research article open access probiotics for infantile colic: a … · 2017. 8. 25. · colic and...

Anabrees et al. BMC Pediatrics 2013, 13:186http://www.biomedcentral.com/1471-2431/13/186

RESEARCH ARTICLE Open Access

Probiotics for infantile colic: a systematic reviewJasim Anabrees1*, Flavia Indrio2, Bosco Paes3 and Khalid AlFaleh4

Abstract

Background: Infantile colic is a common paediatric condition which causes significant parental distress. Increasedintestinal coliform colonization in addition to alteration in Lactobacillus abundance and distribution may play animportant role in its pathogenesis.The objectives of this systematic review are to evaluate the efficacy of probiotic supplementation in the reductionof crying time and successful treatment of infantile colic.

Methods: Literature searches were conducted of MEDLINE, EMBASE and the Cochrane Central Register of ControlledTrials. Only randomized controlled trials enrolling term, healthy infants with colic were included. A meta-analysis ofincluded trials was performed utilizing the Cochrane Collaboration methodology.

Results: Three trials that enrolled 220 breastfed infants met inclusion criteria, of which 209 infants wereavailable for analysis. Two of the studies were assessed as good quality. Lactobacillus reuteri (strains-AmericanType Culture Collection Strain 55730 and DSM 17 938) was the only species utilized in the therapeuticintervention. Two of the trials were industry funded. Probiotic supplementation compared to simethicone orplacebo significantly and progressively shortened crying times to 7 days reaching a plateau at three weeks postinitiation of therapy [mean difference −56.03 minutes; 95% CI (−59.92, -52.15)]. Similarly, probiotics compared toplacebo significantly increased the treatment success of infantile colic with a relative risk (RR) of 0.06; 95% CI(0.01, 0.25) and a number needed to treat of 2.

Conclusions: Although L. reuteri may be effective as a treatment strategy for crying in exclusively breastfedinfants with colic, the evidence supporting probiotic use for the treatment of infant colic or crying in formula-fed infantsremains unresolved. Results from larger rigorously designed studies will help draw more definitive conclusions.

Keywords: Infantile colic, Probiotics, Systematic review, Lactobacillus reuteri

BackgroundInfantile colic is a common problem in healthy thrivinginfants that is associated with excessive crying over aregular period during the day and is sustained for thefirst few months of life [1,2]. The condition has beenhistorically described as irritable or compulsive crying orparoxysmal fussing with a multifactorial etiology [3]. Al-though it affects 5% -19% of young infants, [2,4,5] it re-mains a frustrating problem for parents and care giversbecause it is difficult to treat and may result in signifi-cant psychosocial consequences. A number of cross sec-tional studies report significant links between infantilecolic and maternal depression and child abuse [6-11].

* Correspondence: [email protected] Care, Sulaiman Al Habib Medical Group, Arrayan Hospital, P.O. Box272069, Riyadh 11352, Saudi ArabiaFull list of author information is available at the end of the article

© 2013 Anabrees et al.; licensee BioMed CentrCommons Attribution License (http://creativecreproduction in any medium, provided the or

Despite forty years of research, the etiology of infantilecolic remains elusive. The current literature suggestsseveral causative mechanisms such as behavioral, foodallergy and hypersensitivity, immaturity of gut functionand dysmotility [12-14]. Of note, Shenassa et al. througha comprehensive review of 5 studies identified a possiblelink between maternal smoking and infantile colic whichmay be mediated through increased plasma and intestinalmotilin levels [15]. Recently, the composition of intestinalmicrobiota has been addressed as an independent risk fac-tor for infantile colic [16-18]. Studies indicate that inad-equate lactobacilli in the first few months of life mayaffect intestinal fatty acid profile favoring the developmentof infantile colic [16,17]. Coliform bacteria have also beenfound more abundantly in colicky infants and it is specu-lated that altering the intestinal microbiota compositionmay positively influence the management of affected in-fants [19]. In practice, the only probiotic used for infantile

