Over the past few years, interest in the efficacy of probiotics in paediatric patients with specific conditions has steadily increased. Studies show that the addition of probiotics may have a positive effect on paediatric patients with acute infectious gastroenteritis (AGE), antibiotic-associated diarrhoea (AAD), Helicobacter pyloriinfection, necrotising enterocolitis (NEC), atopic diseases, and functional gastrointestinal disorders (FGDs).1-24

In 2020 a new name for the genus Lactobacillus was adopted. The new name is Limosilactobacillus reuteri.

The most commonly used probiotics are bacteria of the genera Limosilactobacillus (including several new genera formerly under the Lactobacillus umbrella) or Bifidobacterium, which present either as single or mixed species.1,25

Paediatric conditions that may benefit from treatment with probiotics

Acute infectious gastroenteritis

AGE, caused by viral pathogens, is generally self-limiting. However, it is associated with significant morbidity in paediatric as well as elderly patients. It is estimated that globally, AGE accounts for more than 200 000 deaths in paediatric patients per year. Apart from diarrhoea, AGE can cause nausea, vomiting, anorexia, weight loss, and dehydration.26

A Cochrane review, which included 63 randomised controlled studies (RCT) involving 8014 paediatric patients, evaluated the effect of administering probiotics for the treatment of AGE. The reviewers found that probiotics reduced the duration of diarrhoea by about one day, as well as the risk of diarrhoea lasting more than four days.2

A meta-analysis comparing the efficacy of Lactobacillus reuteri (L. reuteri) with placebo or no treatment, supports this finding.  The researchers found that the addition of L. reuteri to standard rehydration therapy compared to placebo or not intervention,  reduced the duration of diarrhoea by about 21 hours. It also reduced hospitalisation duration by between five and 13 hours. The addition of L. reuteri to standard rehydration therapy also increased the chance for cure on the first two days of treatment.3

Antibiotic-associated diarrhoea

The prevalence of AAD in paediatric patients younger than two-years old is estimated to be around 11%.Another Cochrane review of 33 RCTs (n=6352), evaluated the efficacy of probiotics (Limosilactobacillus,Bifidobacterium, Streptococcus, S. boulardii or combinations), compared to placebo or other treatments in paediatric patients with ADD.4,27

The reviewers concluded that probiotics may be effective for preventing AAD. The incidence of AAD was 8% in the probiotic group, compared to 19% in the control patients.4

Helicobacter pylori infections

The global prevalence of H. pylori infection in paediatric patients is around 32%. Higher rates have been reported in low-income and middle-income compared to high-income countries (43.2% vs 21.7%). Older paediatric patients (13- to 18-years) are more affected than their younger counterparts (41.6% vs 33.9% [seven- to 12-years] vs 26·0% [0- to six-years).28

A 2014 meta-analysis, which included seven RCTs, evaluated the efficacy of probiotic supplementation in paediatric patients undergoing H. pylori eradication therapy. Compared with the control group, participants in the probiotic arm experienced a significant increased eradication rate and reduced risk of adverse effects.5

In another study, researchers showed that Limosilactobacillus as an adjunct to triple eradication therapy increased H. pylori eradication rates by about 13% (71% in the control group versus 84% in the probiotic arm).6

Necrotising enterocolitis in very low birth weight infants

NEC is an ischaemic and inflammatory necrosis of the bowel after the initiation of enteral feeding in preterm infants. The incidence of NEC ranges from 2.6% to 28% and is associated with ~25% increased risk of mortality. Early symptoms indicative of NEC include feeding intolerance, abdominal distention, and discoloration as well as bloody stools.7,8

The 2020 American Academy of Paediatrics (APA) guidelines suggest using a combination of Limosilactobacillus and Bifidobacterium spp., or B. animalis lactis, or L. reuteri, or L. rhamnosus over no and other probiotics in preterm infants with NEC. However, the APA cautions that current evidence cannot support the routine use of probiotics – especially preterm infants weighing <1kg at birth. 9

Paediatric atopic diseases 

The  2015 World Allergy Organization guidelines on the prevention of allergic diseases state that there is a possible prophylactic benefit of using probiotics in pregnant women at high risk for having an allergic child, who breastfed infants at high risk of developing an allergy, or in infants at high risk of developing an allergy.10

