The J shaped association of age at menarche and cardiovascular events: systematic review and meta-analysis.

This study aimed to evaluate the association between age at menarche and cardiovascular (CV) events through a systematic review and meta-analysis of observational studies. A comprehensive literature search covering studies published from January 1, 2000, to October 31, 2023, was conducted in PubMed, MEDLINE, Embase, and Scopus. Twenty-nine observational studies involving 4,931,160 adult women aged 18 years or older were included. The meta-analysis revealed a J-shaped association between age at menarche and CV events. Individuals with menarche at 12-13 years exhibited the lowest risk, while those with younger (≤ 11 years) or older ages (14-15 years and ≥ 16 years) showed an increased risk. Notably, individuals with age at menarche of 16 years and older had the highest risk of CV events. The pooled odds of CV mortality in age at menarche categories 14-15 years and ≥ 16 years were 37% (OR: 1.37, 95% CI 1.14-1.64, I2: 76.9%) and 64% (OR: 1.64, 95% CI 1.20-2.24, I2: 87%) higher than referent age at menarche 12-13 years. No statistically significant difference was found in CV mortality risk between individuals with age at menarche ≤ 11 years and those with age at menarche 12-13 years. The ORs for coronary heart disease were significantly higher for age at menarche ≥ 16 years (35% increase), while no significant difference was found for age at menarche ≤ 11 years or 14-15 years compared to age at menarche 12-13 years. Regarding stroke, the ORs for age at menarche ≤ 11, 14-15, and ≥ 16 years were significantly higher (7%, 24%, and 94% increase, respectively) compared to age at menarche 12-13 years. Dose-response meta-analysis and one-stage random-effect cubic spline models confirmed the J-shaped risk pattern. Meta-regression indicated that age and BMI were not significant sources of heterogeneity. Sensitivity analyses and the absence of publication bias further supported the robustness of the findings. This study concludes that age at menarche is independently associated with CV events, with a J-shaped pattern. The findings underscore the significance of considering menarche age as an independent risk factor for CV events. Further research is warranted to validate these findings and explore potential underlying mechanisms.

Prevalence of depression, stress and suicide tendency among individuals with long COVID and determinants: a protocol of a systematic review and meta-analysis.

BACKGROUND: It is well known that the COVID-19 pandemic has had a devastating impact on mental health, especially among individuals with long COVID. This systematic review and meta-analysis aims to investigate the prevalence of depression, stress and suicide tendencies among individuals with long COVID, as well as to explore the factors that contribute to these conditions. METHODS AND ANALYSIS: A comprehensive review of literature will be conducted in various databases of including PubMed, including Medline, Embase, PsycINFO, CINAHL and Cochrane Library. The studies to be included in this review will be published in the English language, and the time frame of included studies will be from the date of inception of COVID-19 until 30 December 2023. Two independent reviewers will identify studies for inclusion based on a screening questionnaire, and the JBI standardised critical appraisal checklist for studies reporting prevalence data will be used to assess the methodological quality. The strength of the body of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. To analyse the data, a robust Bayesian approach will be applied using the STATA software package (V.14; STATA) and JASP software. The findings of this systematic review and meta-analysis will provide valuable insights into the prevalence of depression, stress and suicide tendencies among individuals with long COVID, as well as the factors that contribute to these conditions. ETHICS AND DISSEMINATION: There is no research ethics board approval required. The dissemination plan is to publish results in a peer-reviewed academic journal. PROSPERO REGISTRATION NUMBER: CRD42022346858.

The prevalence of thyroid disorders in COVID-19 patients: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to evaluate the prevalence of thyroid disorders in COVID-19 patients. DATA SOURCES: Scopus, PubMed, ISI Web of Science, and Google Scholar databases were used in this review. We also consider the results of grey literature. STUDY SELECTIONS: Cohort, cross-sectional, and case-control studies were included. DATA EXTRACTION AND SYNTHESIS: The required data were extracted by the first author of the article and reviewed by the second author. The Pooled prevalence of outcomes of interest was applied using the meta-prop method with a pooled estimate after Freeman-Tukey Double Arcsine Transformation to stabilize the variances. OUTCOMES AND MEASURED: The different thyroid disorders were the main outcomes of this study. The diseases include non-thyroidal illness syndrome, thyrotoxicosis, hypothyroidism, isolated elevated free T4, and isolated low free T4. RESULTS: Eight articles were included in our meta-analysis(Total participants: 1654). The pooled prevalence of events hypothyroidism, isolated elevated FT4, isolated low FT4, NTIS, and thyrotoxicosis were estimated (Pooled P = 3%, 95% CI:2-5%, I2: 78%), (Pooled P = 2%, 95% CI: 0-4%, I2: 66%), (Pooled P = 1%, 95% CI: 0-1%, I2: 0%), (Pooled P = 26%, 95% CI: 10-42%, I2: 98%), and (Pooled P = 10%, 95% CI: 4-16%, I2: 89%), respectively. CONCLUSION: Thyroid dysfunction is common in COVID-19 patients, with a high prevalence of non-thyroidal illness syndrome (NTIS) and thyrotoxicosis. Our meta-analysis found a 26% prevalence of NTIS and a 10% prevalence of thyrotoxicosis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022312601.

