Investigation of the relationship between air pollution and gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) can have negative effects on both the pregnancy and perinatal outcomes, as well as the long-term health of the mother and the child. It has been suggested that exposure to air pollution may increase the risk of developing GDM. This study investigated the relationship between exposure to air pollutants with gestational diabetes. METHODS: The present study is a retrospective cohort study. We used data from a randomised community trial conducted between September 2016 and January 2019 in Iran. During this period, data on air pollutant levels of five cities investigated in the original study, including 6090 pregnant women, were available. Concentrations of ozone (O3), nitric oxide (NO), nitrogen dioxide (NO2), nitrogen oxides (NOx), sulphur dioxide (SO2), carbon monoxide (CO), particulate matter < 2.5 (PM2.5) or <10 µm (PM10) were obtained from air pollution monitoring stations. Exposure to air pollutants during the three months preceding pregnancy and the first, second and third trimesters of pregnancy for each participant was estimated. The odds ratio was calculated based on logistic regression in three adjusted models considering different confounders. Only results that had a p < .05 were considered statistically significant. RESULTS: None of the logistic regression models showed any statistically significant relationship between the exposure to any of the pollutants and GDM at different time points (before pregnancy, in the first, second and third trimesters of pregnancy and 12 months in total) (p > .05). Also, none of the adjusted logistic regression models showed any significant association between PM10 exposure and GDM risk at all different time points after adjusting for various confounders (p > .05). CONCLUSIONS: This study found no association between GDM risk and exposure to various air pollutants before and during the different trimesters of pregnancy. This result should be interpreted cautiously due to the lack of considering all of the potential confounders.

The health of pregnant women and their children can be impacted by gestational diabetes mellitus (GDM), one of the prevalent pregnancy complications. Some of studies showed that the incidence of gestational diabetes can be influenced by genetic or environmental factors. Air pollution is an environmental stimulus that may predispose pregnant women to GDM. This research explored whether air pollution could increase the risk of developing gestational diabetes. Over 6000 pregnant women in five cities of Iran participated in the study and were screened for gestational diabetes. Their exposure to the various air pollutants during the three months preceding pregnancy and total pregnancy period was measured. In this study, we found no clear association between air pollution and gestational diabetes. However, this finding needs to be interpreted cautiously since all the influential factors were not assessed.

Adiposity trajectories and cardiovascular disease risk in women: a population-based cohort study with a focus on menopausal status.

Objectives: A single measurement of adiposity indices could predict the incidence of cardiovascular disease (CVD); nonetheless their long-term pattern and its association with incident CVD are rarely studied. This study aimed to determine distinct trajectories of adiposity indices among participants of Tehran Lipid and Glucose Study (TLGS) and their association with incident CVD. Furthermore, this study aimed to investigate whether this association differed among individuals according to their menopausal status. Method: A total of 6840 women participated in TLGS, aged 20 years and older were included in this study; they were followed for a median of 16 years. Body mass index (BMI), waist circumference (WC), conicity index (CI) and body roundness index (BRI) were included in the analysis as adiposity indices. The cohort outcome panel of medical specialists identified the CVD outcomes. Trajectory analyses were used to identify homogeneous distinct clusters of adiposity indices trajectories. The association between the trajectory group membership and incident CVD were explored by Cox proportional hazard models, with unadjusted and adjusted model for baseline age, physical activity, smoking status, menopause and family history of CVD. Results: Three BMI trajectory groups of low, medium, and high and two trajectories for WC, BRI and CI were identified. Adjusted cox proportional hazard models revealed significant associations between the hazard of CVD experience and the high trajectory group of the BMI (HR: 2.06, 95% CI: 1.38-3.07), WC (HR: 2.71, 95% CI: 1.98-3.70), CI (HR: 1.87, 95% CI: 1.26-2.77) and BRI (HR: 1.55-95% CI: 1.12-2.15), compared to the low trajectory group. Subgroup analysis based on the menopausal status of participants showed that the HR of CVD incidences for all of trajectories adiposity indices, except BMI, was statistically significant. Adjusted cox proportional hazard models, in those women not reached menopause during study, revealed that the HR (95% CI) of CVD incidences for high trajectory of BMI, WC, CI and BRI were 2.80 (1.86-7.05); 2.09 (1.40-6.16); 1.72 (1.42-5.61), and 3.09 (1.06-9.01), respectively. These values for those were menopause at the initiation of the study were 1.40 (1.11, 2.53); 1.65 (1.04-2.75); 1.69 (1.01-2.87), and 1.61 (0.98-2.65), respectively. Conclusion: Our findings suggest that adiposity trajectories, particularly central adiposity index of CI, could precisely predict the CVD risk. Consequently, preventive strategies should be tailored accordingly.