Risk factors for developing allergy include a biological parent or sibling with existing or a history of allergic rhinitis, asthma, eczema, or food allergy.11

A systematic review of 29 RCTs, which evaluated 12 different probiotics or combinations, concluded that there are significant benefits of probiotic supplementation in reducing the risk of eczema. Probiotic supplementation does, however, not reduce the risk of other allergic diseases in paediatric patients.12

Functional gastrointestinal disorders

Infantile colic

Between 10% and 30% of otherwise healthy newborns develop infantile colic. Colic is defined by Wessel’s criteria of crying or fussing for three hours or more a day, for three days or more per week, for three weeks in infants aged less than three months.13

Evidence suggests that in breastfed infants, L. reuteri decreases infantile colic, resulting in a mean difference of crying time per day at the age of three weeks of 56 min.14,15

Regurgitation

Gastroesophageal reflux (GER) is defined as the passive passage of gastric contents back into the oesophagus with or without regurgitation and vomiting. This is caused by a transient relaxation of the lower oesophageal sphincter due to postprandial gastric distension. GER leads to troublesome symptoms of excessive crying, feeding refusal, failure to thrive, sleep disturbance, chronic cough or opisthotonos (a condition in which a person holds their body in an abnormal position).16

L. reuteri prevents regurgitation during the first month of life in breast-fed term infants. A RCT compared 40 infants who received probiotic supplementation or placebo and showed, when treated with L. reuteri 108 CFU daily for four weeks, a decrease in the number of regurgitation episodes a day.17

Another RCT studied the impact of L. reuteri during the first three months of life on the onset of colic, reflux, and constipation in term children. The study showed a significant difference for regurgitation episodes a day, 2.9 versus 4.6 in the probiotic and the placebo group, respectively.18,19

Irritable Bowel Syndrome

Irritable bowel syndrome is a type of functional abdominal pain (FAP) disorder. The paediatric Rome IV criteria define it as: abdominal pain for at least four days per month (at least two months prior to diagnosis) associated with a change in frequency of stool and a change in appearance of stool.20

A RCT – involving paediatric patients between six- and 16-years with confirmed diagnosis of FAP – compared the efficacy of L. reuteri in reducing the frequency and intensity of pain, compared to placebo. The authors found that paediatric patients in the L. reuteri arm had significantly lower pain intensity compared with the placebo controls. They concluded that L. reuteri reduces perceived abdominal pain intensity, which may encourage clinicians to use this probiotic in children with FAP.21

Key messages

  1. European guidelines currently recommend the use of  rhamnosusGG, S. boulardiiL. rhamnosus and L. reuteri in the treatment of AGE – especially in patients at risk of developing Clostridioides difficile-associated disease. They should be initiated as early as possible in the course of the disease and reduce duration of diarrhoea22,23,24
  2. Probiotics may be effective for preventing AAD4
  3. Probiotics significant increase pylorieradication rates and reduce the risk of side effects5
  4. The 2020 APA guidelines suggest using a combination of Limosilactobacilluand Bifidobacterium, or B. animalis lactis, or L. reuteri, or L. rhamnosus over no and other probiotics in preterm infants with NEC, but cautions that current evidence cannot support the routine use of probiotics in preterm babies – especially if birth weight is <1kg 9
  5. Probiotics are effective in reducing the risk of eczema but not other allergic diseases12
  6. In breastfed infants  reuteridecreases the duration of crying associated with infantile colic14,15
  7. reuteri prevents regurgitation during the first month of life in breast-fed term infants17
  8. reuteri reduces perceived abdominal pain intensity.21

 

