Low molecular weight heparin and pregnancy outcomes in women with inherited thrombophilia: A systematic review and meta-analysis.

AIM: To determine whether the use of low molecular weight heparin (LMWH) improves the pregnancy outcomes in women with inherited thrombophilia by conducting a meta-analysis of randomized controlled trials and observational studies. METHODS: A systematic literature search of several databases was conducted through September 19, 2020 to identify relevant studies. The outcomes of interest included live birth and adverse pregnancy outcomes (APOs). The overall risk estimates were pooled using random-effects meta-analysis. RESULTS: Ten randomized controlled trials and 12 cohort studies were included. In the meta-analyses of randomized controlled trials, the effectiveness of LMWH-treatment was found to be statistically significant in decreasing the risk of APOs (risk ratio [RR] = 0.76; 95% confidence interval [CI]: 0.61-0.95; p = 0.020), rather than in increasing the rate of live birth (RR = 1.12; 95% CI: 0.93-1.34; p = 0.230). In the meta-analyses of cohort studies, results showed that the use of LMWH was associated with a significantly higher proportion of live birth (RR = 1.86; 95% CI: 1.09-3.19; p = 0.020) as well as a significantly lower ratio of APOs (RR = 0.46; 95% CI: 0.31-0.69; p < 0.001) in women with inherited thrombophilia. CONCLUSIONS: The use of LMWH may have a potentially beneficial effect on reducing the risk of APOs and even increasing the live birth rate in women with inherited thrombophilia. Further well-designed clinical trials with large samples are needed to address the role of LMWH in improving pregnancy outcomes among pregnant women with inherited thrombophilia.

Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis.

STUDY QUESTION: Is there an association between hereditary thrombophilia in pregnant women and risk of recurrent pregnancy loss (RPL)? SUMMARY ANSWER: Pregnant women with hereditary thrombophilia have an increased risk of RPL, especially for pregnant women with the G1691A mutation of the factor V Leiden (FVL) gene, the G20210A mutation of the prothrombin gene (PGM), and deficiency of protein S (PS). WHAT IS KNOWN ALREADY: Prior studies have suggested that pregnant women with hereditary thrombophilia have a higher risk of RPL, however, the results are inconsistent; furthermore, a complete overview is missing. This lack of information is an obstacle to the risk assessment of RPL in pregnant women with hereditary thrombophilia. A comprehensive meta-analysis on the relation between hereditary thrombophilia and the risk of RPL is needed. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis was performed using observational studies published in English before 1 April 2020 to evaluate the relation between hereditary thrombophilia and risk of RPL. PARTICIPANTS/MATERIALS, SETTING, METHODS: Relevant studies were identified from PubMed, Web of Science, and EMBASE searches and complemented with perusal of bibliographies of retrieved articles. The exposure of interest was hereditary thrombophilia, including FVL mutation, PGM, deficiency of antithrombin (AT), deficiency of protein C (PC), and deficiency of PS. The overall risk estimates were pooled using random effects models. Subgroup and sensitivity analyses were carried out to explore possible sources of heterogeneity and assess the robustness of the results. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 89 studies involving 30 254 individuals were included. Results showed that women with FVL mutation (odds ratio (OR): 2.44, 95% CI: 1.96-3.03), PGM (OR: 2.08, 95% CI: 1.61-2.68), or deficiency of PS (OR: 3.45, 95% CI: 1.15-10.35) had higher risks of developing RPL. Compared with the reference group, there was no observed relation between a deficiency in AT or PC and RPL (all P > 0.05). Heterogeneity in the risk estimates of RPL was partially explained by geographic region, definitions of RPL, types of RPL, and controlled confounders. Sensitivity analyses validated the robustness of the findings. LIMITATIONS, REASONS FOR CAUTION: Only 39 of the included studies controlled for one or more confounders, and the heterogeneity across all included studies was high. Based on the data available, we cannot determine whether this association is confounded by other potential risk factors of RPL. WIDER IMPLICATIONS OF THE FINDINGS: This systematic review and meta-analysis show a possible association between hereditary thrombophilia and an increased risk of RPL, suggesting that testing for hereditary thrombophilia should be considered in individuals with RPL. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Hunan Provincial Key Research and Development Program (Grant number: 2018SK2062) and National Natural Science Foundation Program (Grant number: 81973137). There are no conflicts of interest. REGISTRATION NUMBER: N/A.