Lack of beneficiary effect of levothyroxine therapy of pregnant women with subclinical hypothyroidism in terms of neurodevelopment of their offspring.

PURPOSE: Despite the beneficial effects of levothyroxine (LT4) therapy on pregnancy outcomes of women with subclinical hypothyroidism (SCH), its impact on the developmental status of offspring remains unclear. We aimed to assess the effects of LT4 therapy on the neurodevelopment of infants of SCH women in the first 3 years of life. METHODS: A follow-up study was conducted on children born to SCH pregnant women who had participated in a single-blind randomized clinical trial (Tehran Thyroid and Pregnancy Study). In this follow-up study, 357 children of SCH mothers were randomly assigned to SCH + LT4 (treated with LT4 after the first prenatal visit and throughout pregnancy) and SCH-LT4 groups. Children born of euthyroid TPOAb-women served as the control group (n = 737). The neurodevelopment status of children was assessed in five domains (communication, gross motor, fine motor, problem-solving, and social-personal domains) using the Ages and Stages Questionnaires (ASQ) at the age of 3 years. RESULTS: Pairwise comparisons of ASQ domains between euthyroid, SCH + LT4, and SCH-LT4 groups show no statistically significant difference between groups in the total score [median 25-75 total score: 265 (240-280); 270 (245-285); and 265 (245-285); P-value = 0.2, respectively]. The reanalyzing data using the TSH cutoff value of 4.0 mIU/L indicated no significant difference between groups in the score of ASQ in each domain or total score with TSH levels < 4.0 mIU/L, however, a statistically significant difference in the median score of the gross motor was observed between those SCH + LT4 with baseline TSH values ≥ 4.0 mIU/L and SCH-LT4 [60 (55-60) vs. 57.5 (50-60); P = 0.01]. CONCLUSIONS: Our study does not support the beneficiary effect of LT4 therapy for SCH pregnant women in terms of the neurological development of their offspring in the first three years of life.

Prevalence of preterm birth in Scandinavian countries: a systematic review and meta-analysis.

OBJECTIVES: As welfare societies, Scandinavian countries share characteristics of equality related to healthcare access, gender, and social services. However, cultural and lifestyle variations create country-specific health differences. This meta-analysis assessed the prevalence of preterm birth (PTB) and its categories in Scandinavian countries. METHODS: A systematic search in key databases of literature published between 1990 and 2021 identified studies of the prevalence of PTB and its categories. Following the use of the Freeman-Tukey double arcsine transformation, a meta-analysis of weighted data was performed using the random-effects model and meta-prop method. RESULTS: We identified 109 observational studies that involved 86,420,188 live births. The overall pooled prevalence (PP) of PTB was 5.3% (PP = 5.3%, 95% confidence interval [CI] 5.1%, 5.5%). The highest prevalence was in Norway (PP = 6.2%, 95% CI 5.3%, 7.0%), followed by Sweden (PP = 5.3%, 95% CI 5.1%, 5.4%), Denmark (PP = 5.2%, 95% CI 4.9%, 5.3%), and Iceland (PP = 5.0%, 95% CI 4.4%, 5.7%). Finland had the lowest PTB rate (PP = 4.9%, 95% CI 4.7%, 5.1%). CONCLUSIONS: The overall PP of PTB was 5.3%, with small variations among countries (4.9%-6.2%). The highest and lowest PPs of PTB were in Norway and Finland, respectively.

The effect of exercise and physical activity-interventions on step count and intensity level in individuals with multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.

