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Table 1 Studies included in the systematic review and meta-analysis

From: Probiotics for prevention of necrotizing enterocolitis in preterm infants: systematic review and meta-analysis

Author, year Study details Study population Intervention Type of milk Placebo
- Strain
- Dose (D)
- Start of treatment (S)
- End of treatment (E)
Al-Hosni, 2012 [33] P Preterm infants with BW 501–1000 g, appropriate for gestational age, and ≤ 14 days of age at time of feeding initiation Lactobacillus rhamnosus GG LGG Non specified Extra milk
DB Bifidobacterium infantis
R D: 0.5 × 109 CFU each probiotic, OD
C S: first enteral feeding
Multic. E: discharge or until 34 w postmenstrual age
Bin-Nun, 2005 [40] P Preterm infants with BW < 1500 g, who began enteral feeding on a weekday Bifidobacterium infantis OMM, PFM HM or FM
B Streptococcus thermophilus
R Bifidobacterium bifidus
C D: 0.35 × 109 CFU each probiotic, OD
S: start of enteral feeding
E: 36 w postconceptual age
Braga, 2011 [35] P Inborn infants with BW 750–1499 g Lactobacillus casei HM Extra HM
DB Bifidobacterium breve
R D: 3.5 × 107 CFU to 3.5 × 109 CFU OD
C S: day 2
E: day 30, NEC diagnosis, discharge, death, whichever occurred first
Costalos, 2003 [49] P GA 28–32 w Saccharomyces boulardii PFM MDX
R No major GI problem D: 1 × 109 CFU BD
C Not receiving antibiotics S: non-specified
Not receiving breast milk Median duration of probiotic supplementation: 30 days
Dani, 2002 [42] P Infants with GA < 33 w or BW < 1500 g Lactobacillus rhamnosus GG OMM, DM or FM MDX
DB D: 6 × 109 CFU OD
R S: first feed
C E: discharge
Multic.
Demirel, 2013 [28] P Preterm infants with GA ≤ 32 w and BW ≤ 1500 g, who survived to feed enterally Saccharomyces boulardii HM, FM None
B D: 5 × 109 CFU OD
R S: first feed
C E: discharge
Dilli, 2015 [44] P Preterm infants with GA <32 weeks and BW <1500 g, born at or transferred to the NICU within the first week of life and fed enterally before inclusion Bifidobacterium HM, FM MDX powder
DB Lactis
R D: 5 × 109 CFU
C S: beyond d7 after birth
Multic. E: death or discharge (max 8 weeks)
Fernández-Carrocera, 2013 [32] P Preterm infants with BW < 1500 g Lactobacillus acidophilus 1 CFU/g OMM, PFM None
DB Infants with NEC IA and IB were excluded Lactobacillus rhamnosus 4.4 × 108 CFU/g
R Lactobacillus casei 1 × 109 CFU/g
C Lactobacillus plantarum 1.76 × 108 CFU/g
Bifidobacterium infantis 2.76 × 107 CFU/g
Streptococcus thermophilus 6.6 × 105 CFU/g
Total D: 1 g powder OD
S: start of enteral feeding
E: non-specified
Jacobs, 2013 [26] P Preterm infants with GA <32 w and BW < 1500 g Bifidobacterium infantis BB-02 300 CFU × 106 HM, FM MDX powder
DB Streptococcus thermophilus Th-4 350 CFU × 106
R Bifidobacterium lactis BB-12 350 CFU × 106
C Total D: 1 × 109 CFU × 1.5 g maltodextrin powder OD
Multic. S: enteral feed ≥ 1 ml every 4 h
E: discharge or term corrected age
Kitajima, 1997 [52] P Preterm infants with BW < 1500 g Bifidobacterium breve YIT4010 OMM, FM after full enteral feeding had been reached Distilled water
R D: 0.5 × 109 CFU OD
C S: within 24 h of life
Duration of probiotic supplementation: 28 days
Lin, 2005 P Infants with BW < 1500 g, who started to feed enterally and survived beyond day 7 Lactobacillus acidophilus OMM, DM None
M Bifidobacterium infantis
R D: ≥ 106 CFU each probiotic (=125 mg/kg), BD
C S: start of enteral feeding
E: discharge
Lin, 2008 P Preterm infants with GA < 34 w and BW ≤ 1500 g, who survived to feed enterally Lactobacillus acidophilus NCDO 1746 HM, FM None
B Bifidobacterium bifidum NCDO 1453
R D: 1 × 109 CFU each probiotic (=125 mg/kg) BD
C S: day 2 of age
Multic. Duration: 6 weeks
