Probiotic Supplementation for Promotion of Growth in Undernourished Children: A Systematic Review and Meta-Analysis.

OBJECTIVES: Probiotic supplementation has been proposed as a therapeutic intervention to improve growth outcomes in children with undernutrition. The objective of this review is to synthesize the current evidence on probiotic supplementation for promotion of growth in undernourished children. METHODS: We searched MEDLINE, Cochrane CENTRAL, CINAHL, Embase, LILACS, and Scopus for randomized controlled trials (RCTs) that administered probiotics or eligible comparators to undernourished children below 5 years of age. Our primary outcomes of interest were weight-for-age, height-for-age, and weight-for-height at the longest follow-up points reported. Random-effects meta-analysis was used to calculate standardized mean differences (SMD) for continuous outcomes and risk ratios for dichotomous outcomes. The Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess certainty of the evidence. RESULTS: Nine RCTs with 5295 children in total were included. Durations of treatment ranged from 1 month to 1 year. Pooled analyses from 7 studies showed that probiotics may have little to no effect on weight-for-age (SMD 0.05 standard deviation [SD], 95% CI: -0.04 to 0.13, n = 2115 children; low-certainty evidence) and height-for-age (SMD -0.04 SD, 95% CI: -0.14 to 0.07, n = 1357 children; low-certainty evidence). The evidence was very uncertain about the effect on weight-for-height. CONCLUSIONS: Probiotics may have little to no effect on anthropometry in undernourished children, though there is considerable heterogeneity among the trials reviewed thus far. The interaction between gut microbiota and human nutrition is complex, and further research is needed to determine how the gut microbiome may contribute to undernutrition and how probiotics may affect growth in this vulnerable population.

The Effect of Consumption of Animal Milk Compared to Infant Formula for Non-Breastfed/Mixed-Fed Infants 6-11 Months of Age: A Systematic Review and Meta-Analysis.

Many infants do not receive breastmilk for the recommended 2-year duration. Instead, alternative milk beverages are often used, including infant formula and raw animal milk products. The purpose of this systematic review was to summarize the effect of animal milk consumption, compared to infant formula, on health outcomes in non-breastfed or mixed-fed infants aged 6-11 months. We searched multiple databases and followed Cochrane guidelines for conducting the review. The primary outcomes were anemia, gastrointestinal blood loss, weight-for-age, length-for-age, and weight-for-length. Nine studies were included: four randomized controlled trials (RCT) and five cohort studies. All studies, except one, were conducted in high income countries. There was a low certainty of evidence that cow's milk increased the risk of anemia compared to formula milk (Cohort studies RR: 2.26, 95% CI: 1.15, 4.43, RCTs: RR: 4.03, 95% CI: 1.68, 9.65) and gastrointestinal blood loss (Cohort study RR: 1.52, 95% CI: 0.73, 3.16, RCTs: RR: 3.14, 95% CI: 0.98, 10.04). Additionally, there was low certainty evidence that animal milk consumption may not have a differential effect on weight and length-for-age compared to formula milk. Overall, the evidence was of low certainty and no solid conclusions can be drawn from this data. Further studies are needed from low- and middle-income countries to assess optimal milk type in non-breastfed infants aged 6-11 months.

Probiotic Supplementation for Promotion of Growth in Children: A Systematic Review and Meta-Analysis.

Probiotics are commonly prescribed to promote a healthy gut microbiome in children. Our objective was to investigate the effects of probiotic supplementation on growth outcomes in children 0-59 months of age. We conducted a systematic review and meta-analysis which included randomized controlled trials (RCTs) that administered probiotics to children aged 0-59 months, with growth outcomes as a result. We completed a random-effects meta-analysis and calculated a pooled standardized mean difference (SMD) or relative risk (RR) and reported with a 95% confidence interval (CI). We included 79 RCTs, 54 from high-income countries (HIC), and 25 from low- and middle-income countries (LMIC). LMIC data showed that probiotics may have a small effect on weight (SMD: 0.26, 95% CI: 0.11-0.42, grade-certainty = low) and height (SMD 0.16, 95% CI: 0.06-0.25, grade-certainty = moderate). HIC data did not show any clinically meaningful effect on weight (SMD: 0.01, 95% CI: -0.04-0.05, grade-certainty = moderate), or height (SMD: -0.01, 95% CI: -0.06-0.04, grade-certainty = moderate). There was no evidence that probiotics affected the risk of adverse events. We conclude that in otherwise healthy children aged 0-59 months, probiotics may have a small but heterogenous effect on weight and height in LMIC but not in children from HIC.

