What is the aim of this review?
The aim of this Cochrane Review was to find out whether probiotics can be used to treat chronic constipation without a physical explanation in children (aged 0 to 18 years).
We analysed data from 14 studies to answer this question.
Key messages
We were unable to draw conclusions when comparing probiotics to placebo for frequency of defecation in children treated for chronic constipation without a physical explanation. There may be no difference in treatment success between the two groups.
There may not be a difference in frequency of defecation or treatment success when comparing probiotics and laxatives to using laxatives alone.
We were unable to draw conclusions when comparing probiotics to magnesium oxide for frequency of defecation or treatment success.
There may be a higher frequency of defecation in children treated with synbiotic preparations compared to placebo.
There may not be a difference in participants withdrawing from the studies due to adverse events when comparing probiotic preparations to placebo.
We were unable to draw conclusions on the safety of any of the other comparisons due to the low number of people who withdrew from the studies.
What was studied in the review?
Children often suffer from constipation for long periods of time, and when there is no underlying physical cause that can be found we call it 'functional constipation'.
It has been suggested that probiotic and synbiotic preparations might help improve symptoms in these children. Probiotics are preparations that contain living bacteria that have been proposed to be beneficial to the digestive system. Synbiotics also include food substances that support the growth of these bacteria.
There is currently no consensus about whether this is the case, or how these preparations are best used.
What are the main results of the review?
We searched for randomised controlled trials (studies in which participants are assigned to one of two or more treatment groups using a random method) comparing any probiotic or synbiotic treatment with any other treatment (such as dummy/placebo treatments) in children with chronic constipation without a physical explanation. We found 14 trials including a total of 1127 participants who were aged under 18. We made the following conclusions.
• There may be no difference in treatment success when comparing probiotics to placebo.
• We were unable to draw conclusions on whether there is a difference in the frequency of defecation.
• There may be no difference in treatment success when comparing probiotics and laxatives to laxatives alone.
• We were unable to draw conclusions on frequency of defecation or treatment success when comparing probiotics to magnesium oxide.
• Synbiotics may be better than placebo in improving the frequency of defection.
• There may be no difference in how many people withdrew from the trials because of side effects when comparing probiotics to placebo, or probiotics and laxative to laxative alone.
• We have limited confidence in the evidence because the studies only included a small number of children, and due to lack of detail on some of the methods used.
All analyses were limited due to differences in the specific probiotics or the treatments they were compared with, low numbers of children included in the studies and, most importantly, the use of a range of different measures of success. This meant that combining studies was difficult, so the overall ability of this review to answer its core questions was limited.
What next?
Future studies are needed to find out how helpful probiotics are for childhood constipation. Researchers need to agree whether probiotics should be a first option therapy, an add-on to other therapies, a second option after other therapies have failed, or a combination of all the above.
Future research should measure the same items (known as a core outcome set) to ensure these results can support future reviews.
How up-to-date is this review?
This review is current to June 2021.
There is insufficient evidence to conclude whether probiotics are efficacious in successfully treating chronic constipation without a physical explanation in children or changing the frequency of defecation, or whether there is a difference in withdrawals due to adverse events when compared with placebo. There is limited evidence from one study to suggest a synbiotic preparation may be more likely than placebo to lead to treatment success, with no difference in withdrawals due to adverse events.
There is insufficient evidence to draw efficacy or safety conclusions about the use of probiotics in combination with or in comparison to any of the other interventions reported. The majority of the studies that presented data on serious adverse events reported that no events occurred. Two studies did not report this outcome.
Future studies are needed to confirm efficacy, but the research community requires guidance on the best context for probiotics in such studies, considering where they should be best considered in a potential treatment hierarchy and should align with core outcome sets to support future interpretation of findings.
Functional constipation is defined as chronic constipation with no identifiable underlying cause. It is a significant cause of morbidity in children, accounting for up to 25% of visits to paediatric gastroenterologists. Probiotic preparations may sufficiently alter the gut microbiome and promote normal gut physiology in a way that helps relieve functional constipation. Several studies have sought to address this hypothesis, as well as the role of probiotics in other functional gut disorders. Therefore, it is important to have a focused review to assess the evidence to date.
To evaluate the efficacy and safety of probiotics for the management of chronic constipation without a physical explanation in children.
On 28 June 2021, we searched CENTRAL, MEDLINE, Embase, CINAHL, AMED, WHO ICTR, and ClinicalTrials.gov, with no language, date, publication status, or document type limitations.
We included randomised controlled trials (RCTs) that assessed probiotic preparations (including synbiotics) compared to placebo, no treatment or any other interventional preparation in people aged between 0 and 18 years old with a diagnosis of functional constipation according to consensus criteria (such as Rome IV).
We used standard methodological procedures expected by Cochrane.
We included 14 studies (1127 randomised participants): 12 studies assessed probiotics in the treatment of functional constipation, whilst two studies investigated synbiotic preparations.
Three studies compared probiotics to placebo in relation to the frequency of defecation at study end, but we did not pool them as there was very significant unexplained heterogeneity. Four studies compared probiotics to placebo in relation to treatment success. There may be no difference in global improvement/treatment success (RR 1.29, 95% CI 0.73 to 2.26; 313 participants; low-certainty evidence). Five studies compared probiotics to placebo in relation to withdrawals due to adverse events, with the pooled effect suggesting there may be no difference (RR 0.64, 95% CI 0.21 to 1.95; 357 participants; low-certainty evidence).
The pooled estimate from three studies that compared probiotics plus an osmotic laxative to osmotic laxative alone found there may be no difference in frequency of defecation (MD -0.01, 95% CI -0.57 to 0.56; 268 participants; low-certainty evidence). Two studies compared probiotics plus an osmotic laxative to osmotic laxative alone in relation to global improvement/treatment success, and found there may be no difference between the treatments (RR 0.95, 95% CI 0.79 to 1.15; 139 participants; low-certainty evidence). Three studies compared probiotics plus osmotic laxative to osmotic laxative alone in relation to withdrawals due to adverse events, but it is unclear if there is a difference between them (RR 2.86, 95% CI 0.12 to 68.35; 268 participants; very low-certainty evidence).
Two studies compared probiotics versus magnesium oxide. It is unclear if there is a difference in frequency of defecation (MD 0.28, 95% CI -0.58 to 1.14; 36 participants), treatment success (RR 1.08, 95% CI 0.74 to 1.57; 36 participants) or withdrawals due to adverse events (RR 0.50, 95% CI 0.05 to 5.04; 77 participants). The certainty of the evidence is very low for these outcomes.
One study assessed the role of a synbiotic preparation in comparison to placebo. There may be higher treatment success in favour of synbiotics compared to placebo (RR 2.32, 95% CI 1.54 to 3.47; 155 participants; low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group.
One study assessed a synbiotic plus paraffin compared to paraffin alone. It is uncertain if there is a difference in frequency of defecation (MD 0.74, 95% CI -0.96, 2.44; 66 participants; very low-certainty evidence), or treatment success (RR 0.91, 95% CI 0.71 to 1.17; 66 participants; very low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group.
One study compared a synbiotic preparation to paraffin. It is uncertain if there is a difference in frequency of defecation (MD -1.53, 95% CI -3.00, -0.06; 60 participants; very low-certainty evidence) or in treatment success (RR 0.86, 95% CI 0.65, 1.13; 60 participants; very low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group.
All secondary outcomes were either not reported or reported in a way that did not allow for analysis.