Pub Date : 2025-10-13DOI: 10.1016/S2352-4642(25)00219-6
Anna de Geus BSc , Prof Morris Gordon PhD , Vassiliki Sinopoulou PhD , Aderonke Ajiboye MSc , Alexander J Thornton MSc , Shiyao Liu PhD , Daniel Arruda Navarro Albuquerque MD , Prof Marc A Benninga PhD , Merit M Tabbers PhD
<div><h3>Background</h3><div>There has been a substantial increase in studies on functional constipation in children as new therapies are deployed. We aimed to provide an up-to-date, methodologically robust systematic review and meta-analysis on the efficacy and safety of pharmacological therapies for functional constipation in children.</div></div><div><h3>Methods</h3><div>In this systematic review and meta-analysis, we searched PubMed, Medline, Embase, and the Cochrane library from inception to Feb 5, 2025. We included randomised controlled trials that involved children aged 0 years to younger than 18 years with functional constipation treated with pharmacological interventions compared with placebo, no treatment, or other interventions and with at least a 2-week follow-up period. Studies were excluded if there was no definition of functional constipation, children with organic causes for constipation or previous bowel surgery were included, children with faecal incontinence without the presence of constipation were included, or the aim of treatment was faecal disimpaction rather than maintenance therapy. Pairs of authors independently extracted summary data from published reports and critiqued studies. We assessed risk of bias with the Cochrane tool. Meta-analyses estimated risk ratios (RRs) or mean differences, and 95% CIs. Certainty of evidence was established with GRADE. Our main outcomes were treatment success (as defined by study authors), defecation frequency, and withdrawals due to adverse events. This study was registered on PROSPERO (CRD42022368719).</div></div><div><h3>Findings</h3><div>Our search identified 4595 articles, of which 59 randomised controlled trials were included, representing 7045 participants with functional constipation. Interventions included polyethylene glycol (n=36 studies), lactulose (n=18), magnesium oxide or magnesium hydroxide (n=7), picosulfate (n=1), liquid paraffin (n=4), prucalopride (n=1), lubiprostone (n=2), linaclotide (n=3), plecanatide (n=1), enemas (n=2), and domperidone (n=1). Meta-analyses for treatment success showed that polyethylene glycol was probably more effective than placebo (RR 1·74 [95% CI 1·25–2·41], moderate certainty of evidence) and may be more effective than lactulose (1·35 [1·11–1·64], low certainty of evidence). There might be no difference in treatment success for linaclotide compared with placebo (1·21 [0·69–2·13], low certainty of evidence), but linaclotide probably leads to higher defecation frequency per week (mean difference 1·10 [95% CI 0·40–1·80], moderate certainty of evidence). There is low to moderate certainty evidence that prucalopride is not more effective than placebo (RR 1·68 [95% CI 0·77 to 3·68]).</div></div><div><h3>Interpretation</h3><div>Polyethylene glycol is probably more effective than placebo and key comparator therapies and should be considered the standard of first-line care. Future studies should consider polyethylene glycol as an index therapy, and cle
{"title":"Efficacy and safety of pharmacological therapies for functional constipation in children: a systematic review and meta-analysis","authors":"Anna de Geus BSc , Prof Morris Gordon PhD , Vassiliki Sinopoulou PhD , Aderonke Ajiboye MSc , Alexander J Thornton MSc , Shiyao Liu PhD , Daniel Arruda Navarro Albuquerque MD , Prof Marc A Benninga PhD , Merit M Tabbers PhD","doi":"10.1016/S2352-4642(25)00219-6","DOIUrl":"10.1016/S2352-4642(25)00219-6","url":null,"abstract":"<div><h3>Background</h3><div>There has been a substantial increase in studies on functional constipation in children as new therapies are deployed. We aimed to provide an up-to-date, methodologically robust systematic review and meta-analysis on the efficacy and safety of pharmacological therapies for functional constipation in children.</div></div><div><h3>Methods</h3><div>In this systematic review and meta-analysis, we searched PubMed, Medline, Embase, and the Cochrane library from inception to Feb 5, 2025. We included randomised controlled trials that involved children aged 0 years to younger than 18 years with functional constipation treated with pharmacological interventions compared with placebo, no treatment, or other interventions and with at least a 2-week follow-up period. Studies were excluded if there was no definition of functional constipation, children with organic causes for constipation or previous bowel surgery were included, children with faecal incontinence without the presence of constipation were included, or the aim of treatment was faecal disimpaction rather than maintenance therapy. Pairs of authors independently extracted summary data from published reports and critiqued studies. We assessed risk of bias with the Cochrane tool. Meta-analyses estimated risk ratios (RRs) or mean differences, and 95% CIs. Certainty of evidence was established with GRADE. Our main outcomes were treatment success (as defined by study authors), defecation frequency, and withdrawals due to adverse events. This study was registered on PROSPERO (CRD42022368719).</div></div><div><h3>Findings</h3><div>Our search identified 4595 articles, of which 59 randomised controlled trials were included, representing 7045 participants with functional constipation. Interventions included polyethylene glycol (n=36 studies), lactulose (n=18), magnesium oxide or magnesium hydroxide (n=7), picosulfate (n=1), liquid paraffin (n=4), prucalopride (n=1), lubiprostone (n=2), linaclotide (n=3), plecanatide (n=1), enemas (n=2), and domperidone (n=1). Meta-analyses for treatment success showed that polyethylene glycol was probably more effective than placebo (RR 1·74 [95% CI 1·25–2·41], moderate certainty of evidence) and may be more effective than lactulose (1·35 [1·11–1·64], low certainty of evidence). There might be no difference in treatment success for linaclotide compared with placebo (1·21 [0·69–2·13], low certainty of evidence), but linaclotide probably leads to higher defecation frequency per week (mean difference 1·10 [95% CI 0·40–1·80], moderate certainty of evidence). There is low to moderate certainty evidence that prucalopride is not more effective than placebo (RR 1·68 [95% CI 0·77 to 3·68]).