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1.
Association between abnormal maternal serum levels of vitamin B12 and preeclampsia: a systematic review and meta-analysis.
Mardali, F, Fatahi, S, Alinaghizadeh, M, Kord Varkaneh, H, Sohouli, MH, Shidfar, F, Găman, MA
Nutrition reviews. 2021;(5):518-528
Abstract
CONTEXT Some evidence has shown an association between maternal vitamin B12 levels and the development of preeclampsia in pregnant women, but the relationship between preeclampsia and vitamin B12 is not clear. OBJECTIVE The aim of this systematic review was to compare serum vitamin B12 levels in women with preeclampsia with those in normotensive pregnant women. DATA SOURCES The PubMed/MEDLINE, Scopus, and Web of Science databases were searched up to August 2019, along with the reference lists of included articles. STUDY SELECTION The literature was searched for observational studies that investigated vitamin B12 levels in women with preeclampsia. DATA EXTRACTION Data were extracted independently by 2 authors. Data were pooled using a random-effects model. RESULTS Vitamin B12 levels in women with preeclampsia were significantly lower than those in healthy women (mean, -15.24 pg/mL; 95%CI, -27.52 to -2.954; P < 0.015), but heterogeneity between studies was high (I2 = 97.8%; P = 0.0103). Subgroup analyses based on folic acid supplementation, homocysteine concentrations, and gestational age at the time of sampling for vitamin B12 assessment did not identify the sources of heterogeneity. CONCLUSIONS Women with preeclampsia had significantly lower vitamin B12 concentrations than normotensive pregnant women.
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2.
Probiotics for preventing gestational diabetes.
Davidson, SJ, Barrett, HL, Price, SA, Callaway, LK, Dekker Nitert, M
The Cochrane database of systematic reviews. 2021;(4):CD009951
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Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes for mother and infant. The prevention of GDM using lifestyle interventions has proven difficult. The gut microbiome (the composite of bacteria present in the intestines) influences host inflammatory pathways, glucose and lipid metabolism and, in other settings, alteration of the gut microbiome has been shown to impact on these host responses. Probiotics are one way of altering the gut microbiome but little is known about their use in influencing the metabolic environment of pregnancy. This is an update of a review last published in 2014. OBJECTIVES To systematically assess the effects of probiotic supplements used either alone or in combination with pharmacological and non-pharmacological interventions on the prevention of GDM. SEARCH METHODS We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (20 March 2020), and reference lists of retrieved studies. SELECTION CRITERIA Randomised and cluster-randomised trials comparing the use of probiotic supplementation with either placebo or diet for the prevention of the development of GDM. Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over design studies were not eligible for inclusion in this review. Studies presented only as abstracts with no subsequent full report of study results were only included if study authors confirmed that data in the abstract came from the final analysis. Otherwise, the abstract was left awaiting classification. DATA COLLECTION AND ANALYSIS Two review authors independently assessed study eligibility, extracted data and assessed risk of bias of included studies. Data were checked for accuracy. MAIN RESULTS In this update, we included seven trials with 1647 participants. Two studies were in overweight and obese women, two in obese women and three did not exclude women based on their weight. All included studies compared probiotics with placebo. The included studies were at low risk of bias overall except for one study that had an unclear risk of bias. We excluded two studies, eight studies were ongoing and three studies are awaiting classification. Six included studies with 1440 participants evaluated the risk of GDM. It is uncertain if probiotics have any effect on the risk of GDM compared to placebo (mean risk ratio (RR) 0.80, 95% confidence interval (CI) 0.54 to 1.20; 6 studies, 1440 women; low-certainty evidence). The evidence was low certainty due to substantial heterogeneity and wide CIs that included both appreciable benefit and appreciable harm. Probiotics increase the risk of pre-eclampsia compared to placebo (RR 1.85, 95% CI 1.04 to 3.29; 4 studies, 955 women; high-certainty