Cólica Infantil

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A verdadeira amizade começacom um sentimento de felicidade na barriga.

O meu amigo

A microbiota do bebé e da criançaA microbiota intestinal do bebé recém-nascido define-se a partir do momento do nascimento e durante os dois anos seguintes. As bactérias benéficas como as lactobacilli e as bifidobactérias são normalmente das primeiras a colonizar1. Os nascimentos por cesariana atrasam o desenvolvimento das bactérias benéficas, em comparação com bebés nascidos de parto natural, o que pode ter consequências signifcativas a nível da saúde.2

A amamentação serve de base a uma microbiota saudável, visto que fornece a bactéria com os oligossacarídeos do leite humano, em grandes quantidades, que atuam como probióticos naturais. Uma microbiota diversificada ajuda o bebé a maximizar o desenvolvimento da anatomia e das funções do trato intestinal.3

A microbiota contribui para:• Uma barreira intestinal reforçada• Uma digestão melhorada• Uma motilidade melhorada• A maturação das funções de imunidade do intestino

Os probióticos e a importância da especificidade da estirpeOs probióticos, definidos como estirpes vivas de bactérias com efeitos na saúde documentados,4 tornaram-se uma opção bem reconhecida para apoiar a composição da microbiota benéfica em bebés e crianças. As espécies de bactérias mais comummente utilizadas como probióticos pertencem ao género Lactobacillus e Bifidobacterium. Diferentes estirpes de uma espécie específica têm diferentes propriedades e efeitos de probióticos. Consequentemente, os benefícios de uma estirpe específica não podem ser extrapolados em relação aos efeitos de outros probióticos.

L. reuteri Protectis

Lactobacillus reuteri Protectis é especial

O Lactobacillus reuteri Protectis é uma bactéria indígena ao trato digestivo humano e um dos poucos probióticos que evoluiram juntamente com os humanos desde o princípio dos tempos.8,9

O L. reuteri Protectis é um colonizador natural e foi demonstrado que coloniza tanto o estômago como o intestino delgado.10 O probiótico exerce os seus efeitos, ou modos de atuação, de muitas formas diferentes. Foi provado que o L. reuteri Protectis influencia a motilidade intestinal e pode também reduzir as dores intestinais, devido à libertação de moléculas neuromodelantes. Além disso, influencia a microbiota intestinal ao libertar reuterina, ácido lático e ácido acético, que ajudam a promover o crescimento de outras bactérias benéficas e inibem os agentes patogénicos. O L. reuteri Protectis pode também reforçar a integridade da mucosa ao reforçar a barreira epiletial e melhorar a resposta imunitária.11-19

Provas científicasInúmeros ensaios demonstraram a segurança e os efeitos significativos do L.reuteri Protectis nos distúrbios gastrointestinais funcionais e proteção contra infeções em bebés e crianças, incluíndo recém nascidos prematuros sob cuidados intensivos.

• 130 estudos completos em 12 300 temas, dos quais:• 59 estudos em bebés e crianças até aos 3 anos de idade

Lactobacillus reuteri Protectispossíveis modos de atuação

Efeito na motilidade do intestinoDor intestinal reduzida

Microbiota reforçadaMucosa reforçada

Resposta imunitária melhorada

Distúrbios GI funcionais em

crianças

Gastroenteriteaguda

Proteção contra

infeções

Efeitos secundários associados a antibióticos

RegurgitaçãoPrisão de

ventre funcional

Cólica Dor abdominal funcional

Distúrbios gastrointestinais funcionais• Tempo de choro reduzido em bebés com cólicas20-24

• Motilidade do intestino melhorada e menos regurgitação25-27

• Prisão de ventre reduzida27-29

• Dor abdominal funcional reduzida30-32

Gastroenterite aguda• Duração reduzida de diarreia líquida e vómito33-40

Proteção contra infeções• Incidência de diarreia reduzida41-43

• Crescimento melhorado em crianças com um baixo estado nutricional44

• Incidência reduzida de efeitos secundários associados a antibióticos45

CólicasInfantis

A cólica infantil é uma condição comum, apesar de pouco compreendida, que frustra muitas vezes os progenitores e cuidadores. De acordo com os critérios de diagnóstico Rome III para distúrbios gastrointestinais funcionais, uma criança tem cólicas infantis se experenciar episódios inexplicáveis de agitação ou choros paroxísticos durante pelo menos três horas por dia, três dias por semana ou mais, durante pelo menos uma semana, sem insuficiência de crescimento.46 Este tipo de choro normalmente atinge o ponto alto em aproximadamente seis semanas de vida e termina mais ou menos no quarto mês.25

26% das crianças são diagnosticadas com cólicas,47 fazendo desta condição o motivo mais frequente para as visitas aos médicos de família.

