A Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus reuteri for Chronic Functional Abdominal Pain in Children


Kambiz Eftekhari 1 , * , Zahra Vahedi 2 , Mojtaba Kamali Aghdam 2 , Diana Noemi Diaz 2

1 Department of Pediatrics, Bahrami Hospital, Tehran University of Medical Sciences, Tehran, IR Iran

2 Department of Pediatrics, Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, IR Iran

How to Cite: Eftekhari K, Vahedi Z, Kamali Aghdam M, Noemi Diaz D. A Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus reuteri for Chronic Functional Abdominal Pain in Children, Iran J Pediatr. 2015 ; 25(6):e2616. doi: 10.5812/ijp.2616.


Iranian Journal of Pediatrics: 25 (6); e2616
Published Online: December 23, 2015
Article Type: Research Article
Received: May 30, 2015
Revised: August 11, 2015
Accepted: August 22, 2015


Background: Functional abdominal pain (FAP) is one of the most common diseases, and large percentages of children suffer from it.

Objectives: The purpose of the study was to evaluate the effect of Lactobacillus reuteri in treatment of children with functional abdominal pain.

Patients and Methods: This study was a randomized double-blind placebo-controlled trial. Children aged 4 to 16 years with chronic functional abdominal pain (based on Rome III criteria) were enrolled in the study. They were randomly divided into two groups, one receiving probiotic and the other placebo.

Results: Forty children received probiotic and forty others placebo. There were no significant differences in age, weight, sex, location of pain, associated symptoms, frequency and intensity of pain between the groups. The severity and frequency of abdominal pain in the first month compared to baseline was significantly less and at the end of the second month, there was no significant difference between both groups compared to the end of the first month.

Conclusions: This study showed that the severity of pain was significantly reduced in both groups. There was no significant difference in pain scores between them. The effect of probiotic and placebo can probably be attributed to psychological effect of the drugs.

2. Objectives

The purpose of this study was to determine the efficacy of Lactobacillus reuteri (BioGaia®) for treating chronic functional abdominal pain in children.

4. Results

During a 14-month study, 270 children with abdominal pain were referred to the pediatrics gastroenterology clinic. Of these, only 80 children fulfilled the criteria of functional abdominal pain (Rome III), which were divided into two groups. Forty children were in the case group (BioGaia® recipient group) half of whom were boys. Other children (40 cases) were in the control group (placebo recipient group), 52.5% of these were males and 47.5% females. The mean and standard deviation of age in the case and control group were 6.26 ± 2.10 and 6.26 ± 2.61 years, respectively. (P = 0.16). There was no statistically significant difference in terms of mean and standard deviation of weight (Table 1) (P = 0.99). At baseline 97.5% of children in case group and 90% of the control group did not have any associated symptoms. However, constipation was seen in 2.5% of children in case group. Fever and anorexia were seen in 2.5% and 7.5% of children in control group, respectively. In this sense, both groups were consistent (P = 0.16), 95% of patients in the case group and 97.5% in the control group had periumbilical pain, and the remaining had hypogastric pain. (P = 0.55). At initiation of the study, intensity of abdominal pain in the case group according to scoring system of Wong-Baker faces scale was about 30% More, 57.7% Even More and 12.5% Whole. In the control group it was 22.5% More, 50% Even More and 27.5% Whole. In this sense, there was no significant difference between the groups (Table 2). At the end of the second month, 40% in case group and 65% in control group were No Hurt. Again, no significant difference was found between the groups (Table 2).

Table 1. Comparison of Mean and Standard Deviation of Age and Weight in Children at Two Study Groups
Age6.26 ± 2.106.26 ± 2.610.16
Weight20.86 ± 5.2422.71 ± 10.300.87
Table 2. Comparison of Abdominal Pain Intensity Based on Wong-Baker Scale System Between the Two Groups Before and After the First and Second Month
Time/GroupsPain IntensityP-Value
No HurtLittleMoreEven MoreWhole
Case0 (0)0 (0)12 (30)23 (57.5)5 (12.5)
Control0 (0)0 (0)9 (22.5)20 (50)11 (12.5)
End of the first month0.16
Case16 (40)5 (12.5)5 (12.5)11 (27.5)3 (7.5)
Control26 (65)0 (0)2 (5)9 (22.5)9 (22.5)
End of the second month0.20
Case15 (37.5)6 (15)5 (12.5)11 (27.5)3 (7.5)
Control21 (52.5)2 (5)6 (15)8 (20)3 (7.5)

Wong-Baker faces scale has 6 scores for comparison of abdominal pain intensity.