Background: Reduced physical activity is a worldwide challenge in individuals with multiple sclerosis (MS). The aim of this systematic review and meta-analysis was to identify devise-measured effects of physical activity, exercise and physiotherapy-interventions on step count and intensity level of physical activity in individuals with MS. Methods: A systematic search of the databases of PubMed (including Medline), Scopus, CINHAL and Web of Science was carried out to retrieve studies published in the English language from the inception to the first of May 2023. All trials concerning the effectiveness of different types of exercise on step count and intensity level in people with MS were included. The quality of the included studies and their risk of bias were critically appraised using The modified consolidated standards of reporting trials and the Cochrane Risk of Bias tool, respectively. The pooled standardized mean difference (SMD) and 95% CI of the step-count outcome and moderate to vigorous intensity level before versus after treatment were estimated in both Intervention and Control groups using the random effect model. The Harbord test were used to account for heterogeneity between studies and assess publication bias, respectively. Further sensitivity analysis helped with the verification of the reliability and stability of our review results. Results: A total of 8 randomized clinical trials (involving 919 individuals with MS) were included. The participants (including 715 (77.8%) female and 204 (22.2%) male) had been randomly assigned to the Intervention (n = 493) or Control group (n = 426). The pooled mean (95% CI) age and BMI of participants were 49.4 years (95% CI: 47.4, 51.4 years) and 27.7 kg/m2 (95% CI: 26.4, 29 kg/m2), respectively. In terms of the comparison within the Intervention and the Control groups before and after the intervention, the results of the meta-analysis indicate that the pooled standardized mean difference (SMD) for step-count in the Intervention group was 0.56 (95% CI: -0.42, 1.54), while in the Control group it was 0.12 (95% CI: -0.05, 0.28). Furthermore, there was no significant difference in the pooled SMD of step-count in the physical activity Intervention group compared to the Controls after the intervention (pooled standard mean difference = 0.19, 95% CI: -0.36,0.74). Subgroup analysis on moderate to vigorous intensity level of physical activity revealed no significant effect of the physical activity intervention in the Intervention group compared to the Control group after the intervention, or within groups before and after the intervention. Results of meta regression showed that age, BMI, duration of disease and Expanded Disability Status Scale (EDSS) score were not the potential sources of heterogeneity (all p > 0.05). Data on the potential harms of the interventions were limited. Conclusion: The results of this meta-analysis showed no significant differences in step count and moderate to vigorous physical activity level among individuals with MS, both within and between groups receiving physical activity interventions. More studies that objectively measure physical activity are needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022343621.

Does fasting plasma glucose values 5.1-5.6 mmol/l in the first trimester of gestation a matter?

Objectives: The aim of the study was to investigate the effect of treatment on pregnancy outcomes among women who had fasting plasma glucose (FPG) 5.1-5.6 mmol/l in the first trimester of pregnancy. Methods: We performed a secondary-analysis of a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. All pregnant women with FPG values range 5.1-5.6 mmol/l in the first trimester of gestation were included in the present study (n=3297) and classified to either the (i) intervention group who received treatment for GDM along with usual prenatal care (n=1,198), (ii) control group who received usual-prenatal-care (n=2,099). Macrosomia/large for gestational age (LGA) and primary cesarean-section (C-S) were considered as primary-outcomes. A modified-Poisson-regression for binary outcome data with a log link function and robust error variance was used to RR (95%CI) for the associations between GDM status and incidence of pregnancy outcomes. Results: The mean maternal age and BMI of pregnant women in both study groups were similar. There were no statistically significant differences in the adjusted risks of adverse pregnancy outcomes, including macrosomia, primary C-S, preterm birth, hyperbilirubinemia, preeclampsia, NICU-admission, birth trauma, and LBW both groups. Conclusions: It is found that treating women with first-trimester FPG values of 5.1-5.6 mmol/l could not improve adverse pregnancy outcomes including macrosomia, Primary C-S, Preterm birth, hypoglycemia, hypocalcemia, preeclampsia, NICU admission, Birth trauma and LBW. Therefore, extrapolating the FPG cut-off point of the second trimester to the first -which has been proposed by the IADPSG, might therefore not be appropriate. Clinical Trial Registration: https://www.irct.ir/trial/518, identifier IRCT138707081281N1.

Maternal weight latent trajectories and associations with adverse pregnancy outcomes using a smoothing mixture model.

Class membership is a critical issue in health data sciences. Different types of statistical models have been widely applied to identify participants within a population with heterogeneous longitudinal trajectories. This study aims to identify latent longitudinal trajectories of maternal weight associated with adverse pregnancy outcomes using smoothing mixture model (SMM). Data were collected from the Khuzestan Vitamin D Deficiency Screening Program in Pregnancy. We applied the data of 877 pregnant women living in Shooshtar city, whose weights during the nine months of pregnancy were available. In the first step, maternal weight was classified and participants were assigned to only one group for which the estimated trajectory is the most similar to the observed one using SMM; then, we examined the associations of identified trajectories with risk of adverse pregnancy endpoints by applying logistic regression. Three latent trajectories for maternal weight during pregnancy were identified and named as low, medium and high weight trajectories. Crude estimated odds ratio (OR) for icterus, preterm delivery, NICU admission and composite neonatal events shows significantly higher risks in trajectory 1 (low weight) compared to trajectory 2 (medium weight) by 69% (OR = 1.69, 95%CI 1.20, 2.39), 82% (OR = 1.82, 95%CI 1.14, 2.87), 77% (OR = 1.77, 95%CI 1.17, 2.43), and 85% (OR = 1.85, 95%CI 1.38, 2.76), respectively. Latent class trajectories of maternal weights can be accurately estimated using SMM. It is a powerful means for researchers to appropriately assign individuals to their class. The U-shaped curve of association between maternal weight gain and risk of maternal complications reveals that the optimum place for pregnant women could be in the middle of the growth curve to minimize the risks. Low maternal weight trajectory compared to high had even a significantly higher hazard for some neonatal adverse events. Therefore, appropriate weight gain is critical for pregnant women.Trial registration International Standard Randomized Controlled Trial Number (ISRCTN): 2014102519660N1; http://www.irct.ir/searchresult.php?keyword=&id=19660&number=1&prt=7805&total=10&m=1 (Archived by WebCite at http://www.webcitation.org/6p3lkqFdV ).

