University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• Does probiotic administration in Very Low Birth Weight (VLBW) infants reduce the incidence of Necrotizing Enterocolitis (NEC) when compared to placebo?

Clinical Bottom Lines

1. Oral Infloran (L acidophilus and B infantis) administration in VLBW infants reduces the incidence and severity of NEC.¹
2. The number needed to treat in order to prevent one case of NEC is 24.
3. Further studies are necessary to determine the safety and long term consequences of probiotic administration.
4. Additional investigation is warranted before this practice becomes universally recommended.

Summary of Key Evidence

1. 367 VLBW infants were enrolled in this study between 7/1/1999 and 12/31/2003 at the Level IIII NICU of China Medical University Hospital in central Taiwan.¹
2. Criteria for eligibility included VLBW < 1500 grams, receiving enteral feeds, and age beyond day of life 7.
3. 180 patients randomized to study group, 187 to control group.
4. Study group received Infloran 125 mg/kg/dose BID mixed with breast milk (either mother’s, or from breast milk bank) through entire NICU course.
5. Providers & families blinded to randomization; Infloran mixed by breast milk team prior to provision to NICU.
6. There were no statistically significant differences between the two groups in regards to initial prognostic variables and subsequent clinical variables throughout the hospital course.
7. All infants were fed using the same clinical protocols/guidelines.
8. Primary outcomes were incidence of NEC or death.
9. Results revealed that the study group had a statistically significant lower incidence of NEC or death compared to the control group; NNT to prevent one case of NEC was 24.
10. Six cases of stage III NEC occurred in the control group; none in the study group.
11. No patients in this study with culture proven sepsis grew L acidophilus or B infantis.

Additional Comments

• Comments on the study validity: Were there variations in NEC incidence throughout different time periods of the study? Could blinding have been affected by physical differences in appearance of milk? What about clues from patients’ stool consistencies/patterns? How consistent were the guidelines for re-starting feeds if they were held?
• Hypothesized that probiotics may provide nonpathologic flora, with an increased barrier to the translocation of pathogenic bacteria, while also limiting growth of these other pathogens.
• Encouraging data thus far; still not universally recommended practice, but further multi-center trials are underway.
• Different strains/formulations of probiotics, doses, timing, length of treatment, and other factors still need to be considered.
• Study not adequately powered or designed to fully evaluate side effects or long-term effects of probiotic administration.
• NEC remains multifactorial.

Citation

1. Lin HC, Su BH, Chen AC, et al. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics 2005;115:1-4

CAT Author: Win Boon, MD

CAT Appraisers: Amanda Dempsey, MD

Date appraised: April 25, 2007