title: Effect of a Low-Allergen Maternal Diet on Colic Among Breastfed Infants: A Randomized, Controlled Trial Lactobacillus reuteri DSM 17938 for the management of infantile colic in breastfed infants: a randomized, double-blind, placebo-controlled trial. Tolerance and safety of Lactobacillus paracasei ssp. paracasei in combination with Bifidobacterium animalis ssp. lactis in a prebiotic-containing infant formula: a randomised controlled trial. Lactobacillus reuteri (American Type Culture Collection Strain 55730) Versus Simethicone in the Treatment of Infantile Colic: A Prospective Randomized Study An α-lactalbumin-enriched and symbiotic-supplemented v. a standard infant formula: a multicentre, double-blind, randomised trial. Treatment of Infantile Colic with Surface Active Substance (Simethicone) Health and well-being in school-age children following persistent crying in infancy. Probiotic Intervention in the First Months of Life: Short-Term Effects on Gastrointestinal Symptoms and Long-Term Effects on Gut Microbiota Safety and Tolerance of a Probiotic Formula in Early Infancy Comparing Two Probiotic Agents: A Pilot Study Growth during the first 6 months of life in infants using formula enriched with Lactobacillus rhamnosus GG: double-blind, randomized trial. Effectiveness of casein hydrolysate feedings in infants with colic Infantile colic: crying time reduction with a whey hydrolysate: A double-blind, randomized, placebo-controlled trial. Long-Term Safety and Impact on Infection Rates of Postnatal Probiotic and Prebiotic (Synbiotic) Treatment: Randomized, Double-Blind, Placebo-Controlled Trial A prospective 10-year study on children who had severe infantile colic. The effects of probiotics on feeding tolerance, bowel habits, and gastrointestinal motility in preterm newborns. Lactobacillus reuteri DSM 17938 in Infantile Colic: A Randomized, Double-Blind, Placebo-Controlled Trial
abstract: Background . There is controversy regarding whether hypersensitivity to food proteins contributes to colic among breastfed infants . Methods . A r and omized , controlled trial of a low-allergen maternal diet was conducted among exclusively breastfed infants presenting with colic . In the active arm , mothers excluded cow 's milk , eggs , peanuts , tree nuts , wheat , soy , and fish from their diet ; mothers in the control group continued to consume these foods . Outcomes were assessed after 7 days , as the change in cry/fuss duration over 48 hours , with vali date d charts . The primary end point was a reduction in cry/fuss duration of ≥25 % from baseline . Mothers also assessed the responses to diet with categorical and visual analog scales . Results . Of 107 infants , 90 completed the trial ( mean age : 5.7 weeks ; range : 2.9–8.6 weeks ; 54 male infants ) . Infants in both groups presented with significant distress ( geometric mean : low-allergen group : 690 minutes per 48 hours ; control group : 631 minutes per 48 hours ) . In follow-up assessment s on days 8 and 9 , there were significantly more responders in the low-allergen group ( 74 % vs 37 % ) , ie , an absolute risk reduction of 37 % ( 95 % confidence interval : 18–56 % ) . Cry/fuss duration per 48 hours was reduced by a substantially greater amount in the low-allergen group ; the adjusted geometric mean ratio was 0.79 ( 95 % confidence interval : 0.63–0.97 ) , ie , an average reduction of 21 % ( 95 % confidence interval : 3–37 % ) . Mothers ' subjective assessment s of the responses to diet indicated little difference between the groups . Conclusion . Exclusion of allergenic foods from the maternal diet was associated with a reduction in distressed behavior among breastfed infants with colic presenting in the first 6 weeks of life OBJECTIVE To determine whether administration of Lactobacillus reuteri ( L reuteri ) DSM 17938 is beneficial in breastfed infants with infantile colic . STUDY DESIGN Eighty infants aged < 5 months with infantile colic ( defined as crying episodes lasting 3 or more hours per day and occurring at least 3 days per week within 7 days prior to enrollment ) , who were exclusively or predominantly ( > 50 % ) breastfed were r and omly assigned to receive L reuteri DSM 17938 ( 10(8 ) colony-forming units ) ( n = 40 ) or an identically appearing and tasting placebo ( n = 40 ) , both orally , in 5 drops , 1 time daily , for 21 days . The primary outcome measures were the treatment success , defined as the percentage of children achieving a reduction in the daily average crying time ≥ 50 % , and the duration of crying ( minutes per day ) at 7 , 14 , 21 , and 28 days after r and omization . RESULTS The rate of responders to treatment was significantly higher in the probiotic group compared with the placebo group at day 7 ( P = .026 ) , at day 14 ( relative risk ( RR ) 4.3 , 95 % CI 2.3 - 8.7 ) , at day 21 ( RR 2.7 , 95 % CI 1.85 - 4.1 ) , and at day 28 ( RR 2.5 , 95 % CI 1.8 - 3.75 ) . In addition , throughout the study period , the median crying