Running Head: USE of PROBIOTICS in CHILDREN

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Running head: USE OF PROBIOTICS IN CHILDREN

An Evidence-Based Exploration of the Use of Probiotics in Children With Chronic

Constipation

Student’s Name

Institution

Abstract

Background: Chronic constipation among children is a worldwide problem that has negative economic and quality of life effects. Standard treatment with laxatives can cause uncomfortable side effects and have mixed results, prompting interest in alternative treatments. Probiotics have long been used to treat many human conditions, and recently have been purported in the media to treat gastrointestinal issues. This evidence-based project explored the effectiveness of probiotics in treating constipation in children. PICO question: In children with constipation (P), is the use of probiotics (I) as effective as a laxative (C) in relieving constipation symptoms (O)?

Methods: Using Pubmed, CINAHL, Ovid, and the Cochrane Library databases to search the literature, one systematic review, three randomized controlled trials and two cohort studies met the inclusion criteria and were selected as best evidence.

Results: Although the overall results were supportive of the use of probiotics to treat children with chronic constipation, inconclusive findings across studies were found.

Conclusion: Probiotics may represent an opportunity to treat a common condition more comfortably and conveniently. In order for a clear recommendation to be made, further research is needed. Randomized controlled trials with larger sample sizes that do not include adjunctive interventions and involve longer follow up represent the best opportunities for future research.

The National Institute of Health and Clinical Excellence(NICE 2010) defined constipation as the passage of hard stools that cause discomfort. Symptoms include abdominal pain, nausea and vomiting, loss of appetite, and malaise. Childhood constipation has worldwide prevalence rate of between 0.7% and 29.6% (Mugie, Benninga, & Lorenzo, 2011). Caparell, Pitetti, and Cross (2013) found constipation to be the most frequent diagnosis in children presenting to the ER with abdominal painand children with constipation have been found to require more healthcare services, resulting in nearly three times the cost compared to children without constipation(Liem, Harman, Benninga, Kelleher, Mousa, & Lorenzo, 2009). Besides the financial costs, quality of life is negatively affected when childhood constipation continues into adulthood despite treatment(Bongers, Maurice-Stan, & Grootenhuis, 2008).

The treatments for constipation recommended by NICE(2010) were initial dis-impaction using oral cathartics, followed by daily maintenance using oral laxatives, specifically polyethylene glycol (PEG) or lactulose. Besides the cost of these medications, deterrents to compliance include negative side effects like abdominal cramping, diarrhea, flatulence, nausea and bad taste (Tabbers, Chmielewska, Roseboom, Boudet, Perrin, Szajewska, & Benninga, 2009). These factors have led to interest in alternative treatments.

Probiotics are microorganisms that are believed to have a benefit to a host. Their use has a long history, and though their popularity has increased in popular culture of late, especially related to gastrointestinal effects, questions remain about their effectiveness(Hempel et al., 2011). The purpose of this investigation was to address the PICO question, “In children with constipation (P),is the use of probiotics (I) as effective as a laxative (C) in relieving constipation symptoms (O)”?

EBP Investigation Process

Selection Criteria and Search Process

There are many dietary supplements available that claim to promote bowel motility and relieve constipation, and probiotics are purported to treat many conditions within the bowel and elsewhere in the body. Therefore, to stay true to the PICO question and to control bias, it was necessary to limit the search to probiotics used in children with chronic constipation. Studies were limited to English-language only, but because of the relatively recent popularity of probiotics, no other limits were initially established because it was necessary to ascertain the scope of evidence available.

A search of five databases (Pubmed/MEDLINE, CINAHL, Ovid, and the Cochrane library) was conducted using the MeSH terms “ constipation,”AND “child,” AND “probiotics.” This search yielded a total of twenty-one articles. Limiters such types of research design, year, Human, age were used to narrow the search. According to the Hierarchy of Evidence Table featured in Melnyk and Fineout-Overholt (2012, p. 11), randomized control trials (RCTs) represent Level 2, and are second only to systematic reviews. Therefore, the limitation of clinical trial was applied, which reduced the yield to seven articles. Ancestral searching was usedthrough scanning the reference lists of the three articles with the list of articles in which each study was referenced.

