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Three Part Question

In [babies presenting with infantile colic], does [the use of probiotics] [reduce crying time]?

Clinical Scenario

A mother attends the Emergency Department with her breastfed 8-week-old baby girl who is crying inconsolably. History and examination point towards a diagnosis of infantile colic. You wonder whether you should suggest a proprietary over-the-counter remedy or whether you should just say that this is a self-limiting condition. A passing paediatrician notices your dilemma and suggests probiotic therapy to reduce the baby's distress. You wonder if there is any evidence to support her advice.

Search Strategy

MEDLINE 1950 to April 2015 using the OVID interface. EMBASE 1980 to March 2015 using the OVID interface: [Exp Probiotics or probiotics.mp OR exp Lactobacillus or Lactobacillus.mp OR probiotic bacteria.mp OR probiotic.mp] AND [Exp colic or Baby colic.mp OR Infant colic.mp OR infantile colic.mp OR colicky infants.mp] LIMIT to human AND English Language.

The Cochrane Library Issue 4 of 12, April 2015: MeSH descriptor: [Probiotics] explode all trees AND MeSH descriptor: [Colic] explode all trees 7 records 1 unique article.

Search Outcome

Eighty-eight papers were found from the literature search and eight journal articles were considered relevant to the research question. One was a meta-analysis including three of the other papers. There was no Cochrane review on this topic. Five papers are therefore included in the table below

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Chau et al 2015 Canada	52 infants with colic that met modified Wessel’s criteria. Randomised to either receive L. reuteri (24) or placebo (28) for 21 days. Maternal questionnaire- daily crying and fussing times	Randomised, double blind, placebo-controlled trial.	Reduced total average crying and fussing times and daily crying times	Median 60 min per day vs 102 min per day (p=0.045)	Infants up to 6 months of age. Does not reflect age of incidence of colic. Large inter-quartile range of crying time may not reflect clinical significance
			Number with 50% reduction in crying time	17 vs 6, p=0.035; relative risk, 3.3; CI (1.55 to 7.03)
Indrio et al 2014 Italy	468 term newborns (age <1 week) randomly allocated L. reuteri or placebo for 90 days	Prospective, multicentre, double-blind, placebo controlled RCT	Duration of inconsolable crying at 90 days	38  min in probiotic group vs 71  min in placebo group (p<0.01)	Study recruited unselected general population of neonates. CIs not available in study
Sung et al 2014 Australia	167 breastfed or formula-fed infants aged <3 months (Wessel’s criteria for colic) assigned to receive probiotic or placebo	Phase 3 double blind, randomised placebo controlled trial	Daily duration of crying or fussing at 1 month	Probiotic group cried or fussed for 49  min more than placebo group (95% CI 8 to 90  min, p=0.02)	Reduced dose of L reuteri compared to other studies. Majority of infants selected were from emergency or urgent care setting
Calderon et al 2014 Spain	17 ‘healthy infants’. Age of infants and duration of monitoring unclear. Symptoms associated with colic monitored using questionnaires and two physical visits. All children prescribed L. reuteri	Observational prospective study	Crying and infant discomfort	Reduced during the study	No control group. Very small pilot study. The study's external validity is limited
Anabrees et al, 2013 Saudi Arabia	220 breastfed infants enrolled into 3 selected studies were given Lactobacillus reuteri or control (placebo or simethicone)	Meta-analysis of randomised trials	Crying times at 21 days after starting treatment Treatment success	Mean difference −56.03 min; 95% CI (−59.92 to −52.15) RR of 0.06; (95% CI 0.01 to 0.25) NNT 2	Breast fed infants only. 1 study included was assessed as poor quality

Comment(s)

Infantile colic is a common disturbance occurring in the first 3 months of life; it is a self-limiting condition associated with parental anxiety, exhaustion and early cessation of breastfeeding. There is uncertainty regarding geographical and socioeconomic prevalence of infantile colic. Most studies use reported clinically significant benefits to babies in reduced crying times. Apart from one multicentred RCT, most other studies included small study samples. No adverse effects were reported, and probiotics were well tolerated. The search uncovered one study protocol (Sung et al 2014)6 for an individual patient data meta-analysis into this issue, but no results three were yet reported.

Clinical Bottom Line

There is evidence that the administration of probiotics decreases the severity and duration of infantile colic.

References

1. Chau K , Lau E , Greenberg S et al . Probiotics for Infantile Colic: A randomised, double-blind, placebo controlled trial investigating Lactobacillus reuteri DSM 17938. J Paediatr 2015;166:74–8.
2. Indrio F , Di Mauro A , Riezzo G , et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomised clinical trial. JAMA Paediatrics 2014;168:228–331.
3. Sung V , Hiscock H , Tang M , et al.. Treating infant colic with the probiotic Lactobacillus reuteri: double blind, placebo controlled randomised trial. BMJ 2014;348:g2107
4. Calderon V , et al . Valuation of the use of Lactobacillus reuteri in the treatment of infant colic: a pilot study ACTA Pediatrica Esp 2014;72:154–9.
5. Sung V , Cabana MD , D’Amico F , et al Lactobacillus reuteri DSM 17938 for managing infant colic: protocol for an individual participant data meta-analysis. BMJ Open 2014;4:e006475.
6. Anabrees J , Indrio F , Paes B , et al . Probiotics for infantile colic: a systematic review. BMC Pediatr 2013;13:186.