Microbiota-targeted interventions and clinical implications for maternal-offspring health: An umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Background: Microbes in the human body are the determinants of life-long health and disease. Microbiome acquisition starts in utero and matures during early childhood through breastfeeding. However, maternal gut dysbiosis affects the maternal-offspring microbiome interplay. Lines of evidence on dysbiosis-targeted interventions and their effect on maternal-offspring health and gut microbiome are inconsistent and inconclusive. Therefore, this study summarised studies to identify the most common microbiota-targeted intervention during pregnancy and lactation and to comprehensively evaluate its effects on maternal and offspring health. Methods: This umbrella review was conducted by systematically searching databases such as PubMed and the Web of Science from inception to 2 September 2023. The quality was assessed using the Assessment of Multiple Systematic Reviews-2 checklist. The Grading of Recommendations Assessment, Development, and Evaluation was used for grading the strength and certainty of the studies. The overlap of primary studies was quantified by the corrected covered area score. Results: A total of 17 systematic reviews and meta-analyses with 219 randomised controlled trials, 39 113 mothers, and 20 915 infants were included in this study. About 88% of studies had moderate and above certainty of evidence. Probiotics were the most common and effective interventions at reducing gestational diabetes risk (fasting blood glucose with the mean difference (MD) = -2.92, -0.05; I2 = 45, 98.97), fasting serum insulin (MD = -2.3, -2.06; I2 = 45, 77), glycated haemoglobin (Hb A1c) = -0.16; I2 = 0.00)), Homeostatic Model Assessment of insulin resistance (HOMA-IR) (MD = -20.55, -0.16; I2 = 0.00, 72.00), and lipid metabolism (MD = -5.47, 0.98; I2 = 0.00, 90.65). It was also effective in preventing and treating mastitis (risk ratio (RR) = 0.49; I2 = 2.00), relieving anxiety symptoms (MD = -0.99, 0.01; I2 = 0.00, 70.00), depression in lactation (MD = -0.46, -0.22; I2 = 0.00, 74.00) and reducing recto-vaginal bacterial colonisation (odds ratio (OR) = 0.62; I2 = 4.80), and with no adverse events. It also effectively remodelled the infant gut microbiome (MD = 0.89; I2 = 95.01) and prevented infant allergies. However, studies on pregnancy outcomes and preeclampsia incidences are limited. Conclusions: Our findings from high-quality studies identify that probiotics are the most common microbiome interventions during pregnancy and lactation. Probiotics have a strong impact on maternal and offspring health through maintaining gut microbiome homeostasis. However, further studies are needed on the effect of microbiota-targeted interventions on maternal cardiometabolic health, pregnancy, and neonatal outcomes. Registration: This umbrella review was registered with PROSPERO, CRD42023437098.

Proteomics approach to discovering non-invasive diagnostic biomarkers and understanding the pathogenesis of endometriosis: a systematic review and meta-analysis.

BACKGROUND: Endometriosis is one of the most common gynaecological diseases, yet it lacks efficient biomarkers for early detection and unravels disease mechanisms. Proteomic profiling has revealed diverse patterns of protein changes in various clinical samples. Integrating and systematically analysing proteomics data can facilitate the development of biomarkers, expediting diagnosis and providing insights for potential clinical and therapeutic applications. Hence, this systematic review and meta-analysis aimed to explore potential non-invasive diagnostic biomarkers in various biological samples and therapeutic targets for endometriosis. METHODS: Online databases, including Scopus, PubMed, Web of Science, MEDLINE, Embase via Ovid, and Google Scholar, were searched using MeSH terms. Two independent authors screened the articles, extracted the data, and assessed the methodological quality of the included studies. GO and KEGG analyses were performed to identify the pathways that were significantly enriched. Protein­protein interaction and hub gene selection analyses were also conducted to identify biomarker networks for endometriosis. RESULTS: Twenty-six observational studies with a total of 2,486 participants were included. A total of 644 differentially expressed proteins (180 upregulated and 464 downregulated) were identified from 9 studies. Proteins in peripheral blood exhibited a sensitivity and specificity of 38-100% and 59-99%, respectively, for detecting endometriosis, while proteins in urine had a sensitivity of 58-91% and specificity of 76-93%. Alpha-1-antitrypsin, albumin, and vitamin D binding proteins were significantly DEPs in both serum and urine. Complement C3 is commonly expressed in serum, menstrual blood, and cervical mucus. Additionally, S100-A8 is commonly expressed in both menstrual blood and cervical mucus. Haptoglobin is commonly detected in both serum and plasma, whereas cathepsin G is found in urine, serum, and plasma. GO and KEGG enrichment analyses revealed that proteoglycans in cancer pathways, which regulate cell-to-cell interactions, modulate the extracellular matrix, and promote the proliferation and invasion of endometrial cells, are commonly enriched in serum and urine. CONCLUSION: This comprehensive study revealed potential proteomes that were significantly differentially expressed in women with endometriosis utilizing various non-invasive clinical samples. Exploring common differentially expressed proteins in various biological samples provides insights into the diagnosis and pathophysiology of endometriosis, as well as potential clinical and therapeutic applications.

