Functional Gastro-Intestinal Disorders & Gut Discomfort (1).pptx

GI Disorder

1. Functional Gastro-Intestinal Disorders & Gut Discomfort

2. Breastfeeding is the best for the baby. Start Breastfeeding ASAP, within first hour of birth. Exclusive breastfeeding till 6 months. Continue breastfeeding 2 years and beyond…..

3. Breastfeeding Mothers Milk is Best for Baby WHO - Recommends Exclusive Breast feeding for 6 months Post 6 months, Breast feeding to be continued for 2 years and beyond along with appropriate Complementary feeding Breast feeding is Species specific Breast Feeding - Multiple benefits

4. Start complementary feeding at 6 months with continued breast feeding to ≥2 yrs Provide appropriate complementary feeding: - Timely - Adequate - Safe - Properly fed WHO, Report of Global Consultation, 2002 WHO Global Infant Feeding Recommendations, 2002

5. Zeevenhooven J, et al. Pediatr Gastroenterol, Hepatol Nutr . 2017;20(1):1. Functional Gastrointestinal Disorders Functional gastrointestinal disorders affect not only the sense of physical and emotional well-being of the child/ infant but also that of the family members and caregiver.

6. Reflux and regurgitation 1,3 Anatomical immaturity Food hyper- sensitivity & allergy Issues Associated with a Maturing GI Tract (1/2) GI: Gastrointestinal. 1. Vonk RJ, et al . Probiotics and Lactose Intolerance. 2012. 2. Roberts DM, et al. Am Fam Physician. 2004;70:735-40:741-742. 3. Hillemeier AC, et al . J Pediatr . 1981;98(2):190-193. Immature gut cannot readily digest all nutrients; residual proteins/lactose are fermented by the locally residing microbiota, leading to painful GI problems Food hyper-sensitivity & allergy Infantile colic 1,2 Gut microbiota alterations Lactose maldigestion Protein maldigestion

7. Issues Associated with a Maturing GI Tract (2/2) Lactose maldigestion Gut microbiota alterations Protein maldigestion Flatulence Lactose maldigestion Food hypersensitivity and allergy Diarrhoea Gut microbiota alterations 1. Vonk RJ, et al. Probiotics and Lactose Intolerance. 2012. GI: Gastrointestinal.

8. Functional Gastro-Intestinal Disorders in Infants

9. Infantile Colic

10. New Rome IV criteria - Easy for Clinical Diagnosis of Infantile Colic The classic Rule of 3- Wessel Criteria : When an otherwise healthy infant cries for: >3 hours a day on >3 day a week for >3 weeks 1 (or alternative definition : for >1 week 2 ) Rome IV criteria for diagnosis of infantile colic : For clinical purpose , must include all of the following symptoms : Infant <5 months of age when symptoms start and stop Recurrent and prolonged period of infant crying , fussing or irritability that occur without obvious cause and cannot be prevented or resolved Incessant crying for ≥3 hours per day, during 3 or more days in the preceding week and total amount of crying and fussing is >3 hours per 24 hours Wessel MA, Cobb JC, Jackson EB et al. Pediatrics 1954; 14:421-34. Hyman et al. Gastroenterology; 2006;130(5):1519-26. 1. Zeevenhooven J, Koppen I, Benninga M. Pediatric Gastroenterology, Hepatology & Nutrition. 2017;20(1):1.

11. Infantile Colic Peaks at 5-6 weeks of Age and Between 6:00pm- 12:00pm Recording week Minutes / Day distress Crying patterns in “unselected” infants have remained consistent over the last 40 years Barr et al. Child Abuse & Neglect 2006;30:7-16. Brazelton TB. Pediatrics 1962;29:579-88. Number of babiesx Time of day of fussing Incessant crying peaks between 6:00pm- 12:00pm time of the day

12. de Weerth C, et al. Pediatrics . 2013;131:e550. Infantile Colic: Possible Mechanisms 01 02 03 04 05 06 Influence on the duration of colon transit Influence on gut motor function Influence on inflammatory responses Enforcement of the gut barrier function Production of short-chain fatty acids Maturation of the gut immune system

13. de Weerth C, et al. Pediatrics . 2013;131:e550 Infantile Colic: Slower Development of Intestinal Microbiota Temporal development of intestinal microbiota in colic and control samples Proteobacteria were significantly increased, while bifidobacteria and lactobacilli were significantly reduced, in infants with colic compared with control infants.

