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.

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.

Knowledge on anaemia and benefit of iron-folic acid supplementation among pregnant mothers attending antenatal care in Woldia town, Northeastern Ethiopia: a facility-based cross-sectional study.

BACKGROUND: Anaemia in pregnancy is the leading cause of maternal morbidity and mortality and poor birth outcomes in low- and middle-income countries. The most common cause of anaemia during pregnancy is acute blood loss and iron deficiency due to physiological changes and increasing demand for iron on the mother and growing foetus. Iron and folic acid supplementation is the most widely employed strategy to alleviate iron deficiency anaemia during pregnancy. The mother's knowledge of anaemia and the benefit of iron-folic acid is crucial in reducing the magnitude of anaemia due to iron deficiency. In Woldia town, despite the efforts made to reduce iron deficiency anaemia during pregnancy, information on pregnant mother knowledge on anaemia and the benefit of iron-folic acid and its associated factors are scarce. METHODS: A facility-based cross-sectional study design was conducted, on 414 pregnant mothers attending antenatal care in Woldia town, Northern Ethiopia. Systematic random sampling methods were used to select study participants. The data were entered into Epi-data version 4.2 and analysed using SPSS version 24. Bivariable and multivariable analysis was done to see the association between the dependent variable and independent variables. RESULTS: This study revealed that 54.1% and 57.7% of pregnant women had good knowledge of anaemia and the benefit of iron-folic acid, respectively. Maternal education status (AOR = 2.19, 95% CI 1.32-3.64), good knowledge of iron-folic acid (AOR = 5.85, 95% CI 3.60-9.50) and residence (AOR = 5.43, 95% CI 2.36-12.51) were statistically associated with pregnant mothers knowledge on anaemia. Obtained counselling on the benefit of iron-folic acid (AOR = 2.04, 95% CI 1.11-3.75), having four or more antenatal care visit (AOR = 3.12, 95% CI 1.38-7.07) and good knowledge of anaemia (AOR = 5.88, 95% CI 3.63-9.50) was statistically associated with pregnant mothers knowledge on the benefit of iron-folic acid. CONCLUSIONS: Promoting frequent antenatal care visits and giving counselling on the benefit of iron-folic acid and cause, prevention and treatment of anaemia were essential strategies to raise knowledge of pregnant mother on anaemia and the benefit of iron-folic acid.

Post-abortion family planning use, method preference, and its determinant factors in Eastern Africa: a systematic review and meta-analysis.

BACKGROUND: Utilization of post-abortion family planning is very critical to reduce high levels of unintended pregnancy, which is the root cause of induced abortion. In Eastern Africa, it is estimated that as many as 95% of unintended pregnancies occurred among women who do not practice contraception at all. Therefore, this meta-analysis aimed to assess post-abortion family planning utilization and its determinant factors in Eastern Africa. METHODS: Published papers from Scopus, HINARI, PubMed, Google Scholar, and Web of Science electronic databases and grey literature repository were searched from database inception to January 30, 2020, with no restriction by design and date of publishing. We screened records, extracted data, and assessed risk of bias in duplicate. Cochrane I2 statistics were used to check the heterogeneity of the studies. Publication bias was assessed by Egger and Biggs test with a funnel plot. A random-effects model was calculated to estimate the pooled prevalence of post-abortion family planning utilization. RESULTS: A total of twenty-nine cross-sectional studies with 70,037 study participants were included. The overall pooled prevalence of post-abortion family planning utilization was 67.86% (95% CI 63.59-72.12). The most widely utilized post-abortion family methods were injectable 33.23% (95% CI 22.12-44.34), followed by implants 24.71% (95% CI 13.53-35.89) and oral contraceptive pills 23.42% (95% CI 19.95-26.89). Married marital status (AOR=3.20; 95% CI 2.02-5.05), multiparity (AOR=3.84; 95% CI 1.43-10.33), having a history of abortion (AOR=2.33; 95% CI 1.44-3.75), getting counselling on post-abortion family planning (AOR=4.63; 95% CI 3.27-6.56), and ever use of contraceptives (AOR=4.63; 95% CI 2.27-5.21) were factors associated with post-abortion family planning utilization in Eastern Africa. CONCLUSIONS: This study revealed that the marital status of the women, multiparity, having a history of abortion, getting counselling on post-abortion family planning, and ever used contraceptives were found to be significantly associated with post-abortion family planning utilization.

