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Infantile colic: Management and outcome

Official reprint from UpToDate www.uptodate.com 2014 UpToDate

Infantile colic: Management and outcome Authors Teri Lee Turner, MD, MPH, MEd Shea Palamountain, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jan 2014. | This topic last updated: Dez 9, 2013. INTRODUCTION Persistent or excessive crying is one of the most distressing problems of infancy. It is distressing for the infant, the parents, and the clinician [1]. The parents of the infant may view the crying as an indictment of their caregiving ability or as evidence of illness in their child [2]. Colic is a benign, self-limited condition that resolves with time. However, the family's beliefs concerning the cause of crying and their interactions with the healthcare system related to the crying may affect the way in which they view the child and the healthcare system long after the crying has resolved. The management of infantile colic is reviewed here. The clinical features, proposed etiologies, and diagnosis are discussed separately. (See "Infantile colic: Clinical features and diagnosis".) TERMINOLOGY We broadly define colic as crying for no apparent reason (eg, hunger, soiled diaper, etc) that lasts for 3 hours/day and occurs on 3 days per week in an otherwise healthy infant <3 months of age. Stricter definitions include criteria for minimum duration (eg, three weeks) or associated clinical features. Other terms that interchangeable with colic include cry-fuss behavior, excessive crying, unsettled infant behavior, and period of purple crying [3]. (See "Infantile colic: Clinical features and diagnosis", section on 'Definitions'.) NATURAL HISTORY Colic improves spontaneously with time [4-8]. Symptoms resolve in 60 percent of infants by three months of age and in 80 to 90 percent of infants by four months of age [5-8]. The presumptive diagnosis of colic is confirmed after it resolves. MANAGEMENT Overview Management of the otherwise well infant with prolonged or excessive crying is individualized based upon the history, examination, and family characteristics [9,10]. Some parents and families tolerate crying better than others. Interventions are targeted to decrease crying and bolster the infant-family relationship. The goals of management are to help the parents cope with the child's symptoms and to prevent long-term sequelae in the parent-child relationship [11,12]. Parental support is the mainstay of management. First-line interventions consist of addressing feeding problems and suggesting techniques to soothe the infant and/or decrease environmental stimuli. Parents can be encouraged to experiment with these interventions to see which, if any work. Although the evidence supporting first-line interventions is limited, they are inexpensive, unlikely to be harmful, and may be helpful for parents who find it hard to have nothing to do while awaiting spontaneous remission (which confirms the diagnosis) [13]. Several interventions for colic have been evaluated in randomized trials; however, most of the trials had methodologic weaknesses (eg, small sample size, inadequate blinding) [14-18]. The lack of strong supporting evidence for any one strategy, combined with the number of proposed etiologies, may lead practitioners to recommend a variety of interventions, alone or in combination [5]. Each of the soothing techniques may work in some infants, or in a given infant, some of the time, but none of the intervention works all of the time. (See 'Soothing techniques' below.)