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.

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.

A Bayesian model to estimate the cutoff value of TSH for management of preterm birth.

BACKGROUND: Determining a thyroid hormone cutoff value in pregnancy is challenging issue and several approaches have been introduced to optimize a utility function. We aimed to estimate the cutoff value of TSH using Bayesian method for prediction of preterm-birth. METHODS: This study was a secondary-analysis of the population-based data collected prospectively within the framework of the Tehran Thyroid and Pregnancy Study. A total of 1,538 pregnant women attending prenatal clinics. RESULTS: Using Bayesian method resulted a TSH-cutoff of (3.97mIU/L,95%CI:3.95-4.00) for distinguishing pregnant women at risk of preterm-birth. The cutoff was associated with acceptable positive predictive and negative predictive values (0.84,95% CI:0.80-0.88) and 0.92 (95%CI: 0.91-0.94), respectively). In women who were negative for thyroid peroxides antibody (TPOAb) with sufficient urinary iodine concentration (UIC), the TSH cutoff of 3.92 mIU/L(95%CI:3.70-4) had the highest predictive value; whereas in TPOAb positive women with insufficient UIC, the cutoff of 4.0 mIU/L(95%:CI 3.94-4) could better predict preterm birth. Cutoffs estimated in this study are close to the revised TSH value of 4.0mIU/L which is currently recommended by the American Thyroid Association. CONCLUSION: Regardless of TPOAb status or iodine insufficiency, risk of preterm labor is increased in pregnant women with TSH value of > 3.92 mIU/L; these women may benefit from Levothyroxine (LT4) therapy for preventing preterm birth.

Prediction of adverse pregnancy outcomes by first-trimester components of metabolic syndrome: a prospective longitudinal study.

PURPOSE: This study aimed to identify the optimal cutoff values of each component of metabolic syndrome (MetS) in the first trimester of pregnancy for predicting adverse pregnancy outcomes. METHODS: A total of 1076 pregnant women in the first trimester of gestation were recruited in this prospective longitudinal cohort study. Specifically, 993 pregnant women at 11-13 weeks of gestation who were followed up until the end of pregnancy were included in the final analysis. The cutoff values of each component of MetS in the occurrence of adverse pregnancy outcomes including gestational diabetes (GDM), gestational hypertensive disorders, and preterm birth were obtained via receiver operating characteristic (ROC) curve analysis using the Youden's index. RESULTS: Among the 993 pregnant women studied, the significant associations between the first trimester MetS components and adverse pregnancy outcomes were as follows: triglyceride (TG) and body mass index (BMI) with preterm birth; mean arterial pressure (MAP), TG, and high-density lipoprotein cholesterol (HDL-C) with gestational hypertensive disorders; BMI, fasting plasma glucose (FPG), and TG with GDM (all p values < 0.05). The cutoff point values for the above-mentioned MetS components were: TG > 138 mg/dl and BMI < 21 kg/m2 for the occurrence of preterm birth; TG > 148 mg/dL, MAP > 84, and HDL-C < 84 mg/dl for gestational hypertensive disorders; BMI > 25 kg/m2, FPG > 84 mg/dl, and TG > 161 mg/dl for GDM. CONCLUSION: The study findings imply the importance of early management of metabolic syndrome in pregnancy to improve maternal-fetal outcomes.

