Table 1. General characteristics of the included randomised controlled trials.
| First author | Country | Study period (year published) | # Participants1 | AB or CS SG? |
Feeding method | Intervention | Control | Start of intervention | Duration intervention | Outcomes (relevant subgroup) | Follow-up | Comments | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I | C | T | ||||||||||||
| Chua [24] | Singapore & Thailand | 2011–2013 (2017, 2021) | 52 + 51 | 50 | 153 | CS | Mixed (FF + BF) | Prebiotic (scGOS/lcFOS) or synbiotic (scGOS/ICFOS and Bifidobacterium breve M-16V) | Control formula | 1–3 D | 16 W | Total faecal Bifidobacterium, Bifidobacterium species abundance, other members of the gut microbiota, pH, sc fatty acids, lactate | 3, 5 D 2, 4, 8, 12, 16, 22 W |
Infants born via CS were also exposed to intrapartum AB prophylaxis. Lay et al.: some results were based on a SG |
| Lay [23] | 39 + 44 | 44 | 127 | |||||||||||
| Berger [25] | Italy & Belgium | 2012–2015 (2020, 2017) | 19 | 24 | 43 | CS SG | Exclusive FF | Prebiotics: 2 HMOs (2’-fucosyllactose and lacto-N-neotetraose) | Control formula | 0–14 D | 6 M | Stool microbiota diversity | 3, 12 M | - |
| Korpela [29] | Finland | 2000–2003 (2018, 2018, 2009, 2017) | 35 | 44 | 79 | CS SG | Exclusive BF, mixed feeding or FF | Probiotic: Lactobacillus rhamnosus LC705, Bifidobacterium breve Bb99, Propionibacterium freudenreichii spp., shermanii JS | Placebo (micro-crystalline cellulose) | 36 W gestation + from birth | 6 M | Microbiota composition | 3 M | Infants had to be at risk for atopic disease (at least one parent with asthma, allergic rhinitis or eczema) and this intervention was initiated prenatally (36 W gestation) |
| Baglatzi [30] | Greece | 2009–2011 (2016) | 84 | 80 | 164 | CS | Exclusive or mixed FF | Probiotic: regular dose of Bifidobacterium lactis | Low dose of B. lactis | Birth | 6 M | Detection of B. lactis | 12 M | No control group that was fed formula without pre-, pro-, or synbiotics |
| Cooper [27] | South Africa | 2008–2013 (2016) | 92 | 101 | 193 | CS SG | Exclusive FF | Synbiotic: BMOs (containing GOS and MOS such as 3’- and 6’ sialyllactose) + Bifidobacterium lactis CNCM-I-3446 | Control formula | Birth (≤3 D) | 6 M | Faecal (bifido)bacteria, anthropometrics, faecal pH, lean mass, fat mass and bone mineral content, digestive tolerance, immune parameters, HIV infection status, frequency of morbidity episodes | 1 Y | All included infants had HIV+ mothers and all mothers and infants received antiretroviral medication. Infants who tested positive for HIV were excluded |
| Estorninos [26] | Philippines | 2016–2018 (2022) | 115 | 115 | 230 | CS SG | Exclusive FF | Prebiotic: bovine MOS (GOS and sialylated-oligosaccharides) | Control formula | 3 W | 6 M | Phylogenetic distance/microbiota composition, Bifidobacteria abundance | 4 M | At the 2.5 month time point, only a subgroup of 75 infants for each group provided a faecal sample |
| Frese [31] | USA | 2015–2016 (2017) | 11 | 9 | 20 | CS SG | Any | Probiotic: Bifidobacterium infantis EVC001 | None | 7 D | 27 D | Microbiota composition, relative abundances of the most abundant taxonomic groups | 60 D | Significantly more mothers in the control group were primiparous |
| Garcia Rodenas [32] | Greece | 2010–2011 (2016) | 11 | 10 | 21 | CS SG | Exclusive FF | Probiotic: Lactobacillus reuteri DSM 17938 | Control formula | <72 H | 6 M | Relative abundance of OTUs, weighted UniFrac distances, relative abundance of Bifidobacterium | 4 M | - |
| Hurkala [33] | Poland | 2014–2017 (2020) | 71 | 77 | 148 | CS | Exclusive FF | Probiotic: Bifidobacterium breve PB04 and Lactobacillus rhamnosus KL53A | None | <1 H | Until discharge (5 or 6 D) | Abundance of lactobacilli in faeces, populations of Bifidobacterium in faeces, populations of potentially pathogenic bacteria | 1 M | Significantly more missing stool samples from the control group (29 compared to 13 in the intervention group) |
| Roggero [34] | Italy | 2015–2016 (2020) | 16 | 16 | 32 | CS SG | Exclusive FF | Probiotic: Lactobacillus paracasei CBA L74 | Control formula | <7 D | 3 M | sIgA production, antimicrobial peptides, microbiota diversity, metabolome, abundance of bacterial genera | 90 D | Infants may have been breastfed for a few days before enrolment |
| Yang [28] | China | 2018 (2021) | 7 + 7 | 9 | 23 | CS | BF | Synbiotic: high and low dose of Bifidobacterium lactis Bi-07 and Lactobacillus rhamnosus HN001 + GOS | No probiotic | Birth | 28 D | Diversity of gut microbiota, gut microbiota composition, COGs | 28 D | - |
| Zhong [35] | China | 2017–2018 (2021) | 25 + 13 | 17 | 55 | 1 week AB | Any | Probiotic: Bifidobacterium longum, Lactobacillus acidophilus and Enterococcus faecalis during or after AB treatment | None | Beginning or end of AB treatment (AB treatment started <3 D after birth) | 42 D | Gut microbiota, relative abundance of OTUs | 42 D | Children were not necessarily born via CS, but received AB in the first week of life |
1 # participants in a subgroup, if applicable.
I Intervention.
C Control.
T Total.
CS Caesarean section.
SG subgroup.
BF breastfeeding.
FF formula feeding.
HMOs human milk oligosaccharides.
(sc) GOS: (short chain) galactooligosaccharides.
(lc) FOS: (long chain) fructooligosaccharides.
Spp. Several species.
BMOs bovine milk oligosaccharides.
MOS: Milk oligosaccharides.
D days.
M months.
W weeks.
H hours.
Y year.
AB antibiotic.
LRTI lower respiratory tract infection.
URTI upper respiratory tract infection.
OTU operational taxonomic unit.
sIgA secretory Immunoglobulin A.
COG: Clusters of orthologous groups of proteins.