Participants. probiotic. /placebo)

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1 Table S1. Demographic characteristics of trials included in the meta-analysis. Study Birth weight (mean±sd) Gestation (wk) Feeding patterns Participants (probiotic /placebo) Probiotic agents Dosage Duration Outcomes Kitajima (7) 1026±241g/1026±205g wk MM;FM 45/46 BB organisms From first feed for 28 Dani (8) 1325±361g/1345±384g <37 wk MM;DM;F 295/290 LB-GG CFU Since first feed until M Costalos (9) 1651g/1644g* wk FM 51/36 SB 10 9 organisms/kg twice From first feed for 30 Bin-Nun (10) 1152±262g/1111±278g <37 wk MM;FM 72/73 BI;ST;BBB CFU once of BI, From first feed to 36 ST, and BBB wk corrected age Lin (11) 1104±242g/1171±243g NP MM;DM 180/187 LB-A;BI 125mg/kg twice of LB-A, From day 7 until BI Manzoni (12) 1212±290g/1174±340g <37 wk MM;DM 39/41 LB-C CFU once From day 3 of life to 6 weeks or Mohan (13) NP <37 wk FM 21/17 BB-L CFU from day 1; From first feed to CFU from day 4 once day 21 Stratiki (14) 1500g/1500g* wk FM 38/31 BB-L CFU/g every 2h Started within 48 h of life to 30 Ke (15) NP <37 wk FM 438/446 BB-LG;LB-A; CFU twice From first feed to E. faecalis Lin (16) ±246.0g/1077.3±214.4g <34 wk MM;FM 217/217 BBB;LB-A CFU of L B-A and Since first feed for CFU of BBB twice weeks Huang (17) 1100±400g/1100±300g wk FM 95/88 BA organisms twice Started from day 7 of life to day 14 Rougé (18) 1115±251g/1057±260g <32 wk MM;DM;F 45/49 LB-GG CFU once Since first feed until M Samanta (19) 1172±143g/1210±143g <32 wk MM 91/95 BI;BBB;BB CFU twice of each Since first feed until Underwood (20) NP <35 wk MM;DM;F M LG; LB-A 61/29 LB-GG;LB-A; BB-LG; BBB;BI probiotic organisms of LB-GG and organisms of LB-A, BB-LG, BBB, BI twice Since first feed for 28 or until Di (21) NP <37 wk FM 182/173 E. faecium; B. subtilis organisms Since first feed until Mihatsch (22) 856±251g/871±287g <30 wk MM;FM 91/89 BB-L CFU/kg for 6 times a day For the first 6 weeks of life Ren (23) NP wk FM 80/70 BI;LB-A; E. 0.25g organisms twice Since first feed for 7 faecalis; B. cereus Deng (24) 1588±450g/1670.±472g <37 wk FM 63/62 BB-LG;LB-A; E. faecalis Yang (25) NP <37 wk FM 31/31 BB-LG;LB-A; E. faecalis Li (26) NP <37 wk FM 207/205 BB-LG;LB- B;ST For BW<1500g, CFU and for BW>1500g, CFU of each probiotic twice CFU of each probiotic twice CFU of BB-LG and CFU of LB-B, ST thrice Since first feed for 14 Since first feed for 14 Since first feed until Braga (27) ±206.3g/1151.4±224.9g <37 wk MM;DM 119/112 LB-C;BB to CFU Since second day of life until 30 Sari (28) 1231±262g/1278±282g <37 wk MM;FM 110/111 LB-S CFU once Since first feed until Gut colonization; vomit; apnea; weight gain; sepsis; ; death URI; sepsis; ; death Stool colonization; ; sepsis; weight gain; vomit ; mortality; sepsis ; death; sepsis Gut colonization; ; death; sepsis; IFI; ROP Gut colonization and enteric pathogens; Intestinal permeability; sepsis; ; death; weight gain ; death; sepsis; weight gain ; weight gain; gut colonization ; death; sepsis; weight gain; intestinal colonization ; sepsis; death ; weight gain ; sepsis; death ; sepsis; death ; sepsis; death; weight gain

