structural abnormality in 4 (22%) and normal pelvic floor function in 5 (28%). In 12 children (67%) the outcome of fluoroscopic defecography directly influenced therapeutic management. After defecography 4 children (22%) were referred for anorectal biofeedback treatment, 4 children (22%) for surgery, 2 children (11%) for additional MR defecography, and 1 child to the psychology department, and medication was changed in 1 child. In 6 children (33%) the result did not change the management. In 9 children (75%) the change of management was successful. CONCLUSIONS: Fluoroscopic defecography can be a useful tool in understanding the pathophysiology and it may provide information that impacts management of children with refractory defecation disorders.

Risk Factors for Neurodevelopmental Impairment at 2- and 5-Years Corrected Age in Preterm Infants with Established Bronchopulmonary Dysplasia.

INTRODUCTION: The objective of this study was to identify risk factors for neurodevelopmental impairment (NDI) at 2- and 5-years corrected age (CA) in a cohort of preterm infants with established bronchopulmonary dysplasia (BPD). METHODS: This single-center retrospective cohort study included infants born between 2009 and 2016 at a gestational age (GA) <30 weeks with moderate or severe BPD at 36 weeks' postmenstrual age. Perinatal characteristics, (social) demographics, and comorbidities were collected from the electronic patient records. Odds ratios for NDI were calculated with univariate and multivariate logistic regression analyses adjusting for potential confounders. RESULTS: Of the 602 eligible infants, 123 infants were diagnosed with BPD. NDI was present in 30.3% and 56.1% at 2- and 5-years CA, respectively. The only independent risk factors associated with NDI in the multivariate analyses were birthweight (adjusted odds ratio [aOR] 0.74, 95% CI 0.57-0.95; aOR 0.70, 95% CI 0.54-0.91, respectively), small for GA (SGA) (aOR 3.25, 95% CI 1.09-9.61; aOR 5.44, 95% CI 1.62-18.2, respectively) at both time points, and male gender at 5-years CA (OR 2.49, 95% CI 1.11-5.57). CONCLUSION: Birthweight and SGA are independent risk factors for NDI at 2- and 5-years CA and male gender at 5-years CA in preterm infants with BPD. In contrast, well-known other risk factors for NDI in the general population of preterm infants, such as GA, maternal education, and neonatal comorbidities were not independently associated with NDI.

Management of functional constipation in children with lower urinary tract symptoms: report from the Standardization Committee of the International Children's Continence Society.

PURPOSE: We present a consensus view of members of the International Children's Continence Society (ICCS) together with pediatric gastroenterologists, experts in the field of functional gastrointestinal disorders, on the management of functional constipation in children with lower urinary tract symptoms. MATERIALS AND METHODS: Discussions were held by the board of the ICCS and a multidisciplinary core group of authors was appointed. The draft document review process was open to all ICCS members via the website. Feedback was considered by the core authors and, by agreement, amendments were made as necessary. RESULTS: Guidelines on the assessment, and pharmacological and nonpharmacological management of functional constipation in children with lower urinary tract symptoms are outlined. CONCLUSIONS: The final document is not a systematic literature review. It includes relevant research when available, as well as expert opinion on the current understanding of functional constipation in children with lower urinary tract symptoms. The document is intended to be clinically useful in primary, secondary and tertiary care settings.

Colonic manometry and colonic scintigraphy as a diagnostic tool for children with severe constipation.

OBJECTIVE: In adults, colonic manometry and colonic scintigraphy are both valuable studies in discriminating normal and abnormal colonic motility. The objective of this study was to compare the diagnostic yield and tolerability of colonic manometry and colonic scintigraphy in children with severe constipation. METHODS: Twenty-six children (mean age 11.4 years, 77% boys) who had received colonic manometry and colonic scintigraphy as part of a colonic motility evaluation were included. Manometry was performed as per department protocol. After swallowing a methacrylate-coated capsule containing indium-111, images were taken at 4, 24, and 48 hours, and geometric centers were calculated. Results of both tests were categorized in 3 groups: normal, abnormal function in the distal part of the colon, and colonic inertia. Cohen κ was used for the level of agreement. Patients and parents completed a questionnaire regarding their experience. RESULTS: Colonic scintigraphy showed normal transit time in 20%, delay in the distal colon in 48%, and colonic inertia in 32% of patients. Colonic manometry was normal in 40%, abnormal in the distal colon in 40%, and colonic inertia was diagnosed in 20%. The κ score was 0.34. All 5 patients with colonic inertia during manometry had a similar result by scintigraphy. Eighty-eight percent of patients preferred scintigraphy over manometry and 28% of parents preferred colonic manometry over scintigraphy. CONCLUSIONS: Colonic manometry and colonic scintigraphy have a fair agreement regarding the categorization of constipation. Scintigraphy is well tolerated in pediatric patients and may be a useful tool in the evaluation of children with severe constipation.