Manzoni, 2006 [37] P Infants with BW < 1500 g, ≥ 3 days of life, who started enteral feeding with HM Lactobacillus rhamnosus LGG OMM, DM None
DB D: 6 × 109 CFU/day
R S: day 3 of life
C E: end of the 6th week or discharge
Mihatsch, 2010 [43] P Preterm infants with GA < 30 w and BW ≤ 1500 g Bifidobacterium lactis BB12 HM, PFM Indistinguishable powder
R D: 2 × 109 CFU/kg 6 times a day
C S: start of enteral feeding
E: non-specified
Mohan, 2006 [53] P Preterm infants (GA < 37 w) Bifidobacterium lactis BB12 FM Not stated
DB D: 1.6 × 109 CFU on day 1 to 3, and 4.8 × 109 CFU from day 4 onwards
R S: first day of life
C Duration: 21 days
Oncel, 2013 [25] P Preterm infants with GA ≤ 32 w and BW ≤ 1500 g, who survived to feed enterally Lactobacillus reuteri DSM 17938 HM, FM Oil base
DB D: 1 × 108 CFU OD
R S: first feed
C E: death or discharge
Patole, 2014 [45] P Preterm infants with GA < 33 w and BW < 1500 g Bifidobacterium breve M16-V HM, FM Dextrin
DB D: 3 × 109 CFU OD (1.5 × 109 CFU OD for newborns ≤ 27 w until they reached 50 ml/kg/day enteral feeds)
R S: start of enteral feed
C E: corrected age of 37 w
Rojas, 2012 [30] P Preterm infants with BW ≤ 2000 g, hemodynamically stable, ≤ 48 h of age (regardless start of enteral feeding) Lactobacillus reuteri DSM 17938 HM, FM Oil base
DB D: 1 × 108 CFU OD
R S: age ≤ 48 h
C E: death or discharge
Multic.
Rougé, 2009 [50] P Preterm infants with GA < 32 w and BW < 1500 g, ≤ 2 w of age, without any disease other than those linked to prematurity, who started enteral feeding before inclusion Bifidobacterium longum BB536 OMM, DM or PFM MDX
DB Lactobacillus rhamnosus GG BB536-LGG
R Total D: 1 × 108 CFU/day
C S: start of enteral feeding
Bic. E: discharge
Roy, 2014 [58] P Preterm infants (GA < 37w) and BW < 2500 g, with stable enteral feeding within 72 h of birth Lactobacillus acidophilus 1.25 × 109 CFU × 1 g HM Sterile water
DB B. longum 0.125 × 109 CFU × 1 g
R B. bifidum 0.125 × 109 CFU × 1 g
C B. lactis 1 × 109 CFU × 1 g
D: half a 1 g sachet
S: from 72 h of life
E: after 6 w or at discharge
Saengtawesin, 2014 [48] P Preterm infants with GA ≤ 34 w and BW ≤ 1500 g Lactobacillus acidophilus 1 × 109 CFU HM, PFM None
R Bifidobacterium
C bifidum 1 × 109 CFU
D: 125 mg/kg BD
S: start of feeding
E: 6 w of age or discharge.
Samanta, 2009 P Preterm infants with GA < 32 w and BW < 1500 g, who started enteral feeding and survived beyond 48 h of age Bifidobacterium infantis HM None
DB Bifidobacterium bifidum
R Bifidobacterium longum
C Lactobacillus acidophilus
D: 2.5 × 109 CFU each probiotic, BD
S: start of enteral feeding
E: discharge
Sari, 2011 [34] P Preterm infants with GA < 32 w or BW < 1500 g, who survived to feed enterally Lactobacillus sporogenes HM, FM None
B D: 0.35 × 109 CFU OD
R S: first feed
C E: discharge
Serce, 2013 [27] P Preterm infants with GA ≤ 32 w and BW ≤ 1500 g, who survived to feed enterally Saccharomyces boulardii HM, FM Distilled water
M D: 0.5 × 109 CFU/kg BD
R S: non-specified
C E: non-specified
Stratiki, 2007 [39] P Preterm infants with GA 27–32 w, formula-fed, without major congenital anomalies Bifidobacterium lactis FM None
B D: 2 × 107 CFU/g of milk powder
R S: start of enteral feeding
C E: non-specified
Totsu, 2014 [46] P Infants with BW < 1500 g Bifidobacterium bifidum HM, FM Dextrin
DB   D: 2.5 × 109 CFU, divided in two doses
CLR   S: within 48 h after birth
C   E: body weight 2000 g
Multic.
  1. P prospective, DB double-blinded, R randomized, C controlled, Multic multicentric, B blinded, M masked, Bic bicentric, BW birth weight, GA gestational age, NEC necrotizing enterocolitis, HM human milk, CFU colony forming unit, OD once daily, BD twice daily, OMM own mother’s milk, PFM preterm formula, DM donor milk, FM formula, MDX maltodextrin