Table 1.
Clinical trials of probiotics for prevention of NEC and sepsis in neonates.
| Study | GA (wk) BW (g) |
Probiotic used | Dose and duration | Primary outcome | Comments |
|---|---|---|---|---|---|
| Kitajima et al. 1997, Japan [25] | <1500 N = 91 |
BB | 0.5 × 109 once daily from first feed for 28 days | Gut colonization by BB | No difference in sepsis |
| Dani et al. 2002, Italy [26] | <33 <1500 N = 585 |
LGG | 6 × 109 CFU once daily from first feeds till discharge | Urinary tract infection, bacterial sepsis, NEC | No difference in all three outcomes |
| Costalos et al. 2003, Greece [27] | 28–32 N = 87 |
SB | 109/kg twice daily from first feed for 30 days | Gut function and stool colonization | No difference in sepsis |
| Lin et al. 2005, Taiwan [28] | <1500 N = 367 |
LA, BI
|
LA: 1004356 BI: 1015697 twice daily from day 7 until discharge | NEC | ↓ NEC and sepsis rate in probiotic group (12.2% versus 19.3%) |
| Bin-Nun et al. 2005 Israel [29] | ≤1500 N = 145 |
BI, ST, BB | BI: 0.35 × 109 CFU ST: 0.35 × 109 CFU BB: 0.35 × 109 CFU once daily from first feed to 36 wks |
NEC | ↓ NEC in probiotic group. No difference in sepsis (43% versus 33%) |
| Manzoni et al. 2006, Italy [30] | <1500 N = 80 |
LBC | 6 × 109 CFU once daily from third day of life to 6 wks or discharge from NICU | Gut colonization by Candida | No difference in sepsis |
| Stratiki et al. 2007, Greece [31] | 27–37 N = 78 |
BL | Preterm formula 2 × 107 CFU/g started within 48 h. | Intestinal permeability | No difference in sepsis |
| Lin et al. 2008, Taiwan [32] | <34 <1500 N = 434 |
BB, LA | 2 × 109 CFU/day for 6 weeks | NEC or death | ↓ NEC and mortality. ↑ sepsis risk in probiotic (19.8% versus 11.5%), but nonsignificant |
| Samanta et al. 2009, India [33] | <32 <1500 N = 186 |
BI, BB, BL, LA | 2.5 × 109 CFU/day till discharge | NEC, feed tolerance | ↓ Sepsis in probiotic group (14.3% versus 29.5%) |
| Rougé et al. 2009 France [34] | <32 <1500 N = 94 |
BL, LGG | 1 × 108 CFU per day until discharge | Enteral feed intake at day 14 | No difference in sepsis (33.3% versus 26.5%) |
| Awad et al. 2010, Egypt [35] | All neonate N = 150 |
LA (live and killed) | 6 × 109 CFU twice daily from day 1 till discharged | Sepsis and NEC | ↓ sepsis rate in probiotic groups |
| Mihatsch et al. 2010, Germany [36] | <30 and <1500 N = 183 |
BL | 12 × 109 CFU/Kg/day for 6 weeks | Incidence density of nosocomial infection | No difference in sepsis |
| Romeo et al. 2011, Italy [37] | <37 <2500 N = 249 |
LR
LGG |
LR: 1 × 108 CFU daily LGG: 6 × 109 CFU daily from first 72 hrs to 6 wks or until discharge |
Gut fungal colonization and late onset sepsis | Probiotics effective in prevention of gut colonization by Candida. No difference in sepsis |
| Braga et al. 2011, Brazil [38] | <1500 N = 231 |
LC, BBr | 3.5 × 107–3.5 × 109 CFU Starting from day 2 till 30 days of life |
NEC | No difference in sepsis (33.6% versus 37.5%) |
| Sari et al. 2011, Turkey [39] | <33 <1500 N = 221 |
LS | 3.5 × 109 till discharged | NEC, and mortality | No difference in sepsis (26.4% versus 23.4%) |
| Fernández-Carrocera et al. 2013, Mexico [40] | <1500 N = 150 |
LA, LGG,
LC, LP, BI, ST |
Multispecies probiotics 1 g/day |
NEC | No difference in NEC and sepsis rate (56% versus 58.7%) |
BB: Bifidobacterium bifidus; BL: Bifidobacteruim lactis; LB: Bifidobacterium breve; LGG: Lactobacillus rhamnosus GG; LS: Lactobacillus sporogenes; SB: Saccharomyces boulardii; BBr: Bifidobacteria breve; BLo: Bifidobacterium longum; LC: Lactobacillus casei; NEC: necrotizing enterocolitis; ST: Streptococcus thermophillus; BI: Bifidobacterium infantis; CFU: colony forming units; LP: Lactobacillus plantarum; LR: Lactobacillus reuteri.