DOI: 10.1542/pir.28-10-3812007;28;381Pediatrics in Review 

VohraLawrence D. Rosen, Cecilia Bukutu, Christopher Le, Larissa Shamseer and Sunita

Complementary, Holistic, and Integrative Medicine: Colic

http://pedsinreview.aappublications.org/content/28/10/381located on the World Wide Web at:

The online version of this article, along with updated information and services, is

http://pedsinreview.aappublications.org/content/suppl/2007/10/05/28.10.381.DC1.htmlData Supplement at:

Pediatrics. All rights reserved. Print ISSN: 0191-9601. Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2007 by the American Academy of published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1979. Pediatrics in Review is owned, Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly

at Umea University Library on November 16, 2014http://pedsinreview.aappublications.org/Downloaded from at Umea University Library on November 16, 2014http://pedsinreview.aappublications.org/Downloaded from

Complementary, Holistic, andIntegrative Medicine: ColicLawrence D. Rosen, MD,*

Cecilia Bukutu, PhD,†

Christopher Le,† Larissa

Shamseer,† Sunita Vohra,

MD, MSc†

Author Disclosure

This article was

funded in part by

PasseportSante.net. Dr

Vohra is an Alberta

Heritage Foundation

for Medical Research

Population Health

Investigator and

recipient of a

Canadian Institute of

Health Research New

Investigator Award

IntroductionAccording to the Wessel criteria, infantile colic is defined as excessive crying for more than3 hours a day at least 3 days a week for 3 weeks or more in an otherwise healthy baby. (1)As many as 26% of infants are diagnosed with colic, (2) making the condition one of themost common reasons for infant visits to primary care practitioners today. Colic is aself-limiting condition that resolves in approximately 50% of cases at about 3 months ofage. (3) Due, in part, to poor understanding of its causes, (2) there is no widely acceptedconventional treatment, and families often turn to complementary and alternative medical(CAM) therapies. (4) The largest systematic review to date of treatments for colic foundlittle evidence to support many conventional therapies, while noting that some nutritional-and botanical-based approaches were relatively safe and effective. (5) This review ofpublished scientific literature assesses the efficacy and safety of common CAM therapies intreating infantile colic.

Natural Health ProductsNatural health products have been used historically to treat infantile colic, due, in part, topresumed antispasmodic and anti-inflammatory activity. (6)(7) However, few of theseproducts have been assessed in terms of efficacy and safety for use in infants throughwell-designed clinical trials.

Fennel Seed OilThe effectiveness of fennel (Foeniculum vulgare) seed oil in treating infantile colic wasinvestigated in a randomized controlled trial (RCT) in Russia of 125 colicky infantsbetween the ages of 2 and 12 weeks. (8) Infants were assigned randomly to receive 5 to20 mL of a 0.1% fennel seed oil emulsion and 0.4% polysorbate-80 or a placebo(0.4% polysorbate-80 in water) up to four times per day for 1 week. Parents recordedsymptoms in a diary for 3 weeks that included the week before, the week during, and theweek after the trial. The primary outcome measure was a decrease in cumulative crying tofewer than 9 hours per week. At the end of the study, colic symptoms had improvedsignificantly in 40 of 62 (65%) infants from the fennel group compared with 14 of 59 (24%)infants in the placebo group (P�0.01). No adverse effects were reported in this study.However, fennel may cause allergic reactions of the skin (rashes) and respiratory tract(asthma and breathing difficulties). Fennel also has been reported to cause seizures. (6)The safety of using fennel long-term is unknown.

Botanical BlendsThe efficacy of an herbal tea containing fennel, chamomile, vervain, licorice, and lemonbalm to treat colic was investigated in an RCT of 68 Israeli infants ages 2 to 8 weeks. (9)Over a 7-day period, up to a 150-mL dose of herbal tea was offered to infants in theintervention group at the onset of a colic episode up to a maximum of three times a day.The actual average daily intake was two servings per day for a cumulative total of

*Chair, Integrative Pediatrics Council, Old Tappen, NJ.†Complementary and Alternative Research and Education (CARE) Program, Department of Pediatrics, University of Alberta,Edmonton, Alberta, Canada. On behalf of the American Academy of Pediatrics Provisional Section on Complementary, Holistic,and Integrative Medicine.Note: The agents discussed in this series are designated as dietary supplements rather than drugs. Although dietarysupplements are regulated by the United States Food and Drug Administration (FDA), their manufacturers may make claimswith little evidence and need not prove safety prior to marketing. The burden is on the FDA to monitor safety after theproduct is on the market. Readers are referred to the 1994 Dietary Supplement Health and Education Act (www.cfsan.fda.gov/�dms/dietsupp.html).