REFERENCES:
  1. Kechagia M, Basoulis D, Konstantopoulou S, et al. Health Benefits of Probiotics: A Review. ISRN Nutr, 2013.
  2. Allen SJ, Martinez EG, Gregorio GV, and Dans LF. Probiotics for Treating Acute Infectious Diarrhea. Cochrane Database Syst Rev, 2010.
  3. Patro-Golab B and Szajewska H. Systematic Review with Meta-Analysis: Lactobacillus reuteri DSM 17938 for Treating Acute Gastroenteritis in Children. An Update. Nutrients, 2019.
  4. Guo Q, Goldenberg JZ, Humphrey C, et al. Probiotics for the Prevention of Pediatric Antibiotic-Associated Diarrhea. Cochrane Database Syst Rev, 2019.
  5. Li S, Huang XL, Sui JZ, et al. Meta-Analysis of Randomized Controlled Trials on the Efficacy of Probiotics in Helicobacter pylori Eradication Therapy in Children. Eur J Pediatr, 2014.
  6. Fang HR, Zhang GQ, Cheng JY, and Li ZY. Efficacy of Lactobacillus-Supplemented Triple Therapy for Helicobacter pyloriInfection in Children: A Meta-Analysis of Randomized Controlled Trials. Eur J Pediatr, 2019.
  7. Gomella T, Cunningham M, and Eyal F.Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs. 7th ed. McGraw-Hill Medical Books; New York, NY, USA: 2013.
  8. Neu J, and Walker W. Necrotizing Enterocolitis. NEJM, 2011.
  9. Su GL, Ko CW, Bercik P, et al. AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology, 2020.
  10. Fiocchi A, Pawankar R, Cuello-Garcia C, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J, 2015.
  11. Boyce JA, et al. Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel. J Allergy Clin Immunol, 2010.
  12. Cuello-Garcia CA, Brozek JL, Fiocchi A, et al. Probiotics for the Prevention of Allergy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Allergy Clin Immunol, 2015.
  13. Wessel MA, Cobb JC, Jackson EB, et al. Paroxysmal Fussing in Infancy, Sometimes Called Colic. Pediatrics, 1954.
  14. Sung V, D’Amico F, Cabana MD, et al.Lactobacillus reuterito Treat Infant Colic: A Meta-Analysis. Pediatrics, 2018.
  15. Harb T, Matsuyama M, David M and Hill RJ. Infant Colic—What Works: A Systematic Review of Interventions for Breast-Fed Infants. J Pediatr Gastroenterol Nutr, 2016.
  16. Rosen R, Vandenplas Y, Singendonk M, et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr, 2018.
  17. Garofoli F, Civardi E, Indrio F, et al. The Early Administration of Lactobacillus reuteri DSM 17938 Controls Regurgitation Episodes in Full-Term Breastfed Infants. Int J Food Sci Nutr, 2014.
  18. 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.
  19. Indrio F, Riezzo G, Raimondi F, et al.Lactobacillus reuteriAccelerates Gastric Emptying and Improves Regurgitation in Infants. Eur J Clin Investig, 2011.
  20. Sandhu BK, and Paul SP. Irritable Bowel Syndrome in Children: Pathogenesis, Diagnosis and Evidence-Based Treatment. World J Gastroenterol, 2014.
  21. Romano C, Ferrau’ V, Cavataio F, et al.Lactobacillus reuteri in Children with Functional Abdominal Pain (FAP). J Paediatr Child Health, 2014.
  22. Szajewska H, Guarino A, Hojsak I, et al. Use of Probiotics for the Management of Acute Gastroenteritis in Children: An Update. J Pediatr Gastroenterol Nutr, 2020.
  23. Szajewska H, Guarino A, Hojsak I, et al. Use of Probiotics for Management of Acute Gastroenteritis: A Position Paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr, 2014.
  24. Szajewska H, Canani RB, Guarino A, et al. Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Children. J Pediatr Gastroenterol Nutr, 2016.
  25. Sanders ME. Researchers submit recommendations for revised Lactobacillus taxonomy https://isappscience.org/researchers-submit-recommendations-for-revised-lactobacillus-taxonomy/
  26. Stuempfig ND, and Seroy J. Viral Gastroenteritis. [Updated 2021 Jun 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK518995/
  27. Alam S and Mushtaq M. Antibiotic associated diarrhea in children. Indian Pediatr, 2009.
  28. Yuan C, Adeloye D, Luk TT, et al. The global prevalence of and factors associated with Helicobacter pyloriinfection in children: a systematic review and meta-analysis. The Lancet, 2020.