Health Effects of Infant Formula Supplemented with Probiotics or Synbiotics in Infants and Toddlers: Systematic Review with Network Meta-Analysis

Abstract

Supplementation of infant and follow-up formula with probiotics or synbiotics has become a common practice. In 2011 and 2017, the evidence regarding the impact of these interventions was analysed systematically. Recently new evidence was published. To evaluate through a systematic review with network meta-analysis the evidence on the impact of infant formula supplemented with probiotics or synbiotics for healthy infants and 36-month-old toddlers. RCTs published between 1999–2019 for infant formulas supplemented with probiotics alone or synbiotics in healthy infants and toddlers were identified. Data analysis included clinical (gastrointestinal symptoms, risk reduction of infectious diseases, use of antibiotics, weight/height gain and frequency of adverse events) and non-clinical outcomes (changes in faecal microbiota and immune parameters). A random effect model was used. Hedges’ standard mean difference (SMD) and risk ratio (RR) were calculated. Rank analysis was performed to evaluate the superiority of each intervention. Twenty-six randomised controlled trials with 35 direct comparisons involving 1957 children receiving probiotic-supplemented formula and 1898 receiving control formula were reviewed. The mean duration of intervention was 5.6 ± 2.84 months. Certain strains demonstrated a reduction in episodes of colic, number of days with fever and use of antibiotics; however, there was considerable heterogeneity which reduced the level of certainty of effect. No significant effects were observed on weight, height or changes in faecal proportions of Bifidobacteria, Lactobacillus, Bacteroides or Clostridia. Although there is some evidence that may support a potential benefit of probiotic or synbiotic supplementation of infant formulas, variation in the quality of existing trials and the heterogeneity of the data preclude the establishment of robust recommendations.

The effects of prebiotic, probiotic or synbiotic supplementation on overweight/obesity indicators: an umbrella review of the trials’ meta-analyses

“…Some research indicated increased weight gain in full-term infants fed prebiotic-enriched formula, while others noted improved growth and weight gain in toddlers consuming synbiotic-fortified milk ( 25 , 27 ). Conversely, supplementing infant formula with probiotics or synbiotics showed no significant weight effect in another systematic review ( 26 ). Additionally, a meta-analysis found no noteworthy differences in mean end-of-trial weight or gestational weight gain between intervention and control groups ( 24 ).…”

“…Additionally, toddlers consuming milk with synbiotics demonstrated improved growth and greater weight gain ( 25 , 27 ). However, another systematic review reported that infant formula intake enriched with probiotics or synbiotics did not impact weight in infants and toddlers ( 26 ). A meta-analysis showed that probiotic and synbiotic supplements can improve newborn weight among gestational diabetes mellitus patients ( 23 ).…”

“…Numerous systematic reviews with meta-analysis, though yielding conflicting results, have been conducted to assess the effects of biotics on anthropometric indices such as weight, body mass index (BMI), and waist circumference (WC) (9,22,(25)(26)(27)(28)(29).…”

Life at the borderlands: microbiomes of interfaces critical to One Health

“…A similar result regarding opportunistic pathogens was observed in ruminants since bottle-fed lambs showed higher levels of Escherichia/Shigella compared to suckled lambs (Bi et al 2019 ). Supplementation of infant formula with probiotic strains, such as Bifidobacterium longum and Lactobacillus rhamnosus , has become a common practice (Braegger et al 2011 , Indrio et al 2022 ). However, due to the heterogeneity of trial design and outcomes, no evidence currently supports the hypothesis that probiotic supplemented formula can effectively shift infant gut microbiota towards a desirable initial configuration (Indrio et al 2022 ).…”

Diurnal rhythmicity of fecal microbiota and metabolite profiles in the first year of life: a randomized controlled interventional trial with infant formula

“…Human breastmilk oligosaccharides (HMOs) selectively shape the early life colonization [11][12][13] and the supplementation of infant formula with complex oligosaccharides such as galactooligosaccharides (GOS) partially mimics the effect of breastmilk 14,15 . Considering the welldocumented effects of the early life microbiota on health outcomes later in life 8,16,17 , the attempts to optimize infant formula are numerous [18][19][20][21] but often lack well-controlled intervention strategies to directly compare supplements in infant formula.Circadian clocks (lat. circa = approximately, dies = day) have developed in almost all organisms to anticipate recurring environmental changes.…”