Elsevier

The Journal of Pediatrics

Volume 166, Issue 3, March 2015, Pages 545-551.e1
The Journal of Pediatrics

Original Article
The ProPre-Save Study: Effects of Probiotics and Prebiotics Alone or Combined on Necrotizing Enterocolitis in Very Low Birth Weight Infants

https://doi.org/10.1016/j.jpeds.2014.12.004Get rights and content

Objective

To test the efficacy of probiotic and prebiotic, alone or combined (synbiotic), on the prevention of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants.

Study design

A prospective, randomized, controlled trial was conducted at 5 neonatal intensive care units in Turkey. VLBW infants (n = 400) were assigned to a control group and 3 study groups that were given probiotic (Bifidobacterium lactis), prebiotic (inulin), or synbiotic (Bifidobacterium lactis plus inulin) added to breastmilk or formula for a maximum of 8 weeks before discharge or death. The primary outcome was NEC (Bell stage ≥2).

Results

The rate of NEC was lower in probiotic (2.0%) and synbiotic (4.0%) groups compared with prebiotic (12.0%) and placebo (18.0%) groups (P < .001). The times to reach full enteral feeding were faster (P < .001), the rates of clinical nosocomial sepsis were lower (P = .004), stays in the neonatal intensive care unit were shorter, (P = .002), and mortality rates were lower (P = .003) for infants receiving probiotics, prebiotics, or synbiotic than controls. The use of antenatal steroid (OR 0.5, 95% CI 0.3-0.9) and postnatal probiotic (alone or in synbiotic) (OR 0.5, 95% CI 0.2-0.8) decreased the risk of NEC, and maternal antibiotic exposure increased this risk (OR 1.9, 95% CI 1.1-3.6).

Conclusions

In VLBW infants, probiotic (Bifidobacterium lactis) and synbiotic (Bifidobacterium lactis plus inulin) but not prebiotic (inulin) alone decrease NEC.

Section snippets

Methods

The ProPre-Save trial is a multicenter, prospective, randomized, double-blind, randomized controlled trial (RCT) in which the supplementation of VLBW infants with probiotic, prebiotic, or synbiotic was compared with placebo. The trial was conducted from June 2011 to June 2014 at 5 tertiary NICU centers from different geographical regions of Turkey (Dr Sami Ulus Maternity and Children Research and Training Hospital, Ankara; Diyarbakır Maternity and Children Hospital, Diyarbakır; Şevket Yılmaz

Results

There were 677 VLBW infants admitted to the 5 NICUs during the 3-year study period. Of these infants, 277 were excluded. A total of 400 VLBW infants were eligible for the study: 300 were randomly assigned to 1 of the 3 active intervention groups (100 in each group) and 100 to the placebo group (Figure; available at www.jpeds.com).

The maternal and infants demographic characteristics did not differ (Table I). Enteral feeding was initiated at a similar postnatal age in groups. Oral supplementation

Discussion

Bifidobacterium lactis alone or in combination with inulin reduces the incidence of NEC in VLBW infants. The prebiotic alone had no effect in the prevention of NEC. Late-onset infection in the NICU is associated with prolonged hospitalization, morbidity, and mortality. In premature infants hospitalized in NICU, GI colonization with normal bacterial flora (eg, Bifidobacterium spp. and Lactobacillus spp.) is delayed and lacks biodiversity, whereas colonization with potentially pathogenic bacteria

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    The authors declare no conflicts of interest.

    Registered with ClinicalTrials.gov: NCT01807858.

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