time was significantly reduced in the probiotic group compared with the control group . CONCLUSION Exclusively or predominantly breastfed infants with infantile colic benefit from the administration of L reuteri DSM 17938 compared with placebo The addition of probiotics to infant formula has been shown to be an efficient way to increase the number of beneficial bacteria in the intestine in order to promote a gut flora resembling that of breast-fed infants . The objective of the present study was to evaluate the safety and tolerance of a combination of two probiotic strains in early infancy . A group of 126 newborns were r and omised to receive a prebiotic-containing starter formula supplemented with Lactobacillus paracasei ssp . paracasei and Bifidobacterium animalis ssp . lactis or the same formula without probiotics for the first 3 months of life . A total of eighty infants continued the study until they were aged 6 months .  Growth measurements were taken monthly at healthy baby clinics . Diaries were used to monitor behaviour , infections , use of antibiotics , as well as stool characteristics . Normal growth occurred in all infants and no statistically significant differences were detected between the probiotics group and the control group for gain in weight , length and head circumference . Infants in the probiotics group produced softer and more frequent stools during the first 3 months of life . No differences were found in crying and sleeping hours , number of parent-diagnosed infections , antibiotic use , visits to the general practitioner and number of adverse events . The use of a prebiotic-containing starter formula supplemented with L. paracasei ssp . paracasei and B. animalis ssp . lactis in early infancy is safe , well tolerated and has no adverse effects on growth and infant behaviour OBJECTIVE . The goal was to test the hypothesis that oral administration of Lactobacillus reuteri in a prospect i ve r and omized study would improve symptoms of infantile colic .  METHODS . Ninety breastfed colicky infants were assigned r and omly to receive either the probiotic L reuteri ( 108 live bacteria per day ) or simethicone ( 60 mg/day ) each day for 28 days . The mothers avoided cow 's milk in their diet . Parents monitored daily crying times and adverse effects by using a question naire . RESULTS . Eighty-three infants completed the trial : 41 in the probiotic group and 42 in the simethicone group . The infants were similar regarding gestational age , birth weight , gender , and crying time at baseline . Daily median crying times in the probiotic and simethicone groups were 159 minutes/day and 177 minutes/day , respectively , on the seventh day and 51 minutes/day and 145 minutes/day on the 28th day . On day 28 , 39 patients ( 95 % ) were responders in the probiotic group and 3 patients ( 7 % ) were responders in the simethicone group . No adverse effects were reported . CONCLUSIONS . In our cohort , L reuteri improved colicky symptoms in breastfed infants within 1 week of treatment , compared with simethicone , which suggests that probiotics may have a role in the treatment of infantile colic The aim of the present study was to evaluate the safety , tolerance and preventive effect on atopic dermatitis of an experimental α-lactalbumin-enriched and symbiotic-supplemented infant formula . A total of ninety-seven non-breastfed term neonates were enrolled into a double-blind , multicentre , r and omised controlled trial in which they received experimental ( n 48 ) or st and ard formula ( n 49 ) for 6 months . The primary outcome was weight at 6 months of age . Secondary outcomes were gastrointestinal tolerance and manifestation of atopic dermatitis . Faecal secretory IgA ( SIgA ) concentration and microbiota composition of forty-three infants were analysed at 1 and 6 months . Growth was similar in both groups . At 1 month , compared to those in the control group , infants in the experimental group exhibited less crying or agitation , and more quiet behaviour ( P=0·03 ) . At 6 months , atopic dermatitis was less frequently observed in the experimental group ( P<0·05 ) . Decrease of faecal SIgA concentration between 1 and 6 months was mainly observed in the control group . This decrease was significantly associated with atopic dermatitis ( P<0·014 ) and negatively correlated to the level of colonisation by bifidobacteria ( P<0·005 ) . In conclusion , compared to the control formula , the experimental formula guaranteed a similar growth , was better tolerated at 1 month and had a protective effect against the development of atopic dermatitis ABSTRACT . The effect of Simethicone on  “ colicky ” ( n=27 ) infants was tested in a double‐blind cross‐over study . Three different parameters were used to measure the efficiency of the treatment : interviews , 24‐hour records and behavioral observations . No effects of Simethicone on the symptoms of infantile colic could be demonstrated . However , 67 % of the infants