Causas multifatoriais podem e irão mais tarde afetar a saúde A etiologia da cólica infantil é multifatorial e não totalmente compreendida. A disfunção do intestino e a hipersensibilidade intestinal são consideradas os principais fatores por detrás desta condição.48

Na última década, o papel da microbiota gastrointestinal tem-se tornado central. Quantidades menores de lactobacilli, assim como concentrações crescentes de bactérias coliformes foram observadas em bebés com cólicas, em comparação com bebés sem cólicas.49-50

A microbiota intestinal imatura ou disfuncional pode levar a uma inflamação de baixo grau e a um metabolismo intestinal anormal, resultando em sintomas de cólica.48 Foi mostrado que a cólica na infância está ligada a uma maior suscetibilidade a dores abdominais recorrentes, alergias e a distúrbios psicológicos mais tarde durante a infância.51

L. reuteri Protectis - o único probiótico com provas científicas nas cólicas infantis As possibilidades de tratar as cólicas têm sido limitadas. O simeticone tem sido extensivamente utilizada em muitos países mas as pesquisas clínicas mostram que tem o mesmo efeito que um placebo.49

Cólicas infantis

Até à data, cinco estudos independententes com L. reuteri Protectis demonstraram uma redução no tempo de choro em bebés com cólicas.20-24 O efeito do L. reuteri Protectis nas cólicas infantis foi também provado em dois estudos preventivos publicados.27,52 Para além do mais, foram conduzidas oito meta-análises, todas com a mesma conclusão de que o L. reuteri Protectis é o único probiótico com uma eficácia comprovada em cólicas infantis, especialmente em bebés que foram amamentados, ou com uma alimentação combinada.53-60

O L. reuteri Protectis é o único probiótico com recomendações de especialistas para tratar e prevenir as cólicas infantis.61

Efeitos de L. reuteri Protectis em cólicas infantiscomprovados por cinco estudos

Referências:Mi GL et al. Antonie van Leeuwenhoek 2015;107:1547-1553. Chau K et al. J Pediatr. 2014;166:74-78. Szajewska H et al.J. Pediatr. 2013;162:257-262. Savino F et al. Pediatrics 2010;126;e526-e533. Savino F et al. Pediatrics 2007;119:124-130.

SIM: Significativo em comparação com o placebons: Não significativona: : Não analisado* Significativo em comparação com simeticone** No 28.º diaRespondente: bebé com ≥ 50% de redução na duração média de choro e agitação em comparação com a baseline

Estudo

Mi 2015

Chau 2014

Szajewska 2013

Savino 2010

Savino 2007*

Redução do tempode choro no 7º dia

SIM

SIM

SIM

ns

SIM

Redução do tempode choro no 21º dia

SIM

SIM

SIM

SIM

SIM

Respondentesno 7º dia

na

ns

SIM

SIM

na

Respondentesno 21º dia

SIM**SIM SIM SIM SIM**

Menos choro e agitaçãoComparado com o placebo, o L. reuteri Protectis:• Reduziu o tempo de choro e agitação em 40 minutos a partir do 7.º dia e seguintes• 71% de respostas ao tratamento* com L. reuteri Protectis após 21 dias

*Bebés com uma redução de 50% ou mais no tempo de choro e agitação em comparação com a baseline

150

120

90

60

30

0

Duração médiade choro e agitação(min/dia)

Dia 0(p=0.804)

Dia 7(p=0.032)

Dia 14(p=0.018)

Day 21(p=0.045)

Chau K et al. J Pediatr. 2014. 2014;166:74-78

L. reuteri Protectis (n=24)

Placebo (n=28)

Redução de choro excessivo e qualidade de vida familiar melhorada O L. reuteri Protectis comparado com o placebo:• Efeito uma semana após iniciar a suplementação• Choro diário reduzido por uma hora no 28.º dia• Qualidade de vida familiar melhorada

100

80

60

40

20

0Dia 7(p=0.026)

Dia 14(p<0.001)

Dia 21(p<0.001)

Dia 28**(p<0.001)