Risk factors for preterm birth: a prospective cohort study. / æ—©äº§å±é™©å› ç´ çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To investigate the incidence of preterm birth and risk factors for preterm birth. METHODS: A prospective cohort study was performed for the pregnant women in early pregnancy and their spouses, who underwent prenatal examination for the first time in Hunan Provincial Maternal and Child Health Care Hospital from May 2014 to December 2016 and decided to be hospitalized for delivery. A questionnaire survey was performed to collect exposure information possibly related to preterm birth. The hospital's medical record system was used for information verification and to record the pregnancy outcome. A multivariate logistic regression analysis was used to investigate the risk factors for preterm birth. RESULTS: A total of 6 764 pregnant women with complete data were included, and the incidence rate of preterm birth was 17.09%. The multivariate logistic regression analysis showed that a history of adverse pregnancy outcomes, eating areca nut before pregnancy, a history of pregnancy complications, a history of hepatitis, no folate supplementation during pregnancy, medication during pregnancy, active smoking and passive smoking during pregnancy, drinking during pregnancy, unbalanced diet during pregnancy, high-intensity physical activity during pregnancy, and natural conception after treatment of infertility or assisted conception as the way of conception were risk factors for preterm birth (P<0.05). Additionally, the pregnant women whose spouses were older, had a higher body mass index or smoked had an increased risk for preterm birth (P<0.05). A higher level of education of pregnant women or their spouses and lower gravidity were protective factors against preterm birth (P<0.05). CONCLUSIONS: There are many risk factors for preterm birth. Special attention should be paid to the life behaviors of pregnant women during pregnancy, and health education should be strengthened for pregnant women and their spouses to develop good living habits and reduce the incidence of preterm births.

Hypertensive Disorders of Pregnancy and Risk of Cardiovascular Disease-Related Morbidity and Mortality: A Systematic Review and Meta-Analysis.

INTRODUCTION: Several studies have demonstrated that there is a higher risk of cardiovascular disease (CVD) in women with a history of hypertensive disorders of pregnancy (HDP). However, effect sizes varied greatly between these studies, and a complete overview of the existing data in the literature is lacking. We aimed to evaluate the association between HDP and the risk of CVD-related morbidity and mortality. METHODS: Systematic literature searches were conducted in several electronic databases from inception to July 2019. Exposure of interest was any type of HDP. Outcomes of interest included any CVD, CVD-related mortality, and hypertension. RESULTS: Sixty-six cohort and 7 case-control studies involving >13 million women were included. The overall combined relative risks (RRs) for women with a history of HDP compared with the reference group were 1.80 (95% confidence interval [CI] 1.67-1.94) for any CVD, 1.66 (1.49-1.84) for coronary artery heart disease, 2.87 (2.14-3.85) for heart failure, 1.60 (1.29-2.00) for peripheral vascular disease, 1.72 (1.50-1.97) for stroke, 1.78 (1.58-2.00) for CVD-related mortality, and 3.16 (2.74-3.64) for hypertension. Significant heterogeneity was partially explained by all or part of the variables including type of exposure, follow-up time, geographic region, and sample source. CONCLUSIONS: Women with a history of HDP are at an increased risk of future CVD-related morbidity and mortality. Our study highlights the importance of life-long monitoring of cardiovascular risk factors in women with a history of HDP.

Effect of hypertensive disorders of pregnancy on pubertal development in daughters and sons: a systematic review and meta-analysis.

Hypertensive disorders of pregnancy (HDP) are a major cause of maternal and offspring morbidity and mortality worldwide. Several studies in recent years have focused on the link between HDP and pubertal development in offspring. The goal of this study was to synthesize the published literature on the effect of HDP on pubertal development in offspring by a systematic review and meta-analysis (PROSPERO 2021: CRD42020148736). A systematic literature search of several databases was conducted through December 2021, focusing on studies reporting pubertal development in offspring of women with and without HDP exposure. Primary outcomes of interest included offspring body mass index (BMI), height, waist and hip circumference, fat mass, pubarche, thelarche, and age at menarche. A total of 21 studies were finally included. Significantly higher values of BMI (SMD: 0.16 [0.11, 0.22]; p < 0.01) and waist circumference (SMD: 0.21 [0.14, 0.29]; p < 0.01) were found in offspring exposed to maternal HDP. In addition, a tendency of the early development of secondary sexual characteristics only in daughters was presented in offspring whose mothers were diagnosed with HDP. The findings imply a possible effect of HDP on pubertal development in offspring, especially for their BMI and waist circumference, which highlights the importance of focusing on adolescent developmental abnormalities in offspring exposed to HDP.

Maternal Body Mass Index, Gestational Weight Gain, and Risk of Cancer in Offspring: A Systematic Review and Meta-Analysis.