Preterm birth and its associated factors in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Preterm birth is a public health concern globally. In low- and middle-income countries, like Ethiopia, preterm birth is under reported and underestimated. Therefore, this systematic review and meta-analysis assessed the pooled prevalence and associated risk factors for preterm birth in Ethiopia. METHODS: In this review the databases used were PubMed, Google scholar, EMBASE, HINARI and African journal online. Publication bias was checked using a funnel plot and Eggers test. RESULTS: A total of 30 studies were included in this systematic review and meta-analysis. The overall pooled prevalence of preterm birth in Ethiopia was 11.4% (95% CI; 9.04, 13.76). On pooled analysis, preterm birth was associated with pregnancy-induced hypertension being HIV-positive, premature rupture of membrane, rural residence, the mother having a history of abortion, multiple pregnancies, and anemia during pregnancy. CONCLUSION: The national prevalence of preterm birth in Ethiopia was low. Early identifying those pregnant women who are at risk of the above determinants and proving quality healthcare and counsel them how to prevent preterm births, which decrease the rate of preterm birth and its consequences. So, both governmental and non-governmental health sectors work on the minimization of these risk factors.

Adherence to iron-folic acid supplementation among pregnant women in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Despite the supplementation of iron-folic acid is the recommended strategy during the antenatal period; iron deficiency anemia is the commonest hematologic complication during pregnancy. Therefore, this systematic review and meta-analysis aimed to assess the level of adherence to iron-folic acid supplementation and its associated factors among pregnant women in Ethiopia. METHODS: Systematic review and meta-analysis guideline was followed for this study. Different online databases were used for the review: PubMed, HINARI, EMBASE, Google Scholar and African Journals Online. Different searching terms were applied based on the adapted PICO principles to achieve and access all the essential articles. The data were entered and analyzed using Microsoft Excel and Stata 11 software respectively. RESULTS: Fifteen studies were included in this systematic review and meta-analysis with a total of 5808 pregnant women. The overall pooled prevalence of adherence to iron-folic acid supplementation among pregnant women in Ethiopia was 41.38% (95% CI: 33.09, 49.67). Having secondary and above educational status of the women (AOR:2.68,95%CI:1.25, 5.74), having an early registration of antenatal care follow-up (≤16 weeks) (AOR:2.54,95%CI:1.99, 3.24), having anemia complication during current pregnancy (AOR:3.01,95%CI:1.88, 4.81), having good knowledge of iron-folic acid supplementation (AOR: 2.96, 95%CI:1.76, 4.99), having four times or more antenatal care follow up (AOR:3.66, 95%CI:2.81, 4.77), getting health education about benefit of iron and folic acid (AOR:2.62,95%CI:1.46,4.72), and having good knowledge about anemia (AOR:2.99,95%CI:2.32, 3.85) were associated risk factors for adherence to iron-folic acid supplementation. CONCLUSION: The overall pooled prevalence adherence of IFAS among pregnant women was lower than the WHO recommendations. Educational status, early registration of ANC, anemia in the current pregnancy, good knowledge of IFAS, number of ANC visits, good knowledge of anemia and receiving health education about the benefit of IFAS were factors associated with the adherence of IFAS among pregnant women in Ethiopia. This finding is important to design strategic policies and to prevent anemia and congenital anomaly resulted from inadequate intake of iron and folic acid.