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Section Editor Marilyn Augustyn, MD

Deputy Editor Mary M Torchia, MD

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Infantile colic: Management and outcome

The recommendations within this topic are largely consistent with those of the National Institute for Health and Care Excellence Clinical Knowledge Summary for infantile colic [19]. Parental support and education Parental support is the mainstay of the management of colic. It may influence the way the parents view their ability to care for their child. Important aspects of parental education and support include [9,13,19-23]: Education that colic is common and usually resolves spontaneously by three to four months of age (see 'Natural history' above) Reassurance that the infant is not sick; this may require frequent follow-up (either by phone or in person) (see 'Follow-up' below) Education that colic it is not caused by something they are doing or not doing; it does not mean that the infant is rejecting them Acknowledging that the infant is difficult to soothe and that you know that they are doing the best they can; this is essential in preventing the parents from feeling as if they have failed Providing tips for techniques to soothe the baby (see 'Soothing techniques' below) Encouraging the parents to take breaks from the crying infant (eg, taking turns with the infant during the colicky period, asking a relative or friend to babysit so they can have a break, placing the crying infant in his or her crib) and to have a rescue plana prearranged plan in which a relative or friend can step in if the parents feel overwhelmed Acknowledging that feelings of frustration, anger, exhaustion, guilt, and helplessness are normal Clinical studies of parental support/counseling for infantile colic usually find it beneficial [4,24-27]. In a controlled clinical trial, in which parents of colicky infants were counseled regarding effective responses to crying, the crying decreased from 2.6 to 0.8 hours per day [26]. In a randomized trial, parental counseling was more effective than dietary changes (crying decreased from 3.2 to 1.1 hours per day in the counseling group and from 3.2 to 2.0 hours per day in the dietary change group) [25]. Home-based nursing intervention or contact with other parents who have or had infants with colic also may be beneficial. In a randomized trial in 121 infant-family pairs, crying was reduced by 1.7 hours/day in infants following a four-week home-based intervention program (consisting of reassurance, empathy, support, and timeout) compared with infants who received routine care [24]. In another study of 92 mother-infant pairs, specific care suggestions provided by a trained lay counselor was associated with greater reduction in crying (51 percent reduction) than empathetic counseling by a lay counselor (37 percent reduction) or no treatment (35 percent reduction) [27]. First-line interventions As first-line interventions for colic, we suggest changes to the feeding technique and/or experimenting with a number of techniques to soothe the infant [23,28]. These interventions address some of the potential etiologies of colic (eg, swallowed air, overstimulation) and, although the benefits are unproven, the interventions are unlikely to be harmful. Feeding technique Feeding changes may be helpful for infants whose colic is associated with feeding problems (eg, underfeeding, overfeeding, inadequate burping). Bottle-feeding the baby in a vertical position (using a curved bottle) in combination with frequent burping may reduce swallowed air. Using a bottle with a collapsible bag also may help reduce air-swallowing [29]. Changes to breastfeeding technique also may be warranted. However, the management of breastfeeding problems should be individualized; consultation with a lactation specialist may be warranted. (See "Common problems of breastfeeding and weaning".) Soothing techniques We suggest that parents experiment with one or more of the following techniques for soothing the infant and/or decreasing sensory stimulation. They should be instructed to continue those that are helpful and discontinue those that are not [5,13,19].