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Anabrees et al. BMC Pediatrics 2013, 13:186 Page 2 of 9http://www.biomedcentral.com/1471-2431/13/186

colic is Lactobacillus reuteri (strains-American Type Cul-ture Collection Strain 55730 or DSM 17 938). However,other Lactobacillus species such as L.delbrueckii subsp.delbrueckii DSM 20074 and L. plantarum MB 456 haveproven inhibitory activity against gas-forming coliformsand may play a significant role in the management of in-fantile colic [20]. Similarly, Aloisio et al. evaluated fourBifidobacterium strains, namely, B. breve B632 (DSM24706), B2274 (DSM 24707), B7840 (DSM 24708), and B.longum subsp. longum B1975 (DSM 24709), and foundthat they may be potentially useful for the treatment of in-fantile colic or as a preventive strategy for infantilebacterial-related diarrhea [21]. However, exploratory clin-ical trials investigating both the safety and efficacy of pro-biotics incorporating these species are yet to be conducted.The objectives of this systematic review are to evaluate

the efficacy of probiotic supplementation in the reduc-tion of crying time and successful treatment of infantilecolic.

MethodsSearch strategyEligible studies were identified from OVID MEDLINE –National Library of Medicine [January 1966 to Septem-ber 2012] using the following subject MeSH headingsand text word terms: neonate(s), newborn(s), infant(s),probiotics, lactobacillus, bifidobacterium, colic; publica-tion type was limited to controlled trials. No languagerestriction was applied. Other databases were also searchedincluding: EMBASE (January 1980 to September 2012) theCochrane Central Register of Controlled Trials (CEN-TRAL, the Cochrane Library, Issue 9, 2012). Additional ci-tations were sought using references in articles retrievedfrom searches. Content experts were contacted to identifyunpublished and ongoing studies.

Study selectionWe included all randomized or quasi-randomized con-trolled trials that compared probiotics (any dose or com-position) to placebo, control or other forms of treatmentin healthy full term infants with infantile colic who wereless than 4 months of age. All definitions of infantilecolic were deemed acceptable. We considered articles inany language as long as there was an abstract in Englishindicating content.

Data extractionRetrieved articles were assessed for eligibility, and tworeviewers independently abstracted descriptive data onthe subjects, type of intervention, infants allocated ascontrol, outcomes and methodological quality of the ar-ticles. Discrepancies were resolved by discussion andconsensus. Where data were incomplete, the principal

investigator of the primary study was contacted for fur-ther information and clarification.

Methodological quality of the studiesStandard methods of the Cochrane Collaboration [22]were used to assess the methodological quality of includedtrials. For each trial, information was sought regarding themethod of randomization, allocation concealment, blind-ing, and completeness of follow up and on reportedoutcomes of all infants enrolled in the trial. The meth-odological details of the studies were extracted frompublished data and by contacting the primary authorwhere possible.

Data synthesisThe primary outcome was treatment success, defined asthe percentage of children who achieved a reduction inthe daily average crying time >50%. The secondary out-comes were duration of crying (minutes per day) and ad-verse events related to probiotic supplementation. Fordichotomous outcomes, relative risk (RR) and its associ-ated confidence interval were calculated. For continuousoutcomes, treatment effect was expressed as mean dif-ference and its calculated standard deviation. Meta-analysis of pooled data was performed using a fixedeffects model with the assumption that L. reuteri DSM17938 and L. reuteri ATCC 55730 are bioequivalent andthe added recognition that the comparison groups weresimethicone (one trial) or placebo (two trials). ReviewManager (RevMan), Version 5.2 software was used forstatistical analysis. A subgroup analysis was planned apriori to investigate the effect of probiotics in subjectswith a positive family history of atopy, and additionallyon different strains of probiotics utilized. Heterogeneitywas defined as a significant test when the p value was <0.1 and/or if similar differences were identified in treat-ment effects across studies. Tests for between-study het-erogeneity (including the I2 test) were performed.Since included studies expressed their primary outcome

(crying times) as median (range or interquartile range), inorder to statistically pool the data and perform a meta-analysis, this outcome was converted into mean (standarddeviation) as recommended by Hozo et al. [23].