Maternal Subclinical Hyperthyroidism and Adverse Pregnancy Outcomes: A Systematic Review and Meta-analysis of Observational Studies.

Context: Findings from studies evaluating adverse pregnancy outcomes in pregnant women with subclinical hyperthyroidism are conflicting and inconclusive. Objectives: In this systematic review and meta-analysis, our aim was to evaluate the pooled odds ratio (OR) of adverse pregnancy outcomes in women with subclinical hyperthyroidism, compared to euthyroid women. Data Sources: Scopus, PubMed (including Medline), and Web of Science databases were systemically searched for regaining published studies to January 2022 examining adverse pregnancy outcomes in women with subclinical hyperthyroidism. Study Selection: Outcomes of interest were classified into seven composite outcomes, including hypertensive disorders, preterm delivery, macrosomia/large for gestational age (LGA), pregnancy loss, adverse maternal outcomes, adverse neonatal outcomes, and adverse fetal outcomes. Data Extraction: In this meta-analysis, both fixed and random effect models were used. Publication bias was also evaluated by Egger test and the funnel plot, and the trim and fill method was conducted in case of a significant result, to adjust the bias. Results: Of 202 records retrieved through searching databases, 11 studies were selected for the final analyses. There were no significant differences in pooled ORs of hypertensive disorders, preterm delivery, macrosomia/LGA, and pregnancy loss in pregnant women with subclinical hyperthyroidism, compared to the euthyroid controls. The pooled OR of adverse maternal, neonatal, and fetal outcomes in pregnant women with subclinical hyperthyroidism was not statistically significantly different from that of the euthyroid control group. Conclusions: The current meta-analysis demonstrated that subclinical hyperthyroidism in pregnancy is not related with adverse maternal and fetal outcomes. Therefore, clinicians should be avoided unnecessary treatments for pregnant women with subclinical hyperthyroidism.

Adverse Pregnancy Outcomes and International Immigration Status: A Systematic Review and Meta-analysis.

Background: Disparities in health outcomes between immigrant and native-origin populations, particularly pregnant women, pose significant challenges to healthcare systems. The aim of this systematic-review and meta-analysis was to investigate the risk of adverse pregnancy outcomes among immigrant-women compared to native-origin women in the host country. Methods: PubMed (including MEDLINE), Scopus, and Web of Science were searched to retrieve studies published in English language up to September 2020. All observational studies examining the prevalence of at least one of the short-term single pregnancy outcomes for immigrants who crossed international borders compared to native-origin pregnant population were included. The meta-prop method was used for the pooled-estimation of adverse pregnancy-outcomes' prevalence. For pool-effect estimates, the association between the immigration-status and outcomes of interest, the random-effects model was applied using the model described by DerSimonian and Laird. I2 statistic was used to assess heterogeneity. The publication bias was assessed using the Harbord-test. Meta-regression was performed to explore the effect of geographical region as the heterogeneity source. Findings: This review involved 11 320 674 pregnant women with an immigration-background and 56 102 698 pregnant women as the native-origin population. The risk of emergency cesarean section (Pooled-OR = 1.1, 95%CI = 1.0-1.2), shoulder dystocia (Pooled-OR = 1.1, 95%CI = 1.0-1.3), gestational diabetes mellites (Pooled-OR = 1.4, 95%CI = 1.2-1.6), small for gestational age (Pooled-OR=1.3, 95%CI = 1.1-0.4), 5-min Apgar less than 7 (Pooled-OR = 1.2, 95%CI = 1.0-1.3) and oligohydramnios (Pooled-OR = 1.8, 95%CI = 1.0-3.3) in the immigrant women were significantly higher than those with the native origin background. The immigrant women had a lower risk of labor induction (Pooled-OR = 0.8, 95%CI = 0.7-0.8), pregnancy induced hypertension (Pooled-OR = 0.6, 95%CI = 0.5-0.7) preeclampsia (Pooled-OR = 0.7, 95%CI = 0.6-0.8), macrosomia (Pooled-OR = 0.8, 95%CI = 0.7-0.9) and large for gestational age (Pooled-OR = 0.8, 95%CI = 0.7-0.8). Also, the risk of total and primary cesarean section, instrumental-delivery, preterm-birth, and birth-trauma were similar in both groups. According to meta-regression analyses, the reported ORs were not influenced by the country of origin. Conclusion: The relationship between the immigration status and adverse perinatal outcomes indicated a heterogenous pattern, but the immigrant women were at an increased risk of some important adverse pregnancy outcomes. Population-based studies with a focus on the various aspects of this phenomena are required to explain the source of these heterogenicities.