Towards a harmonized bronchopulmonary dysplasia definition: a study protocol for an international Delphi procedure.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth with lifelong consequences. Multiple BPD definitions are currently used in daily practice. Uniformity in defining BPD is important for clinical care, research and benchmarking. The aim of this Delphi procedure is to determine what clinicians and researchers consider the key features for defining BPD. With the results of this study, we hope to advance the process of reaching consensus on the diagnosis of BPD. METHODS AND ANALYSIS: A Delphi procedure will be used to establish why, when and how clinicians propose BPD should be diagnosed. This semi-anonymous iterative technique ensures an objective approach towards gaining these insights. An international multidisciplinary panel of clinicians and researchers working with preterm infants and/or patients diagnosed with BPD will participate. Steering committee members will recruit potential participants in their own region or network following eligibility guidelines to complete a first round survey online. This round will collect demographic information and opinions on key features of BPD definitions. Subsequent rounds will provide participants with the results from the previous round, for final acceptance or rejection of key features. Statements will be rated using a 5-point Likert scale. After completing the Delphi procedure, an (online) consensus meeting will be organised to discuss the results. ETHICS AND DISSEMINATION: For this study, ethical approval a waiver has been provided. However, all participants will be asked to provide consent for the use of personal data. After the Delphi procedure is completed, it will be published in a peer-reviewed journal and disseminated at international conferences.

Ten-year experience using antegrade enemas in children.

OBJECTIVE: To describe a single-center, 10-year experience with the use of antegrade enemas. STUDY DESIGN: Retrospective analysis of 99 patients treated with antegrade enemas at Nationwide Children's Hospital. RESULTS: Study subjects (median age 8 years) were followed for a mean time of 46 months (range 2-125 months) after cecostomy placement. Seventy-one patients had the cecostomy placed percutaneously and 28 by surgery. Thirty-five patients had functional constipation and 64 patients an organic disease (spinal abnormalities, cerebral palsy, imperforate anus, Hirschsprung's disease). While using antegrade enemas, 71% became symptom-free, in 20 subjects symptoms improved, in 2 subjects symptoms did not change, and in 7 subjects symptoms worsened. Poor outcome was associated with surgical placement of the cecostomy (P < .001), younger age (P = .02), shorter duration of symptoms (P = .01), history of Hirschsprung's disease (P = .05), cerebral palsy (P = .03), previous abdominal surgery (P = .001), and abnormal colonic manometry (P = .004). In 88%, successful irrigation solution included use of a stimulant laxative, and subjects who used a stimulant did significantly better (P < .001) than subjects who started without a stimulant. In 13 patients, the cecostomy was removed 49.7 months after placement without recurrence of symptoms. Major complications occurred in 12 patients and minor complications in 47. CONCLUSIONS: Antegrade enemas represent a successful and relatively safe therapeutic option in children with severe defecatory disorders. Prognostic factors are identified.

Epidemiology of constipation in children and adults: a systematic review.

We aimed to review the published literature regarding the epidemiology of constipation in the general paediatric and adult population and to assess its geographic, gender and age distribution, and associated factors. A search of the Medline database was performed. Study selection criteria included: (1) studies of population-based samples; (2) containing data on the prevalence of constipation without obvious organic aetiology; (3) in paediatric, adult or elderly population; (4) published in English and full manuscript form. Sixty-eight studies met our inclusion criteria. The prevalence of constipation in the worldwide general population ranged from 0.7% to 79% (median 16%). The epidemiology of constipation in children was investigated in 19 articles and prevalence rate was between 0.7% and 29.6% (median 12%). Female gender, increasing age, socioeconomic status and educational level seemed to affect constipation prevalence.

Constipation in childhood.

Constipation in children is an often long-lasting pediatric functional gastrointestinal disorder with a worldwide prevalence varying between 0.7% and 29.6%, and estimated health-care costs of US$3.9 billion per year in the USA alone. The pathophysiology of childhood constipation is multifactorial and remains incompletely understood; however, withholding of stools, starting after an experience of a hard, painful, or frightening bowel movement is the most common cause found in children. A thorough medical history and physical examination, including a rectal examination in combination with a bowel diary, is sufficient in the majority of cases to diagnose constipation. The current standard treatment consists of education, toilet training, disimpaction, maintenance therapy and long-term follow-up. In the past decade, well-designed treatment trials in the pediatric population have emerged and long-term outcome studies have been completed. This Review summarizes the current knowledge of the clinical aspects of childhood constipation, including pathogenesis, diagnosis and treatment, with particular emphasis on the latest available data.