ResultsA total of 10 potentially relevant citations were obtainedthrough our primary search strategy (Figure 1). Sevenstudies were excluded because the investigators usedprobiotic based formulae in non-colicky neonates, whichundermined the primary objectives of the meta-analysis.Three trials met our inclusion criteria [24-26]. AlthoughSzajewska et al. [26] planned an inclusion criterion of in-fants aged less than five months, the actual maximumage at enrolment was 81 days. Characteristics of the

Studies identified through database search

(n = 210)

Scree

ning

Included

Elig

ibility

Iden

tifica

tion Additional studies identified through

other sources (n = 0)

Number of studies identified after duplicates removed (n = 157)

Studies screened (n = 10)

147 studies excluded for the following reasons:

Review articles (n= 48)Prebiotics included (n=26)Infant formula used (n=22)

For eczema or diarrhea (n=23)

Non-clinical study (n=28)

Full-text articles excludedbecause probiotic based

formulae were used in non-colicky neonates

(n = 7)

Studies included in qualitative analysis

(n = 3)

Studies included in quantitative meta-analysis

(n = 3)

Full-text articles assessed for eligibility

(n = 3)

Figure 1 PRISMA flow diagram 2009 of included studies.


included trials are summarized in Table 1. Three on-going trials are summarized in Table 2, but the datasince incomplete were not included in this review.Overall, 140 infants were exclusively breastfed [24,25]

while Szajewska et al. additionally reported that 80 ofthe infants in their trial were exclusively or predomin-antly (>50%) breastfed [26]. In general, included trialshad a low risk of bias (Table 3). A total of 209 healthyinfants were enrolled across the three studies and mostof the infants were exclusively breast fed. All of the clinicaltrials utilized the same probiotic species (Lactobacillusreuteri; strains-American Type Culture Collection Strain55730 or DSM 17 938) with identical daily doses. Onestudy evaluated the efficacy of probiotic supplementationagainst simethicone [24]. None of the included studies re-ported any adverse side effects of supplementation.

Effect of L. reuteri on crying timeThe effect of L. reuteri on crying time was compared tosimethicone or placebo. Data on crying time were re-ported by all three trials as a primary outcome and in-volved 209 infants. At seven days after initiation oftreatment, infants in the probiotic group had a signifi-cantly shorter crying time. The crying time at 7 days wassignificant only in the fixed effects model, but was insig-nificant in the random effects model. However, the treat-ment effect was continuous and stabilized at three weeksfollowing the initiation of therapy. Probiotics decreasedcrying times by almost one hour [mean difference −56.03 minutes; 95% CI (−59.92, -52.15)] (Figure 2). Inorder to reduce heterogeneity and the potential effect ofsimethicone, a sensitivity analysis on only the double-blind, placebo-controlled, trials [24,26] was conducted.

Table 1 Characteristics of trials included in the analysis

Study/year/reference Description/study design Birth weight and age atenrolment

Probiotic agent(s) Dosage and duration Control arm Primary outcome

Savino/2007 [24] April 2004 - May 2005. Birth weight 2500-4000 gand aged 21–90 days

L. reuteri (American Type CultureCollection Strain 55730)

108 colony-forming units in 5drops for 28 days

Simethicone A reduction of averagecrying time to less than3 hours a day on day 28.90 exclusively breastfed infants

with a diagnosis ofinfantile colic.

Recruited in the Departmentof Pediatric and AdolescenceScience (Regina MargheritaChildren Hospital, Turin, Italy)

Open prospectiverandomized study.

Savino/2010 [25] March 2008 and August 2009. Birth weight 2500–4000 gand aged 2–16 weeks

L. reuteri DSM 17938 108 colony-forming units in 5drops, once a day, 30 minutesbefore the feed in the morn-ing, for 21 days

Placebo A reduction of averagecrying time to less than3 hours a day on day 21.50 exclusively breastfed infants

were recruited from generalpediatricians and outpatientsat the Department ofPediatrics, University of Turin(Regina MargheritaChildren Hospital)

A Randomized, Double-Blind,Placebo-Controlled Trial

Szajewska/2013 [26] January 2010 andDecember 2011.

Full term infantsaged 50%)breastfed infants

Family primary care practice inWarsaw, Poland

A Randomized, Double-Blind,Placebo-Controlled Trial

Colic in all the trials was defined as crying episodes lasting ≥3 hours/day and occurring at least 3 days/week within 7 days prior to enrollment.