Sucesso do tratamento* em bebés com cólicas

% c

rian

ças

com

tra

tam

ento

sb

em s

uced

ido

s

L. reuteri Protectis(n=40)

Placebo(n=40)

* >_ 50% de redução no tempo de choro médio diário

** Follow-up uma semana depois do fim da intervenção

10

8

6

4

2

0Dia 7(p<0.001)

Dia 21(p<0.001)

Dia 28**(p<0.001)

Qualidade de vida melhorada

Esc

ala

Vis

ual A

naló

gic

am

edia

na

L. reuteri Protectis(n=40)

Placebo(n=40)

0: Sem efeito

10: Efeito Muito Bom

** Follow-up umasemana depois do fimdas intervenções

Szajewska H et al. Pediatr. 2013:162:257-262

Tempo de choro reduzido em mais de 4,5 horas após uma semana• Efeito uma semana depois do suplemento• Em media 1,5h redução no choro diário em comparação com o placebo

400

300

200

100

0

Tempo médio de choropor dia (minutos)

Dias de intervenção

Dia 0(p=0.127)

Dia 7(p=0.082)

Dia 14(p=0.099)

Dia 21(p=0.022)

Savino F et al. Pediatrics 2010;126:e526-e533

L. reuteri Protectis (n=25)

Placebo (n=21)

95% de respostas bem sucedidas ao tratamentoComparado com o simeticone, o L.reuteri Protectis:• Foi superior na redução do tempo de choro diário • Reduziu o tempo de choro em mais do dobro

Uso profilático reduziu o choro em mais de 50%• Após um mês, o choro diário inconsolável foi reduzido a 45 minutos no grupoL. reuteri Protectis comparado com mais de 1½ h no grupo de placebo.• A diferença entre os grupos persistiu até ao final da intervenção de 3 meses.

100

80

60

40

20

0

Taxa de respondentes* of L. reuteri Protectis versus simeticone

Res

po

nden

tes*

(%

) L. reuteri Protectis(n=41)

Simeticone(n=42)

* Bebés com uma redução de 50% ou mais no tempo de choro diário da base

7% (p<0.001)

95%Savino F et al. J. Pediatrics 2007;119:124-130

100

80

60

40

20

01 Mês(p<0.01)

3 Meses(p<0.01)D

uraç

ão m

édia

de

cho

ro d

iári

oco

m c

ólic

a (m

inut

os/

dia

)

L. reuteri Protectis(n=238)

Placebo(n=230)

96

45

71

38

Indrio F et al. JAMA Pediatr. 2014; 168:228-233

R: Randomized DB: Double Blind SB: Single Blind PC: Placebo Controlled

Reference Study Objectives StudyDesign*

Subjects and(Daily Dose) Results

Cólica Infantil - Tratamento

Mi G-L,2015China

Chau K,2014Canada

Sung V,2014Australia

Szajewska H,2013Poland

Savino F,2010Italy

Savino F,2007IItaly

Ashraf MW,2015Pakistan

Evaluate the e�ects of L. reuteriDSM 17938 on colicky infants< 4 months old, exclusively orpredominantly breastfed: on rateof treatment success, reductionin daily crying time, parent satisfaction and maternal depression

Investigate the e�cacy of L. reuteri DSM 17938 for the treatment of infantile colic in breastfed infants ≤ 6 months

E�cacy of L. reuteri DSM 17938on infantile colic in infants < 3months, with mixed feeding types. Colic defined as daily combined screaming or fussingof 180 minutes or more. Maternal mental health and family quality of life (QoL) were also studied.

E�cacy of L. reuteri DSM 17938 on infantile colic in infants younger than 5 months, exclusively or predominantly breastfed. E�ect on screaming intensity and family quality of life. The trial included followup one week after termination of ingestion of the study product.

To study the e�ect of L. reuteriDSM 17938 on infantile colic ininfants 2-16 weeks old, andinvestigate changes in the faecalmicrobiota.

E�cacy on infantile colic in infants 11–80 days old.

