Literature search retrieved 5085 potentially relevant citations. Reviewers HP and GAJ independently completed initial screening of the titles and abstracts, full-text publications of potential studies and published review articles on probiotics. Of the 378 records identified via databases and registers, 208 records were screened of which 98 reports were assessed for eligibility after screening title/abstract. Of the 4707 records identified from other sources such as websites (Google scholar, Open Grey, NTIS, Trove), 471 reports were assessed for eligibility after title/abstract screen. Discrepancies about inclusion or exclusion of studies and interpretation of data were resolved by discussion among all authors. Included study manuscripts were manually reviewed for references to identify key studies to add to final list of eligible studies. After screening the title/abstract, 569 studies were assessed for eligibility, of which 534 were excluded (Fig. 1). Finally, 30 RCTs (n = 4817) with 35 publications were included. Their characteristics are summarized in (Table 1, Supplementary Tables 1 and 2).

Flowchart summarizing study selection and inclusion processes in this systematic review and metaanalysis, including the reasons for exclusion of all articles that were reviewed.

A total of twenty-seven RCTs [34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61] (n = 4018) reported effects of probiotics on short-term growth. Seven RCTs [62,63,64,65,66,67,68] (n = 1982) reported on neurodevelopmental outcomes, of which four [65,66,67,68] (n = 1417) reported on long-term growth. The results of the PROPEL trial [34, 37], Patole et al. [46, 62], Totsu et al. [47, 65], Sari et al. [54, 67] and PROPREMS trial [50, 66] were reported as two separate publications each for different outcomes.

Twenty-two RCTs were single centre [35, 36, 39, 40, 42, 43, 45, 46, 48, 49, 51, 53,54,55,56,57,58, 60,61,62,63,64, 67, 68], while eight were multicentre RCTs [34, 37, 38, 41, 44, 47, 50, 52, 59, 65, 66]. Primary and secondary outcomes in the included studies varied (Supplementary Table 2).

Single-strain probiotic was used in 21 RCTs: Bifidobacteria [36, 44, 46, 47, 56, 57, 60, 62, 65], Lactobacillus [34, 35, 37, 38, 45, 53,54,55, 61, 63, 64, 67] and Saccharomyces [42, 49, 51, 59]. Multi-strain probiotic was used in nine RCTs including one that used two Bifidobacterium strains from same genus [41], whereas eight used a combination of probiotic strains from different genera [39, 40, 43, 48, 50, 52, 58, 66, 68].

Placebo was used for comparison in 17 RCTs: maltodextrin [34, 37, 41, 44, 46, 47, 50, 53, 59, 62, 65, 66], medium chain triglyceride (MCT) oil [48], combination of MCT oil and sunflower oil [38], distilled water [45, 51, 60], human milk fortifier [