Selection of Best Evidence

Upon review, three articles addressed the effect of probiotics in other conditions, such as irritable bowel syndrome or bacterial infections of the bowel, and were eliminated. One article reported a study in which probiotics were tested as an adjunct to lactulose, and was eliminated to control bias and extraneous factors, as lactulose acting alone is a powerful laxative and because of the relative age of the study (2004). This resulted in one systematic review, three randomized control trials, and two cohort studies. Appendix A and B details each of these studies.

Critical Appraisal of Collective Evidence

It was apparent during the database search that the volume of evidence concerning probiotic use for constipation was small, and that concerning children was smaller. Despite that, the search continued diligently and judiciously. The evidence deemed best included one level one systematic review, three level two randomized controlled studies, and two Level four pilot studies (See Appendix C).

The studies found for this EBP project used as inclusion criteria the six Rome foundation criteria for functional constipation. The primary symptom is less than three BMs per week, and the other five are “straining, lumpy or hard stools, sensation of incomplete evacuation, sensation of anorectal obstruction, and manual maneuvers to facilitate passage, in at least 25% of defecations.’ (Rome foundation, 2006, retrieved from romecriteria.org).” The other PICO components were also the same, except for some variance about comparison (placebo control versus baseline data). Bowel movement (BM) frequency was a common outcome measure in all studies selected. All three RCTs reviewed used a computer generated list to randomize their samples, which ranged in size from 20 to 148 subjects, who were recruited from outpatient and hospital settings.

Critical Appraisal

The systematic review (Chmielewska & Szajewska, 2011) examined randomized control trials studying the effect of probiotic treatment on both children and adults with constipation, and corroborated the observation that evidence is limited. A total of five randomized controlled trials were critiqued, and only two of those studied the pediatric population. At that time, the finding was inconclusive that there was not enough evidence to support using or not using probiotics as a treatment for childhood constipation.

Two cohort studies suggested that probiotic use was effective as a treatment for constipation, as subjects in both studies demonstrated significant increases in bowel movement (BM) frequency by the end of their respective four-week trials. Interestingly, these studies, though performed by different researchers, were performed nearly the same way (replicate study). Besides the small sample size in both, applicability of findings are diminished by the additional intervention of toilet training to each trial. Additionally, in each of these studies, bowel prep in the form of rectal enemas was administered for three days consecutively prior to administration of the probiotics. Both of these factors could have increased BM frequency, and cannot be ruled out as the cause of the results (Bekkali, Bongers, Van den Berg, Liem & Benninga, 2007; Tabbers, Miliano, Roseboon, Benninga, 2011).

The randomized control trials were all placebo controlled and blinded, enhancing validity of the results. All used a power analysis of 80% to determine the needed sample size, and all were adequate according to that analysis. All studies used a significance level of p < .05, and used statistics to assess the significance of change in BM frequency. Tabbers, Chmielewska, Roseboon, Crastes, Perrin, Reitsma, Norbruis, Szajewski, and Benninga (2011) were the only researchers to not find a significant difference in BM frequency between the intervention and placebo group, but as found in their pilot study, toilet training and bowel prep were part of their trial.

The remaining randomized control trials found a significant change in BM frequency between the intervention and control (placebo) groups. One study compared the use of probiotics not only to a placebo but to the laxative magnesium oxide. This study also allowed for a rescue laxative or enema, but accounted well for their use. BM frequency was significantly increased and enema use was significantly lower in the group that received the probiotics and the group that received the laxative, but no significant differences between the intervention groups were found (Bu, Chang, Ni, Chen & Cheng 2007). Guerra, Lima, Souza, Mazochi, Penna, Silva, Nioli and Guimares, (2011) controlled confounding variables most effectively and used a compelling crossover design to increase the validity of their promising results, however, they recognized the need for more randomized controlled trials to corroborate the findings.

Collective Results

Summary

One RCT (Guerra et al., 2011) found a significant increase in BMs after probiotic administration. One systematic review, two cohort studies, and the remaining two randomized controlled trials suggest that the administration of probiotics to children with chronic constipation may effectively treat their symptoms (Bekkali et al., 2007; Bu et al., 2007; Chmielewska & Szajewska, 2011; Tabbers et al., 2011; Tabbers et al., 2011). In contrast, none of the selected studies discounted the use of probiotics for treatment of constipation in children for safety or efficacy reasons.