evidence) and may increase the risk of hypertensive disorders of pregnancy (RR 1.39, 95% CI 0.96 to 2.01, 4 studies, 955 women), although the CIs for hypertensive disorders of pregnancy also indicated probiotics may have no effect. There were few differences between groups for other primary outcomes. Probiotics make little to no difference in the risk of caesarean section (RR 1.00, 95% CI 0.86 to 1.17; 6 studies, 1520 women; high-certainty evidence), and probably make little to no difference in maternal weight gain during pregnancy (MD 0.30 kg, 95% CI -0.67 to 1.26; 4 studies, 853 women; moderate-certainty evidence). Probiotics probably make little to no difference in the incidence of large-for-gestational age infants (RR 0.99, 95% CI 0.72 to 1.36; 4 studies, 919 infants; moderate-certainty evidence) and may make little to no difference in neonatal adiposity (2 studies, 320 infants; data not pooled; low-certainty evidence). One study reported adiposity as fat mass (MD -0.04 kg, 95% CI -0.12 to 0.04), and one study reported adiposity as percentage fat (MD -0.10%, 95% CI -1.19 to 0.99). We do not know the effect of probiotics on perinatal mortality (RR 0.33, 95% CI 0.01 to 8.02; 3 studies, 709 infants; low-certainty evidence), a composite measure of neonatal morbidity (RR 0.69, 95% CI 0.36 to 1.35; 2 studies, 623 infants; low-certainty evidence), or neonatal hypoglycaemia (mean RR 1.15, 95% CI 0.69 to 1.92; 2 studies, 586 infants; low-certainty evidence). No included studies reported on perineal trauma, postnatal depression, maternal and infant development of diabetes or neurosensory disability. AUTHORS' CONCLUSIONS Low-certainty evidence from six trials has not clearly identified the effect of probiotics on the risk of GDM. However, high-certainty evidence suggests there is an increased risk of pre-eclampsia with probiotic administration. There were no other clear differences between probiotics and placebo among the other primary outcomes. The certainty of evidence for this review's primary outcomes ranged from low to high, with downgrading due to concerns about substantial heterogeneity between studies, wide CIs and low event rates. Given the risk of harm and little observed benefit, we urge caution in using probiotics during pregnancy. The apparent effect of probiotics on pre-eclampsia warrants particular consideration. Eight studies are currently ongoing, and we suggest that these studies take particular care in follow-up and examination of the effect on pre-eclampsia and hypertensive disorders of pregnancy. In addition, the underlying potential physiology of the relationship between probiotics and pre-eclampsia risk should be considered.
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Maternal prepregnancy overweight and obesity and the risk of preeclampsia: A meta-analysis of cohort studies.
He, XJ, Dai, RX, Hu, CL
Obesity research & clinical practice. 2020;(1):27-33
Abstract
OBJECTIVE The aim of our meta-analysis was to explore whether overweight and obesity was associated with preeclampsia or not. DESIGN Three databases were systematically reviewed and reference lists of relevant articles were checked. Meta-analysis of published cohort studies comparing whether overweight and obesity was associated with preeclampsia and adjusting for potential confounding factors. Calculations of pooled estimates were conducted in random-effects models. Heterogeneity was tested by using Chi-square test with Cochrane and heterogeneity was explored with meta-regression. Publication bias was estimated from Egger's test (linear regression method) and Begg's test (rank correlation method). RESULTS Nineteen studies met the inclusion criteria. The meta-analysis showed that overweight and obesity was associated with an increased risk of preeclampsia. The aOR calculated for 13 studies (compared overweight to normal weight) was 1.71, 95% CI (1.52, 1.91) for random-effects models and 19 studies (compared obesity to normal weight) was 2.48, 95% CI (2.05, 2.90) for random-effects models, stratified analyses showed no differences regarding quality grade, location of study and period of anthropometric measurement. There was no indication of a publication bias either from the result of Egger's test or Begg's test. CONCLUSIONS Our results suggested that prepregnancy maternal overweight and obesity are significantly associated with an increased risk of preeclampsia.
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Environmental risk factors, protective factors, and peripheral biomarkers for ADHD: an umbrella review.