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Table 2 The ongoing trials of probiotics and infant colic

No Study Inclusion and exclusion criteria Primary outcome Estimatedenrollment

Arms

1 Effect of L. rhamnosus GG (LGG)on Infant Colic

Inclusion Criteria: Crying times of infants 60 Experimental: NutramigenLipil with Enflora

Sixty healthy full-term colicky infants(gestational age 32–41 weeks) Control: Nutramigen A +

Hypoallergenic formulawithout lactobacilliExclusion Criteria:

Chronic lung disease,

Diarrhea (stools that take the shapeof a container > 5x daily)

Fever

2 Control of Colic in Infants byDietary Supplementation withthe Probiotic L. reuteri

Inclusion Criteria: Reduction of daily averagecrying time to less than3 hours from baseline

50 Experimental: L. reuteri

Infants aged between 14–60 days Control: Not clear

Breast fed, exclusively during lengthof trial

Diagnosis of infantile colic accordingto Wessel’s criteria

Debut of colic symptoms 6 ± 1 daysbefore randomization

Gestational age between 37–42 weeks

Apgar score higher than 7 at 5 minutes

Mothers willing to follow a cow milk-free diet during the study period

Written informed consent and statedavailability throughout the study period

Exclusion Criteria:

Major chronic disease

Gastrointestinal disease but controlledgastroesophageal reflux disease

Administration of antibiotics theweek before randomization

Administration of probiotics the weekbefore randomization

Participation in other clinical trials

3 Baby Biotics randomisedcontrolled trial

Inclusion criteria Infant crying/fussing time 160 Experimental: L. reuteriDSM 17938.

Infant colic as defined by themodified Wessel’s criteria

(min/day)

Less than 3 months Control: maltodextrose

Greater than 36 weeks gestationat birth

Birth weight of more than 2500 g.

Exclusion criteria

Failure to thrive

Major medical problems

Taking solids, antibiotics or L. reuteriand, if breastfeeding, mother taking

L. reuteri at the time of studycommencement;

Cow’s milk protein allergy

Caregiver has insufficient English tounderstand informed consent andcomplete questionnaires.


Table 3 The quality and risk of bias in the trials included in the analysis

Study/year/reference

Randomsequencegeneration(selection bias)

Allocationconcealment(selection bias)

Blinding ofparticipantsand personnel(performance bias)

Blinding ofoutcomeassessment(detection bias)

Incompleteoutcome data(attrition bias)

Selectivereporting(reporting bias)

Other bias

Savino/2007 [24] Low risk Low risk High risk Low risk Low risk Low risk Low risk

Savino/2010 [25] Low risk Unclear risk Low risk Low risk Low risk Low risk Low risk

Szajewska/2013 [26] Low risk Low risk Low risk Low risk Low risk Low risk Low risk


The heterogeneity remained unaltered with a strikinglysimilar reduction in crying time at 21 days [mean differ-ence −55.48 minutes; 95% CI (−59.46, -51.49)].

Effect of L. reuteri on overall response rateThe overall response rate of L. reuteri was compared tosimethicone or placebo. Responders (or treatment suc-cess) was defined as the percentage of infants achievinga reduction in the daily average crying time of more thanfifty percent. The response rate was reported in two ofthe trials at each assessment interval. Savino et al. re-ported the response rate at 28 days only [24]. A progres-sive, statistically significant response was noted startingat 7 days [25] after initiation of therapy (Figure 3). The ef-fect was maximal at 21 days following the commencementof treatment, with a relative risk (RR) of 0.06; 95% CI(0.01, 0.25) and a number needed to treat (NNT) of 2. Ofnote, a similar progressive improvement was also evidentin the control subjects; however, the positive effect wasmore pronounced in the probiotic group.

Effect with a history of atopyThe impact of atopy was documented in only one study[26]. A concomitant history of atopy did not alter the ef-ficacy of probiotics in treated infants.

DiscussionWe report the first systematic review of randomizedtrials addressing the efficacy of probiotics in infantilecolic. A significant effect of L. reuteri supplementation(strains-American Type Culture Collection Strain 55730and DSM 17 938) in shortening crying times and improve-ment in response rate was noted. This positive responsewas progressive with time and had its peak and plateau atthree weeks after initiation of therapy. A similar positiveeffect was noted in the control group, which could be ex-plained, by the natural history of infantile colic or a pla-cebo effect [22,23]. However, the effect in the probioticgroup was more pronounced. It is important to note thatone of the strains (L. reuteri ATCC 55730) used in one ofthe included trials [24] was found to carry potentiallytransferable resistance traits for tetracycline and lincomy-cin in adults [27] and was replaced in subsequent studies

by L. reuteri DSM 17938, a daughter strain that retainedthe original probiotic characteristics [28,29].Our systematic review included currently available,