Preventive effect of prenatal maternal oral probiotic supplementation on neonatal jaundice (POPS Study): A protocol for the randomised double-blind placebo-controlled clinical trial.

INTRODUCTION: Neonatal jaundice is a common and life-threatening health problem in neonates due to overaccumulation of circulating unconjugated bilirubin. Gut flora has a potential influence on bilirubin metabolism. The infant gut microbiome is commonly copied from the maternal gut. During pregnancy, due to changes in dietary habits, hormones and body weight, maternal gut dysbiosis is common, which can be stabilised by probiotics supplementation. However, whether probiotic supplements can reach the baby through the mother and reduce the incidence of neonatal jaundice has not been studied yet. Therefore, we aim to evaluate the effect of prenatal maternal probiotic supplementation on the incidence of neonatal jaundice. METHODS AND ANALYSIS: This is a randomised double-blind placebo-controlled clinical trial among 94 pregnant women (47 in each group) in a tertiary hospital in Hong Kong. Voluntary eligible participants will be recruited between 28 and 35 weeks of gestation. Computer-generated randomisation and allocation to either the intervention or control group will be carried out. Participants will take either one sachet of Vivomixx (450 billion colony-forming units per sachet) or a placebo per day until 1 week post partum. Neither the study participants nor researchers will know the randomisation and allocation. The intervention will be initiated at 36 weeks of gestation. Neonatal bilirubin level will be measured to determine the primary outcome (hyperbilirubinaemia) while the metagenomic microbiome profile of breast milk and maternal and infant stool samples as well as pregnancy outcomes will be secondary outcomes. Binary logistic and linear regressions will be carried out to assess the association of the microbiome data with different clinical outcomes. ETHICS AND DISSEMINATION: Ethics approval is obtained from the Joint CUHK-NTEC Clinical Research Ethics Committee, Hong Kong (CREC Ref: 2023.100-T). Findings will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT06087874.

Knowledge and skills of newborn resuscitation among health care professionals in East Africa. A systematic review and meta-analysis.