improved during the treatment , which could be ascribed to a high‐ grade placebo‐effect AIM To examine the physical and mental health outcomes at school-age of a cohort of children who participated in a r and omised clinical trial of treatments for persistent crying in infancy . METHODS Participants and parents attended for a st and ard physical examination and clinical mental health assessment of the children . Parents completed the  Strength and Difficulties Question naire ( SDQ ) , Child Health Question naire ( CHQ ) , Forsyth Child Vulnerability Scale , Recent Life Events Question naire , R AND -36 Health Status Inventory and a study question naire about medical and socio-demographic characteristics . RESULTS Seventy-five of 127 ( 59 % ) traced infant-parent dyads participated . There were no significant differences in baseline demographic characteristics , infant crying or maternal stress between those who participated and those who declined . Mothers who participated had higher Edinburgh Postnatal Depression Scale scores . The study group had poorer mental health , as measured on the SDQ , than a community sample ( 26.3 % vs. 9.9 % abnormal cases , risk ratio 2.56 ( confidence interval 1.72 , 3.80 ) ) . Fifteen of 61 ( 24.6 % ) children who attended for the clinical mental health assessment met Diagnostic and Statistical Manual of Mental Disorders , 4th edition , criteria for a mental disorder . In the 4 weeks preceding the assessment , the child 's health limited family activities more than in a community sample ( CHQ-Family Activities ; P < 0.001 ) . Parents had less time for personal needs compared with community norms ( CHQ-Parent Time ; P < 0.001 ) and were more likely to worry about their child 's health ( CHQ-Parent E ; P < 0.001 ) . CONCLUSION At school-age , children with a history of hospitalisation for persistent crying in infancy had a significantly higher prevalence of mental health problems and mental disorders , as compared with community sample Objectives : To determine whether probiotics administered for 6 months postnatally affect  gastrointestinal symptoms , crying  and the compositional development of the gut microbiota through infancy . Methods : The study comprised of 132 newborns whose mothers were r and omized to receive placebo or Lactobacillus rhamnosus GG ( ATCC 53103 ) before delivery . The treatments of mothers/infants continued for 6 months postnatally . A specific symptom chart was used to monitor gastrointestinal symptoms and infant 's crying during the 7th and the 12th weeks of life . Fluorescent in situ hybridization was used to establish the Bifidobacterium , Lactobacillus/Enterococcus , Bacteroides and Clostridium counts in fecal sample s at 6 , 12 , 18 and 24 months of age . Results : Numbers of different types of stools , vomits and crying time were comparable between the groups during the 7th and the 12th weeks of life . Dominant microbiota consisted of bifidobacteria throughout the study . At 6 months , there were less clostridia in faeces in the placebo compared with the probiotic group ( P = 0.026 ) , whereas after long-term follow-up at 2 years , there were less lactobacilli/enterococci and clostridia in faeces in the probiotic group than in the placebo group ( P = 0.011 and P = 0.032 , respectively ) , reflecting the impact of clostridia as a marker of microbiota succession in healthy infants . Conclusions : Probiotic administration in the first months of life was well tolerated and did not significantly interfere with long-term composition or quantity of gut microbiota Objective : To compare the safety and tolerance of two formulas , supplemented with different probiotic agents , in early infancy . Design : Prospect i ve r and omized placebo-controlled trial . Setting : Clinics of a University Medical Center . Subjects : Full-term healthy infants aged less than 4 months . Intervention : Infants were r and omly assigned for 4 weeks to a st and ard milk-based formula supplemented with either Bifidobacterium lactis ( BB-12 ) , Lactobacillus reuteri ( ATCC 55730 ) or a probiotics-free formula . Measures of Outcome : Growth parameters , daily characteristics of feeding , stooling and behavior , and side effects . Results : Fifty-nine infants , aged 3–65 days , were included . Subjects in all three groups were similar at entry in terms of gestational age , birth weight , sex , growth parameters and breast feeding rate prior to the study . The supplemented formulas were well accepted and did not reveal any adverse effects . A comparison of growth parameters , and variables of feeding , stooling and crying and irritability did not reveal any significant differences between groups . Conclusions : The use of formula supplemented with either Lactobacillus reuteri or Bifidobacterium lactis in early infancy , was safe , well tolerated and did not adversely affect growth , stooling habits or infant behavior BACKGROUND Probiotic bacteria have beneficial effects on the immune