Article complementary medicine

Pediatrics in Review Vol.28 No.10 October 2007 381

at Umea University Library on November 16, 2014http://pedsinreview.aappublications.org/Downloaded from

approximately 90 mL/d. The control group received aplacebo tea (a mixture of glucose and unspecified naturalflavorings) that had the same taste, odor, and appearanceas the herbal tea. Parents reported that crying was re-duced to fewer than 3 hours daily in 57% of infants in theintervention group compared with 26% in the controlgroup (P�0.01). This study did not report on adverseeffects of herbal tea consumption and the impact, if any,on infants’ nutritional intake. Long-term safety of thisherbal combination is unknown.

An Italian RCT examined the efficacy of anotherherbal preparation in treating breastfed colicky infantsages 21 to 60 days. (10) Each dose consisted of thefollowing standardized extracts: sweet fennel fruit pow-dered extract (PE) standardized to 0.05% to 0.1% essen-tial oil, chamomile flower PE standardized to 0.3% api-genin, lemon balm essential oil standardized to 2%rosmarinic acid, 0.85 mg of vitamin B1, 3.24 mg ofcalcium pantothenate, and 1.20 mg of vitamin B6. Par-ents administered 2 mL/kg per day of the herbal prepa-ration twice a day before feeding for 7 days to children inthe intervention group (n�41). The control group(n�47) was given a placebo consisting of reverseosmosis-filtered water, fructose, pineapple flavoring, cit-ric acid, and potassium sorbate. Average daily crying timewas reduced from about 200 min/d to 76.9 min/d inthe treatment group and from about 200 min/d to169.9 min/d in the placebo group (P�0.005). Cryingtime was significantly reduced in 85% of infants in theintervention group compared with slightly less than 50%of the control group (P�0.005). These findings suggestthat this standardized herbal preparation relieves infan-tile colic symptoms. No adverse events were reported inthis study; long-term safety is unknown.

ProbioticsProbiotics have been defined as “a preparation of or aproduct containing viable, defined microorganisms insufficient numbers, which alter the microflora (by im-plantation or colonization) in a compartment of the hostand by that exert beneficial health effects in this host.”(11) These microorganisms colonize the intestinal tractsof infants during the birth process and shortly thereafter.They have been implicated in promoting immunologicbalance and digestive health. (12)(13)(14) Savino andassociates (15)(16) described quantitative and qualitativedifferences in probiotic species in colicky versus non-colicky infants.

Most recently, the same research group publishedresults of a trial of Lactobacillus reuteri compared withsimethicone in the treatment of infantile colic. (17) In

this trial, 90 exclusively breastfed colicky infants between21 and 90 days of age were randomized to either probi-otic L reuteri (108 live bacteria per day) or simethicone(60 mg/d) for 28 days. Mothers were instructed to avoidall sources of cow milk during the trial. At the start of thestudy, both groups of infants reportedly cried for approx-imately 200 min/d. The probiotic treatment group had asignificantly reduced crying time by only 7 days into thetrial (159 min/d versus 177 min/d in the simethiconegroup), a disparity that widened at weeks 2, 3, and 4(51 min/d versus 145 min/d). At the endpoint of thestudy, 95% of the probiotic treatment group were con-sidered “responders” (ie, no longer met Wessel criteria)compared with only 7% of the simethicone group. Nosignificant adverse effects were reported.

The use of probiotics in healthy individuals generallyis safe, but incidents of bacteremia/septicemia, pneumo-nia, and meningitis have been documented in immuno-compromised and severely debilitated patients. (18)(19)(20)(21)(22) Similar adverse events were documented intwo pediatric case reports in which Lactobacillus GG (10billion colony-forming units/d) caused bacteremia. (20)Probiotic use should be discussed with the child’s physi-cian because probiotic safety is relative rather than abso-lute.