Assess the e�ectiveness of L. reuteri DSM 17938 in Pakistani, breastfed infants aged 21-90 days, diagnosed with infantile colic according to Wessel’s criteria

R,DB, PC4 weeks

R, DB, PC21 days

R, DB, PC28 days +follow-up at6 months

R, DB, PC21 days +7 days follow-up

R, DB, PC21 days

R, open28 days

Open7 days

Infant formulaas vehicle ofL. reuteri and simethiconeas comparator

L. reuteri: 20(1x108 CFU)Placebo: 19 individuals

L. reuteri: 24(1x108 CFU)Placebo: 28 individuals

L. reuteri: 67(1x108 CFU)Placebo: 60 individuals

Other probiotics thanL. reuteri were allowed for mothers and/or infants, and also use of proton pump inhibitor

L. reuteri: 40(1x108 CFU)Placebo: 40 individuals

L. reuteri: 25(1x108 CFU)Placebo: 21 individuals

L. reuteri: 41(1x108 CFU)Placebo: 42 individuals

L. reuteri: 20(1x108 CFU)Placebo: 19 individuals

The L. reuteri dose was administered twice daily in a total of ~~ 75 mL infant formula with the probiotic. The control group received the same volume of a formula without any probiotic

Significant e�ects compared to placebo:• Treatment success (≥ 50% reduction of crying time vs. baseline) was achieved in 100% of the infants vs. 16% in the placebo group.• Reduction in daily crying time compared to baseline: 32 min vs. 201 min/d. (121 min/d at 4 weeks in the placebo group.) The di�erence compared to placebo was statistically significant at each weekly evaluation.• 100% parental satisfaction vs. 16% in placebo• Improved maternal depression scores throughout the study period (Edinburgh postnatal depression scale)• No report of adverse e�ects in any of the groups.

Compared to placebo:• L. reuteri significantly improved colic symptoms by reducing median crying and fussing times at days 7, 14 and 21.• The rate of responders (50% reduction in daily crying time) was significantly higher in the L. reuteri group compared with the control group at day 21.

Compared to placebo:• At day 28 mean values: 49 min more daily screaming + fussing time in the L. reuteri group (p<0.02), due to more fussing time in this group• At day 28 median values: no di�erence• No di�erence in duration of screaming time• No di�erence in number of episodes of scream-ing/fussing, or in sleeping time• No di�erence between groups in family QoL or maternal mental health

• L. reuteri significantly reduced daily crying time compared to placebo• Significantly more responders on day 7, 14, 21 and 28 (follow-up) compared to placebo• Parents’ rating of screaming intensity and family quality of life was significantly decreased and increased, respectively, at all time points

• L. reuteri significantly reduced daily crying time compared to placebo• Significantly more responders on day 7, 14 and 21 compared to placebo• Reduced faecal E. coli and increased counts of lactobacilli in the L. reuteri group only

• L. reuteri significantly reduced daily crying time compared to simethicone• On day 28, 95% were responders in the probiotic group vs. 7% in the simethicone group

There was a significant di�erence in success rates between groups: 86.7% in the probiotic group vs. 51.1% in the simethicone group at day seven of the intervention. Success was defined as a reduction in colicky crying of at least 50% compared to baseline. Mean crying time at day seven was 39 and 113 minutes, respectively (p<0.001).Note: Study of little significance to elucidate the e�ects of L. reuteri DSM 17938 on infantile colic due to: open design, lack of vital information on the conduct of the study, and no followup after the initial week of intervention.

R: Randomized DB: Double Blind SB: Single Blind PC: Placebo Controlled

Reference Study Objectives StudyDesign*

Subjects and(Daily Dose) Results

Cólica Infantil - Tratamento

Ummarino D,2015(abstract)Italy

Calderon VV,2014Spain

Karadag N,2012(abstract)Turkey

To compare the e�ectivenessof three alternative treatmentsof infantile colic: A) a mixture ofstandardized extract of Matricariachamomilla L., Melissa o�cinalis L.and tyndallized Lactobacillus acidophilus (H122) compared with B) Lactobacillus reuteri DSM 17938,and C) simethicone.

To evaluate the e�ects of L. reuteriDSM 17938 in infants with colic and≤3 months old. Family quality of lifeand a qualitative test of faecal calprotectin, as a marker of gut inflammation, were also investigated. All but one infant, were exclusively breastfed.

E�cacy on infantile colic andmother’s postpartum depressioncomparing L. reuteri DSM 17938with herbal drops and sterile water.Baby massage was practiced in allthree groups.

