Your Family Physician

The use of probiotics and prebiotics may increase a child's resistance to respiratory tract infections, according to the results of a double-blind randomized trial reported in the July issue of Pediatrics.

"Live probiotic bacteria and dietary prebiotic oligosaccharides (together termed synbiotics) increasingly are being used in infancy, but evidence of long-term safety is lacking," write Kaarina Kukkonen, MD, from University of Helsinki in Helskinki, Finland, and colleagues. "Probiotics and prebiotics are known to modulate immune responses."

Study enrollment took place between November 2000 and March 2003. Pregnant mothers carrying infants at high risk for allergy were randomized to receive a mixture of 4 probiotic species (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99, and Propionibacterium freudenreichii ssp shermanii) or a placebo for 4 weeks before delivery. For 6 months after birth, infants received the same probiotics with 0.8 g of galactooligosaccharides or a placebo daily.

Follow-up visits at ages 3, 6, and 24 months included clinical examinations and interviews for collection of safety and growth data. Questionnaires administered at ages 3, 6, 12, and 24 months also assessed these outcomes. Two-year follow-up assessment was completed for 925 of 1018 eligible infants.

In both groups, infants grew normally, with no apparent between-group differences in neonatal morbidity, infantile colic or other feeding-related behaviors, or serious adverse events. Antibiotics were prescribed less often in the synbiotic vs the placebo group (23% vs 28%) during the 6-month intervention. During follow-up, respiratory tract infections were less frequent in the synbiotic vs the placebo group (mean, 3.7 vs 4.2 infections).

"Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life," the study authors write. "Additional in vivo studies are warranted to identify the immunologic mechanisms that produce these benefits."

The Helsinki University Central Hospital Research Funds and Valio (Helsinki, Finland) supported this study. Valio funded Dr. Kukkonen's salary and a grant to another study author, employed 2 other study authors, and provided consulting fees to another study author.

Pediatrics. 2008;122;8-12. Published online July 1, 2008.

Clinical Context

Study Highlights

• 1223 women pregnant with infants at high risk for allergy were randomly assigned to take a probiotic capsule or placebo twice daily for 4 weeks before delivery.
• The probiotic capsule contained 4 probiotic species: L rhamnosus GG and LC705, B breve Bb99, and P freudenreichii ssp shermanii JS.
• Exclusion criteria were birth at less than 37 weeks of gestation, being a B twin, and major malformation.
• Of 1018 infants, 506 received the powder from the probiotic capsule mixed with liquid plus 0.8 g of liquid bovine GOSs, and 512 received the placebo of microcrystalline cellulose and sugar syrup daily.
• The baseline characteristics of the synbiotic and placebo groups were similar for sex (male, 49% - 50%), mean birth weight (3993 - 3995 g), birth length, vaginal delivery (83%), maternal smoking (13% - 16%), daily tobacco smoke exposure (29% - 32%), partially breast-fed for at least 6 months (68% - 71%), breast-feeding duration (8 months), day care attendance before age 2 years (50% - 51%), birth order (firstborn, 52% - 58%), maternal allergy (81%), and both parents allergic (38%).
• A pediatrician examined the infants and interviewed the parents at ages 3, 6, and 24 months.
• Parents completed questionnaires on interim information at ages 3, 6, 12, and 24 months.
• The 2-year evaluation was completed in 925 infants (461 synbiotic and 464 placebo).
• Parent-reported morbidity (including jaundice, hypoglycemia, infection, and oxygen supplementation) was not significantly different for the synbiotic vs placebo groups.
• Infantile colic (crying at least 4 hours per day for at least 3 days per week) occurred in 4% of each group.
• Crying once or twice per week occurred in 10% of each group.
• Defecating at least 3 times a day occurred less in synbiotic vs placebo group (18% vs 29%; P < .001).
• The frequency of feeding related-behaviors (including vomiting, constipation, excessive crying, and abdominal discomfort) was similar for both groups.
• Reasons for discontinuing the synbiotic or placebo product were similar for both groups.
• 1 infant in the synbiotic group had a choking episode related to the powder, which resolved.
• Reasons for hospitalization up to age 2 years were considered to be unrelated to the intervention.
• Measurements of weight, length, and head circumference at ages 6 and 24 months showed normal growth that was similar for both groups.
• Results for the 6-month intervention phase:
  • Antibiotics were prescribed for fewer infants in synbiotic vs placebo group (23% vs 28%; odds ratio [OR], 0.74; 95% confidence interval [CI], 0.55 - 1.00; P = .049).
  • The synbiotic vs placebo groups had similar occurrences of at least 1 respiratory tract infection (66% vs 68%), middle ear infection (15% vs 19%), and gastroenteritis (13% vs 14%).
• Results for follow-up from 6 to 24 months:
  • Respiratory tract infections were less common in synbiotic vs placebo group (93% vs 97%; OR, 0.49; 95% CI, 0.27 - 0.92; P = .023).
  • The number of respiratory tract infections was lower in the synbiotic vs placebo group (geometric mean, 3.7 vs 4.2; P = .009).
  • Antibiotic use was similar for synbiotic vs placebo group (80% vs 83%).
  • The synbiotic vs placebo groups had similar occurrences of middle ear infections (72% vs 76%) and gastroenteritis (74% vs 71%).
• Limitations of the study included lack of data on duration and severity of illnesses.

Pearls for Practice

• Allergy-prone infants who ingest probiotics and prebiotics for 6 months have less antibiotic use during the first 6 months and fewer respiratory tract infections between 6 and 24 months but no decrease in occurrence of middle ear infections or gastroenteritis.
• A 6-month course of probiotics and prebiotics in allergy-prone infants does not affect neonatal morbidity, feeding-related behaviors, growth, or the incidence of serious adverse events. Powder forms should be mixed adequately to prevent choking.

Source : http://cme.medscape.com/viewarticle/577025?sssdmh=dm1.486302&src=nldne