Kim, JH, Kim, JY, Lee, J, Jeong, GH, Lee, E, Lee, S, Lee, KH, Kronbichler, A, Stubbs, B, Solmi, M, et al
The lancet. Psychiatry. 2020;(11):955-970
Abstract
BACKGROUND Many potential environmental risk factors, environmental protective factors, and peripheral biomarkers for ADHD have been investigated, but the consistency and magnitude of their effects are unclear. We aimed to systematically appraise the published evidence of association between potential risk factors, protective factors, or peripheral biomarkers, and ADHD. METHODS In this umbrella review of meta-analyses, we searched PubMed including MEDLINE, Embase, and the Cochrane Database of Systematic Reviews, from database inception to Oct 31, 2019, and screened the references of relevant articles. We included systematic reviews that provided meta-analyses of observational studies that examined associations of potential environmental risk factors, environmental protective factors, or peripheral biomarkers with diagnosis of ADHD. We included meta-analyses that used categorical ADHD diagnosis criteria according to DSM, hyperkinetic disorder according to ICD, or criteria that were less rigorous than DSM or ICD, such as self-report. We excluded articles that did not examine environmental risk factors, environmental protective factors, or peripheral biomarkers of ADHD; articles that did not include a meta-analysis; and articles that did not present enough data for re-analysis. We excluded non-human studies, primary studies, genetic studies, and conference abstracts. We calculated summary effect estimates (odds ratio [OR], relative risk [RR], weighted mean difference [WMD], Cohen's d, and Hedges' g), 95% CI, heterogeneity I2 statistic, 95% prediction interval, small study effects, and excess significance biases. We did analyses under credibility ceilings, and assessed the quality of the meta-analyses with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). This study is registered with PROSPERO, number CRD42019145032. FINDINGS We identified 1839 articles, of which 35 were eligible for inclusion. These 35 articles yielded 63 meta-analyses encompassing 40 environmental risk factors and environmental protective factors (median cases 16 850, median population 91 954) and 23 peripheral biomarkers (median cases 175, median controls 187). Evidence of association was convincing (class I) for maternal pre-pregnancy obesity (OR 1·63, 95% CI 1·49 to 1·77), childhood eczema (1·31, 1·20 to 1·44), hypertensive disorders during pregnancy (1·29, 1·22 to 1·36), pre-eclampsia (1·28, 1·21 to 1·35), and maternal acetaminophen exposure during pregnancy (RR 1·25, 95% CI 1·17 to 1·34). Evidence of association was highly suggestive (class II) for maternal smoking during pregnancy (OR 1·6, 95% CI 1·45 to 1·76), childhood asthma (1·51, 1·4 to 1·63), maternal pre-pregnancy overweight (1·28, 1·21 to 1·35), and serum vitamin D (WMD -6·93, 95% CI -9·34 to -4·51). INTERPRETATION Maternal pre-pregnancy obesity and overweight; pre-eclampsia, hypertension, acetaminophen exposure, and smoking during pregnancy; and childhood atopic diseases were strongly associated with ADHD. Previous familial studies suggest that maternal pre-pregnancy obesity, overweight, and smoking during pregnancy are confounded by familial or genetic factors, and further high-quality studies are therefore required to establish causality. FUNDING None.
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Oxidative stress markers in preeclamptic placentas: A systematic review with meta-analysis.
Ferreira, RC, Fragoso, MBT, Bueno, NB, Goulart, MOF, de Oliveira, ACM
Placenta. 2020;:89-100
Abstract
INTRODUCTION Oxidative stress (OS) is the basis of several diseases. Preeclampsia (PE) is a multisystemic syndrome, considered one of the major causes of maternal and fetal mortality. The placenta is considered the main anatomical pathogenetic substrate for the disease, being the placental OS a likely critical pathway in the pathogenesis of PE. This meta-analysis aimed to verify whether there is OS in the preeclamptic placenta and which markers are altered in this condition. METHODS The search was conducted in the following databases: MEDLINE (via PubMed), Lilacs and Scopus. Relevant studies were identified until May 2020. The quality of the studies was evaluated according to the Newcastle-Ottawa scale. RESULTS From the 3998 screened records, 43 were finally included in the systematic review, and 23 in the meta-analysis. The biomarkers evaluated were related to cell and macromolecules' damage, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OH-dG), lipid peroxides, isoprostane, total oxidant status (TOS), carbonylated proteins and some of the reactive oxygen and nitrogen species (RONS), like hydrogen peroxide and nitric oxide. It was also related to antioxidant activity, both enzymatic, including superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione S-transferase and total antioxidant status, and non-enzymatic, through quantification of reduced glutathione, vitamin C and E, zinc and copper. CONCLUSION It was observed that there was OS in the preeclamptic placentas, based on results, like lower activity of some of the enzymes of the antioxidant system (SOD and GPx) as well as the increase in oxidative damage markers (MDA and lipid peroxide), corroborating literature data.
