Probiotics to Prevent NEC: Get on Board

William T. Basco, Jr., MD, MS


August 15, 2014

Cohort Study of Probiotics in a North American Neonatal Intensive Care Unit

Janvier A, Malo J, Barrington KJ
J Pediatr. 2014;164:980-985

Probiotics in Preterm Infants

Despite extensive evidence on the benefits of probiotics in reducing the incidence of necrotizing enterocolitis (NEC), they are not approved in Canada for NEC prevention. Janvier and colleagues report the experience at a single neonatal intensive care unit (NICU) in Montreal, Quebec, in which they compared outcomes of 17 consecutive months of routine probiotic use with outcomes from the previous 17-month period.

In July 2011, the hospital changed feeding practices and began administering probiotics to all infants < 32 weeks' gestation. The product used was a mixture of 4 Bifidobacterium species and 1 Lactobacillus species, mixed in 1 mL of water and given once daily. The probiotic mixture was continued until the infants reach 34 weeks' postmenstrual age, regardless of patient clinical condition or complications, except when infants were temporarily placed on a nothing-by-mouth (NPO) status.

Standard classification methods were used to diagnose NEC, and the radiologists reading radiographic images were not aware of the change in clinical practice in the NICU. The 2 groups of infants (before and after) were approximately equivalent, with 317 children in the "before" group (the pre-probiotic cohort) compared with 294 in the "after" group (the probiotic cohort).

The mean gestational age was 29 weeks, and the mean birthweight was approximately 1200 g. A slightly higher percentage of the probiotic cohort (16%) were small for gestational age (SGA) compared with 11.4% of the prebiotic cohort. Furthermore, 51% of the probiotic cohort were boys compared with 44% of the prebiotic cohort.

Two outcomes -- NEC and death -- were evaluated, as well as the combined outcome of NEC or death. Infants in the probiotic cohort were much less likely to experience NEC (5%) than those in the pre-probiotic cohort (10%). This difference reached statistical significance, at P < .05. The combined outcome of NEC or death was also lower in the probiotic cohort (11% vs 17% in the pre-probiotic cohort). Another difference of clinical interest was that total parenteral nutrition could be discontinued at a mean age of 18 days in the probiotic cohort vs 28 days in the pre-probiotic cohort.

In a regression analysis that controlled for gestational age, SGA status, sex, the presence of an umbilical arterial catheter, and need for mechanical ventilation for > 3 days, infants in the probiotic cohort had a lower odds of experiencing NEC at 0.51 (95% confidence interval, 0.26-0.98); the odds ratio for experiencing the combined outcome of NEC or death was 0.56, also statistically significant. Being SGA was associated with significantly increased odds of experiencing either NEC or death.

Janvier and colleagues calculated a number needed to treat of 20 to prevent 1 adverse outcome of either death or NEC. There were no cases of sepsis related to probiotic organisms in these cohorts.


The introduction and discussion sections of the article, and the accompanying editorial,[1] are as interesting as the research findings, because Janvier and colleagues review the preponderance of data supporting the use of probiotics in preterm infants, and the dilemmas that neonatal caregivers face in deciding whether to quickly apply what could be a substantial advance in patient care. Janvier and colleagues also report an off-the-cuff calculation of the cost of preventing 1 case of NEC or death with probiotics: a whopping $260!

It is fascinating in this case to reflect on how regulatory issues are lagging behind. I wonder how many other NICUs routinely use probiotics, given the preponderance of evidence, but without knowing how the US Food and Drug Administration will ultimately regulate these products?


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