Table 1 Characteristics of 18 included randomized controlled trials

From: Effects of prebiotics on sepsis, necrotizing enterocolitis, mortality, feeding intolerance, time to full enteral feeding, length of hospital stay, and stool frequency in preterm infants: a meta-analysis

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

  1. Values are means (SDs) unless otherwise indicated
  2. scGOS/lcFOS short chain galacto-oligosaccharides/long chain fructo-oligosaccharides, pAOS pectin-derived acidic oligosaccharides, DB double blind, SB single blind, P/C prebiotic group/control group