high quality studies. However; our overall conclusion iscompromised by the small number of enrolled infantsdespite the common prevalence of infantile colic, andthe heterogeneity of included studies that assessed cry-ing time. This heterogeneity can be explained by theclear imbalance of both groups at baseline, in the studyreported by Savino et al. [25]. The probiotic groupstarted with significantly longer crying times thatquickly moved to a profoundly positive benefit after7 days of treatment. Most of the included subjects wereexclusively breast fed which limits the generalizability ofthe findings to formula fed infants. However, the incidenceof colic in breast and bottle fed infants is similar [30] be-cause the pathogenesis of the disorder is likely multifac-torial and the use of probiotics may be influential in thetreatment of colic by altering faecal microbiota and gut in-flammation irrespective of feeding patterns [16-19,31].The earlier trial by Savino et al. [24] involved the use

of simethicone in the placebo arm. This may have de-creased the magnitude of the effect of probiotics unlessthe effect of simethicone was not indifferent to placebo.The sensitivity analyses confirmed that the inclusion ofthe simethicone treated patients in this study did notsignificantly impact heterogeneity or the crying time at21 days. One well recognized limitation of all studies oninfant colic is the need for a more objective way ofmeasuring duration of crying rather than relying on theparents’ compliance to establish this outcome. Computerrecordings of crying episodes comprise a more concreteform of assessment and should be considered for futurestudies. Two of the included trials were supported by themanufacturer of the probiotic strain under study, whichraises the possibility of bias. However, the likelihood issmall since the trials were fully investigator-initiated anddata controlled with transparent disclosure of potentialconflicts of interest by the respective authors [32,33].Recently few studies have addressed the role of changing

intestinal microbiota in the pathogenesis of colic. Colicky in-fants were found to have increased colonization by coliformsespecially E.coli and decreased and altered colonization

Figure 2 Forest plot of L. reuteri ATCC 55730 and L. reuteri DSM 17938 versus control effect in decreasing mean crying times (min)over 28 days.


patterns by lactobacillus species [17-19]. Furthermore, L.reuteri also exerts an antimicrobial effect against entericpathogens which may induce an immunologic response[34-36]. Immune modulation could also play a role in the ef-ficacy of probiotics in infantile colic as it may represent thefirst sign of food hypersensitivity [37]. Since probiotic sup-plementation appears to require time to exert an effect incolicky infants, it would be interesting to evaluate its efficacyas a prophylactic treatment after birth. It’s unclear whether asimilar or cumulative effect would be observed if other for-mulations of probiotic bacteria are utilized either alone or incombination with the same strains of L. reuteri.

ConclusionsOur review supports the beneficial effects of probioticsupplementation in infantile colic in predominantlybreast fed infants. L. reuteri (strains-American Type Cul-ture Collection Strain 55730 and DSM 17 938) signifi-cantly decreased the rate (minutes/day) of crying and noshort term safety concerns were identified. However, allthree included studies demonstrate a positive outcomewhich may be a reflection of the relatively small, com-bined, sample size that overshadows the true effectwhich may be realized in a single, large-scale, multicen-ter, randomized trial. More independent studies are still

Figure 3 Forest plot of L. reuteri ATCC 55730 and L. reuteri DSM 17938 versus control effect in improving infantile colic treatmentsuccess rate over 28 days.


required in diverse ethnic populations, especially in for-mula fed infants, [38] prior to adopting a change inpractice.

AbbreviationsCI: Confidence interval; NNT: Number needed to treat; RR: Relative risk.

Competing interestsThe authors declare that they have no competing interests.

Authors’ contributionsJA: Conceptualized the study design, protocol development, inclusionselection, quality assessment and statistical analysis, and drafted the initialmanuscript. FI: Was involved in the study conception and design, oversawthe protocol development and data interpretation and participated in themanuscript preparation. BP: Critically reviewed and amended the manuscriptand circulated the final version for approval and submission. KA: Played amajor role in the study conception, design, protocol development, inclusionselection, quality assessment and statistical analysis and workedcollaboratively on the draft of the initial manuscript. All authors read andapproved the final manuscript.

AcknowledgmentsWe extend our sincere appreciation to the Deanship of Scientific Research atKing Saud University for funding this project through the Research Groupproject # RGB-VPP-248.

Funding sourceThis study was funded by King Saud University.