14. Rhoads J, Fatheree N, Norori J et al. J Pediatr 2009; 155(6): 823-8. Colicky Infants have Significantly Less Diverse Fecal Bacteria Colicky babies have a more restricted population of bacteria , reflecting less fecal diversity *mean age 7–8 weeks * * * * 2 fold high fecal calprotectin levels in colicky infants than non-colicky infants

15. Consequences of Infantile Colic

16. Kirjavainen J, et al. J Pediatr. 2001; 138:218–223. Shorter Daily Sleep Time in Infants With Colic Sleeping times according to 1-week daily diaries at home at age of 5 weeks Parents report less sleep for their colicky and excessively crying baby at the age of 5-6 weeks.

17. Rautava P, et al. Pediatrics. 1995;96:43-47. More Sleeping Problems in Children With Infantile Colic Later In Life Sleep disturbances in previously colicky children colicky children at 3 years of age The children in the colic group had more sleeping problems and more frequent temper tantrums (at 3 years of age) than the control group.

18. Clinical Benefits of L.Reuteri

19. 1. Modulation of Gut Microflora

20. Savino F, Cordisco L et al. Pediatrics 2010; 126:e526-533. Significantly More Beneficial Bacteria & Less Gas- forming Bacteria in Infants receiving L.reuteri DSM 17938

21. Chau K, Lau E, Greenberg S, et al. Probiotics for infantile colic: a randomized, double-blind, placebocontrolled trial investigating Lactobacillus reuteri DSM 17938. J Pediatr . 2015;166:74-8 . Mi GL, Zhao L, Qiao DD, et al. Effectiveness of Lactobacillus reuteri in infantile colic and colicky induced maternal depression: a prospective single blind randomized trial. Antonie Van Leeuwenhoek . 2015; 107(6):1547-53 L. reuteri : Reduction of Daily Crying Time by ≥50% >50% reduction of daily crying time & fussing time as recorded by parents owing to L.reuteri intervention

22. Savino F, et al. Pediatrics . 2010 Sep;126(3):e526–533. Symptomatic Improvement With L. reuteri L. reuteri group Placebo group 35 minutes 90 minutes Crying time Number of responders The improvement in the symptoms of infantile colic was significant with L. reuteri compared with placebo, and this effect may be related to the changes induced in the faecal microbiota, particularly E. coli .

23. Anabrees, et al. BMC Pediatrics. 2013;13:186. L. reuteri is More Effective Than Simethicone A systematic analysis showed that L. reuteri supplementation is effective in shortening crying time in infantile colic.

24. Savino et al 2007 Significant Reduction of Infantile Colic & Crying Time by L.reuteri than Simethicone L.reuteri was significantly better than the most prescribed treatment Simethicone Simethicone (n=42) L. Reuteri (n=41) Crying Time (Min/ day ) Significant reduction of infantile colic and excessive crying time by one week of L.reuteri intervention. After one month, excessive crying was reduced by an average of 1 h 34 min per day with response rate of 95% vs 7% in Simethicone

25. Indrio F, Di Mauro A, Riezzo G, et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr . 2014;168(3):228-33 L.Reuteri Prevents Onset of Infantile Colic 53% significant less crying in L.reuteri group than control group Intervention of L.reuteri prevents the onset of colic, both in breastfed and formula fed infants.

26. Gutiérrez-Castrellón, et al. Medicine . 2017;96:51. L. reuteri : The Best Treatment for Reducing Crying Time Ranking plot of multiple treatments for infantile colic Based on a systematic analysis of evidence and networking meta-analysis, the use of L. reuteri DSM 17938 seems to be the most suitable evidence-based intervention to reduce the duration of crying in infantile colic.