Nutritional ModulationNutritional modulation is one of the few potentiallypreventive and therapeutic options for infants who havecolic. It does not appear that breastfeeding exclusivelyprevents colic, (23) but it has been observed that certainfoods (eg, cruciferous vegetables, chocolate) ingested bybreastfeeding mothers may lead to excessive infant irrita-bility. (24)(25) Although there is no clear consensus onavoidance of these foods for allergy prevention, (26) Hilland colleagues (27) demonstrated via an RCT that ex-clusion of certain allergenic foods (cow milk, soy, wheat,eggs, peanuts, tree nuts, and fish) was positively associ-ated with a reduction in colic in breastfed infants. In theirinvestigation, 107 infants (mean age, 5.7 weeks) present-ing with excessive irritability (average crying time morethan 300 min/d) were randomized to a 1-week trial ofmaternal low-allergen diet versus control (nonelimina-tion) diet. At the completion of the trial, 74% of treatedinfants were crying/fussing less frequently comparedwith 37% of the control group.

Whey hydrolyzed formula (hypoallergenic formula)has been shown in a small RCT to be more effective thannonhydrolyzed cow milk formulas in reducing cryingtimes in colicky babies (Table 1). (28) A 2000 reportfrom the American Academy of Pediatrics Committee on

complementary medicine colic

382 Pediatrics in Review Vol.28 No.10 October 2007

at Umea University Library on November 16, 2014http://pedsinreview.aappublications.org/Downloaded from

Nutrition recommended the use of hypoallergenic for-mula for infants who have allergies and a trial of hypoal-lergenic formula for severe colic. (29) A cost-benefitanalysis of hypoallergenic-labeled infant formulas isneeded because they cost up to three times more thanstandard formulas. (29)

Evidence is insufficient to support the use of caseinhydrolyzed formula, soy, or partially hydrolyzed formu-las as therapies for colic (Table 1). (29)(30)(31)(32)(33)(34)(35)(36) Soy infant formula has a highphytoestrogen content, which may pose a risk to futurefertility and sexual development. (37) Because of this

effect, the Chief Medical Officer in England has recom-mended that soy infant milk formula not be the firstchoice for treatment of infants who have lactose intoler-ance or cow milk sensitivity. (38)

A small Norwegian crossover RCT examined the an-algesic effect of sucrose on infant colic (n�19). (39)Parents gave infants 2 mL of 12% sucrose solution (in-tervention) or 2 mL of distilled water (control) afterpersistent crying and failed attempts to console the in-fant. Parents reported that symptoms improved in 63% ofthe infants given sucrose and in only one child (5%) givenplacebo (P�0.01). In this study, the observed benefit of

Table 1. Summary of Nutritional InterventionsAuthors Study Type Population Intervention Control Outcome Adverse Effects

Lucassen(28)

Randomized,double-blind,parallel trial

43 healthy,formula-fedinfants agesyounger than24 wk

Hypoallergenicwheyhydrolysateformula milk

Standard cowmilkformula

Decreased duration ofcrying by 63 min/d

None reported

Forsythe(33)

Randomizeddouble-blind,multiplecrossover trial

17 infants agesyounger than8 wk

Hypoallergeniccaseinhydrolysateformula milk

Standard cowmilkformula

No notable differencein incidence of colicbetween groups

None reported

Hill et al.(32)

Randomizeddouble-blind,placebo-controlled trial

115 infantsages 4 to16 wk

Hypoallergeniccaseinhydrolysateformula milk

Modified cowmilkformula

Number of bottle-fedinfants too small todetermine effect onthe bottle-fedsubgroup

None reported

Campbell(34)

Randomized,double-blind,placebo-controlledcrossover trial

19 infants ages3 to 14 wk

Soy formula milk Standard milkformula

Duration of colicsymptoms significantlyreduced with soy milk(P<0.01)

None reported

Evans et al.(35)

Double-blind,placebo-controlledcrossover trial

20 exclusivelybreast-fedinfants ages3 to 18 wk,who hadpersistentcolic

Soy formula milkconsumedby thebreastfeedingmother

Cow milkconsumedby thebreastfeedingmother

No beneficial effects onthe incidence of colic

None reported

Lothe et al.(36)

Double-blindcrossover study

60 infants ages2 to 12 wk

Soy formula milk Cow milkformula

Colic symptomsdisappeared in 11infants (18%) 48 hafter receiving soyformula but not afterreceiving cow milkformula. In 32 infants(53%), the symptomswere unchanged onsoy and cow milkformula.