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Using a pacifier Taking the infant for a ride in the car or a walk in the stroller/buggy Holding the infant or placing them in a front carrier [30] Rocking the infant Changing the scenery (or minimizing visual stimuli) Placing the child in an infant swing Providing a warm bath Rubbing the infants abdomen Hip healthy swaddling (ie, with room for hip flexion, knee flexion, and free movement of the legs [31-33] (see "Developmental dysplasia of the hip: Epidemiology and pathogenesis", section on 'Swaddling') Providing white noise (eg, vacuum cleaner, clothes drier, dishwasher, commercial white noise generator, etc) Playing an audiotape of heartbeats These interventions are suggested by experts [5,13,19]. They have not been proven effective in randomized trials, but are inexpensive, unlikely to be harmful, involve the parents, and may help to reduce parental or infant anxiety [4,13,14,18,19]. In a large observational study, holding, walking, and rocking were found to be effective in calming breastfed infants (with or without colic) younger than 16 weeks [34]. Second-line interventions A time-limited trial of second-line interventions may be warranted for infants who do not respond to first-line interventions [19]. Second-line interventions vary depending upon whether the infant is formula-fed or breast-fed. Formula-fed infants A one-week trial of an extensive hydrolysate infant formula (eg, Alimentum, Nutramigen, Pregestimil) is an option for formula-fed infants with colic that has not responded to first lineinterventions. A subgroup of infants with colic may have an allergy or intolerance to cows milk formula, although infants with allergy or intolerance usually have associated clinical features (eg, bloody stool, vomiting, rash, etc). (See "Milk allergy: Clinical features and diagnosis", section on 'Clinical features' and "Food protein-induced enterocolitis syndrome (FPIES)", section on 'Clinical features' and "Introducing formula and solid foods to infants at risk for allergic disease", section on 'Types of formulas'.) Hydrolysate formula may be continued if there is a decrease in crying/fussiness. The response usually occurs within 48 hours [35]. The original formula is resumed if there is no change in the infant's symptoms (hydrolysate formulas more expensive than cow's-milk-based formulas). Two 2012 systematic reviews of small randomized trials with methodologic limitations suggest that hydrolysate formulas may reduce distress in infants with colic [15,17]. Additional studies are necessary to confirm these results. Breastfed infants A time-limited trial of a decrease in maternal milk product consumption or a hypoallergenic maternal diet (eg, no milk, eggs, nuts, wheat) is an option for breast-fed infants with colic that has not responded to first-line interventions and whose parents have difficulty coping. A subgroup of infants with colic may have food allergy or allergy to cows milk, although infants with allergy usually have associated clinical features (eg, rash, wheezing). Maternal dietary changes may be particularly beneficial if the mother is atopic or the baby has symptoms of cow's-milk allergy (eg, eczema, wheezing, diarrhea, or vomiting) [36]. (See "Milk allergy: Clinical features and diagnosis", section on 'Clinical features'.) Two 2012 systematic reviews of small randomized trials with methodologic limitations suggest that a hypoallergenic diet may reduce distress in infants with colic [15,17]. Additional studies are necessary to confirm these results. Other interventions A number of other interventions for infantile colic have been evaluated in randomized trials with methodologic weaknesses or inconsistent results. Given these limitations, we generally do not suggest these interventions for infantile colic. However, they may be suggested for some patients on a case-bycase basis after a discussion of the potential risks and benefits. Probiotics Although the data are insufficient to recommend probiotics for the routine management of
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colic, especially in formula-fed infants, we occasionally suggest probiotics (specifically Lactobacillus reuteri) on a case-by-case basis for breast-fed infants with colic. A 2013 systematic review of five trials of the efficacy of probiotics in reducing crying found inconsistent results, depending upon probiotic strain and feeding method [37]: Three trials [38-40] concluded that L. reuteri is effective in breast-fed infants; meta-analysis of these trials (209 infants) found that L. reuteri reduced median crying time by 65 minutes (95% CI 44 to 86 minutes) at 21 days compared with baseline One trial concluded that L. rhamnosus is not effective for breast-fed infants [41] One trial concluded that L. rhamnosus is possibly effective for formula-fed infants [42] Seven trials (1554 infants) that evaluated the effectiveness of probiotics in preventing colic also had inconsistent results (two suggested possible benefit; five found no difference) [37]. Soy protein formula We do not suggest changing from cows milk to soy protein formula for formula-fed infants with colic. The benefits of soy versus cows milk protein in the prevention and management of colic are unproven [43]. Studies