INTRODUCTION: Newborn resuscitation is a medical intervention to support the establishment of breathing and circulation in the immediate intrauterine life. It takes the lion's share in reducing neonatal mortality and impairments. Healthcare providers' knowledge and skills are the key determinants of the success of newborn resuscitation. Many primary studies have been conducted in various countries to examine the level of knowledge and skills of newborn resuscitation and associated factors among healthcare providers. However, these studies had great discrepancies and inconsistent results across East Africa. Hence, this review aimed to synthesize the pooled level of knowledge and skills of newborn resuscitation and associated factors among healthcare providers in East Africa. METHOD: Studies were systematically searched from February 11, 2023, to March 10, 2023, using PubMed, Google Scholar, HINARI, and grey literature. The effect size measurement of knowledge and skill of health care newborn resuscitation was estimated using the Random Effect Model. The data were extracted by Excel and analyzed using Stata 17 software. The Cochran's Q test and I2 statistic were used to assess the heterogeneity of studies. The symmetry of the funnel plot and Egger's test were used to check for publication bias. A subgroup analysis was done on the study years, sample sizes, and geographical location. Percentages and odds ratios (OR) with 95% CI were used to pool the effect measure. RESULTS: In this systematic review and meta-analysis, a total of 1953 articles were retrieved from various databases and registers. Finally, 17 studies with 7655 participants were included. The overall levels of knowledge and skills of healthcare providers on newborn resuscitation were 58.74% (95% CI: 44.34%, 73.14%) and 46.20% (95% CI: 25.16%, 67.24%), respectively. Newborn resuscitation training (OR = 3.95, 95% CI: 2.82, 5.56) and the availability of newborn resuscitation guidelines (OR = 2.71, 95% CI: 1.90, 3.86) were factors significantly associated with knowledge of health care professionals on newborn resuscitation. Work experience (OR = 5.92, 95% CI, 2.10, 16.70), newborn resuscitation training (OR = 2.83, 95% CI, 1.8, 4.45), knowledge (OR = 3.05, 95% CI, 1.78, 5.30), and the availability of newborn resuscitation equipment (OR = 4.92, 95% CI, 2.80, 8.62) were determinant factors of skills of health care professionals on newborn resuscitation. CONCLUSION: The knowledge and skills of healthcare providers on newborn resuscitation in East Africa were not adequate. Newborn resuscitation training and the availability of resuscitation guidelines were determinant factors of knowledge, whereas work experience, knowledge, and the availability of newborn resuscitation equipment and training were associated with the skills of healthcare providers in newborn resuscitation. Newborn resuscitation training, resuscitation guidelines and equipment availability, and work experience are recommended to improve healthcare providers' knowledge and skills.

Effects of maternal probiotic supplementation on breast milk microbiome and infant gut microbiome and health: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The early-life microbiome is formed during the perinatal period and is critical for infants' lifelong health. This is established by maternal-infant microbiome crosstalk, which is mediated by the breast milk microbiome. The milk microbiome is dependent on the maternal gut microbiome, suggesting that it could potentially be restored through oral probiotic supplements. Therefore, we conducted this systematic review and meta-analysis to summarize the effect of maternal probiotic supplements on breast milk and infant gut microbiome composition and on infant health. DATA SOURCES: The PubMed, EMBASE, Web of Science, Scopus, CINAHL, and Science Direct databases were searched until December 15, 2022. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials following the population, intervention, comparison, and outcome (population: pregnant or lactating women; intervention: probiotics; control: placebo or follow-up; outcome: breast milk and infant gut microbiome composition and infant health) principles were included. METHODS: Using a random effect model, the standard mean difference, risk difference, and risk ratio with 95% confidence interval were used to measure each outcome. All analyses were conducted using the intention-to-treat approach. Heterogeneity was evaluated using I2 statistics. RESULTS: The final data set included 24 randomized controlled trials with a total of 2761 mothers and 1756 infants. The overall effect of probiotics on the beneficial bacteria detection rate in breast milk had a risk difference of 24% (95% confidence interval, 0.1-0.37; P<.001; I2=91.12%). The pooled mean beneficial and pathogenic bacteria abundance in breast milk had a standard mean difference of 1.22 log10 colony forming units/mL (95% confidence interval, 0.48-1.97; P<.001; I2=95.51%) and -1.05 log10 colony forming unites/mL (95% confidence interval, -1.99 to -0.12; P=.03; I2=96.79%), respectively. The overall abundance of beneficial bacteria in the infant gut had a standard mean difference of 0.89 log10 colony forming units/g (95% confidence interval, 0.22-1.56; P=.01; I2=95.01%). It also controlled infant weight gain (standard mean difference, -0.49 kg/equivalent age; 95% confidence interval, -0.82 to -0.17; P<.001; I2=0.00%) and decreased the occurrence of infantile colic (risk ratio, 0.30; 95% confidence interval, 0.16-0.57; P<.001; I2=0.00%). CONCLUSION: Maternal probiotic supplements effectively orchestrate the breast milk and infant gut microbiome with a wide range of clinical benefits and safety. Lactobacillus, Bifidobacterium, Streptococcus thermophilus, and S. boulardii can be used as maternal supplements to promote infant health.