de Geus, Anna, Gordon, Morris ORCID: 0000-0002-1216-5158, Sinopoulou, Vasiliki
ORCID: 0000-0002-2831-9406, Ajiboye, Aderonke, Thornton, Alexander J, Liu, Shiyao
ORCID: 0000-0002-5245-1810, Arruda Navarro albuquerque, Daniel
ORCID: 0000-0003-1539-8798, Benninga, Marc A and Tabbers, Merit M
(2025)
Efficacy and safety of pharmacological therapies for functional constipation in children: a systematic review and meta-analysis.
The Lancet Child & Adolescent Health
.
ISSN 2352-4642
(In Press)
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Official URL: https://doi.org/10.1016/S2352-4642(25)00219-6
Abstract
Background
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.
Methods
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).
Findings
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]).
Interpretation
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 clearly describe methods, patient characteristics, and previous therapeutics.
Funding
None.
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