comparing the effects of soy and hypoallergenic formulas on the reduction of colicky symptoms are lacking. Based on four small randomized trials with methodologic limitations (eg, inadequate blinding) [35,44-46], a 2012 systematic review concluded that soy protein formulas may improve colic symptoms, but additional studies are necessary [15]. Neither the American Academy of Pediatrics Committee on Nutrition nor the National Institute for Health and Care Excellence recommend soy protein formula for the treatment of infantile colic [19,43]. Fiber-enriched formula We do not suggest fiber-enriched formulas for formula-fed infants with colic. In a randomized cross-over trial in 27 term infants in which the investigators were blinded but the parents were not, fiber supplementation of soy-protein formula did not affect the average daily duration of crying [47]. However, the parents of 18 infants found the fiber-supplemented formula beneficial in alleviating colic symptoms. Lactase We do not suggest lactase for the treatment of infantile colic. The benefits of lactase remain unproven. Randomized trials of lactase treatment for infantile colic have conflicting results [48-51]. The National Institute for Health and Care Excellence Clinical Knowledge Summary for infantile colic suggests a one-week trial of lactase as an option for infants of parents who feel unable to cope despite advice and reassurance [19]. Sucrose We do not suggest sucrose for the treatment of colic. Although oral sucrose appears to reduce some types of pain in neonates, the evidence that it is beneficial in reducing crying in colicky infants is limited. (See "Prevention and treatment of neonatal pain", section on 'Oral sucrose'.) In a randomized crossover trial in 19 infants, 12 improved subjectively with sucrose [52]. However, the effect was short-lived (30 minutes to 1 hour maximum). A separate case-control study found that the duration of response of colicky infants to sucrose was3 minutes [53]. Infant massage We do not suggest infant massage for the treatment of infantile colic. A 2010 systematic review found no evidence of benefit and the potential harm of unsettling or over-stimulating colicky infants [18]. In a randomized trial comparing four weeks of treatment with infant massage and a crib vibrator, crying decreased from baseline in both groups [54]. The authors attributed the decrease in crying to the natural course of colic (ie, resolution by three to four months of age) rather than to the specific interventions. Simethicone We do not suggest simethicone for the treatment of infantile colic. Simethicone is a medication that causes gas bubbles to coalesce, facilitating expulsion [21]. However, a 2012 systematic review of small randomized trials with conflicting results [55-57] found little evidence to support its use in the treatment of infantile colic [17]. Simethicone is generally considered to be safe, but it may interact with levothyroxine in
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infants being treated for congenital hypothyroidism resulting in hypothyroidism [58]. The National Institute for Health and Care Excellence Clinical Knowledge Summary for infantile colic suggests a one-week trial of simethicone as an option for infants of parents who feel unable to cope despite advice and reassurance [19]. Herbal remedies We do not suggest herbal remedies (eg, herbal teas, fennel seed, Gripe water [a mixture of herbs and water]) for the treatment of infantile colic. Although a few randomized trials suggest that specific herbal remedies may be beneficial in reducing crying compared with placebo [59-61], the benefits are largely unproven. Given the lack of standardization and regulation of herbal products, the benefits do not outweigh the potential risks (eg, contamination with bacteria, toxins, or particulate matter; unlabeled ingredients, such as alcohol) [62,63]. Prolonged ingestion of herbal teas may lead to decreased milk intake [61]. Homeopathic remedies We do not suggest homeopathic remedies for the treatment of colic. They have not been proven to be effective. Homeopathic remedies often are considered nontoxic because of the low concentrations of active ingredients. However, the labels of homeopathic products may not report all of the ingredients, some of which may have toxic effects [64]. As an example, gas chromatography-mass spectrometry analysis of a homeopathic remedy for colic that was associated with an increased risk of apparent life-threatening events found that it contained ethanol, propanol, and pentanol, in addition to three potentially toxic substances that were listed as active ingredients (colocynthis [bitter apple], Veratrum album [white hellebore], and strychnos nux-vomica [strychnine