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Pre-eclampsia is associated with later kidney chronic disease and end-stage renal disease: Systematic review and meta-analysis of observational studies.
Ferreira, RC, Fragoso, MBT, Dos Santos Tenório, MC, Silva, JVF, Bueno, NB, Goulart, MOF, de Oliveira, ACM
Pregnancy hypertension. 2020;:71-85
Abstract
OBJECTIVES To assess whether there is a risk of kidney disease during the postpartum period of women who had preeclampsia (PE). STUDY DESIGN Observational trials were searched in the PubMed, Science Direct, Clinical trials, Cochrane, LILACS and Web of Science databases. The data extracted from the studies were systematized, and the risk of bias was evaluated for each of them. Meta-analyses were performed with studies that evaluated chronic kidney disease (CKD) and end-stage renal disease (ESRD), pooling the natural logarithms of the adjusted risk measures and the confidence intervals of each study in a random effects model. RESULTS Of the 4149 studies evaluated, 35 articles were included in the review, of which 3 of the CKD and 6 of the ESRD presented the necessary outcomes to compose the meta-analysis. A formal registration protocol was included in the PROSPERO database (number: CRD42019111821). There was a statistically significant difference between the development of CKD (hazard ratio (HR): 1.82, confidence interval to 95% (95% CI): 1.27-2.62, P < 0.01) and ESRD (HR: 3.01, confidence interval to 95% (95% CI): 1.92-4.70, P < 0.01) in postpartum women affected by PE. CONCLUSIONS PE was considered a risk factor for the onset of CKD and ESRD in the postpartum period. Thus, more research is needed to clarify the underlying mechanisms of this association, and to assist in determining the most appropriate and effective clinical conduct to prevent and/or treat such complications.
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Systematic and meta-analysis of factors associated with preeclampsia and eclampsia in sub-Saharan Africa.
Meazaw, MW, Chojenta, C, Muluneh, MD, Loxton, D
PloS one. 2020;(8):e0237600
Abstract
BACKGROUND Preeclampsia and eclampsia are common complications of pregnancy globally, including sub-Saharan African (SSA) countries. Although it has a high burden on maternal and neonatal mortality and morbidity, evidence on the risk of the problem is limited. Therefore, the aim of this review was to examine the factors associated with preeclampsia and eclampsia among mothers in SSA countries. METHODS We searched article from SSA countries using electronic database MEDLINE, EMBASE, PubMed, CINAHL published in English from January 2000 to May 2020. Two reviewers independently screened, extracted and assessed the quality of the articles. Both random and fixed effect model were used for analysis. Heterogeneity of the studies and publication bias were checked. STATA 16 used for analysis. RESULTS Fifty-one studies met the inclusion criteria and included in this review. The following factors were identified through meta-analysis: being primiparous (OR: 2.52; 95% CI:1.19, 3.86), previous history of maternal preeclampsia/eclampsia (OR:5.6; 95% CI:1.82, 9.28), family history of preeclampsia/eclampsia (OR:1.68; 95% CI:1.26, 2.11), high maternal body mass index (OR: 1.69; 95% CI:1.17, 2.21), chronic hypertension (OR: 2.52; 95% CI:1.29, 3.74), anaemia during pregnancy (OR: 3.22; 95% CI:2.70, 3.75) and lack of antenatal care visits (OR: 2.71; 95% CI:1.45, 3.96). There was inconclusive evidence for a relationship with a number of other factors, such as nutrition and related factors, antenatal care visits, birth spacing, and other factors due to few studies found in our review. CONCLUSIONS The risk of preeclampsia and eclampsia is worse among women who have a history of preeclampsia/eclampsia (either themselves or family members), primiparous, obesity and overweight, living with chronic disease, having anaemia during pregnancy and absence from ANC visits. Therefore, investment must be made in women's health needs to reduce the problem and health service providers need to give due attention to high-risk women.
