‘Should we be treating infantile colic at all?’ Such a legitimate question was asked in the Editorial accompanying one of the recent publications on infantile colic (1). Should we?
Infantile colic is among the most distressing conditions both for infants and parents. Yet, there is little agreement on the definition of colic, its prevalence, etiology, and management. According to the Rome III criteria, the diagnostic criteria for infantile colic must include all of the following in infants from birth to 4 months of age: paroxysms of irritability, fussing, or crying that start and stop without obvious cause, episodes lasting 3 h or more per day and occurring at least 3 days per week for at least 1 week, and no failure to thrive (2). However, a recent systematic review that identified 39 trials reporting on infantile colic found that in these trials, 20 different definitions of colic were used (3).
The worldwide prevalence of infantile colic is uncertain, but it is estimated to be approximately 20%; nonetheless, good quality data are lacking (4). One in six families will consult a health professional. A number of therapies have been tried, including use of hydrolyzed formulas, sucrose, herbal teas, soy formula, lactose-reduced formula, and fiber-enriched formulas, increased carrying, music, vibration or massage, and spinal manipulation; however, their effectiveness often remains unproven (5).
The cause of infantile colic remains unclear; however, a number of possible causes have been considered. These include painful intestinal contractions, lactose intolerance, food hypersensitivity, gas, parental misinterpretation of the normal crying pattern, or various combinations of the above. Psychosocial and gastrointestinal causes have been suggested but not proven (6). Evidence suggests that dysbiosis (altered gut microbiota) affects gut motor function and gas production in infants, resulting in abdominal pain/colic. Moreover, the gut microbiota in subjects with infantile colic differs from the gut microbiota in an unaffected population. A more recent study found that compared with controls, infants with colic showed lower microbiota diversity and stability in the first weeks of life. In addition, differences between colic and control microbiota in the infants’ first month of life (before the colic peak takes place) were found. At approximately 3 to 4 mo of age (when colic usually disappears), no significant differences were observed (7). These findings possibly explain the excessive crying.
If the alterations of gut microbiota indeed play a role in the pathogenesis of infantile colic, it is logical to assume that manipulation of the gut microbiota could be a preventive measure in the evolution of these disorders and also may play a therapeutic role. To date, modification of gut microbiota via the provision of probiotics defined as ‘live microorganisms that, when administered in adequate amounts, confer a health benefit on the host’(8) is the most extensively studied strategy. The exact mechanism by which probiotics may be effective in infantile colic remains unclear. However, it has been documented that some probiotics, such as Lactobacillus reuteri, have a proven inhibitory effect against gas-forming coliforms (9). Moreover, probiotics modulate the composition of the intestinal microbiota and increase the mucosal barrier by colonization of beneficial bacteria (10). Among other mechanisms, probiotics can reduce intestinal inflammation (11).
The purpose of this review is to summarize current evidence on the efficacy of probiotics used to treat or prevent infantile colic. To identify current data, an electronic database search of MEDLINE was performed with specific key words in January 2016. A summary of the identified randomized controlled trials (RCTs) on the effects of probiotics on the treatment and prevention of infantile colic is presented in the Table 1.
Lactobacillus reuteri DSM 17938
Four independent RCTs showed that use of L reuteri DSM 17938 reduced crying times in breastfed infants with infantile colic (12–15). In contrast, one RCT that involved both breast- and formula-fed infants did not confirm this effect (16). A 2014 meta-analysis of 3 RCTs found that compared with placebo, the administration of L reuteriDSM 17938 reduced crying time on day 21 by approximately 43 minutes (mean difference, MD, −43 min/day, 95% confidence interval, CI, −68 to −19). This effect was mainly seen in exclusively or predominantly breastfed infants (MD −57 min/day, 95% CI −67 to −46) (17). To better understand the role of L reuteri DSM 17938 for managing infantile colic, an individual participant data meta-analysis is currently underway (18).
A 2014 RCT carried out in Italy in 589 breast- and formula-fed infants revealed that compared with placebo, the administration of L reuteri DSM 17938 daily from day 3 for 90 days resulted in a significant reduction in crying time by approximately 51 min/day at 1 month and 33 min/day at 3 months (19). Thus, preliminary data suggest that L reuteri DSM 17938 also may be useful in the prevention of infantile colic.
Lactobacillus rhamnosus GG
A 2015 RCT performed in 30 infants with colic found that compared with placebo, administration of Lactobacillus rhamnosus GG for 4 weeks in addition to the cow's milk elimination diet either in infants or in breastfeeding mothers had no effect on the daily crying time at the end of the intervention (174 versus 173 minutes, respectively; P = 0.99) (20).
Mixture of Probiotics
One 2014, double-blind, placebo-controlled RCT performed in 50 breastfed infants aged 15–120 days with infantile colic found that compared with placebo, the administration of a synbiotic containing L casei, L rhamnosus, Strthermophilus, Bifidobacterium breve, L acidophilus, B infantis, L bulgaricus, and fructooligosaccharides significantly increased the treatment success, defined as a reduction in the daily crying time >50%, at 30 days (46% versus 87%, respectively; P < 0.01) (21).
Back to the question asked at the beginning: ‘Should we be treating infantile colic at all?’ Should we? Researchers and parents may differ in their opinions. With regard to probiotics, given the lack of effective therapy for infantile colic and the good safety profile of L reuteri DSM 17938, this therapeutic option could be discussed with caregivers. The administration of L reuteri DSM 17938 is likely to reduce crying times in breastfed infants with infantile colic, although its role in formula-fed infants is less clear. The use of L reuteri DSM 17938 for preventing infantile colic both in breast-and formula-fed infants is promising, but needs further evaluation by an independent research team. Data on other probiotics, either positive or negative, are too limited to allow one to draw reliable conclusions.
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4. Vandenplas Y, Abkari A, Bellaiche M, et al. Prevalence and health outcomes of functional gastrointestinal symptoms in infants from birth to 12 months of age. J Pediatr Gastroenterol Nutr
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13. Savino F, Cordisco L, Tarasco V, et al. Lactobacillus reuteri DSM 17938 in infantile colic: a randomized, double-blind, placebo-controlled trial. Pediatrics
14. Chau K, Lau E, Greenberg S, et al. Probiotics for infantile colic: a randomized, double-blind, placebo-controlled trial investigating Lactobacillus reuteri DSM 17938. J Pediatr
15. Mi GL, Zhao L, Qiao DD, et al. Effectiveness of Lactobacillus reuteri in infantile colic and colicky induced maternal depression: a prospective single blind randomized trial. Antonie Van Leeuwenhoek
16. Sung V, Hiscock H, Tang ML, et al. Treating infant colic with the probiotic Lactobacillus reuteri: double blind, placebo controlled randomised trial. BMJ
17. Urbańska M, Szajewska H. The efficacy of Lactobacillus reuteri DSM 17938 in infants and children: a review of the current evidence. Eur J Pediatr
18. 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
19. Indrio F, Di Mauro A, Riezzo G, et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr
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21. Kianifar H, Ahanchian H, Grover Z, et al. Synbiotic in the management of infantile colic: a randomised controlled trial. J Paediatr Child Health