Author details1Neonatal Care, Sulaiman Al Habib Medical Group, Arrayan Hospital, P.O. Box272069, Riyadh 11352, Saudi Arabia. 2Department of Pediatrics, University ofBari, Bari, Italy. 3Department of Pediatrics (Neonatal Division), McMasterUniversity, Hamilton, Ontario, Canada. 4Department of Pediatrics, King SaudUniversity, Riyadh, Saudi Arabia.

Received: 11 May 2013 Accepted: 14 November 2013Published: 15 November 2013

References1. Illingworth RS: Infantile colic revisited. Arch Dis Child 1985, 60:981–985.2. Lucassen PL, Assendelft WJ, van Eijk JT, et al: Systematic review of the

occurrence of infantile colic in the community. Arch Dis Child 2001,84:398–403.

3. Wessel MA, Cobb JC, Jackson EB, Harris GS Jr, Detwiler AC: Paroxysmalfussing in infancy, sometimes called colic. Pediatrics 1954, 14:421–435.

4. Castro-Rodríguez JA, Stern DA, Halonen M, et al: Relation between infantilecolic and asthma/atopy: a prospective study in an unselectedpopulation. Pediatrics 2001, 108:878–882.

5. Gelfand AA, Thomas KC, Goadsby PJ: Before the headache: infant colic asan early life expression of migraine. Neurology 2012, 79:1392–1396.

6. Vik T, Grote V, Escribano J, European Childhood Obesity Trial Study Group,et al: Infantile colic, prolonged crying and maternal postnatal depression.Acta Paediatr 2009, 98:1344–1348.

7. Akman I, Kuscu K, Ozdemir N, et al: Mothers’ postpartum psychologicaladjustment and infantile colic. Arch Dis Child 2006, 91:417–419.

8. Dennis CL, Ross L: Relationships among infant sleep patterns, maternalfatigue, and development of depressive symptomatology. Birth 2005,32:187–193.

9. Miller AR, Barr RG, Eaton WO: Crying and motor behavior of six-week-oldinfants and postpartum maternal mood. Pediatrics 1993, 92:551–558.


10. Miller-Loncar C, Bigsby R, High P, et al: Infant colic and feeding difficulties.Arch Dis Child 2004, 89:908–912.

11. Smart J, Hiscock H: Early infant crying and sleeping problems: a pilotstudy of impact on parental well-being and parent-endorsed strategiesfor management. J Paediatr Child Health 2007, 43:284–290.

12. Miller AR, Barr RG: Infantile colic. Is it a gut issue? Pediatr Clin North Am1991, 38:1407–1423.

13. Treem WR: Infant colic. A pediatric gastroenterologist’s perspective.Pediatr Clin North Am 1994, 41:1121–1138.

14. Lucassen PL, Assendelft WJ, Gubbels JW, et al: Effectiveness of treatmentsfor infantile colic: systematic review. BMJ 1998, 316:1563–1569.

15. Shenassa ED, Brown MJ: Maternal smoking and infantile gastrointestinaldysregulation: the case of colic. Pediatrics 2004, 114:e497–e505.

16. Lehtonen L, Korvenranta H, Eerola E: Intestinal microflora in colicky andnoncolicky infants: bacterial cultures and gas–liquid chromatography.J Pediatr Gastroenterol Nutr 1994, 19:310–314.

17. Savino F, Cresi F, Pautasso S, et al: Intestinal microflora in breastfed colickyand non-colicky infants. Acta Paediatr 2004, 93:825–829.

18. Savino F, Bailo E, Oggero R, et al: Bacterial counts of intestinalLactobacillus species in infants with colic. Pediatr Allergy Immunol 2005,16:72–75.

19. Savino F, Cordisco L, Tarasco V, et al: Molecular identification of coliformbacteria from colicky breastfed infants. Acta Paediatr 2009, 98:1582–1588.

20. Savino F, Cordisco L, Tarasco V, et al: Antagonistic effect of Lactobacillusstrains against gas-producing coliforms isolated from colicky infants.BMC Microbiol 2011, 11:157. Doi: 10.1186/1471-2180-11-157.

21. Aloisio I, Santini C, Biavati B, et al: Characterization of Bifidobacterium spp.strains for the treatment of enteric disorders in newborns. Appl MicrobiolBiotechnol 2012, 96:1561–1576.

