Table 1.
Summary of probiotic RCTs in premature infants
| Author Year |
Country | Probiotic Species (strain) |
Brand (Company) |
Population | Dose × duration |
Number enrolled |
NEC cases Stage 2, 3 |
Culture + sepsis cases |
Deaths | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Prob | Cont | Prob | Cont | Prob | Cont | Prob | Cont | ||||||
| Costeloe 201560 | UK | B breve (BBG 001) | NR (Yakult) | GA 23-30w | 1.6e8-1.6e9/d until 36w | 650 | 660 | 62 | 66 | 73 | 77 | 54 | 56 |
| Dilli 201561 | Turkey | B lactis (NR) | Maflor (Mamse l) | BW < 1500g + GA < 32w | 5e9/d × 8w | 100 | 100 | 2 | 18 | 8 | 13 | 3 | 12 |
| Saengtawes in 201562 | Thailand | L acidophilus + B bifida (NR) | Infloran (NR) | BW < 1500g + GA < 34w | 2e9 BID × 6w | 31 | 29 | 1 | 1 | 2 | 1 | 0 | 0 |
| Tewari 201563 | India | Bacillus clausii (NR) | Enterogermina (Sanofi Aventis) | GA < 34w | 8e8 TID × 3-5w | 123 | 121 | 0 | 0 | 20 | 25 | 12 | 14 |
| Hays 201564 | France | B lactis + B longum(NR) | NR | BW 700-1600g + GA 25-31w | 1e9/d × 4-6w | 48 | 52 | 5 | 3 | 8 | 10 | 1 | 1 |
| B lactis (NR) | 50 | 2 | 9 | 1 | |||||||||
| B longum (NR) | 49 | 1 | 8 | 3 | |||||||||
| Van Niekirk 201565 | South Africa | B infantis (NR) + L rhamnosus (GG) | Pro-B2 (C Pharm) | BW < 1250g | 7e8/d × 28d | 91 | 93 | 0 | 4 | 15 | 10 | 5 | 7 |
| Dutta 201566 | India | L acidophilus + L rhamnos | NR (Aristo) | GA 27-33 w | 1e10 BID × 21d us + B longum + S boulardii (NR) | 38 | 35 | 1 | 0 | 3 | 6 | 3 | 2 |
| 1e10 BID × 14d | 38 | 3 | 1 | 3 | |||||||||
| 1e9 BID × 21d | 38 | 2 | 6 | 2 | |||||||||
| Patole 201467 | Australia | B breve (M-16V) | NR (Morinaga) | BW < 1500g + GA < 33w | 3e9/d until 37w | 79 | 80 | 0 | 1 | 17 | 12 | 0 | 0 |
| Oncel 201468 | Turkey | L reuteri (DSM 17938) | NR (Biogaia AB) | BW < 1500g + GA < 32w | 1e8/d until discharge | 200 | 200 | 8 | 10 | 13 | 25 | 15 | 20 |
| Totsu 201469 | Japan | B bifidum (OLB 6378) | NR (Meiji) | BW < 1500g | 1.25e 9 BID until > 2kg | 153 | 130 | 0 | 0 | 6 | 10 | 2 | 0 |
| Jacobs 201370 | Australia + NZ | B infantis (BB-02) + S thermophiles (TH-415957) + B lactis (BB-1215954) | ABC Dophilus (Solgar) | BW < 1500g + GA < 32w | 1e9/d until discharge | 548 | 551 | 11 | 24 | 72 | 89 | 27 | 28 |
| Serce 201371 | Turkey | Saccharomyces boulardii (NR) | Reflor (Biocodex) | BW < 1500g + GA < 32w | 5e8/kg BID until discharge | 104 | 104 | 7 | 7 | 72 | 89 | 27 | 28 |
| Demirel 201372 | Turkey | Saccharomyces boulardii (NR) | Reflor (Biocodex) | BW < 1500g + GA < 32w | 5e9/kg BID until discharge | 135 | 136 | 6 | 7 | 20 | 21 | 5 | 5 |
| Rojas 201273 | Colombia | L reuteri(DSM 17938) | NR (Biogaia AB) | BW < 2000g | 1e8/d until discharge | 372 | 378 | 9 | 15 | 24 | 17 | 22 | 28 |
| Fernandez-Carrocera 201274 | Mexico | L acidophilus + L rhamnosus + L casei + L plantarum + B infantis + S thermophiles (NR) | 107M96 y 106M96 (Italmex) | BW < 1500g | 3e9/d (NR) | 75 | 75 | 6 | 12 | NR | NR | 1 | 7 |
| Al-Hosni 201275 | USA | B infantis (NR) + L rhamnosus (GG) | Align (Proctor and Gamble) + Culturelle (Amerifit) | BW 501-1000g | 1e9/d until 34w | 50 | 50 | 2 | 2 | 13 | 16 | 3 | 4 |