Open,multi-centre,randomized21 days + 7days of follow-up

Open, pilotstudy. No controlgroup.28 days

R, open21 days +follow-up ofmother’s mentalheath after 2months

L. reuteri: 45(?x10? CFU)Herbs + tyndallizedL. acidophilus: 45Simethicone: 43

L. reuteri: 17(1x108 CFU)

L. reuteri: 25(1x108 CFU)Herbal drops: 24Sterile water: 25

• Rate of treatment success was significantly better in Group A and B, 30/45 and 31/45, respectively vs. 19/43 in group C.• Mean daily crying time was significantly reduced in both Group A (from 211.3 ± 40 min/day to 69.6 ± 59 min/day) and in Group B (from 201.6 ± 32.5 min/day to 58.1 ± 48.9 min/day) vs. Group C (from 199.5 ± 32 min/day to 106 ± 56.5 min/day).• No significant di�erence was observed between Group A and B (p = 0.4).• No adverse events were reported in any of the groups.

During the study period:• Crying time was reduced, which paralleled parents’ perception of good response of the treatment.• The number of infants positive for calprotectin in faeces decreased.• Growth in weight and length as expected.

• L. reuteri and sterile water significantly reduced daily crying time compared to herbal drops at three weeks• At three weeks the daily crying time was 35 minutes in the L. reuteri group compared to 188 minutes in the sterile water group and 300 min in the herbal drops group• a significant drop in depression and anxiety scores were seen only for mothers in the L. reuteri group at the follow-up at two months

R: Randomized DB: Double Blind SB: Single Blind PC: Placebo Controlled

Reference Study Objectives StudyDesign*

Subjects and(Daily Dose) Results

Cólica Infantil - Prevenção

Indrio F, 2014Italy

Savino F, 2015aItaly

Investigate if oral supplementationwith L. reuteri DSM 17938 duringthe first 3 months of life can reducethe onset of colic, gastro-oesophageal reflux, and constipation in term newborns, and in addition reduce the socio-economic impact of these conditions

Test the preventive e�ect ofL. reuteri DSM 17938 combinedwith vitamin D, on infantile colic

R, DB, PC90 daysMulticentrestudy

12 weeksRandomized,open label study,blinded outcomeanalyst.Commercialvitamin D dropproduct as thecomparator.

L. reuteri: 238(1x108 CFU)Placebo: 230 individuals

L. reuteri + vit. D: 51(1x108 CFU)Vit. D only: 54

Compared to placebo:• Daily administration of L. reuteri early in life reduced the duration of daily inconsolable type of crying, frequency of regurgitation, and incidence of functional constipation in the first 3 months of life• Private and public costs for the management of these conditions were significantly reduced for infants receiving L. reuteri

Prevention of colic was significantly more successfully achieved in the L. reuteri group compared with the control group. The e�ectwas indirectly measured, and demonstrated by significantly less use of pain-relieving agents, contacts with doctor (calls and visits due to symptoms of colic), and change of feeding to partially or exclusively infant formula.