A Systematic Review and Meta-Analysis of the Risk of Stillbirth, Perinatal and Neonatal Mortality in Immigrant Women.

Objectives: This study aimed to investigate the risk of stillbirth, perinatal and neonatal mortality in immigrant women compared to native-origin women in host countries. Methods: A systematic literature review and meta-analysis was conducted. Relevant studies were identified using a thorough literature search and their quality was appraised. The analysis of heterogeneous data was carried out using the random effects model and publication bias was assessed using the Harbord-test. Also, the pooled odds ratio of events was calculated through the DerSimonian and Laird, and inverse variance methods. Results: In the search process 45 studies were retrieved consisting of 8,419,435 immigrant women and 40,113,869 native-origin women. The risk of stillbirth (Pooled OR = 1.35, 95% CI = 1.22-1.50), perinatal mortality (Pooled OR = 1.50, 95% CI = 1.35-1.68), and neonatal mortality (Pooled OR = 1.09, 95% CI = 1.00-1.19) in the immigrant women were significantly higher than the native-origin women in host countries. According to the sensitivity analyses, all results were highly consistent with the main data analysis results. Conclusion: The immigrant women compared to the native-origin women had the higher risks of stillbirth, perinatal and neonatal mortality. Healthcare providers and policy makers should improve the provision of maternal and neonatal healthcare for the immigrant population.

Changes in functional independence after inpatient rehabilitation in patients with spinal cord injury: A simultaneous evaluation of prognostic factors.

OBJECTIVE: This study aimed to investigate the improvements of functional independence following inpatient rehabilitation and compare those improvements between different levels and severities of Spinal Cord Injury (SCI). Prognostic factors affecting the patient's outcomes were also studied. SETTINGS: Rofeideh Rehabilitation Hospital. OUTCOME MEASURES: Spinal Cord Independence Measure version III (SCIM III), and Functional Independence Measure (FIM). METHOD: In this retrospective cohort study, 180 patients with SCI were enrolled to record their functional independence upon admission and discharge, and the changes were compared between different levels and severities of injury using non-parametric tests. The prognostic factors of outcomes were studied by generalized estimating equation (GEE) analysis. RESULTS: The independence changes were significant for all the severities (American Spinal Injury Association Impairment Scale (AIS)) and levels of injury except for the patients with AIS A and B at upper cervical levels (P < 0.05). The level of injury, AIS, Length of Stay (LOS), and pressure ulcer had a significant prognostic value on patient's outcomes. Furthermore, there was a significant difference between different levels of injury with the same AIS grade in functional improvement (P < 0.05), while there was a significant difference between AIS groups with the same level of injury only at upper and middle cervical lesions (P < 0.05). CONCLUSION: Recording the values of functional independence before and after rehabilitation in individuals with SCI can help clinicians approximately expect the outcomes of future patients. Moreover, a deeper study of the prognostic factors can provide a more logical expectation of rehabilitation outcomes.

Perinatal and Neonatal Outcomes in Immigrants From Conflict-Zone Countries: A Systematic Review and Meta-Analysis of Observational Studies.

