Table 1 Characteristics of 18 included randomized controlled trials
Studies | Participants at beginning, n (P/C) | Design, location | Gestational age, P/C, week | Birth weight, P/C, g | Sex, n (P/C, M/F) | Treatment duration, days | Prebiotics used | Dose | Placebo | Measured outcomes | Key outcomes | Quality of studies assessed by PEDro tool | Form |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Armanian et al. [11] | 50 (25/25) | DB, Iran | 30.48 (2.31)/29.80 (2.16) | 1.262 (0.213)/1.188 (0.194) | Not mentioned | 21 | scGOS/lcFOS | 1.5 g/kg/day | Distilled water | Fecal microbiota pattern, duration of dependency to oxygen, hospitalization, and death | Led to the rapid growth of beneficial Lactobacillus colonies | 11 | Mixture solution |
Van den Berg et al. [18] | 77 (38/39) | SB, Netherlands | 29.9 (1.7)/29.6 (2.1) | 1.32 (0.38)/1.28 (0.28) | 21/17, 24/15 | 28 | scGOS/lcFOS/pAOS | 1.5 g/kg/day | Breast milk or formula | Neurodevelopment, cytokines, and infections | No significant improvement of neurodevelopmental outcomes | 8 | With breast milk or formula |
Armanian et al. [12] | 50 (25/25) | DB, Iran | 30.4 (2.3)/29.8 (2.1) | 1.262 (0.213)/1.188 (0.194) | Not mentioned | 7 | scGOS/lcFOS | 1.5 g/kg/day | Distilled water | Bilirubin level and stool frequency | Increase stool frequency, improve feeding tolerance, and reduce bilirubin level | 11 | Mixture solution |
Dilli et al. [19] | 200 (50/50) | DB, Turkey | 29.0 (1.7)/28.2 (2.2) | 1.229 (0.246)/1.147 (0.271) | 52/48, 58/42 | 56 | Inulin | 1.35 g/kg/day | Maltodextrin | NEC, sepsis, mortality, duration of hospital | Inulin could not decrease NEC | 10 | With breast milk or formula |
Armanian et al. [10] | 75 (25/50) | SB, Iran | 30.48 (2.31)/30.38 (2.53) | 1.263 (0.213)/1.206 (0.177) | Not mentioned | 14 | scGOS/lcFOS | 1.5 g/kg/day | Distilled water | NEC, mortality, sepsis, feeding intolerance, and days to reach full enteral feeding | Lower NEC, mortality, sepsis rates, and shorter days to reach full enteral feeding | 8 | With breast milk or formula |
Dasopoulou et al. [21] | 167 (85/82) | DB, Greece | 34.0 (0.33)/34.0 (0.33) | 2.019 (0.30)/1.987 (0.38) | Not mentioned | 16 | scGOS/lcFOS | 1.2 g/kg/day | Formula | Motilin, NEC, mortality, sepsis, and feeding intolerance | Increase motilin, reduce gastric residue | 11 | With formula |
Luoto et al. [22] | 47 (23/24) | DB, Finland | 32–35 | 2.123 (0.39)/2.412 (0.84) | 11/12, 19/5 | 57 | scGOS/polydextrose | 1.2 g/kg/day | Microcrystalline cellulose and dextrose anhydrate | Respiratory tract infections and its duration | Reduce the risk of rhinovirus infections | 11 | With breast milk or formula |
Van den Berg et al. [16] | 103 (55/58) | SB, Netherlands | 29.9 (1.9)/29.3 (2.1) | 1.3 (0.4)/1.2 (0.3) | 31/24, 36/22 | 28 | scGOS/lcFOS/pAOS | 1.5 g/kg/day | Maltodextrin | Serious infectious morbidity | Does not improve the immunization response | 10 | With breast milk or formula |
LeCouffe et al. [17] | 113 (48/45) | SB, Netherlands | 30.2 (1.6)/29.5 (2.0) | 1.37 (0.4)/1.26 (0.3) | 26/48, 26/45 | 28 | scGOS/lcFOS/pAOS | 1.5 g/kg/day | Maltodextrin | Neurodevelopmental outcome | No effect on neurodevelopmental | 8 | With breast milk or formula |
Niele et al. [15] | 114 (48/46) | DB, Netherlands | 30.1 (1.6)/29.5 (2.0) | 1.40 (0.4)/1.30 (0.3) | Not mentioned | 28 | scGOS/lcFOS/pAOS | 1.5 g/kg/day | Maltodextrin | Allergic and infectious diseases | Does not decrease the incidence of allergic and infectious diseases | 10 | With breast milk or formula |
Westerbeek et al. [14] | 103 (55/58) | DB, Netherlands | 29.9 (1.9)/29.3 (2.1) | 1.3 (0.4)/1.2 (0.3) | 31/24, 36/22 | 28 | scGOS/lcFOS/pAOS | 1.5 g/kg/day | Maltodextrin | Stool viscosity, stool frequency, and stool pH | Decreases stool viscosity and stool pH, increased stool frequency | 11 | With breast milk or formula |
Campeotto et al. [23] | 58 (24/34) | DB, France | 33.5 (1.3)/33.4 (1.1) | 1.91 (0.35)/1.93 (0.39) | 15/9, 16/18 | 30 | Fermente induced non-digestible oligosaccharides | Not mentioned | Formula | Inflammatory and immune markers | Benefits on inflammatory and immune markers | 10 | Formula |
Riskin et al. [24] | 28 (15/13) | DB, Israel | 30.3 (2.8)/28.7 (2.9) | 1.52 (0.55)/1.21 (0.45) | 10/5, 5/8 | 35 | Lactulose | 1.5 g/kg/day | Dextrose | NEC, mortality, sepsis, feeding intolerance, and days to reach full enteral feeding | Suggest positive prebiotic effects | 10 | Mixture solution |
Modi et al. [25] | 154 (73/81) | DB, UK | 30.0 (0.5)/31.0 (0.5) | 1.57 (0.88)/1.52 (0.91) | 48/25, 50/31 | 28 | scGOS/lcFOS | 1.2 g/kg/day | Formula | NEC, mortality, sepsis, feeding intolerance | Safe and may benefit enteral tolerance | 11 | Formula |
Kapiki et al. [20] | 56 (36/20) | SB, Greece | 33.4 (1.8)/33.9 (1.3) | 1.59 (0.33)/1.64 (0.17) | 16/17, 8/12 | 7 | scGOS | 0.6 g/kg/day | Maltodextrin | Bifidogenic effect, stool characteristics | Small quantity of prebiotic is well accepted | 7 | Formula |
Mihatsch et al. [26] | 20 (10/10) | DB, Germany | 27.1 (2.2)/27.6 (3.3) | 0.89 (0.64)/0.90 (0.69) | Not mentioned | 14 | scGOS/lcFOS | 1.5 g/kg/day | Maltodextrin | Stool characteristics | Reduce stool viscosity | 11 | Formula |
Boehm et al. [27] | 27 (12/15) | SB, Italy | 31.2 (0.6)/31.4 (0.9) | 1.59 (0.24)/1.60 (0.32) | 8/7, 7/5 | 28 | scGOS/lcFOS | 1.5 g/kg/day | Maltodextrin | Stool characteristics | More frequent and softer stools | 8 | Formula |