tree]) [65]. Colocynthis is also found in Cocyntal and Hyland colic tablets. Manipulative therapies We do not suggest manipulative therapies (eg, chiropractic, osteopathy, cranial manipulation) for the treatment of colic. A 2012 meta-analysis of six randomized trials (325 infants) concluded that methodologic limitations preclude definitive conclusions about the effectiveness or safety of manipulative therapies for infantile colic [16]. Follow-up The frequency of follow-up for colicky infants is individualized. Some infants and families may require frequent follow-up (by phone or in person) and reexamination to be reassured that the infant is continuing to do well and growing normally [5]. Other infants, whose parents are coping well and have strong support networks can be seen less frequently (eg, at regularly scheduled health maintenance visits). In all cases, parents should be counseled to return if the infant develops symptoms that were not present during the initial evaluation (eg, vomiting, rash). INDICATIONS FOR REFERRAL Most infants with colic can be managed by the primary care provider. Referral to a developmental behavioral pediatrician or mental health provider may be warranted for parents who are extremely anxious or in need of additional reassurance [28]. OUTCOMES Parents of colicky infants experience stress, fatigue, guilt, and depression [66]. Some researchers have postulated that colic may disturb the child-parent interaction and thus have long-term effects on the family and child [67]. However, the data on the sequelae of colic are conflicting. Temperament and behavior Several studies show that temper tantrums are more common among formerly colicky infants. In two follow-up studies, parents of formerly colicky infants reported more frequent temper tantrums at three and four years of age than parents of control children [67,68]. In a meta-analysis of longitudinal studies, the risk of behavior problems in later childhood was increased when colic persisted at five months of age [69]. The risk was greatest when persistent colic was accompanied by other regulatory problems (eg, feeding, sleeping) and psychosocial risk factors, which makes it difficult to establish a causal relationship [3]. Parents of formerly colicky children perceive their toddlers' temperaments as more difficult than parents of noncolicky children. In a follow-up study, parents described their formerly colicky children as more emotional at age four years (eg, "cries easily" or "tends to be somewhat upset") than noncolicky infants [68]. Mothers in another one-year follow-up survey also rated their formerly colicky children as more difficult [70]. However, these children did not differ from control children according to the Toddler Temperament Scale. The discrepancy
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between the mother's perception of the child's temperament and the child's actual temperament may reflect the long-term effects of colic on mother-child interaction [71]. Another possibility is that factors that predispose an infant to colic also cause problems with mother-child interactions. In a prospective study, 48 infants (31 to 87 days of age) who were hospitalized with severe colic and 48 infants without chronic or severe illness who were hospitalized for problems unrelated to colic, gastrointestinal, allergic, or psychologic disease were followed up with at 10 years of age [72]. Fussiness, aggressiveness, and feelings of supremacy were reported more often by the parents of colicky infants than of controls. Sleep patterns Prospective studies regarding the relationship between colic and the development of childhood sleep problems have conflicting results [67,72-75]. The conflicting results may reflect differences in parental perception or in parent-child interaction for parents of children with and without histories of colic. Family functioning Studies also differ regarding the effects of colic on family functioning. In a case-control study, family functioning was assessed at one year of age in families of infants with and without colic [70]. Families in the severe colic group had more difficulties in communication, unresolved conflicts, dissatisfaction, and lack of empathy and flexibility. However, another case-control study, performed when the child was three years old, found no difference in family psychological characteristics between case and control families [73]. Perhaps the effects of colic on family functioning are present early on but do not persist to three years of age. Asthma and atopy Prospective studies evaluating the development of asthma and atopy among infants with colic have conflicting results. In a study in which 983 infants were followed from infancy through 11 