Synthesis Conclusions

Although an exhaustive search was performed, the volume of quality evidence was limited. The evidence discovered yielded mixed results, and there were confounding variables, making a recommendation impossible at this time. Future clinical trials that study the effect of probiotics alone, without additional intervention, would provide more compelling and valid evidence to support or to discourage their use.

Intervention Decision

EBP Model Application

The Stetler model for EBP implementation has five phases: 1)preparation, 2) validation, 3)comparative evaluation/decision making, 4) translation/application, and 5) evaluation(Ciliska, Dicenso, Melnyk, Fineout-Overholt, Stetler, Cullen, Larrabee, Schultz, Rycroft-Malone, Newhouse & Dang, 2011, pp. 248-249). This project represents phases one and two. A search of the evidence concerning the effectiveness of probiotics in treating children with constipation was performed, and the yielded evidence was critiqued. In accordance with the Stetler model, because there is insufficient credible evidence to support or discourage use at this time, the process has stopped. The increasing interest in this topic and call for more evidence points to future promise, and future exploration. At that time the remaining phases of the process can be completed. Once there is adequate credible evidence, phase 3 will involve making a decision if probiotics should be used in practice to treat childhood constipation, and in phase 4, a practitioner will be able to decide to informally implement usage with his or her patients, or to develop a formal pilot study or EBP package for dissemination. Phase five will be an evaluation of the results on his or her patients or subjects or to evaluate routine practice after the dissemination of findings.

Implementation Implications

The use of probiotics to treat childhood constipation, if found to be effective,could be implemented in the primary care setting as a more affordable and comfortable solution to the problem. To recommend a commercially available yogurt to parents would take minimal clinical resources and the increasing movement toward more ‘natural’ remedies to health problems could appeal to some parents, but because it is a relatively new concept, confidence in their use would take time. This is true of colleagues and administrators as well, but a comprehensive search and review of evidence, as performed here, would help to dissuade any misgivings about initial implementation.

Implementation Plan

An advanced practice nurse wishing to implement the use of probiotics as a treatment for childhood constipation could, according to the Stetler model for EBP implementation either use a formal or informal approach (Ciliska et al., 2011). If future evidence indicates probiotics are an effective treatment, a practitioner would have to assess many factors for feasibility before implementing a plan. Barriers to implementation include attitudes of administration, fellow practitioners and parents about the efficacy and appropriateness of use, as well as the availability of the product, depending on whether a commercially available yogurt or prescription capsule is used.

The simplest way to implement this intervention as mentioned in phase 4 of Stetler’s model would be to start recommending the use of probiotics in practice for one’s pediatric patients with chronic constipation (Ciliska et al., 2011). Discussion with the parents regarding their values and eating preferences, as well as their willingness to try a new approach would need to be evaluated. Recording patients’ reported symptoms and BM frequency before administration would be the marker against which to evaluate effectiveness. Within four weeks, parents would be expected to report an increase of BMs to greater than three a week, and a decrease in other symptoms, like abdominal pain. Long-term follow up at eight weeks, three, six and twelve months would be expected and discussed. The practitioner would need to make clear that regular follow up appointments would be expected, or follow up phone calls would need to be made. Obviously, if the probiotics were ineffective, a back-up rescue plan of laxatives would need to be available to patients.

If finances from administration are available, and it would be feasible to obtain manpower assistance and institutional review board (IRB) approval, a pilot study, like the ones critiqued in this project, could be developed and implemented according to the Stetler model (Ciliska et al., 2011). Strict attention to inclusion and exclusion criteria as well as to protocol would be key, and data would have to be recorded at more frequent intervals. BM frequency at baseline and at weekly intervals after implementing the use of probiotics in either yogurt or capsule form would be appropriate data to collect and analyze. Barriers to this approach would vary depending on the location of the study. In rural areas, participants would likely be more sparse, and qualified research assistants and statisticians are rare. The sample would be undoubtedly homogenous in terms of ethnicityeating habits and socioeconomic status, making generalizability an issue. An advantage to a rural pilot study would be the relative ease of follow-up and increased compliance of subjects due to the physical and emotional closeness of most patients and families to their providers in these areas.