Objectives: There are controversies regarding the risk of adverse pregnancy outcomes among immigrants from conflict-zone countries. This systematic review and meta-analysis aimed to investigate the risk of perinatal and neonatal outcomes among immigrants from conflict-zone countries compared to native-origin women in host countries. Methods: A systematic search on the databases of PubMed/MEDLINE, Scopus, and Web of Science was carried out to retrieve studies on perinatal and neonatal outcomes among immigrants from Somalia, Iraq, Afghanistan, Yemen, Syria, Nigeria, Sudan, Ethiopia, Eritrea, Kosovo, Ukraine, and Pakistan. Only peer-reviewed articles published in the English language were included in the data analysis and research synthesis. The odds ratio and forest plots were constructed for assessing the outcomes of interests using the DerSimonian and Laird, and the inverse variance methods. The random-effects model and the Harbord test were used to account for heterogeneity between studies and assess publication bias, respectively. Further sensitivity analysis helped with the verification of the reliability and stability of our review results. Results: The search process led to the identification of 40 eligible studies involving 215,718 pregnant women, with an immigration background from the conflict zone, and 12,806,469 women of native origin. The adverse neonatal outcomes of the risk of small for gestational age (Pooled OR = 1.8, 95% CI = 1.6, 2.1), a 5-min Apgar score <7 (Pooled OR = 1.4, 95% CI = 1.0, 2.1), stillbirth (Pooled OR = 1.9, 95% CI = 1.2, 3.0), and perinatal mortality (Pooled OR = 2, 95% CI = 1.6, 2.5) were significantly higher in the immigrant women compared to the women of native-origin. The risk of maternal outcomes, including the cesarean section (C-S) and emergency C-S, instrumental delivery, preeclampsia, and gestational diabetes was similar in both groups. Conclusion: Although the risk of some adverse maternal outcomes was comparable in the groups, the immigrant women from conflict-zone countries had a higher risk of neonatal mortality and morbidity, including SGA, a 5-min Apgar score <7, stillbirth, and perinatal mortality compared to the native-origin population. Our review results show the need for the optimization of health care and further investigation of long-term adverse pregnancy outcomes among immigrant women.

Effect of Different Types of Diagnostic Criteria for Gestational Diabetes Mellitus on Adverse Neonatal Outcomes: A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: Evidence supporting various diagnostic criteria for diagnose gestational diabetes mellitus (GDM) are consensus-based, needs for additional evidence related to outcomes. Therefore, the aim of this systematic-review and meta-analysis was to assess the impact of different GDM diagnostic-criteria on the risk of adverse-neonatal-outcomes. METHODS: Electronic databases including Scopus, PubMed, and Web of Sciences were searched to retrieve English original, population-based studies with the universal GDM screening approach, up to January-2020. GDM diagnostic criteria were classified in seven groups and International Association of the Diabetes and Pregnancy Study Groups (IADPSG) was considered as reference one. We used the Mantel-Haenszel method to calculate the pooled odds of events. The possibility of publication bias was examined by Begg's test. RESULTS: A total of 55 population-based studies consisting of 1,604,391 pregnant women with GDM and 7,770,855 non-GDM counterparts were included. Results showed that in all diagnostic-criteria subgroups, the risk of adverse neonatal outcomes including macrosomia, hyperbilirubinemia, respiratory distress syndrome, neonatal hypoglycemia, neonatal intensive care unit admission, preterm birth, and birth-trauma were significantly higher than the non-GDM counterparts were significantly higher than non-GDM counterparts. Meta-regression analysis revealed that the magnitude of neonatal risks in all diagnostic-criteria subgroups are similar. CONCLUSION: Our results showed that the risk of adverse-neonatal-outcome increased among women with GDM, but the magnitude of risk was not different among those women who were diagnosed through more or less intensive strategies. These findings may help health-care-providers and policy-makers to select the most cost-effective approach for the screening of GDM among pregnant women.

A Cluster Randomized Noninferiority Field Trial of Gestational Diabetes Mellitus Screening.

CONTEXT: Although it is well-acknowledged that gestational diabetes mellitus (GDM) is associated with the increased risks of adverse pregnancy outcomes, the optimal strategy for screening and diagnosis of GDM is still a matter of debate. OBJECTIVE: This study was conducted to demonstrate the noninferiority of less strict GDM screening criteria compared with the strict International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria with respect to maternal and neonatal outcomes. METHODS: A cluster randomized noninferiority field trial was conducted on 35 528 pregnant women; they were scheduled to have 2 phases of GDM screening based on 5 different prespecified protocols including fasting plasma glucose in the first trimester with threshold of 5.1 mmol/L (92 mg/dL) (protocols A, D) or 5.6 mmol/L (100 mg/dL) (protocols B, C, E) and either a 1-step (GDM is defined if one of the plasma glucose values is exceeded [protocol A and C] or 2 or more exceeded values are needed [protocol B]) or 2-step approach (protocols D, E) in the second trimester. Guidelines for treatment of GDM were consistent with all protocols. Primary outcomes of the study were the prevalence of macrosomia and primary cesarean section (CS). The null hypothesis that less strict protocols are inferior to protocol A (IADPSG) was tested with a noninferiority margin effect (odds ratio) of 1.7. RESULTS: The percentages of pregnant women diagnosed with GDM and assigned to protocols A, B, C, D, and E were 21.9%, 10.5%, 12.1%, 19.4%, and 8.1%, respectively. Intention-to-treat analyses satisfying the noninferiority of the less strict protocols of B, C, D, and E compared with protocol A. However, noninferiority was not shown for primary CS comparing protocol E with A. The odds ratios (95% CI) for macrosomia and CS were: B (1.01 [0.95-1.08]; 0.85 [0.56-1.28], C (1.03 [0.73-1.47]; 1.16 [0.88-1.51]), D (0.89 [0.68-1.17]; 0.94 [0.61-1.44]), and E (1.05 [0.65-1.69]; 1.33 [0.82-2.00]) vs A. There were no statistically significant differences in the adjusted odds of adverse pregnancy outcomes in the 2-step compared with the 1-step screening approaches, considering multiplicity adjustment. CONCLUSIONS: The IADPSG GDM definition significantly increased the prevalence of GDM diagnosis. However, the less strict approaches were not inferior to other criteria in terms of adverse maternal and neonatal outcomes.