27. Szajewska H, Gyrczuk E, Horvarth A. J Pediatr 2013;162:257-62. L. reuteri DSM 17938 L. Reuteri Intervention for Infantile Colic Improves Quality of Life for Parents and Families Visual Analog Scale (VAS) ( Median ) Follow up L.reuteri intervention Day 7 Day 21 Day 28 L.reuteri (n=40) Placebo (n=40) VAS: 0-no effect; 10-very good effect Upto 66% improved quality of life of family by L.reuteri intervention

28. 2. Modulation of Immune and Inflammatory Responses

29. Is an abnormal faecal microbiota composition the result of gut inflammation ? Gut inflammation could produce differences in faecal osmolarity, pH and the concentrations of luminal nutrients, variables that affect the composition of the microbiota 1. Pärtty A, et al. J Pediatr Gastroenterol Nutr . 2017 May;64(5):691-695. 2. Rhoads JM,, et al. J Pediatr . 2018 Dec;203:55-61.e3. New Evidence: Gut Inflammation May be the Potential Origin of Colic Gut Inflammation? 1,2 Infantile colic is linked with gut inflammation and dysbiosis. 1,2

30. Mu Q, et al. Frontiers in Microbiology . 2018;9. Multiple Benefits of the Metabolites of L. reuteri Remodels the gut microbiota Activates bile salt hydrolase Enhances the functioning of the enteric nervous system Influences immunity secretory IgG- A Induces anti-inflammatory T reg cells production of pro-inflammatory cytokines mucosal barrier function bacterial translocation from GI tract to mesenteric lymph nodes lactulose-to-mannitol ratio Eliminate infections Attenuate GI diseases

31. L. reuteri as an Immunoregulator in the Intestinal Tract Smits HH, et al. J Allergy Clin Immunol . 2005;115:1260-1267. L. reuteri stimulates T cells to produce IL-10 anti-inflammatory cytokine, an essential immunoregulator in the intestinal tract.

32. 3. Improves Digestive Comfort

33. Indrio F, et al. Eur J Clin Invest . 2011;41(4):417–422. Decreased Frequency of Regurgitation Linked to Improved Gastric Motility Change in gastric emptying rate In infants with functional gastroesophageal reflux, L . reuteri  reduced gastric distension and accelerated gastric emptying.

34. Indrio F, et al. J Pediatr. 2008;152:801–806. L. reuteri Ameliorates Feeding Tolerance L reuteri group Placebo group 32 minutes 88 minutes Regurgitation Crying time The study outcome suggest a useful role for L. reuteri supplementation in ameliorating feeding tolerance and improving gut function in new borns.

35. Coccorullo P, et al . J Pediatr. 2010 Oct;157(4):598–602. L. reuteri in Infants Improves Functional Chronic Constipation Frequency of bowel movement Stool consistency L. reuteri had a positive effect on bowel frequency in infants with chronic constipation

36. Indrio F, Di Mauro A, Riezzo G, et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr . 2014;168(3):228-33 L.Reuteri Reduces the Onset Of Constipation L.Reuteri group had significantly more bowel movements than control group Intervention of L.reuteri was associated with more bowel movements further associating with reduced onset of constipation

37. 4. Effect of L.reuteri in Management of diarrhea

38. Therapeutic Effect of L.Reuteri on Infant Diarrhea Francavilla R, Lione E, Castellaneta S, Ciruzzi F, Indrio F, Masciale A, Fontana C, La Rosa MM, Cavallo L, Francavilla A. Aliment Pharmacol Ther 2012; Epub Eom T, Oh E, Kim Y, Lee H, Jang P, Kim D, Kim J, Lee B. Korean Journal of Peditarics 2005; vol 48. Infants with persisting watery diarrhea 1 % of infants with watery diarrhea Days after therapy initiation Infants with persisting watery diarrhea 2 L.reuteri ( n =35) Placebo ( n =34) % of infants with watery diarrhea Days after therapy initiation L.reuteri ( n =25) Placebo ( n =25) S LF AR CR The frequency of watery diarrhea per 24-h period was significantly reduced on the 2 nd and 3 rd day of intervention in L.reuteri group compared to placebo