</div></div><div><h3>Interpretation</h3><div>Polyethylene glycol is probably more effective than placebo and key comparator therapies and should be considered the standard of first-line care. Future studies should consider polyethylene glycol as an index therapy, and cle","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"9 12","pages":"Pages 848-856"},"PeriodicalIF":15.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-08DOI: 10.1016/S2352-4642(25)00211-1
Renske Lok PhD , Neha Deshpande MSc , Siddhi Nair MSc , Thomas Andrillon PhD , Grace Gatera MSc , Prof Catherine M Hill MD PhD , Prof Samuele Cortese MD PhD , Sarah L Chellappa MD PhD
Autism and attention-deficit hyperactivity disorder (ADHD) are among the most common neurodivergent neurotypes worldwide. Epidemiological evidence shows that sleep and circadian disturbances, such as difficulty initiating and maintaining sleep, and delayed sleep–wake phase, are highly prevalent in autistic children, children with ADHD, and those with both neurotypes. Despite scientific advancements, a comprehensive framework integrating sleep and circadian mechanisms with targeted interventions for autism and ADHD remains underdeveloped. In this Review we examine sleep and circadian rhythm differences in autistic children and adolescents, and in those with ADHD or both neurotypes, focusing on the underlying biological mechanisms. We discuss recent advances in the genetic and molecular links between sleep, circadian rhythms, and neuroplasticity, alongside the influence of these systems on physiology and therapeutic strategies. Both pharmacological and non-pharmacological interventions are considered, with an emphasis on the need for an integrated support model that accounts for the dynamic interplay between sleep and circadian rhythms in these populations. We identify key gaps in the current evidence base, particularly in relation to non-pharmacological interventions, and outline future research directions. Although most randomised controlled trials in children and adolescents have focused on behavioural sleep interventions, we also discuss emerging findings from trials using alternative approaches, such as targeted light therapy in adults, with implications for paediatric populations. Finally, we emphasise the importance of incorporating the perspectives of autistic children and adolescents and those with ADHD, as well as their parents and caregivers, into research designs.
{"title":"The sleep–circadian connection: pathways to understanding and supporting autistic children and adolescents and those with attention-deficit hyperactivity disorder","authors":"Renske Lok PhD , Neha Deshpande MSc , Siddhi Nair MSc , Thomas Andrillon PhD , Grace Gatera MSc , Prof Catherine M Hill MD PhD , Prof Samuele Cortese MD PhD , Sarah L Chellappa MD PhD","doi":"10.1016/S2352-4642(25)00211-1","DOIUrl":"10.1016/S2352-4642(25)00211-1","url":null,"abstract":"<div><div>Autism and attention-deficit hyperactivity disorder (ADHD) are among the most common neurodivergent neurotypes worldwide. Epidemiological evidence shows that sleep and circadian disturbances, such as difficulty initiating and maintaining sleep, and delayed sleep–wake phase, are highly prevalent in autistic children, children with ADHD, and those with both neurotypes. Despite scientific advancements, a comprehensive framework integrating sleep and circadian mechanisms with targeted interventions for autism and ADHD remains underdeveloped. In this Review we examine sleep and circadian rhythm differences in autistic children and adolescents, and in those with ADHD or both neurotypes, focusing on the underlying biological mechanisms. We discuss recent advances in the genetic and molecular links between sleep, circadian rhythms, and neuroplasticity, alongside the influence of these systems on physiology and therapeutic strategies. Both pharmacological and non-pharmacological interventions are considered, with an emphasis on the need for an integrated support model that accounts for the dynamic interplay between sleep and circadian rhythms in these populations. We identify key gaps in the current evidence base, particularly in relation to non-pharmacological interventions, and outline future research directions. Although most randomised controlled trials in children and adolescents have focused on behavioural sleep interventions, we also discuss emerging findings from trials using alternative approaches, such as targeted light therapy in adults, with implications for paediatric populations. Finally, we emphasise the importance of incorporating the perspectives of autistic children and adolescents and those with ADHD, as well as their parents and caregivers, into research designs.</div></div>","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"9 12","pages":"Pages 868-879"},"PeriodicalIF":15.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-07DOI: 10.1016/S2352-4642(25)00267-6
Matheus van Rens , Robin van der Lee , Giovanni Barone , Fiammetta Piersigilli
{"title":"Innovation in neonatology – Authors' reply","authors":"Matheus van Rens , Robin van der Lee , Giovanni Barone , Fiammetta Piersigilli","doi":"10.1016/S2352-4642(25)00267-6","DOIUrl":"10.1016/S2352-4642(25)00267-6","url":null,"abstract":"","PeriodicalId":54238,"journal":{"name":"Lancet Child & Adolescent Health","volume":"9 11","pages":"Page e21"},"PeriodicalIF":15.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：