Eleanor Danan Sadler, PharmD

The Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO) define probiotics as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.”

 Probiotics usually include members of the bacteria genera 

 The evidence supporting the use of probiotics in pediatrics is variable, with no fully comprehensive guidelines for probiotic use available.

As there is no regulatory framework for the manufacturing of probiotics, preparations differ in the types of bacteria, numbers of strains, and colony-forming units (CFUs) of microorganisms that they contain. Additionally, prescriptions are not needed to obtain probiotics and appropriate dosing recommendations are not well defined for children or adults, illustrating the need for more well-designed clinical studies to support their routine use.

Probiotics have been used for many indications, ranging from prevention of antibiotic-associated diarrhea (AAD) to the treatment of inflammatory bowel disease.

 Based on reviews and guidelines from several key working groups, including the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN), the European Society for Gastroenterology, Hepatology, and Nutrition (ESPGHAN), and the Latin American Expert Group, the efficacy of probiotics is shown in preventing AAD, severe recurrent 

-associated diarrhea (CDAD), and mild-to-moderate acute diarrhea, mainly with 

Although a recent meta-analysis of 17 randomized controlled trials (RCTs; n=3953) demonstrated that children receiving probiotics (majority of studies evaluated 

 cfu/mL) had a 29% risk reduction (95% confidence interval [CI]: 0.54-0.94) of being prescribed antibiotics compared with those who received placebo,

 additional studies are needed to substantiate these findings.

Some other uses of probiotics in children include the treatment of travelers’ diarrhea and acute infectious diarrhea; irritable bowel syndrome (IBS); constipation; infantile colic; necrotizing enterocolitis (NEC); and 

 Probiotics may be beneficial in maintaining remission in ulcerative colitis (UC), reducing the risk of NEC in premature infants, and improving symptoms of IBS.

Lately, the use of probiotics also has extended beyond that of preventing or treating gastrointestinal conditions. With growing studies that show possible associations of the gut microbiome with immune development, vaccine responses, and other conditions such as asthma, eczema, diabetes, and autism spectrum disorder,

 the use of probiotics has been raised by patients, researchers, and health professionals to attempt to improve nongastrointestinal-related health outcomes. Patients supplemented with prebiotics or probiotics have enhanced influenza antibody titers after vaccination,

 showing promise for the possible use of such products to improve vaccine efficacy. Whereas there is potential for probiotics to play a role in therapy, further investigations including RCTs should be pursued.

The Table provides a summary of selected meta-analyses and individual studies for probiotic use in various conditions in pediatrics.

There are limited data on the safety of probiotics in pediatric patients. Cases of serious infections attributed to organisms that may be contaminants of the probiotic product,

 or by breakthrough bacterial infections from the probiotics themselves, have been reported in the literature.

 Some experts have proposed major risk factors for infection including prematurity and immunocompromised states, and minor risk factors including the presence of a central venous catheter, impaired intestinal epithelial barrier, administration through jejunostomy tubes, and cardiac valvular disease (

 Caution is advised for patients with a single major risk factor or more than 1 minor risk factor.

In December 2014, the US Food and Drug Administration (FDA) issued a warning to healthcare providers about the risk of probiotic use in immunocompromised patients, referring to an example involving a premature infant who developed fatal gastrointestinal mucormycosis from 

 The infection was attributed to a contaminant in an unopened container of probiotic powder with active ingredients listed as 

. This is a reminder that probiotics are dietary supplements not subject to FDA review, and providers wishing to use these products as drugs (eg, to treat, mitigate, cure, or prevent a disease or condition) should submit an Investigational New Drug (IND) application for review. On the other hand, infant formulas with added probiotics are under FDA regulation and must be made in compliance with good manufacturing practices, although probiotics’ proven benefit is unclear with a paucity of robust evidence.

Whereas there also have been several studies showing that probiotic use has been safe in certain patient populations, such as LGG use in very-low-birth-weight preterm infants,

 interpreting the data on efficacy and safety of probiotics is complicated, especially because of the heterogeneity of probiotic formulations and the wide variety of diseases in which they have been used. Because of the lack of studies evaluating the safety and efficacy of probiotic use in immunocompromised children, current recommendations do not recommend the use of probiotics for the prevention of 

 infection in pediatric patients with cancer or hematopoietic stem cell transplants.

Several studies suggest the beneficial use of probiotics in some circumstances. However, there is insufficient evidence for recommendations on the routine use of probiotics in children.

 As the probiotics industry continues to grow, consistent global regulations, more well-designed human studies, and better safety data are needed to clarify the benefits of probiotics.

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More clinical studies and safety data are needed to clarify any benefits of using probiotics for children.

Eleanor Danan Sadler, PharmD

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Probiotics in children: To use or not to use?