Eight infantshad adversereactionscaused byother typesof food, twohad a severeform ofmultiplefoodintolerance,and tworeacted tosoy oil

complementary medicine colic

Pediatrics in Review Vol.28 No.10 October 2007 383

at Umea University Library on November 16, 2014http://pedsinreview.aappublications.org/Downloaded from

sucrose seems to have been short-lived (�30 min), whichmay indicate that it is not a practical treatment. (5)Although no adverse effects were reported, those consid-ering using sucrose should not substitute honey becauseunpasteurized honey may cause botulism in infants. (40)

Manipulative TherapiesChiropractic

The World Federation of Chiropractic defines chiroprac-tic as “a health profession concerned with the diagnosis,treatment, and prevention of mechanical disorders of themusculoskeletal system, and the effects of these disorderson the function of the nervous system and generalhealth.” (41) Chiropractic manual treatments includevertebral adjustment and other joint and soft-tissue ma-nipulation. Very few reliable data are available regardingthe safety of using spinal manipulation in pediatric pop-ulations. (42) The Canadian Coordinating Office forHealth Technology Assessment assessed the sum of evi-dence on spinal manipulative therapy (SMT) in the treat-ment of infantile colic in a systematic review of threerandomized controlled trials. (43) These three trials werebelieved to suffer from significant methodologic flaws.Two (44)(45) of the trials reported SMT to be effectivein treating colic, but the third and largest study (46)found it to be of no benefit (Table 2). At this point, it isnot possible to conclude that chiropractic care is aneffective treatment for colic. More RCTs are needed to

determine the safety and efficacy of chiropractic adjust-ments in treating colic.

OsteopathyThe World Osteopathy Health Organization defines os-teopathy as a “system of healthcare which relies onmanual contact for diagnosis and treatment.” (47) Itemphasizes the structural and functional integrity of thebody and the body’s intrinsic tendency for self-healing.One United Kingdom study has investigated the efficacyof osteopathic treatment for infantile colic. (48) In thisopen, controlled, prospective study, 28 colicky infantswere randomized to receive either individualized cranialosteopathic manipulation by the same osteopath onceweekly for 4 weeks or to receive no treatment (control).Time spent crying, sleeping, and being held or rockedwas recorded in a parent-completed diary. Children inthe osteopathic group had reduced crying (63% com-pared with 23% for controls) and improved sleeping(11% compared with 2% for controls). Children in theintervention group also required less holding/rocking.No adverse events were reported. These findings suggestthat cranial osteopathic treatment benefits some infantswho have colic. Confirmatory, larger clinical trials andcost-benefit analyses are needed before general publicpolicy recommendations about osteopathic treatmentfor colic can be made.

Table 2. Summary of Chiropractic InterventionsAuthors Study Type Population Intervention Control Outcome Adverse Effects

Wiberget al. (45)

Randomizedcontrolled trial

50 infants ages2 to 10 wk

Spinalmanipulativetherapyapplied withlight fingertips

Infants given thedrugdimethicone

At days 8 to 11,crying reducedby 2.7 h intreated groupcompared with1 h in controlgroup (P�0.004)

Symptomsreported tohaveworsened infour infantsfrom thedimethiconegroup

Olafsdottiret al. (46)

Randomizedcontrolled trial

86 infants ages3 to 9 wk

Spinalmanipulativetherapyapplied withlight fingertips

Infants held for10 min by thenurse

No improvement None reported

Merceret al. (44)

Pilot randomizedcontrolled trial

30 infants ages0 to 8 wk

Spinalmanipulativetherapy

Treated with anonfunctionaldetunedultrasonographymachine

Colic symptomsresolved in 93%of infants whohad received upto six treatmentsduring 2 wk

None reported

complementary medicine colic

384 Pediatrics in Review Vol.28 No.10 October 2007

at Umea University Library on November 16, 2014http://pedsinreview.aappublications.org/Downloaded from