system and gastrointestinal tract , but the impacts of their long-term consumption on health and growth in early infancy are not well documented . The aim of this study was to evaluate the influence of Lactobacillus rhamnosus GG (LGG)-enriched formula on growth and faecal microflora during the first 6 months of life in normal healthy infants . MATERIAL S AND METHODS One hundred and twenty healthy infants ( up to 2 months ) received LGG-supplemented formula or regular formula in a double-blind , r and omized manner until the age of 6 months . Weight , length and head circumference were measured monthly and transformed into st and ard deviation scores ( SDS ) . Faecal sample s were obtained from a r and om sample of infants ( n=25 ) at entry and at the end of the study . RESULTS One hundred and five infants ( 51 in the LGG group ) completed the study . Children receiving LGG-supplemented formula grew better : their changes in their length and weight SDS ( DeltaSDS ) at the end of the study were significantly higher than those receiving regular formula ( 0.44+/- 0.37 versus 0.07+/- 0.06 , P < 0.01 and 0.44+/- 0.19 versus 0.07+/- 0.06 , P < 0.005 , respectively ) . The LGG group had a significant , higher defecation frequency 9.1+/-2.06 versus 8.0+/- 2.8 ( P<0.05 ) . More frequent colonization with lactobacilli was found in the LGG group , 91 % versus 76 % ( P<0.05 ) at the end of the study . CONCLUSIONS Infants fed with LGG-enriched formula grew better than those fed with regular formula . Further studies are necessary to clarify the mechanism of LGG in infant growth This study found that two casein hydrolysate formulas varying in composition were equally effective in managing  colicky symptoms associated with protein sensitivity . Both hydrolysate formulas were associated with a significant , comparable reduction in crying duration and intensity from baseline in 15 of 22 infants with complete data . Subsequent challenge data suggest that the population studied were infants experiencing colicky symptoms due to protein sensitivity . A greater proportion of infants showed a positive reaction ( ≥1.5h of crying/d ) to the protein challenges than the placebo challenge , and crying was rated as more intense during whey and milk protein challenges OBJECTIVE To determine the effectiveness of whey hydrolysate formula in the treatment of infantile colic in a primary care setting in the Netherl and s. STUDY DESIGN R and omized , double-blind , parallel trial with a 1-week qualification period and a 1-week intervention period . Participants . Forty-three healthy , thriving , formula-fed infants , < 6 months old , crying > 3 hours per day on at least 3 days per week . Infants were r and omized to whey hydrolysate formula ( n = 23 ) or st and ard formula ( n = 20 ) . MAIN OUTCOME MEASURE Difference in duration of crying ( minutes per day ) between qualification week and intervention week . RESULTS Analysis according to the intention to treat principle showed a difference in the decrease of crying duration of 63 minutes per day [ 95 % confidence interval : 1 - 127 minutes per day ] in favor of the whey hydrolysate formula .  Five infants did not complete the trial . The scope of the study was not sufficient to expect significant differences in the subgroup analyses . CONCLUSIONS An extensively hydrolyzed whey formula is effective in reducing the duration of crying in a primary care setting OBJECTIVE . Live probiotic bacteria and dietary prebiotic oligosaccharides ( together termed synbiotics ) increasingly are being used in infancy , but evidence of long-term safety is lacking . In a r and omized , placebo-controlled , double-blind trial , we studied the safety and long-term effects of feeding synbiotics to newborn infants . METHODS . Between November 2000 and March 2003 , pregnant mothers carrying infants at high risk for allergy were r and omly assigned to receive a mixture of 4 probiotic species ( Lactobacillus rhamnosus GG and LC705 , Bifidobacterium breve Bb99 , and Propionibacterium freudenreichii ssp shermanii ) or a placebo for 4 weeks before delivery . Their infants received the same probiotics with 0.8 g of galactooligosaccharides , or a placebo , daily for 6 months after birth . Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3 , 6 , and 24 months and from question naires at ages 3 , 6 , 12 , and 24 months . Growth data were collected at each time point . RESULTS . Of the 1018 eligible infants , 925 completed the 2-year follow-up assessment . Infants in both groups grew normally . We observed no difference in neonatal morbidity , feeding-related behaviors ( such as infantile colic ) , or serious adverse events between the study groups . During the 6-month intervention , antibiotics were prescribed less often in the synbiotic group than in the placebo group ( 23 % vs 28 % ) . Throughout the follow-up period , respiratory infections occurred less frequently in the synbiotic group ( geometric mean : 3.7 vs 4.2 infections ) . CONCLUSION . Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life AIM To evaluate the association between infantile colic and gastrointestinal , allergic and psychological disorders in childhood . METHODS A prospect i ve study was conducted on 103 infants aged 31 - 87 d. After 10 y , between 2001 and 2003 , the children were recalled and a paediatrician evaluated the selected disorders by anamnesis , medical examination , laboratory tests and parent interviews . RESULTS Of the 103 infants enrolled , 96 completed the study . There was an association between infantile colic and recurrent abdominal pain ( p=0.001 ) and allergic disorders : allergic rhinitis , conjunctivitis , asthmatic bronchitis , pollenosis , atopic eczema and food allergy ( p<0.05 ) . Sleep disorders , fussiness , aggressiveness and feelings of supremacy are more frequent in children who suffered from colic during early infancy ( p<0.05 ) . A family history of gastrointestinal diseases and atopic diseases was significantly higher in infants with colic than in controls ( p<0.05 ) . CONCLUSION Susceptibility to recurrent abdominal pain , allergic and psychological disorders in childhood may be increased by infantile colic . Our findings confirm that severe infantile colic might be the early expression of some of the most common disorders in childhood OBJECTIVE To investigate the effect of dietary supplementation with a probiotic on feeding tolerance and gastrointestinal motility in healthy formula-fed preterm infants . STUDY DESIGN Thirty preterm newborns were enrolled ; 10 were exclusively breast-fed , and the remaining 20 were r and omly assigned in a double-blind manner to receive either Lactobacillus reuteri ATCC 55730 ( at dose of 1 x 10(8 ) colony forming units a day ) or placebo for 30 days . Clinical symptoms of gastrointestinal function ( regurgitation , vomiting , inconsolable crying , and evacuation ) and physiological variables ( gastric electrical activity and emptying ) were recorded before and after the dietary intervention . RESULTS Body weight gains per day were similar for the 3 groups , and no adverse events were recorded . Newborns receiving probiotics showed a significant decrease in regurgitation and mean daily crying time and a larger number of stools compared with those given placebo .  Gastric emptying rate was significantly increased , and fasting antral area was significantly reduced in both the newborns receiving L. reuteri and breast-fed newborns compared with placebo . CONCLUSIONS Our results suggest a useful role for L. reuteri supplementation in improving feeding tolerance and gut function in formula-fed preterm newborns OBJECTIVE : To test the efficacy of Lactobacillus reuteri on infantile colic and to evaluate its relationship to the gut microbiota . STUDY DESIGN : Fifty exclusively breastfed colicky infants , diagnosed according to modified Wessel 's criteria , were r and omly assigned to receive either L reuteri DSM 17 938 ( 108 colony-forming units ) or placebo daily for 21 days . Parental question naires monitored daily crying time and adverse effects . Stool sample s were collected for microbiologic analysis . RESULTS : Forty-six infants ( L reuteri group : 25 ; placebo group : 21 ) completed the trial . Daily crying times in minutes/day ( median [ interquartile range ] ) were 370 ( 120 ) vs 300 ( 150 ) ( P = .127 ) on day 0 and 35.0 ( 85 ) vs 90.0 ( 148 ) ( P = .022 ) on day 21 , in the L reuteri and placebo groups , respectively . Responders ( 50 % reduction in crying time from baseline ) were significantly higher in the L reuteri group versus placebo group on days 7 ( 20 vs 8 ; P = .006 ) , 14 ( 24 vs 13 ; P = .007 ) , and 21 ( 24 vs 15 ; P = .036 ) . During the study , there was a significant increase in fecal lactobacilli ( P = .002 ) and a reduction in fecal Escherichia coli and ammonia in the L reuteri group only ( P = .001 ) . There were no differences in weight gain , stooling frequency , or incidence of constipation or regurgitation between groups , and no adverse events related to the supplementation were observed . CONCLUSION : L. reuteri DSM 17 938 at a dose of 108 colony-forming units per day in early breastfed infants improved symptoms of infantile colic and was well tolerated and safe . Gut microbiota changes induced by the probiotic could be involved in the observed clinical improvement
target: AND RELEVANCE Although L reuteri may be effective as treatment for crying in exclusively breastfed infants with colic , there is still insufficient evidence to support probiotic use to manage colic , especially in formula-fed infants , or to prevent infant crying .
background: IMPORTANCE  Excessive infant crying  is common , distressing , but without proven effective prevention or management options .
  Probiotics may be a promising solution .
  OBJECTIVE To examine whether probiotics are effective in the prevention/management of crying ( " colic " ) in infants 3 months or younger .