Spindle abnormalities and chromosome misalignment in bovine oocytes after exposure to low doses of bisphenol A or bisphenol S.

STUDY QUESTION: What are the effects of exposure to bisphenol A (BPA) or bisphenol S (BPS) during IVM on bovine oocyte maturation, spindle morphology and chromosome alignment? SUMMARY ANSWER: Exposure to BPA or BPS during IVM resulted in increased spindle abnormalities and chromosome misalignment, even at very low concentrations. WHAT IS KNOWN ALREADY: BPA is an endocrine disrupting chemical that alters oocyte maturation, spindle morphology and chromosome alignment in a range of species. The use of BPA substitutes, such as BPS, is increasing and these substitutes often display different potencies and mechanisms of action compared with BPA. STUDY DESIGN, SIZE, DURATION: Bovine cumulus-oocyte complexes (COCs) underwent IVM with BPA or BPS for 24 h, together with vehicle-only controls. Overall, 10 different concentrations of BPA or BPS were used ranging from 1 fM to 50 µM in order to detect low dose or non-monotonic effects. An incomplete block design was utilized for the study, with at least three replicates per block. A total of 939 oocytes (250 of which were controls) were used for the BPA experiments, and 432 (110 controls) for the BPS experiments. Following the IVM period, the oocytes were denuded and fixed for immunocytochemistry. PARTICIPANTS/MATERIALS, SETTING, METHODS: Immunocytochemistry was used to label the chromatin, actin, and microtubules in the fixed oocytes. The meiotic stage was assessed using immunofluorescence, and the metaphase-II (MII) oocytes were further assessed for spindle morphology and chromosome alignment (in all MII oocytes regardless of spindle morphology) using immunofluorescence and confocal microscopy. Significant differences between the treatment and control groups were determined using chi-square and Fisher's exact tests. MAIN RESULTS AND THE ROLE OF CHANCE: There was no effect of BPA or BPS on the proportion of bovine oocytes that reached MII (P > 0.05). BPA and BPS increased spindle abnormalities in MII oocytes at almost all concentrations tested, including those as low as 1 fM (P = 0.013) or 10 fM (P < 0.0001), respectively, compared to control. Oocytes with flattened spindles with broad poles were observed at a higher frequency at some concentrations of BPA (P = 0.0002 and P = 0.002 for 10 nM and 50 µM, respectively) or BPS (P = 0.01 for 100 nM BPS), while this spindle phenotype was absent in the controls. BPA increased chromosome misalignment at concentrations of 10 fM, 10 nM and 50 µM (P < 0.0001 to P = 0.043 depending on the dose). BPS increased chromosome misalignment at concentrations of 10 fM, 100 pM, 10 nM, 100 nM and 50 µM (P < 0.0001 to P = 0.013 depending on the dose). LIMITATIONS REASONS FOR CAUTION: Exposures to BPA or BPS were performed during the IVM of COCs to allow for determination of direct effects of these chemicals on oocyte maturation. Whole follicle culture or in vivo studies will confirm whether follicular cell interactions modify the effects of BPA or BPS on oocyte meiotic maturation. Investigation into the effects of BPA or BPS on other oocyte functions will determine whether these chemicals alter oocyte quality via mechanisms independent of the meiotic endpoints characterized here. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study show that both BPA and BPS induce spindle abnormalities and chromosome misalignment in bovine in a non-monotonic manner, and at concentrations that are orders of magnitude below those measured in humans. Taken in context with previous studies on the effects of BPA in a range of species, our data support the literature that BPA may reduce oocyte quality and lead to subsequent infertility. Additionally, these results contribute to the burgeoning field of research on BPS and suggest that BPS may indeed be a 'regrettable substitution' for BPA. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by funding from the National Institutes of Health (NIH) (Grant 1R15ES024520-01). The authors declare no conflict of interest.