22. Higgins JPT, Green S (Eds): Cochrane Handbook for Systematic Reviews ofInterventions Version 5.1.0, The Cochrane Collaboration; 2011. Available fromwww.cochrane-handbook.org.

23. Hozo SP, Djulbegovic B, Hozo I: Estimating the mean and variance fromthe median, range, and the size of a sample. BMC Med Res Methodol2005, 5:13.

24. Savino F, Pelle E, Palumeri E, et al: Lactobacillus reuteri (American TypeCulture Collection Strain 55730) versus simethicone in the treatment ofinfantile colic: a prospective randomized study. Pediatrics 2007,119:e124–e130.

25. Savino F, Cordisco L, Tarasco V, et al: Lactobacillus reuteri DSM 17938 ininfantile colic: a randomized, double-blind, placebo-controlled trial.Pediatrics 2010, 126:e526–e533.

26. Szajewska H, Gyrczuk E, Horvath A: Lactobacillus reuteri DSM 17938 forthe Management of Infantile Colic in Breastfed Infants: A Randomized,Double-Blind, Placebo-Controlled Trial. J Pediatr 2013, 162:257–262.

27. Egervärn M, Danielsen M, Roos S, Lindmark H, Lindgren S: Antibioticsusceptibility profiles of Lactobacillus reuteri and Lactobacillusfermentum. J Food Prot 2007, 70:412–418.

28. Savino F, Tarasco V: New treatments for infant colic. Curr Opin Pediatr2010, 22:791–797.

29. Rosander A, Connolly E, Roos S: Removal of antibiotic resistancegene-carrying plasmids from Lactobacillus reuteri ATCC 55730 andcharacterization of the resulting daughter strain, L. reuteri DSM17938. Appl Environ Microbiol 2008, 74:6032–6040.

30. Lucas A, St J-RI: Crying, fussing and colic behaviour in breast- andbottle-fed infants. Early Hum Dev 1998, 53:9–18.

31. Rhoads JM, Fatheree NY, Norori J, et al: Altered fecal microflora andincreased fecal calprotectin in infants with colic. J Pediatr 2009,155:823–828. e1.

32. Ross JS, Gross CP, Krumholz HM: Promoting transparency inpharmaceutical industry-sponsored research. Am J Public Health 2012,102:72–80.

33. Dunn AG, Gallego B, Coiera E: Industry influenced evidence production incollaborative research communities: a network analysis. J Clin Epidemiol2012, 65:535–543.

34. Spinler JK, Taweechotipatr M, Rognerud CL, et al: Human-derived probioticLactobacillus reuteri demonstrate antimicrobial activities targetingdiverse enteric bacterial pathogens. Anaerobe 2008, 14:166–171.

35. Lin YP, Thibodeaux CH, Pena JA, et al: Probiotic Lactobacillus reuterisuppress proinflammatory cytokines via c-Jun. Inflamm Bowel Dis 2008,14:1068–1083.

36. Liu Y, Fatheree NY, Mangalat N, et al: Human-derived probioticsLactobacillus reuteri strains differentially reduce intestinal inflammation.Am J Physiol Gastrointest Liver Physiol 2010, 299:G1087–G1096.

37. Smits H, Engering A, van der Kleij D, et al: Selective probiotic bacteriainduce IL-10-producing regulatory T cells in vitro by modulating dendriticcell function through dendritic cell-specific intercellular adhesion molecule3-grabbing nonintegrin. J Allergy Clin Immunol 2005, 115:1260–1267.

38. Sung V, Hiscock H, Tang M, et al: Probiotics to improve outcomes of colicin the community: Protocol for the Baby Biotics randomised controlledtrial. BMC Pediatr 2012, 12:135. Doi: 10.1186/1471-2431-12-135.

doi:10.1186/1471-2431-13-186Cite this article as: Anabrees et al.: Probiotics for infantile colic: asystematic review. BMC Pediatrics 2013 13:186.

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AbstractBackgroundMethodsResultsConclusions

BackgroundMethodsSearch strategyStudy selectionData extractionMethodological quality of the studiesData synthesis

ResultsEffect of L. reuteri on crying timeEffect of L. reuteri on overall response rateEffect with a history of atopy

DiscussionConclusionsAbbreviationsCompeting interestsAuthors’ contributionsFunding sourceAuthor detailsReferences

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