Referências1. Thum C et al. Can Nutritional Modulation of Maternal Intestinal Microbiota Influence the Development of the Infant Gastrointestinal Tract? J Nutr. 2012;142:1921-1928. 2. Neu J et al. Cesarean versus Vaginal Delivery: Long term infant outcomes and the Hygiene Hypothesis. Clin Pernatol. 2011;38:321-331. 3. Guarner F et al. Gut flora in health and disease.Lancet 2003;361:512-519. 4. Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria, October 2001. http://www.who.int/foodsafety/publications/fs_management/en/ probiotics.pdf. 5. Casas IA, Dobrogosz WJ. Lactobacillus reuteri: Overview of a new probiotic for humans and animals. Microecology and Therapy 1997;26:221-23. 6. Rosander A et al. Removal of antibiotic resistance plasmids from Lactobacillus reuteri ATCC 55730 and characterization of the resulting daughter strainL. reuteri DSM 17938. Appl Environ Microbiol. 2008;74:6032-6040. 7. Sinkiewicz G et al. Occurrence of Lactobacillusreuteri in human breast milk. Microb Ecol Health Dis. 2008;20:122-126. 8. Reuter G. The Lactobacillus and Bifidobacterium microflora of the human intestine: composition and succession. Curr Issues Intest Microbiol 2001;2:43-53. 9. Walter J et al. Microbes and Health SacklerColloquium: Host-microbial symbiosisin the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm. Proc Natl Acad Sci USA. (PNAS) 2011;108 (Suppl. 1):4645-52. 10. Valeur et al. Colonization and Immunomodulationby Lactobacillus reuteri Protectis in the Human Gastrointestinal Tract Applied and environmental microbiology. 2004;1176-1181. 11. Chung TC et al. In vitro studies on reuterin synthesis by Lactobacillus reuteri. Microb Ecol Health Dis, 1989;2:137-144. 12. De Weerth et al. Intestinal microbiota of infants with colic: development and specific signatures. Pediatrics 2013;131:e550-8. 13. Liu Y et al. Lactobacillus reuteri strains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF{kappa}B signaling in the intestine. Am J Physiol Gastrointest Liver Physiol. 2012;302:G608-G617. 14. Mayer EA et al. The brain-gut axis in abdominal pain syndromes. Annu Rev Med. 2011;62:381-96. 15. Preidis GA et al. Probiotics stimulate enterocyte migration and microbial diversity in the neonatalmouse intestine. FASEB J. 2012;26:1960-1969. 16. Preidis GA et al. Host response to probiotics determined by nutritional status of rotavirus-infected neonatal mice. J Ped Gastroenterol Nutr. 2012;55:299-307. 17. Schaefer L et al. The antimicrobial compoundreuterin (3-hydroxypropionaldehyde) induces oxidative stress via interaction with thiol groups. Microbiology 2010;156:1589-1599. 18. Wu RY et al. Spatiotemporal maps reveal regional di�erences in the e�ects on gut motility for Lactobacillus reuteri and rhamnosus strains. Neurogastroenterol Motil. 2013;25:e205-e214. 19. Perez-Burgos A et al. Transient receptor potential vanilloid 1 channel in rodents is a major target for antinociceptive e�ect of the probiotic L. reuteri DSM 17938. J Physiol. 2015;593:3943-3957. 20. Chau K et al. Probiotics for infantile colic: a randomized double-blind placebocontrolled trial investigating Lactobacillus euteri DSM 17938. J Pediatr. 2014;166:74-78. 21. Savino F et al. Lactobacillus reuteri ATCC 55730 versus Simethicone in the treatment of infantile colic: a prospective randomized study. Pediatrics 2007;119:124-130. 22. Savino F et al. Lactobacillus reuteri DSM 17 938 in infantile colic: A randomized, double-blind, placebo- controlled trial. Pediatrics 2010;126: e526-e533. 23. Szajewska H et al. Lactobacillus reuteri DSM 17938 for the management of infantile colic in breastfed infants: A randomized, double-blind, placebo-controlled trial. J Pediatr. 2013;162:257-262. 24. Mi GL et al. E�ectiveness of Lactobacillus reuteri in infantile colic and colicky induced maternal depression:a prospective single blind randomized trial. Antonie Van Leeuwenhoek. 2015;107:1547-1553. 25. Indrio F et al. The e�ects of probiotics on feeding tolerance, bowel habits, and gastrointestinal motility in preterm newborns. J Pediatr. 2008;152:801-806. 26. Indrio F et al. Lactobacillus reuteri accelerates gastric emptying and improves regurgitation in infants. Eur J Clin Invest. 2011;41:417-422. 27. Indrio F, et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation. A randomised clinical trial. JAMA Pediatr. 2014;168:228-233. 28. Coccorullo P et al. Lactobacillus reuteri (DSM 17938) in infants with functional chronic constipation:a double-blind, randomized, placebo-controlled study. J Pediatrics 2010;157: 598-602. 29. Olgaç MAB et al. 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Lactobacillus reuteri DSM 17938 e�ectively reduces the duration of acute diarrhoea in hospitalised children. Acta Paediatr. 2014;103:e300-e305. 34. Dinleyici EC et al. Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric outpatient setting. J Pediatr (Rio J) 2015;91:392-396. 35. Eom T-H et al. The therapeutic e�ect of Lactobacillus reuteri in acute diarrhea in infants and toddlers. Korean J Ped. 2005;48:986-989. 36. Francavilla R et al. Randomised clinical trial: Lactobacillus reuteri DSM 17938 vs. placebo in children with acute diarrhoea - a double-blind study. Aliment Pharmacol Ther. 2012;36: 363-369. 37. Shornikova AV et al. Lactobacillus reuteri as a therapeutic agent in acute diarrhea in young children. J Pediatr Gastroenterol Nutr. 1997;24:399-404. 38. Shornikova AV et al. Bacteriotherapy with Lactobacillus reuteri in rotavirus gastroenteritis. Pediatr Infect Dis J. 1997;16:1103-1107. 39. Szajewska H et al. 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