Probiotics and infant colic

BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g2286 (Published 01 April 2014) Cite this as: BMJ 2014;348:g2286
  1. William E Bennett Jr, assistant professor of paediatrics
  1. 1Department of Paediatrics, Indiana University School of Medicine, IN, USA
  1. W E Bennett Jr webjr{at}iu.edu

Still a hammer in search of a nail

In a linked paper, Sung and colleagues (doi:10.1136/bmj.g2107) describe a large, randomised, placebo controlled trial of Lactobacillus reuteri for the management of infant colic.1 This represents the most definitive and well designed study to date on this controversial topic.

Infant colic is a challenging problem for many parents, but the cause and effective treatment remain elusive. As its name suggests, colic was thought to arise in the gastrointestinal tract, but after centuries of this supposition we still do not know if this is true. A host of home remedies and drug treatments have circulated over the years, ranging from whisky, to acid suppression, to anticholinergic agents, and onwards to medicine’s most recent “hammer looking for a nail,” probiotics.

Sung and colleagues used a well defined case definition of colic (the Wessell criteria), and then enrolled patients at urgent care centres who met these criteria. In total, 167 infants were randomised to L reuteri or to placebo. At multiple follow-up intervals, the authors found no improvement in the duration of crying time in infants who received probiotic compared with placebo (in fact, infants receiving probiotic cried significantly more). The authors also assessed secondary outcomes, including measures of maternal mental health, family functioning, and family quality of life, none of which differed between arms.

In contrast, last month Indrio and colleagues published the results of a multi-institutional trial.2 They found that prophylactic probiotic use for the first three months of life in normal newborns reduced the number of parent reported crying time compared with placebo (mean 71 v 38 minutes a day at 3 months). Additionally, the frequency of regurgitation and bowel movements was also “improved,” although defining these quantities as disease states is often specious in infants.

Unfortunately, these two large studies—both of which constitute the best evidence to date—assessed two different clinical scenarios. Indrio and colleagues sought to answer the question: “Should we give probiotics to all infants to help prevent fussiness/colic?,” whereas Sung and colleagues asked: “Should we give probiotics to infants with colic to improve their symptoms?”

Fifty years ago, paediatrician Morris Green coined the term “the vulnerable child syndrome” to describe the far reaching family effects of a perceived threat to a child’s life.3 Since then many investigators have studied the effects of labelling a child as ill. Tarini and colleagues have shown that labelling a normal, benign process as a disease (such as infant regurgitation) has a substantial impact on parents’ expectations for treatment, even if they are informed that the treatment is ineffective.4 This process has resulted in hundreds of thousands of prescriptions for acid suppressants in infants over the past decade, despite evidence that their use increases the risk of respiratory and gastrointestinal infections.5 We should be careful not to walk this same road with probiotics and colic.

Furthermore, we know little about the acquisition and development of the microbiota in an infant’s gut. We are far from a sufficiently thorough understanding that would allow us to link changes in specific bacterial populations to changes in infant behaviour, given the enormous variation and complexity of both behaviour and microbiome composition between and among individuals. For instance, some investigators have described higher levels of faecal calprotectin (an inflammatory marker) in colicky infants,6 whereas others have found equally high levels in healthy, asymptomatic breastfed infants.7 This all points to our strikingly poor understanding of the normal intestinal milieu in infants, so we should hesitate to proclaim victory over colic just yet, or to aggressively alter the development of intestinal microbiota without a better understanding of normal intestinal development.

Some recent studies have shown an association between colic and the later development of functional disorders such as migraine.8 Some investigators cite this fact as justification for drug intervention for colic, under the auspices of preventing these later problems. This is a fallacious path. Functional disorders, especially those heavily influenced by social environment and parental perception, will naturally cluster together, and to suppose that early treatment of colic will somehow prevent children from developing functional pain disorders is an oversimplification of a complex set of disorders.

Amid this sea of conflicting evidence, what does work? Nearly all studies evaluating treatments for infant colic have methodological shortcomings or conflicting results. Probiotics have been studied most rigorously and results have been mixed.9 Simethicone and acid suppression have been convincingly shown to be ineffective.10 Dicycloverine (dicyclomine) and cimetroprium have marginal effectiveness but also have potentially worrying side effects.11 Maternal dietary changes or hydrolysed infant formulas are poorly evaluated, but some studies report positive results.12 13

So, with such a dearth of good evidence, perhaps the more important question is: “Should we be treating infant colic at all?” A great deal of accumulated clinical experience tells us that children with colic incur no serious long term effects from the disorder, and that symptoms abate with time. The potential harm associated with diagnostic testing and treatment of infants is likely to surpass the harm from colic itself.

For us to continue to perform drug intervention trials for this problem perhaps underscores our unwillingness to accept that colic is likely to represent a heterogeneous disorder with many complex inputs. As the old adage goes, “babies cry.” Parents and their babies may be better served if we devote more resources to studying the interventions recommended long before the discovery of probiotics: reassurance, family social support, and the tincture of time.


Cite this as: BMJ 2014;348:g2286


  • Research, doi:10.1136/bmj.g2107
  • Competing interests: I have read and understood the BMJ Group policy on declaration of interests and declare the following interests: None.

  • Provenance and peer review: Commissioned, not peer reviewed.