Perinatal asphyxia and its associated factors in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Despite different preventive strategies that have been implemented in different health institutions in the country, neonatal mortality and morbidity are still significantly increasing in Ethiopia. Perinatal asphyxia is the leading cause of neonatal morbidity and mortality worldwide. As a result, this systematic review and meta-analysis aimed to assess the prevalence and associated factors of perinatal asphyxia in Ethiopia. METHODS: Online databases (PubMed, HINARI, EMBASE, Google Scholar and African Journals), other gray and online repository accessed studies were searched using different search engines. Newcastle-Ottawa Quality Assessment Scale (NOS) was used for critical appraisal of studies. The analysis was done using STATA 11 software. The Cochran Q test and I2 test statistics were used to test the heterogeneity of studies. The funnel plot and Egger's test were used to detect publication bias of the studies. The pooled prevalence of perinatal asphyxia and the odds ratio (OR) with a 95% confidence interval was presented using forest plots. RESULT: Nine studies were included in this review, with a total of 12,249 live births in Ethiopia. The overall pooled prevalence of perinatal asphyxia in Ethiopia was 24.06% (95 95%CI: 18.11-30.01). Associated factors of perinatal asphyxia included prolonged labor (OR = 2.79, 95% CI: 1.98, 3.93), low birth weight (OR = 6.52, 95% CI: 4.40, 9.65), meconium-stained amniotic fluid (OR = 5.91, 95% CI: 3.95, 8.83) and instrumental delivery (OR = 4.04, 95% CI: 2.48, 6.60) were the determinant factors of perinatal asphyxia in Ethiopia. CONCLUSIONS: The overall pooled prevalence of perinatal asphyxia was remarkably high. Duration of labor, meconium-stained amniotic fluid, instrumental deliveries, and birth weight were the associated factors of perinatal asphyxia in Ethiopia. Therefore, efforts should be made to improve the quality of intrapartum care service to prevent prolonged labor and fetal complications and to identify and make a strict follow up of mothers with meconium-stained amniotic fluid. This finding is important to early recognition and management of its contributing factors, might modify hypoxic-ischemic encephalopathy and may improve the implementation of the standard guideline effectively and consistently.

Factors associated with unintended pregnancy among women attending antenatal care in Maichew Town, Northern Ethiopia, 2017.

OBJECTIVE: Unintended pregnancy is one of the most public health issues in the world, and it is the major sexual and reproductive health problem which carries a higher risk of morbidity and mortality for women, often due to unsafe abortion. Even though family planning services are effective and available than ever before, unintended pregnancy and unsafe abortion are the major public health problems in the study area. Therefore, this study aimed at assessing the magnitude and associated factors of unintended pregnancy among pregnant women attending antenatal care follow up in Maichew town, northern Ethiopia. An institution based cross-sectional study was conducted on 329 pregnant women selected with a systematic sampling technique from April 5 to May 4, 2017. RESULT: The magnitude of unintended pregnancy among pregnant women attending antenatal care in Maichew was found to be 29.7% (95% CI 24.30, 35.50). On the other hand, single in marital status (AOR = 38.6, 95% CI 10.07, 148.01), living alone (AOR = 9.9, 95% CI 1.80, 53.40) and having three or four children (AOR = 3.5, 95% CI 1.10, 11.04) were factors associated with an unintended pregnancy. Creating awareness about unintended pregnancy associated factors and implication of unintended pregnancy is highly recommended.

Surgical site infection and its associated factors following cesarean section in Ethiopia: a cross-sectional study.

OBJECTIVE: This study aimed to determine the magnitude and associated factors of surgical site infection following cesarean section at Felegehiwot referral hospital, Amhara, Bahir Dar, Ethiopia, 2018. An institution-based retrospective cross-sectional study was conducted from April 1 to May 30, 2018, at Felegehiwot referral hospital. Retrospective chart review was implemented on 383 women who gave birth via cesarean section at Felegehiwot hospital from October 1, 2016 to September 30, 2017. Systematic random sampling technique was implemented to select patient medical charts. RESULTS: This study revealed that the prevalence of surgical site infection following cesarean section was 7.8% with the [95% CI 5.2-10.5%]. Rupture of membrane before cesarean section (AOR = 13.9, 95% CI 2.99-64.8), vertical skin incision/longitudinal abdominal incision (AOR = 4.77, 95% CI 1.74-13.06), duration of operation lasting longer than 30 min (AOR = 4.9, 95% CI 1.8-13.1), interrupted skin closure technique (AOR = 6.29, 95% CI 2.07-19.11) were statistically associated with surgical site infection following cesarean section.