39. L.Reuteri Reduces Stool Frequency Francavilla R, Lionetti E, Castellaneta S, Ciruzzi F, Indrio F, Masciale A, Fontana C, La Rosa MM, Cavallo L, Francavilla A . Aliment Pharmacol Ther 2012; Epub Eom T, Oh E, Kim Y, Lee H, Jang P, Kim D, Kim J, Lee B. Korean Journal of Peditrics 2005; vol 48. Mean frequency of watery diarrhea Days after therapy initiation Frequency of diarrheal stools 2 L.reuteri ( n =35) Placebo ( n =34) Number of stools per day Days after therapy initiation L.reuteri ( n =25) Placebo ( n =25) L. reuteri significantly reduces the number of diarrheal stools in infants and young children having acute diarrhea, as early as the second day of intervention 1,2 Frequency of diarrheal stools 1

40. Benefits of 100% Lactose for Gut Comfort

41. Metabolism of Lactose in the Gut 1. Vonk RJ, et al . Probiotics and Lactose Intolerance. 2012. 2. Nayak S. Pediatric Oncall J. 2014;11(1). 3. van de Heijning BJ, et al . Nutrients . 2014;6(9):3942-3967. GI: Gastrointestinal SCFA: Short-chain fatty acid. As the GI system matures, lactase activity declines 1 Excessive gas formation leads to flatulence, abdominal distension, abdominal pain, diarrhoea, and infantile colic. 1-3

42. Infante D, et al. Nutr J. 2011;10(1):55. Impact of Lactose on Stool Consistency Infants experiencing symptoms of constipation before and after lactose consumption p<0.0001 Owing to its positive effects, lactose, in regulated amounts, can be a viable option to alleviate the symptoms of constipation in infants.

43. Percentage of additional absorption seen with lactose-containing formula 1,2 *1 x – ± SD. 2, Significantly different from lactose-containing formula (paired t test): P = 0.002, compared with lactose-free formula. #Compared with 56% polycose (corn starch hydrolysate) and 44% sucrose. ^Value significantly (p<0.05) greater than the corresponding value on the same line, as determined by analysis of covariance with intake as a covariate. **Data based on 11 balance studies with six infants fed formula L and 12 studies with the same six infants fed formula SCS (p<0.01). 10% 25% 11% 8% 7% Lactose and Nutrient Absorption 1. Ziegler E, et al. J Ped Gastroenter Nutr. 1983;2(2):288–294. 2. Abrams S, et al. Am J Clin Nutr. 2002;76:442–446. Lactose is considered to help support the absorption of various minerals. 1,2 Significant minerals include calcium, copper, and manganese. 2

44. Benefits of Whey-Predominant formulas and Ca:P Ratio for Gut Comfort

45. Khinchi M, Deurell M, Hejl M, Hjelt K. Ca:P Ratio in cows milk formula. The influence on regurgitation, vomiting, bowel habits and uneasiness in healthy newborns less than 6 months old. Journal of Pediatric Gastroenterology & Nutrition. 1999;28(5):591. Ca:P  ratio in formula influenced the stool hardness among exclusively formula-fed infants aged less than 6 months Ca:P Ratio of 2 facilitates soft stool consistency The mean number of hard stools for formula A was 0.9 (range 0–9) and for formula B it was 2.8 (range 0–15)

46. 1. Billeaud C, et al. Eur J Clin Nutr . 1990;44:577 – 583. 2. Khoshoo V, et al. Eur J Clin Nutr . 2002;56:656 – 658. Whey-Based Formulas Have a Faster Gastric Emptying Whey-based formulas have a faster gastric emptying time and can be used to minimise episodes of GER in infants. 1,2 Following human milk, whey-based formula had rapid gastric emptying when compared to casein-based formula and cow’s milk. 1

47. 1. Bae S. Hepatol Nutr. 2014;17(4):203. 2. Malacaman EE,  et al. J Pediatr Gastroenterol Nutr.  1985;4(5):771 –77 3. Whey-Based Formulas May Produce Lesser Hard Stools 2 The percentage of hard stools was lesser among infants fed whey-predominant formula compared with infants fed casein-predominant formula. 2

48. Key Messages

49. Key Messages