Background: Mounting evidence suggests that maternal obesity and gestational weight gain (GWG) may increase the risk of cancer in their offspring; however, results are inconsistent. The purpose of this research is to determine the association between maternal body mass index (BMI) and GWG and the risk of cancer in offspring through a systematic and comprehensive meta-analysis. Methods: A systematic literature search of several databases was conducted on 1 October 2022 to identify relevant studies. The quality of the included studies was evaluated using the Newcastle-Ottawa scale. The overall risk estimates were pooled using a random-effects meta-analysis. Results: Twenty-two studies with more than 8 million participants were included. An increased risk of total cancer was found in offspring whose mothers had a high GWG (odds ratio [OR]: 1.10; 95% CI: 1.01-1.19; p: 0.040) but not in offspring whose mothers had a low GWG (OR: 1.06; 95% CI: 0.96-1.17; p: 0.030), when compared with offspring whose mothers had a suitable GWG. In addition, no statistically significant association was found between maternal underweight (OR: 1.05; 95% CI: 0.97-1.13; p: 0.630), overweight/obesity (OR: 1.07; 95% CI: 0.99-1.16; p: 0.020), and risk of total cancer in offspring. Conclusions: Our study proposes evidence that maternal BMI and GWG may be associated with the risk of cancer in offspring, although statistical significance was found only for high GWG. Further well-designed research is required to clarify the potential relevance of maternal BMI and GWG on offspring cancer, especially for specific cancers.

Prognostic value of N-terminal pro-form B-type natriuretic peptide (NT-proBNP) in patients with congenital heart disease undergoing cardiac surgery: a systematic review and meta-analysis of cohort studies.

Background: To perform an updated and comprehensive meta-analysis on the prognostic value of N-terminal pro-form B-type natriuretic peptide (NT-proBNP) in patients with congenital heart disease (CHD) undergoing cardiac surgery. Methods: A systematic search was conducted until September 2021 for relevant studies published in PubMed, Web of Science Database and Embase. Based on the average values, NT-proBNP concentrations were classified as high and low levels. The outcomes of interest were mortality, cardiovascular events, and other postoperative outcomes. A random-effects model was used to calculate composite risk estimates and corresponding 95% confidence intervals (CIs). Possible sources of heterogeneity and stability of results were analyzed using subgroup and sensitivity analyses. Results: A total of 32 studies published between 2008 and 2021 involving 7,571 participants were included. Results showed CHD patients at high NT-proBNP levels yielded an increased risk of mortality [risk ratio (RR) =1.14; 95% CI: 1.08-1.20] and cardiovascular events (RR =2.02; 95% CI: 1.26-3.24) compared with those at low NT-proBNP levels. No significant association was found between NT-proBNP and risks for other postoperative outcomes in CHD patients undergoing cardiac surgery (RR =1.73; 95% CI: 0.86-3.47). Significant heterogeneity was detected across studies regarding these risk estimates. Subgroup analysis found heterogeneity in the risk estimate of mortality was explained by geographic region, type of CHD, and assay method of NT-proBNP. Sensitivity analysis supported the robustness of results. Conclusions: Compared with CHD patients at low NT-proBNP levels, CHD patients at high NT-proBNP levels had elevated risks of mortality and cardiovascular events. Further large-scale and well-controlled studies are needed to confirm our findings.

Overweight/Obesity in Childhood and the Risk of Early Puberty: A Systematic Review and Meta-Analysis.

Purpose: To determine the relationship between childhood overweight/obesity and early puberty in both boys and girls. Specifically, this is the first time to conduct a meta-analysis of the relationship between childhood overweight/obesity and early puberty in boys. Methods: Relevant studies were identified from PubMed, Web of Science, and EMBASE searches. The exposure of interest was overweight/obesity in childhood. Childhood was defined internationally as the age range of 0-18 years. The overall risk estimates were pooled using random effects models. Subgroup and sensitivity analyses were performed to explore possible sources of heterogeneity and to assess the robustness of the results. Results: A total of 10 studies involving 13,338 girls and 12,796 boys were included. Results showed that childhood overweight/obesity were associated with a significantly higher risk of early puberty in girls [odds ratio (OR): 2.22, 95% CI: 1.65-2.99]. Although without statistical significance, a higher risk of early puberty was also found in boys who were overweight/obese in childhood (OR: 1.29, 95% CI: 0.98-1.70). Heterogeneity in the risk estimates of early puberty was partially explained by study design, sample size, follow-up duration, definitions of early puberty and confounders controlled. Sensitivity analyses validated the robustness of the findings. Conclusions: Our findings showed that for girls the associate between overweight/obesity and early puberty is definite or strong whereas for males, such an association is possible, prompting that future studies need to further explore the possible relationship between overweight/obesity and early puberty in boys. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021264649, PROSPERO CRD42021264649.