Lactobacillus reuteri for Treatment of Infant Colic

May be effective for reducing colic in breastfed infants; small sample sizes limit validity of results

Benefits in NNT

1 in 4 for success at 21 days in all groups
1 in 3 for success at 21 days in breastfed infants
17% reduction in colic compared to placebo at 21 days overall
39% reduction in colic compared to placebo at 21 days for breastfed infants

Harms in NNT

Not reported
Not reported
View As:

Efficacy Endpoints

>50% reduction in crying and/or fussing time from baseline and at 21 days postintervention

Harm Endpoints

Not reported


Infant colic affects approximately 1 in 5 infants under 3 months of age and is defined by crying and/or fussing >3 hours per day for >3 days per week.1, 2 While the exact etiology is unknown, recent evidence suggests that it may be associated with adverse effects on allergies, behavior, and sleep.3, 4 Other studies have suggested that differences in gut microbiota may be a potential cause among patients with colic.5, 6 This has prompted authors to evaluate whether Lactobacillus reuteri DSM17938 reduces colic in breastfed infants.7

This current systematic review and individual patient data meta-analysis (IPDMA) pooled raw data from separate studies.8 The primary objective was to evaluate the efficacy of L. reuteri DSM 17938 compared with placebo for reducing crying and/or fussing at 21 days among children from birth to 23 months of age. Efficacy was defined by >50% reduction in crying and/or fussing from baseline and at 21 days postintervention. Secondary outcomes included crying and/or fussing duration and treatment success at 7 and 14 days postintervention. Authors planned to conduct subgroup analyses regarding feeding type, proton pump inhibitor (PPI) use, hypoallergenic formula use, and maternal dairy elimination diets in breastfed infants.

The authors identified 4 randomized controlled trials (RCTs) (n=345) meeting inclusion criteria and providing individual patient data. All 4 RCTs included breastfed infants with colic, and 1 RCT included formula-fed infants. The selected studies only included children up to 6 months of age with a median age of 5.9 weeks at the time of enrollment. The baseline, pre-intervention length of crying/fussing was 260 minutes per day. No studies identified adverse events. Crying and/or fussing durations were reduced in both the probiotic and placebo groups, but the probiotic group demonstrated significantly greater reduction at 21 days (mean difference −25.4 minutes; 95% confidence interval [CI]: −47.3 to −3.5; absolute reduction 17%). While the authors planned several subgroup analyses, data was only available for the feeding type. Breastfed patients receiving probiotics were 2-3 times as likely to experience treatment success at 7, 14, and 21 days, with a number needed to treat for day 21 success of 3 (95% CI: 2.0 to 3.6) and absolute reduction of 39%.


This is the first IPDMA evaluating the effectiveness of L. reuteri DSM 17938 in infant colic.8 While all studies were double-blind RCTs evaluating the same primary outcome and one strain of probiotic, this meta-analysis has several limitations. The overall number of included patients from the selected trials was only 345, and thus the precision of the point estimates is questionable with wide confidence intervals. For example, the 95% CI for decrease in time spent crying ranged from 3.5 to 47.3 minutes. This IPDMA included studies with different definitions of infant colic and measurement outcomes. Two studies utilized a non-validated diary requiring recall of infant crying duration at the end of the day, and the other two used the Baby’s Day Diary,9 which is a validated measure with less risk of recall bias. These latter 2 RCTs included fussing, but the other 2 RCTs did not. While the IPDMA suggests efficacy in breastfed infants, only 1 RCT evaluated formula-fed infants, which included 78 patients. This is an important consideration, as studies suggest that breastfed and formula-fed infants may have different gut microbiota.10, 11 The IPDMA was unable to determine whether the effects of L. reuteri differed based on PPI or hypoallergenic exposure and maternal dairy-elimination diets. PPIs, concurrent probiotics, and prebiotics may alter the effects of L. reuteri, and further studies are needed to assess the impact of this. Interestingly, 39% of patients in the placebo group and 47% of patients in the formula fed group improved at 21 days without intervention. Consequently, reassurance may be adequate for those with mild symptoms.

In summary, L. reuteri is effective in reducing colic in breastfed infants, but the overall small sample size and wide confidence intervals limit the validity of the findings. Therefore, we have assigned a color recommendation of Yellow (unclear if benefits). Further data are required with larger sample sizes, as well for formula-fed infants.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between and AEM.


Brit Long, MD; Alex Koyfman, MD; Michael Gottlieb, MD, RDMS
Supervising Editor: Shahriar Zehtabchi, MD


March 4, 2020