| Sari 201176 | Turkey | L sporogenes (NR) | NR (DMG Italia) | BW < 1500g or GA <33w | 3.5e8/d (NR) | 110 | 111 | 6 | 10 | NR | NR | 3 | 4 |
| Braga 201177 | Brazil | L casei + B breve (NR) | NR (Yakult) | BW 750-1499g | 3.5e7-3.5e9/d × 28d | 119 | 112 | 0 | 4 | NR | NR | 26 | 27 |
| Romeo 201178 | Italy | L reuteri (ATCC 55730) | NR | BW < 2500g + GA < 37w | 1e8/d until discharge | 83 | 83 | NR | NR | 1 | 9 | NR | NR |
| L rhamnosus (ATCC 53103 | NR | 6e9/d until discharge | 83 | NR | 2 | NR | |||||||
| Awad 201079 | Egypt | L rhamnosus (GG) | Lacteol Fort (Axcan) | GA 28-41w | 6e9 BID until discharge | 60 | 30 | 0 | 5 | NR | NR | NR | NR |
| Killed L rhamnosus (GG) | 60 | 1 | NR | NR | |||||||||
| Mihatsch 201080 | Germany | B lactis (BB12) | NR (Nestle) | BW < 1500g + GA < 30w | 2e9/kg q 4h × 6w | 91 | 89 | 2 | 4 | 28 | 29 | 2 | 1 |
| Samanta 200981 | India | B longum + B infantis + B bifidum + L acidophilus (NR) | NR | BW < 1500g + GA < 32w | 1e10 BID until discharge | 91 | 95 | 5 | 15 | 13 | 28 | 4 | 14 |
| Rouge 200982 | France | B longum (BB536) + L rhamnosus (GG) | NR (Morina + Valio) | BW < 1500g + GA < 32w | 1e8 QID until discharge | 45 | 49 | 2 | 1 | 15 | 13 | 2 | 4 |
| Lin 200883 | Taiwan | L acidophilus (NCDO 1748) + B bifidum (NCDO 1453) | Infloran (Laboratorio Farmaceutico) | BW < 1500g + GA < 34w | 1e9 BID until 6w | 217 | 217 | 4 | 14 | 40 | 24 | 2 | 9 |
| Stratiki 200784 | Greece | B lactis (NR) | Prenan (Nestle) | GA 27-37w | varied with feeding volume × 30d | 41 | 36 | 0 | 3 | 0 | 3 | NR | NR |
| Wang 200785 | Japan | B breve (M-16V) | NR (Morinaga) | GA 23-36w | 1.6e8 BID until discharge | 33 | 33 | 0* | 0* | 0 | 0 | NR | NR |
| Manzoni 200686 | Italy | L rhamnosus (GG) | Dicoflor 60 (Dicofarm) | BW < 1500g | 6e9/d until 6w | 39 | 41 | 1 | 3 | 19 | 22 | 5 | 6 |
| Fujii 200647 | Japan | B breve (M-16V) | NR (Morinaga) | GA 31w (SD 3w) | 1e9 BID until discharge | 11 | 8 | 0 | 0 | 1 | 1 | NR | NR |
| Lin 200587 | Taiwan | L acidophilus + B infantis (NR) | Infloran (Swiss Serum and Vaccine Institute) | BW < 1500g | 1e9 BID until discharge | 180 | 187 | 2 | 10 | 22 | 36 | 7 | 20 |
| Bin-Nun 200588 | Israel | B infantis + S thermophilus + B lactis (NR) | ABC Dophilus (Solgar) | BW < 1500g | 1e9/d until 36w | 72 | 72 | 1 | 10 | NR | NR | 3 | 8 |
| Costalos 200389 | Greece | Saccharomyces boulardii (NR) | NR | GA 28-32w | 1e9/d × 30d | 51 | 36 | 5 | 6 | 3 | 3 | NR | NR |
| Dani 200290 | Italy | L rhamnosus (GG) | Dicoflor (Dicofarm) | BW < 1500g + GA < 33w | 6e9/d until discharge | 295 | 290 | 4 | 8 | 14 | 12 | 0 | 2 |
| Reuman 198691 | USA | L acidophilus (NR) | NR | BW < 2000g | 1e8 BID until discharge | 15 | 15 | NR | NR | NR | NR | 1 | 3 |
| Total | 4668 | 4298 | 161 | 263 | 548 | 601 | 244 | 310 | |||||
| % of reported | 100 | 100 | 3.59 | 6.26 | 13.18 | 15.48 | 5.75 | 7.62 | |||||
NR: not reported, BW: birth weight, GA: gestational age, g: grams, w: weeks, d: days
1.6e8: 1.6×108 organisms
*
number of NEC cases obtained by personal communication with the author