Riddle me this: Probiotics in newborns and children

Among the most common questions parents and caregivers ask pediatricians when gastro issues arise may be about the use of probiotics.

In a world where advertising messaging to concerned parents is both well funded and ubiquitous, they turn to you for the best counsel in a field with few clinical practice guidelines, and a paucity of regulations, but an abundance of health claims. Worse, there seems a pervading sense that such supplements, because they are available over the counter, are innocuous and harmless.

Are you a probiotics pro?

How’s your grasp of fact and fiction in probiotics? Is there a role for them in the treatment or prevention of irritable bowel syndrome, constipation, diarrhea-even autism? Are there legitimate concerns about their use in a patient population with immature immune systems?

By definition, a probiotic is a microorganism that when consumed maintains or restores beneficial bacteria to the digestive tract. Probiotics can be supplied through foods, beverages, and dietary supplements.

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Ilya Ilyich Mechnikov, a Ukrainian and Russian zoologist perhaps best known for his Nobel Prize-winning research in immunology, is regarded as the father of probiotics. In 1907, he hypothesized that replacing or diminishing the number of “putrefactive” bacteria in the gut with lactic acid bacteria could normalize bowel health and prolong life.

Today, although there are data pointing to the microbiome and the role it plays in systemic health and illness from eczema to autism, the wide variance of the efficacy of probiotic therapy appears to be both strain and disease specific-quite effective in some disease processes, not useful in others. So, then, thumbs up on Lactobacillus over Saccharomyces boulardii for infectious diarrhea?

Ready for a gut check on probiotics?

1. Probiotics have a well-established clinical benefit for treatment of gastroenteritis in children and is indicted as standard practice.

True

False

Answer: False

Evidence from controlled trials and pooled data offer support for the use of probiotics to treat acute diarrhea in children and have resulted in its recommendation by some professional societies. However, much of the evidence supporting this recommendation is limited because of methodologic problems, small sample sizes, and other problems.

Recent data published in November 2018 from two high-quality, sufficiently powered, randomized controlled trials provide evidence from the largest trials to date on the benefit of probiotics in this setting. In total, the two studies enrolled 1857 infants (3-48 months) with moderate-to-severe gastroenteritis who presented to the emergency department and subsequently randomized to standard therapy (including antibiotics if indicated) plus a 5-day course of probiotics or placebo.

Neither study showed any benefit to the addition of probiotics as measured by the primary outcome of the study, which assessed the differences in clinical severity of gastroenteritis after 14 days of treatment. Along with no significant difference between the two groups in clinical severity of disease, the studies did not find a difference between the two groups in duration of diarrhea and vomiting, number of unscheduled clinic visits, nor duration of absenteeism from day care.

Notably, both studies only looked at one probiotic (Lactobacillus rhammosus), with one study using a combination of L. rhammosus and L. helveticus. Other probiotics not tested may offer different outcomes, but high-quality clinical trials such as these two recent trials are needed to test these.

Sources

Schnadower D, Tarr PI, Casper C, et al. Lactobacillus rhamnosus GG versus Placebo for Acute Gastroenteritis in Children. N Engl J Med 2018;379:2002-2014.

Freedman SB, Williamson-Urquhart S, Farion KJ, et al. Multicenter Trial of Combination Probiotic for Children with Gastroenteritis. N Engl J Med 2018;379:2015-2026.

LaMont JT. Probiotics for Children With Gastroenteritis. N Engl J Med 2018;379:2076-2077.

2. Some evidence supports the benefit of probiotics on reducing necrotizing enterocolitis in preterm infants, yet questions remain about their routine clinical use in this setting. Which of the following are unresolved questions that clinicians and practices should consider before using probiotics for necrotizing enterocolitis as routine therapy?

a) Currently available commercial probiotics lack regulation oversight so the quality of each probiotic is not evident by its label.

b) Some infants are too small in size and weight to administer probiotics.

c) The safety of introducing live microorganisms to immature infants and case reports of probiotic-associated sepsis

d) All of the above

e) A and C

Answer: E (Both A and C)

A recent review of probiotics and necrotizing enterocolitis showed that pre-clinical, clinical, and observational data generally support the benefits of probiotics for decreasing necrotizing enterocolitis and all-cause mortality (but mixed results for the benefit on sepsis).

However, the author of the review recommends that clinicians consider a number of issues before using probiotics as routine use for this indication. Among the key recommendations is for clinicians and practices to use quality improvement principles to evaluate the benefits or harms of the commercially probiotics currently available for use, and to be aware of concerns over the potential risk of probiotic-related sepsis as has been reported in case studies.

In addition, the author highlights the limited data on long-term outcomes of probiotic use in preterm infant, and also the variability of optimal dose, age, and duration of treatment in the current clinical data.

Source

Patel RM, Underwood MA. Probiotics and necrotizing enterocolitis. Seminars in Pediatric Surgery 2018;27:39-46.

3. What factors predispose a child to experience more severe side effects when given probiotics?

a)        Having a mother who is lactose-intolerant

b)        Having an underlying disease or severe underlying comorbidities

c)         Having been hospitalized

d)        Having a central line catheter

e)         All of the Above

f)         Answers B, C, and D

Answer: F (B, C, and D)

The most common side effects of probiotics are bloating and flatulence. Constipation   and increased thirst have also been reported.

More serious adverse effects include sepsis, fungemia, bacteremia, and endocartitis, and are seen mainly in people who are immunosuppressed. Any prior hospitalization, underlying disease, severe underlying comorbidities, and central line catheters are all factors that predispose people to experiencing a serious adverse effect. Probiotics should be used with caution in these patients.

Source

Mascarenhas MR. Probiotics in Kids: What is the Evidence. Medscape. July 31, 2018. https://www.medscape.com/viewarticle/899905

Hojsak I, Fabiano V, Pop TL, et al. Guidance on the use of probiotics in clinical practice in children with selected clinical conditions and in specific vulnerable groups. Acta Paediatrica 2018;107;927-937. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969308/pdf/APA-107-927.pdf

4. Currently, there is no evidence on specific probiotics to use for specific conditions.

True

False

Answer: False

Specific strains of probiotics have been identified and suggested for a number of conditions. Examples include specific strains to prevent upper respiratory tract infections in children attending day care centers, prevention of nosocomial diarrhea, prevention of antibiotic-associated diarrhea, and treatment of infantile colic in breastfed babies.

Source

Hojsak I, Fabiano V, Pop TL, et al. Guidance on the use of probiotics in clinical practice in children with selected clinical conditions and in specific vulnerable groups. Acta Paediatrica 2018;107;927-937. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969308/pdf/APA-107-927.pdf

5. Probiotics may play a therapeutic role for children with autism.

True

False

Answer: True

Although clinical trials are needed to understand and assess the role probiotics may play in children with autism, some data show that the microbiome in patients with autism is different from those without autism and that gastrointestinal symptoms of children with autism may mirror the symptoms of people with irritable bowel syndrome.

Currently, many families with an autistic child use alternative therapies to augment the standard of care. Among the conditions for which parents seek alternative therapies for their autistic child is for gastrointestinal symptoms. As such, there is speculation that probiotics may provide a therapeutic option for managing gastrointestinal symptoms but no evidence yet shows this.

Source

Lenfestey MW, Neu J. Probiotics in Newborns and Children. Pediatr Clin N Am 2017;64:1271-1289.