2 Fu (29) NP <37 wk FM 126(/124 B. subtilis; E. faecium Zhou (30) 1858±69g/1927.±54g <37 wk FM 75/50 BI;LB-A; E. faecalis; B. cereus organisms of E. faecium and organisms of B. subtilis twice Since first feed for g organisms thrice Since first feed for 7 Hunter (31) 743±175g/ 754±151g NP MM;FM 79/232 LB-R about CFU of LB-R Rojas (32) 1530( )g/1516( )g # wk Fernández- Carrocera (33) 1090 ( )g/ 1170 ( wk MM;FM 75/75 LB-A;LB- 1492)g # RH;LB-C;LB- P;BI;ST Since first feed until death or MM;FM 372/378 LB-B 10 8 CFU of LB-R Began during the first 48 hours of life until death or 1 g organisms Since first feed until death or ; spesis ; death; spesis ; death; sepisis; apnea NP: not reported; wk: week; MM: mother's milk; DM: donor milk; FM: formula milk; BB-L: Bifidobacterium lactis; LB-A: Lactobacillus acidophilus; E. faecalis: Enterococcus faecalis; B. cereus: Bacillus cereus; LB-C: Lactobacillus casei; BB: Bifidobacterium breve; LB-S: Lactobacillus sporogenes; B. subtilis: Bacillus subtilis; E. faecium: Enterococcus faecium; BB-LG: Bifidobacterium longum; LB-B: Lactobacillus bulgaricus; ST: Streptococcus thermophilus; BI: Bifidobacterium infantis; LB-GG: Lactobacillus GG; SB: Saccharomyces boulardii; BBB: Bifidobacterium bifidus; IFI: invasive fungal infection; BA: Bifidobacterium adolescent; UTI: urinary tract infections; ROP: retinopathy; LB-R: Lactobacillus reuteri; LB-RH: Lactobacillus rhamnosus; LB-P: Lactobacillus plantarum. *Did not offer standard deviation; # mean±interquartile range.

3 Table S2. Quality of trials included in the meta-analysis (part of the data are shown). Study Title and Participant Baseline Adverse event Randomization Blinding Follow-up CONSORT Jadad score Abstract flow data items (22) (5) Kitajima (7) Yes Yes Yes Vomit; apnea; sepsis Yes (without description of allocation concealment) No 2 months-3 years 16 3 Dani (8) Yes Yes Yes UTI; sepsis Yes (with description of allocation concealment) Yes No 19 4 Costalos (9) Yes Yes Yes Sepsis; vomit Yes (with description of allocation concealment) Yes No 20 5 Bin-Nun (10) Yes Yes Yes Sepsis Yes (with description of allocation concealment) Yes No 18 3 Lin (11) Yes Yes Yes Sepsis Yes (with description of allocation concealment) Yes No 20 4 Manzoni (12) Yes Yes Yes Yes (with description of allocation concealment) Yes No 19 4 Mohan (13) Yes Yes Yes NF or NR Yes (without description of allocation concealment) Yes No 18 4 Stratiki (14) Yes Yes Yes Intestinal permeability; sepsis Yes (with description of allocation concealment) Yes No 20 5 Ke (15) Yes Yes Yes NF or NR Yes (without description of allocation concealment) Yes No 17 4 Lin (16) Yes Yes Yes Sepsis; flatulence; diarrhea Yes (with description of allocation concealment) Yes No 20 5 Huang (17) Yes No Yes NF or NR No No No 15 3 Rougé (18) Yes Yes Yes Sepsis; nosocomial infection Yes (with description of allocation concealment) Yes No 20 5 Samanta (19) No No Yes Sepsis Yes (with description of allocation concealment) No No 16 3 Underwood (20) Yes Yes Yes NF or NR Yes (with description of allocation concealment) Yes 5 weeks 21 5 Di (21) No Yes No NF or NR Yes (without description of allocation concealment) Yes No 14 3 Mihatsch (22) Yes Yes Yes Sepsis; infection Yes (with description of allocation concealment) Yes No 21 5 Ren (23) Yes Yes Yes NF or NR Yes( without description of allocation concealment) No No 17 3 Deng (24) Yes Yes Yes NF or NR Yes (without description of allocation concealment) No No 17 4 Yang (25) Yes Yes Yes Jaundice; anemia; infection Yes (without description of allocation concealment) Yes No 19 4 Li (26) Yes Yes Yes NF or NR No No No 16 3 Braga (27) Yes Yes Yes Sepsis Yes (with description of allocation concealment) Yes No 21 5 Sari (28) Yes Yes Yes Sepsis; IVH Yes (with description of allocation concealment) Yes No 20 5 Fu (29) Yes Yes No NF or NR No No No 15 3 Zhou (30) Yes Yes Yes NF or NR Yes( without description of allocation concealment) No No 17 3 Hunter (31) Yes Yes Yes NF or NR Yes (without description of allocation concealment) Yes No 20 5 Rojas (32) Yes Yes Yes Infection; pneumonia; sepsis Yes (with description of allocation concealment) Yes No 20 5 Fernández- Yes Yes Yes Sepsis; diarrhea; vomiting Yes (with description of allocation concealment) Yes Yes 21 5 Carrocera (33) NF: not found; NR: not reported; UTI: urinary tract infections; IFI: invasive fungal infection; IVH: intraventricular hemorrhage.

4 Figure S1. Effect of probiotics on in preterm infants ( I). : necrotizing enterocolitis. Figure S2. Effect of probiotics on in preterm infants ( II). : necrotizing enterocolitis.

5 Figure S3. Effect of probiotics on in early preterm infants ( I, GA<34 weeks). : necrotizing enterocolitis; GA: gestational age. Figure S4. Effect of probiotics on mortality in preterm infants. Figure S5. Effect of probiotics on sepsis in preterm infants.

6 Figure S6. Effect of probiotics on weight gain of preterm infants. Figure S7. Effect of probiotics on age reaching full feeds of preterm infants.