MassageA Finnish RCT compared the effectiveness of infantmassage (n�28) with the use of a crib vibrator (n�30) intreating colicky infants younger than 7 weeks of age overa 4-week period. (49) The massage group of infantsreceived parent-administered gentle stroking of the skinover the head, body, and limbs using olive oil and main-taining eye contact three times per day. The crib vibratorwas used for 25-minute periods three times daily on thecontrol group. At the end of the study, parents reportedsimilar reductions in total crying: a mean decrease of 48%in the massage group and 47% in the vibrator group.A 2006 Cochrane Database Systematic Review of theeffectiveness of infant massage in promoting physical andmental health in infants concluded that there is evidenceof benefits on mother-infant interaction, infant sleeping,and crying but noted that more rigorous RCTs areneeded before infant massage can be recommended rou-tinely for treating colic. (50)

Education and Behavioral InterventionsParent education and behavioral management have beenevaluated for treatment of infantile colic. Keefe andassociates (51) demonstrated in an RCT of 121 terminfants (2 to 6 weeks old) that a 4-week home-basedbehavioral intervention was more effective than routinecare in reducing parenting stress. The treatment groupcried, on average, for 1.7 hours less per day than thecontrol group (P�0.02). Dihigo (52) evaluated behav-ior modification in treating colicky infants. Twenty-three

infants were assigned randomly to intervention, nonin-tervention, and control groups. Crying diaries kept bythe parents were used to obtain quantitative measure-ments of crying before and after intervention. Amonginfants whose parents received individualized counselingand education interventions, crying was reduced signifi-cantly from nearly 4 hours to slightly more than 1 hourper child (P�0.05). Parkin and colleagues (53) found nosignificant difference in average daily hours of crying in a2-week RCT comparing three interventions for colic(reassuring mothers, providing mothers with focusedcounseling, and giving infants car ride simulation) in 38mother-infant pairs (mean infant age, 6.8 wk).

ConclusionEvidence from small, often pilot studies indicates poten-tial benefit in integrating specific CAM therapies to treatinfantile colic. Specific therapies that have promise in-clude some natural health products, nutritional modula-tion, cranial osteopathy, infant massage, and parentalbehavioral training. Questions remain regarding boththe safety and efficacy of these therapies for the treatmentof infantile colic. Larger confirmatory trials are needed toassess safety and cost-effectiveness before routine use ofthese therapies for colic can be recommended.

To view references for this article, visitpedsinreview.org and click on this article title.

ClarificationIn the Complementary, Holistic, and Integrative Medicine: Butterbur article that ap-peared in the June 2007 issue of Pediatrics in Review, review of a study that examined theeffects of butterbur treatment in asthma on page 235 states that 50 g of butterbur extractwas administered three times daily. That dose was incorrect. The correct dose is 50 mg.

complementary medicine colic

Pediatrics in Review Vol.28 No.10 October 2007 385

at Umea University Library on November 16, 2014http://pedsinreview.aappublications.org/Downloaded from

DOI: 10.1542/pir.28-10-3812007;28;381Pediatrics in Review 

VohraLawrence D. Rosen, Cecilia Bukutu, Christopher Le, Larissa Shamseer and Sunita

Complementary, Holistic, and Integrative Medicine: Colic

ServicesUpdated Information &

http://pedsinreview.aappublications.org/content/28/10/381including high resolution figures, can be found at:

Subspecialty Collections

http://pedsinreview.aappublications.org/cgi/collection/nutrition_subNutritionubhttp://pedsinreview.aappublications.org/cgi/collection/neonatology_sNeonatology_infant_subhttp://pedsinreview.aappublications.org/cgi/collection/fetus:newbornFetus/Newborn Infanty_-_integrative_medicine_subhttp://pedsinreview.aappublications.org/cgi/collection/complementarComplementary & Integrative Medicineods_-_statistics_subhttp://pedsinreview.aappublications.org/cgi/collection/research_methResearch Methods & Statisticsfollowing collection(s): This article, along with others on similar topics, appears in the

Permissions & Licensing

http://pedsinreview.aappublications.org/site/misc/Permissions.xhtmlin its entirety can be found online at: Information about reproducing this article in parts (figures, tables) or

Reprintshttp://pedsinreview.aappublications.org/site/misc/reprints.xhtmlInformation about ordering reprints can be found online:

at Umea University Library on November 16, 2014http://pedsinreview.aappublications.org/Downloaded from