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Association of Apolipoprotein E gene polymorphism with Preeclampsia: a meta-analysis.
Abyadeh, M, Heydarinejad, F, Khakpash, M, Asefi, Y, Shab-Bidar, S
Hypertension in pregnancy. 2020;(2):196-202
Abstract
Objective: The aim of this meta-analysis was to examine the association of ApoE polymorphism with the risk of developing PE.Methods: A comprehensive search was carried out through PubMed, Scopus, and Embase. The ORs with corresponding 95% CIs were extracted. Fixed model was used for meta-analysis and in case of existing heterogeneity a random-effects model was applied.Results: Association of ApoE polymorphism with the risk of developing PE was not statistically significant (OR = 0.86, 95% CI: 0.67-1.11; OR = 0.92, 95%CI: 0.73-1.15, respectively for ε2 and ε4).Conclusion: ApoE polymorphism might not be associated with the risk of PE.
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Meta-analysis of gene expression profiles in preeclampsia.
Vennou, KE, Kontou, PI, Braliou, GG, Bagos, PG
Pregnancy hypertension. 2020;:52-60
Abstract
OBJECTIVE Preeclampsia (PE) is a serious complication of pregnancy. It is considered a complex condition influenced by maternal genes, environmental factors and a deregulated immune response of the mother, but the etiology is largely unknown. The aim of this study is to identify differentially expressed genes (DEGs) in PE, to help elucidate the identification of the disease etiological mechanisms. STUDY DESIGN The databases Pubmed and GEO were searched according to PRISMA guidelines for the existence of gene expression data on placental samples from case-control studies. After meta-analysis the identified DEGs were further analyzed with STRING and PANTHER to retrieve interaction networks and overrepresented biochemical pathways. RESULTS Only 10 gene expression datasets and articles fulfilled inclusion criteria, containing data on 195 patients and 231 controls, and were analyzed. Meta-analysis identified 629 DEGs to be associated with PE at a False Discovery Rate p-value of 0.01. Network analysis showed few highly interconnected genes involved in innate immunity and signal transduction pathways indicative of a multifaceted disease with etiological heterogeneity. over representation analysis revealed that these genes participate mainly in carbohydrates, amino acids and pyrimidine metabolism, circadian clock system and signal transduction pathways. CONCLUSIONS This work, combining rigorous methods of meta-analysis and the use of modern bioinformatics tools, proposes the existence of novel, overlooked so far, biochemical pathways and mechanisms to contribute to PE development such as carbohydrate, aminoacids and pyrimidine metabolism. Our findings pave the way for further investigation of the above pathways in experimental efforts to decipher the orchestrating mechanisms for PE development.
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10.
Supplementation of folic acid in pregnancy and the risk of preeclampsia and gestational hypertension: a meta-analysis.
Liu, C, Liu, C, Wang, Q, Zhang, Z
Archives of gynecology and obstetrics. 2018;(4):697-704
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OBJECTIVES We aimed to systematically assess the relationship between folic acid supplementation in pregnancy and risk of preeclampsia and gestational hypertension. METHODS The relevant studies were included by retrieving the Embase, PubMed and Cochrane library databases. Data extraction was conducted by two investigators independently. The risk ratio (RR) and 95% confidence interval (CI) were used as effect indexes to evaluate the relationship between folic acid supplementation and risk of gestational hypertension or preeclampsia. A subgroup analysis was performed according to the supplementation patterns of folic acid. The homogeneity of the effect size was tested across the studies, and publication biases were examined. RESULTS In total, 13 cohort studies and 1 randomized controlled trial study was included, containing 160,562 and 149,320 women with and without folic acid supplementation during pregnancy. Pooled results showed that risk of gestational hypertension was not associated with the supplementation of folic acid. However, folic acid supplementation during pregnancy could significantly reduce the risk of preeclampsia. Moreover, the results of subgroup analysis showed that the decreased preeclampsia risk was associated with supplementation of multivitamins containing folic acid rather than folic acid alone. CONCLUSIONS Our findings indicate that the supplementation of multivitamins containing folic acid during pregnancy could significantly lower preeclampsia risk.