Wet-cupping on calf muscles in polycystic ovary syndrome: a quasi-experimental study.

OBJECTIVES: Current modalities for treating polycystic ovary syndrome (PCOS) are not curative and using them for a long period is associated with adverse effects. According to Persian Medicine recommendations, wet cupping on calf muscles can induce menstrual bleeding. In the present study, the effect of wet-cupping (traditional bleeding from capillary vessels) was assessed on menstrual cycles (as primary outcome), hirsutism, and laboratory manifestation of PCOS. METHODS: A quasi-experimental study was conducted from 2016/5/21 until 2017/5/20 on 66 PCOS women within the age range of 20-40 years and a menstrual interval of at least 60 days during the last year. Participants' calf muscles were cupped on day 26 of their last menstruation cycle following the Persian Medicine recommendations. They were followed for 12 weeks and a menstruation history and physical examination was done twice (4 and 12 weeks after wet cupping). Insulin Resistance (IR) and Free Androgen Index (FAI) were evaluated at baseline and end of the study. RESULTS: Wet-cupping on calf muscles significantly improved menstrual cycles' frequency 0.37(95% CI: 0.13, 0.51), p-value=0.001 and hirsutism after 4 and 12 weeks of intervention were -1.9 (95% CI: -2.5, -0.5), p-value<0.001 and -1.4(95% CI: -2.1, -0.8), p-value<0.001, respectively. While it was not significant in changing the IR and FAI. About 33% of participants suffered from mild temporary discomforts (which were resolved within a few minutes of rest) and 9% reported mild long-term side effects. CONCLUSIONS: It is considered that wet-cupping on calf muscles can be propounded as an optional treatment of PCOS for those not willing to use chemical medication.

Relationship between vitamin D status in the first trimester of the pregnancy and gestational weight gain: a mediation analysis.

PURPOSE: To evaluate the total, and direct effects of vitamin D, measured by circulating 25-hydroxyvitamin D [25(OH)D] levels, on GWG after adjustment for confounding variables, and then assess the indirect effects by demonstrating the role of gestational age at birth as a mediator in this association. METHODS: Data collected in "Khuzestan Vitamin D Deficiency Screening Program in Pregnancy" were used for the present study; it included the data of 900 pregnant women referred to the health centers of Shushtar (Khuzestan Province, Iran), whose vitamin D status during the third trimester of pregnancy was available. A mediation analysis was applied to detect the causal relationship between serum level of 25(OH)D, covariates (maternal age, parity, education level, and baseline maternal weight), mediator (gestational age), and outcome (GWG). RESULTS: Of 900 pregnant women referred to the health centers, a total of 726 eligible participants were analyzed for the study. The adjusted total effect of vitamin D on GWG was estimated 0.07 (95% CI 0.06, 0.09; P = 0.000). This study also revealed adjusted direct effect of vitamin D on GWG was statistically significant 0.02 (95% CI: 0.003, 0.04; P = 0.021). In addition, the adjusted indirect effect of this micronutrient on GWG by considering gestational age as a mediator was found to be significant [0.05 (95% CI 0.04, 0.06; P = 0.000)]. This study revealed an increase in the trend of weight gain during pregnancy trimesters for women with different levels of 25(OH)D; however, women with severe vitamin D deficiency had the lowest speed as compared to moderate and normal levels. CONCLUSION: This study shows that maternal vitamin D status directly affects the gestational weight gain independent of gestational age. Therefore, the detection and treatment of women with vitamin D inadequacy can directly improve the trend of their weight gain in addition to its indirect effect on reducing the risk of preterm delivery.

Risk of endometrial, ovarian, and breast cancers in women with polycystic ovary syndrome: A systematic review and meta-analysis.