Zero score is used for No Hurt and 6 for Whole. Applying this scoring system, average score obtained in the control group at baseline was 4.05 ± 0.71, at the end of first month 2.08 ± 1.56 and at the of second month 2.25 ± 1.46. In the case group corresponding scores were 3.83 ± 0.63, 2.50 ± 1.45 and 2.53 ± 1.43, respectively. According to these results, there was significant difference between the groups at baseline and first month after treatment (P = 0.0001), while there was no significant difference at the end of second and first month in both groups (In case group P = 0.317 and control group P = 0.227). At first month, 50% of children in case group and 65% in control group had no pain and at second month 47.5% in case group and 52.5% in control group did not report any pain. In this respect, there were no statistically significant differences between the groups (Table 3). Average pain episodes per week in the control group was 1.33 ± 0.47 at baseline, 0.40 ± 0.59 at first month and 0.53±0.59 at second month. In the case group it was 1.45 ± 0.55 at baseline, 0.68 ± 0.76 at first month and 0.70 ± 0.75 at second month. Here also, there was a significant change in both groups compared to the first month (P = 0.0001), but the change was not significant in the second month compared with the first month (In case group P = 0.317 and control group P = 0.059). Lactobacillus reuteri was well tolerated and did not have any adverse reactions.

Table 3. Comparison of Pain Episodes in the Two Groups Before and After the First and Second Month
Time/GroupPain Episodes per WeekP-Value
No Pain1 - 33 - 66 - 9
Case0 (0)23 (57.5)16 (40)1 (2.5)
Control0 (0)27 (67.5)13 (32.5)0 (0)0.16
End of the first month
Case20 (50)13 (32.5)7 (17.5)0 (0)0.20
Control26 (65)12 (30)2 (5)0 (0)
End of the second month
Case19 (47.5)14 (35)7 (17.5)0 (0)
Control21 (52.5)17 (42.5)2 (5)0 (0)

5. Discussion

This study investigated the effects of Lactobacillus reuteri and placebo in reducing severity and frequency of pain in 80 children aged 4 to 16 years with chronic functional abdominal pain. Functional gastrointestinal disorders (FGID) are one of the most common childhood disorders, pathophysiology of which is still not well defined (14). Number of Intestinal flora plays an important role in creating this problem. Some of the studies have shown that the number of Lactobacillus is significantly reduced in the intestine of these patients (15, 16). Thus, replacement of these microorganisms was an acceptable hypothesis for treatment of functional abdominal pain. In our study both cases and control groups in terms of age, sex, weight, number of pain episodes per week, location of pain and associated symptoms were consistent. After treatment, the pain was significantly reduced in both groups. However, there was no significant difference between the groups in the intensity and frequency of pain episodes. After one month of cessation of drugs, no significant change was observed compared to the first month. Our study revealed that use of probiotics in treating FAP had no preference to placebo. In literature reports regarding the effect of Lactobacillus reuteri in the treatment of FAP, there is a parallel study and a contrary to our study. Niv et al. as in our study, found that the effect of Lactobacillus reuteri was similar to placebo in reducing abdominal pain and no more than that (17). Unlike our study, Claudio Romano et al reorted that Lactobacillus reuteri reduces the severity of pain in children but, similar to our results does not reduce the frequency of pain (18). There are very little studies in this field on children. The dose of probiotic was chosen based on previous published studies (19), its manufacturer’s recommendations (109 CFU) and duration of treatment as mentioned in the literature (20). However, the optimal dose and duration of drug therapy in the treatment of FAP is not clearly identified yet. In this study, we treated the samples randomly divided into two groups, so that the groups were matched for age and sex. We used an appropriate control group and our study was double-blinded. The main limitation of our study was the little number of samples. Other limitation of the study was not having access to patients over 13 years old. Most of them were referred to the adults’ gastroenterology clinic and could not be included in the study. So, average age of the patients in our study was considered lower than that in other studies.

To achieve appropriate management of FAP many evaluations are required. Our results showed that, although Lactobacillus reuteri may be effective in reducing severity and frequency of pain, its effect is not greater than placebo. Again our study proved that the use of placebo in the treatment of functional gastrointestinal disorders can be helpful, which emphasizes the fact that main causes of the disorder are mental and emotional problems, and also environmental stress, whereas the organic causes are less involved.

The major contribution to the treatment of FAP is to ensure the child and parents, so stress could be reduced. Pharmacologic therapy with placebo or other drugs, can lead to increased confidence.




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