years of age, the prevalence of colic was approximately 9 percent; no association was found between infantile colic and asthma, allergic rhinitis, peak flow variability, or markers of atopy (total serum immunoglobulin E and allergy skin prick test) at any age [76]. In a subsequent smaller study with shorter follow-up, there was an association between infantile colic and allergic disorders (eg, allergic rhinitis, atopic eczema, food allergy) [72]. Cognitive development Colic does not appear to influence long-term cognitive development. In a prospective study of 327 children, approximately 15 percent had a history of colic (defined as "daily uncontrolled crying without any obvious cause, persisting for at least two weeks"), and 5 percent had a history of prolonged crying (colic-like crying that was reported at both 6 and 13 weeks) [77]. At five years of age, adjusted mean intelligence quotient (IQ) scores were similar among children with and without a history of colic. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topic (see "Patient information: Colic (The Basics)") Beyond the Basics topic (see "Patient information: Colic (excessive crying) in infants (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS We broadly define colic as crying for no apparent reason (eg, hunger, soiled diaper, etc) that lasts for 3 hours/day and occurs on 3 days per week in an otherwise healthy infant <3 months of age. (See 'Terminology' above.) Colic symptoms resolve spontaneously in 60 percent of infants by three months of age and in 80 to 90 percent of infants by four months of age. (See 'Natural history' above.) Management of colic is individualized based upon the history, examination, and family characteristics. The
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goals are to help the parents cope with the child's symptoms and to prevent long-term sequelae in the parent-child relationship. Parental support is the mainstay of the management. (See 'Overview' above and 'Parental support and education' above.) Beyond parental support, we suggest changes to feeding technique and/or experimenting with a number of techniques to soothe the infant (eg, rubbing the infants abdomen, providing white noise, etc) as first-line interventions (Grade 2C). (See 'First-line interventions' above.) A time-limited trial of second-line interventions (a trial of hydrolysate formula for formula-fed infants or hypoallergenic diet for mothers of breastfed infants) may be helpful for infants who do not respond to firstline interventions. (See 'Second-line interventions' above.) A number of other interventions for infantile colic have been evaluated in randomized trials with methodologic weaknesses or inconsistent results (eg, probiotics, soy protein or fiber enriched infant formulas, simethicone, herbal teas, etc). Given these limitations, we generally do not use these interventions for infantile colic. However, they may be tried on a case-by-case basis after a discussion of the potential risks and benefits. (See 'Other interventions' above.) The frequency of follow-up for colicky infants is individualized. Some infants and families may require frequent (ie, weekly or bi-weekly) follow-up for reassurance, whereas other infants, whose parents are coping well and have strong support networks, can be seen less frequently. (See 'Follow-up' above.) The data on the sequelae of colic with respect to temperament, behavior, sleep patterns, family functioning, asthma, and atopy are conflicting. However, colic does not appear to be related to cognitive development. (See 'Outcomes' above.) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Taubman B. A new answer to the old question of colic. Contemp Pediatr 1991; 8:44. 2. Lehtonen LA, Rautava PT. Infantile colic: natural history and treatment. Curr Probl Pediatr 1996; 26:79. 3. Douglas P, Hill P. Managing infants who cry excessively in the first few months of life. BMJ 2011; 343:d7772. 4. Parkin PC, Schwartz CJ, Manuel BA. Randomized controlled trial of three interventions in the management of persistent crying of infancy. Pediatrics 1993; 92:197. 5. Parker S, Magee T. Colic. In: The Zuckerman Parker Handbook of Developmental and Behavioral Pediatrics for Primary Care, 3rd ed, Augustyn M, Zuckerman B, Caronna EB (Eds), Lippincott Williams & Wilkins, Philadelphia 2011. p.182. 6. St James-Roberts I, Halil T. Infant crying patterns in the first year: normal community and clinical findings. J Child Psychol Psychiatry 1991; 32:951. 7. BRAZELTON TB. Crying in infancy. Pediatrics 1962; 29:579. 8. St James-Roberts I. Persistent infant crying. Arch Dis Child 1991; 66:653. 9. Fleisher DR. Coping with colic. Contemp Pediatr 1998; 15:144. 10. Drug and Therapeutics Bulletin. Management of infantile colic. BMJ 2013; 347:f4102. 11. Lester BM. Definition and diagnosis of colic. In: Colic and Excessive Crying. Report of the 105th Ross Conference on Pediatric Research, Lester BM, Barr RG (Eds), Ross Products Division, Columbus, OH 1997. p.18. 12. Stifter CA, Bono MA. The effect of infant colic on maternal self-perceptions and mother-infant attachment. Child Care Health Dev 1998; 24:339. 13. Hiscock H. The crying baby. Aust Fam Physician 2006; 35:680. 14. Garrison MM, Christakis DA. A systematic review of treatments for infant colic. Pediatrics 2000; 106:184. 15. Iacovou M, Ralston RA, Muir J, et al. Dietary management of infantile colic: a systematic review. Matern