Polit and Beck (2012) indicate that qualitative research exploring the experience of a condition is often a necessary part of a pilot study and enhances preparation for further trials or implementation. Therefore, in order to increase the chance of success, a qualitative study of children with constipation and their parents to learn about their eating habits, toileting habits and day-to-day life could assist a practitioner and the team to develop and evaluate the specific probiotic administration protocol. Documentation of issues encountered and solutions discovered is an essential part of a pilot study (Polit & Beck, 2012), and would be useful for future implementation or research.

Conclusion

Probiotics represent an alternative method to treat a problem that has a great economic impact and affects the quality of life of millions(Liem et al., 2009; Bongers et al., 2009; Mugie et al., 2011). The effect of probiotic use on childhood constipation is just beginning to be evaluated, with some promising results. Future research in the form of randomized controlled trials examining the use probiotics alone to treat childhood constipation could lead to a revolution in how the condition is treated and prevented.

References

Bekkali, N., Bongers, M.E., Van den Berg, M.M., Liem, O., & Benninga, M. A. (2007). The

role of a probiotics mixture in the treatment of childhood constipation: Results from a pi

lot study. Nutrition Journal, 6, 17. doi: 10/1186.1475-2891-6-17.

Bongers, M.E., Benninga, M.A., Maurice-Stam, H., & Grootenhuis, M.A. (2009). Health-related quality of life in young adults with symptoms of constipation continuing from childhood to adulthood. Health and Quality Outcomes, 7, 20. doi: 10.1186/1477-7525-7-20.

Bu, L., Chang, M., Yi, N., Chen, H.,& Cheng, C. ( 2007). Lactobacillus casei rhamnosous Lcr35 in children with constipation. Pediatrics International, 49, 485-490. doi: 10.1111/j. 1442-200x.2007.02397

Ciliska, D. Dicenso, A., Melnyk, B.M., Fineout-Overholt, E., Stetler, C.B., Cullen, L., Larrabee, J.H., Schultz, A.A., Rycroft-Malone, J., Newhouse, R.P., & Dang, D. (2011). Models to guide implementation of evidence-based practice. In B. Melnyk & E. Fineout-Overholt (Eds.), Evidence-based practice in nursing& healthcare: A guide to best practice. (2nd ed., pp. 241-275). Philadelohia, PA: Wolters Kluwer Lipppincott Williams & Wilkins.

Chmielewska, A. & Szajewska, H. (2010). Systematic review of randomized controlled trials: Probiotics for functional constipation. World Journal of Gastroenterology, 16 (1), 69-75. doi 10.3748/wjg.v16.il.69

Guerra, P., Lima, L. N., Souza, T. C., Mazochi, V, Penna, f.J., Silva, A.M., Nicoli, J.R., & Guimaraes, E.V. (2011). Pediatric functional constipation with bifidobacterium containing yogurt: A crossover, double-blind, controlled trial. World Journal of Gastroenterology, 17(34/), 3916-3921. doi: 10.3748/wjg.v17.i34.3916.

Hempel, S., Newberry, S., Ruelaz, A., Wang, Z., Miles, J., Suttorp, M.J., Johnsen, B., Shanman, R., Slusser, W., Fu, N., Smith, A., Roh, B., Polak, J. Motala, A.,Perry, T.,& Shekelle, P.

G. (2011). Safety of probiotics to reduce risk and prevent or treat disease. Agency for Healthcare Research and Quality, publication No. 11-E007. available at

Liem, O., Harman, J., Benninga, M.A., Kelleher, K. Mousa, H. & Di Lorenzo, C. (2009) Health utilization nd cost impact of childhood constipation in the United States. Journal of Pediatrics, 154, 258-262. doi: 10.1016/j.peds208.07060.

Mcbride, D. (2013). Childhood constipation in the emergency department. Journal of Pediatric Nursing, 28, 502-503. doi: 10.1016/j.pedn.2013.06.002