Background: Although several studies have evaluated the risk of gynecological cancers in women with polycystic ovary syndrome (PCOS), there are controversies regarding it. Objective: This study aimed to investigate the association of PCOS with endometrial, ovarian, and breast cancers. Materials and Methods: PubMed, Scopus, Web of Science, and Google Scholar databases based on MESH terms using the combination of the appropriate keywords were searched to retrieve observational studies on endometrial, ovarian, and breast cancers in PCOS women, published from inception to April 2020. This meta-analysis was performed to determine the pooled odds ratio (OR) of these cancers in women with PCOS. Publication bias was assessed by using Begg's test. Results: Of 1347 records retrieved by searching the databases, a total of 14 articles were included in the study. Overall, the pooled OR of the composite outcome, including endometrial, ovarian, and breast cancers in women with PCOS was higher than that of women with no PCOS (pooled OR: 1.4, 95% CI: 1.0-1.9). The pooled OR of endometrial (pooled OR: 2.2, 95% CI: 1.03-4.7) and ovarian (pooled OR: 1.3, 95% CI: 1.0-1.8) cancers in women with PCOS was higher than the control group, whereas the pooled OR of breast cancer was not significantly higher than that of the control group. Conclusion: This meta-analysis indicated an increased risk of endometrial and ovarian cancers in women with PCOS.

Trends in Leading Cancer Incidence among Iranian Women: Annual Cancer Registry Reports, 2003-2015.

BACKGROUND: Cancer is one of the most important causes of death in the world and has an increasing trend globally. We aimed at investigating the five leading cancers in Iranian women based on a 10-year history of cancer registry reports and illustrating the trends in all cancer sites and breast cancer as the top leading one from 2003 to 2015. METHODS: Data were obtained from national cancer registry study. Age-Specific Incidence Rate (ASR) data were obtained from Iran's annual national cancer registry reports between 2003 to 2010 and 2014 to 2015. Using Joinpoint regression, we analyzed incidence trends over time for all cancer sites and the top leading cancer from 2003 to 2015. RESULTS: Breast cancer was ranked first in Iranian women. Its ASR raised from 15.96 in 2003 to 32.63 in 2015. Results of trend analysis based on Annual Percent Change (APC) index showed 5.6 (95%CI: 2.9 to 8.3) and 4.6 (95%CI: 2.0 to 7.2) annual increase in the incidence of all cancer sites and breast cancer from 2003 to 2015, respectively. CONCLUSION: This study indicates significant increasing trends in all cancer sites and breast cancer incidence in Iran. Despite the national coverage of cancer registry over the past decade, more considerations should be taken into account, especially in Breast cancer.

A Systematic Review and Meta-Analysis of Male Infertility and the Subsequent Risk of Cancer.

OBJECTIVES: The primary objective of this systemic review and meta-analysis was to investigate the risk of developing composite outcome of all cancers, regardless of the type of cancer among men with infertility diagnosis compared to fertile counterparts. The secondary objective was to compare the pooled risk of developing individual specific cancers between two groups. METHODS: A systematic literature search was performed on the databases of PubMed (including Medline), Scopus, and Web of Science to retrieve observational studies published in English language from 01.01.1990 to 28. 02. 2021. They assessed cancer events in males with an infertility diagnosis compared to controls without infertility. The outcomes of interest were a composite outcome of cancers including all known cancer types, and also specific individual cancers. The fixed/random effects model was used to analyze heterogeneous and non-heterogeneous results. Publication bias was assessed using the Harbord test, Egger test, Begg test, and funnel plot. The pooled odds ratio of cancers was calculated using the DerSimonian and Laird, and inverse variance methods. Studies' quality and risk of bias were assessed using structured standard tools. RESULTS: We included eight cohort studies involving 168,327 men with the diagnosis of infertility and 2,252,806 men without it. The total number of composite outcome of cancers as well as individual cancers including prostate, testicular and melanoma were 1551, 324, 183 and 121 in the infertile men and 12164, 3875, 849, and 450 in the fertile men, respectively. The pooled OR of the composite outcome of cancers, regardless of the type of cancer, in men with infertility was 1.4 folds higher than those without infertility (pooled OR = 1.43, 95% confidence interval [CI]: 1.25-1.64). Meta-analysis of individual cancers including prostate, testicular and melanoma between two groups was carried out. The pooled ORs of testicular and prostate cancers in men with the diagnosis of infertility were significantly higher than controls without infertility (pooled OR = 1.91, 95% CI: 1.52-2.42 and pooled OR = 1.48, 95% CI: 1.05-2.08, respectively). Additionally, the pooled OR of melanoma in men with infertility was 1.3 folds higher than those without infertility (pooled OR = 1.31, 95% CI: 1.06-1.62). CONCLUSION: A greater risk of cancers in men with male infertility was found suggesting that the history of male infertility might be an important risk factor for developing cancers in later life. Further well-designed long-term population-based prospective studies, considering all known cancers and their accompanying risk factors should be conducted to support our findings.