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Child Health J 2012; 16:1319. 16. Dobson D, Lucassen PL, Miller JJ, et al. Manipulative therapies for infantile colic. Cochrane Database Syst Rev 2012; 12:CD004796. 17. Hall B, Chesters J, Robinson A. Infantile colic: a systematic review of medical and conventional therapies. J Paediatr Child Health 2012; 48:128. 18. Lucassen P. Colic in infants. Clin Evid (Online) 2010; 2010. 19. National Institute for Health and Care Excellence. Colic - infantile. http://cks.nice.org.uk/colic-infantile (Accessed on October 01, 2013). 20. Weissbluth M. Is there a treatment for colic?. In: Colic and Excessive Crying. Report of the 105th Ross Conference on Pediatric Research, Lester BM, Barr RG (Eds), Ross Products Division, Columbus, OH 1997. p.119. 21. Cohen-Silver J, Ratnapalan S. Management of infantile colic: a review. Clin Pediatr (Phila) 2009; 48:14. 22. Cohen GM, Albertini LW. Colic. Pediatr Rev 2012; 33:332. 23. Carey WB. The effectiveness of parent counseling in managing colic. Pediatrics 1994; 94:333. 24. Keefe MR, Lobo ML, Froese-Fretz A, et al. Effectiveness of an intervention for colic. Clin Pediatr (Phila) 2006; 45:123. 25. Taubman B. Parental counseling compared with elimination of cow's milk or soy milk protein for the treatment of infant colic syndrome: a randomized trial. Pediatrics 1988; 81:756. 26. Taubman B. Clinical trial of the treatment of colic by modification of parent-infant interaction. Pediatrics 1984; 74:998. 27. Wolke D, Gray P, Meyer R. Excessive infant crying: a controlled study of mothers helping mothers. Pediatrics 1994; 94:322. 28. Baum R. Colic. In: American Academy of Pediatrics Textbook of Pediatric Care, McInerny TK, Adam HM, Campbell DE, et al. (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2009. p.1931. 29. Balon AJ. Management of infantile colic. Am Fam Physician 1997; 55:235. 30. Barr RG, McMullan SJ, Spiess H, et al. Carrying as colic "therapy": a randomized controlled trial. Pediatrics 1991; 87:623. 31. van Sleuwen BE, L'hoir MP, Engelberts AC, et al. Comparison of behavior modification with and without swaddling as interventions for excessive crying. J Pediatr 2006; 149:512. 32. van Sleuwen BE, Engelberts AC, Boere-Boonekamp MM, et al. Swaddling: a systematic review. Pediatrics 2007; 120:e1097. 33. Ohgi S, Akiyama T, Arisawa K, Shigemori K. Randomised controlled trial of swaddling versus massage in the management of excessive crying in infants with cerebral injuries. Arch Dis Child 2004; 89:212. 34. Howard CR, Lanphear N, Lanphear BP, et al. Parental responses to infant crying and colic: the effect on breastfeeding duration. Breastfeed Med 2006; 1:146. 35. Lothe L, Lindberg T, Jakobsson I. Cow's milk formula as a cause of infantile colic: a double-blind study. Pediatrics 1982; 70:7. 36. Schmitt BD. Crying Baby (Colic). In: Instructions for Pediatric Patients, 1st ed, WB Saunders, Philadalphia 1992. p.141. 37. Sung V, Collett S, de Gooyer T, et al. Probiotics to prevent or treat excessive infant crying: systematic review and meta-analysis. JAMA Pediatr 2013; 167:1150. 38. Savino F, Pelle E, Palumeri E, et al. Lactobacillus reuteri (American Type Culture Collection Strain 55730) versus simethicone in the treatment of infantile colic: a prospective randomized study. Pediatrics 2007; 119:e124. 39. Savino F, Cordisco L, Tarasco V, et al. Lactobacillus reuteri DSM 17938 in infantile colic: a randomized, double-blind, placebo-controlled trial. Pediatrics 2010; 126:e526. 40. Szajewska H, Gyrczuk E, Horvath A. Lactobacillus reuteri DSM 17938 for the management of infantile colic in breastfed infants: a randomized, double-blind, placebo-controlled trial. J Pediatr 2013; 162:257. 41. Mentula S, Tuure T, Koskenala R, et al. Microbial composition and fecal fermentation end products from colicky infants - A probiotic supplementation pilot. Microb Ecol Health Dis 2008; 20:37. 42. Dupont C, Rivero M, Grillon C, et al. Alpha-lactalbumin-enriched and probiotic-supplemented infant formula
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