Various screening and diagnosis approaches for gestational diabetes mellitus and adverse pregnancy outcomes: a secondary analysis of a randomized non-inferiority field trial.

INTRODUCTION: We evaluate which screening and diagnostic approach resulted in the greatest reduction in adverse pregnancy outcomes due to increased treatment. RESEARCH DESIGN AND METHODS: This study presents a secondary analysis of a randomized community non-inferiority trial conducted among pregnant women participating in the GULF Study in Iran. A total of 35 430 pregnant women were randomly assigned to one of the five prespecified gestational diabetes mellitus (GDM) screening protocols. The screening methods included fasting plasma glucose (FPG) in the first trimester and either a one-step or a two-step screening method in the second trimester of pregnancy. According to the results, participants were classified into 6 groups (1) First-trimester FPG: 100-126 mg/dL, GDM diagnosed at first trimester; (2) First trimester FPG: 92-99.9 mg/dL, GDM diagnosed at first trimester; (3) First trimester FPG: 92-99.9 mg/dL, GDM diagnosed at second trimester; (4) First trimester FPG: 92-99.9 mg/dL, healthy at second trimester; (5) First trimester FPG<92 mg/dL, GDM diagnosed at second trimester; (6) First trimester FPG<92 mg/dL, healthy at second trimester. For our analysis, we initially used group 6, as the reference and repeated the analysis using group 2, as the reference group. The main outcome of the study was major adverse maternal and neonatal outcomes. RESULTS: Macrosomia and primary caesarean section occurred in 9.8% and 21.0% in group 1, 7.8% and 19.8% in group 2, 5.4% and 18.6% in group 3, 6.6% and 21.5% in group 4, 8.3% and 24.0% in group 5, and 5.4% and 20.0% in group 6, respectively. Compared with group 6 as the reference, there was a significant increase in the adjusted risk of neonatal intensive care unit (NICU) admission in groups 1, 3, and 5 and an increased risk of macrosomia in groups 1, 2, and 5. Compared with group 2 as the reference, there was a significant decrease in the adjusted risk of macrosomia in group 3, a decreased risk of NICU admission in group 6, and an increased risk of hyperglycemia in group 3. CONCLUSIONS: We conclude that screening approaches for GDM reduced the risk of adverse pregnancy outcomes to the same or near the same risk level of healthy pregnant women, except for the risk of NICU admission that increased significantly in groups diagnosed with GDM compared with healthy pregnant women. Individuals with slight increase in FPG (92-100 mg/dL) at first trimester, who were diagnosed as GDM, had an even increased risk of macrosomia in comparison to those group of women with FPG 92-100 mg/dL in the first trimester, who were not diagnosed with GDM, and developed GDM in second trimester TRIAL REGISTRATION: IRCT138707081281N1 (registered: February 15, 2017).

Umbilical cord blood concentration of connecting peptide (C-peptide) and pregnancy outcomes.

BACKGROUND: C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration. METHODS: For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration. RESULTS: In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 - 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 - 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 - 0.42, p < 0.001; and Coef.= 0.34, 95% CI: 0.06 - 0.63, p = 0.02, respectively). CONCLUSION: UC blood concentration of C-peptide is significantly associated with the incidence of maternal GDM and neonatal macrosomia. Using stratification for maternal BMI and gestational weight gain (GWG) and investigating molecular markers like Leptin and IGF-1 in the future might lay the ground to better understand the link between metabolic disturbances of pregnancy and UC blood C-peptide concentration.

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.

The Impact of Endogenous Estrogen Exposure Duration on Fracture Incidence: a Longitudinal Cohort Study.

CONTEXT: Although it is well documented that estrogen hormone is positively associated with bone mineral density and lower risk of fracture, there are limited studies on the association between duration of endogenous estrogen exposure (EEE) and fracture, especially by longitudinal design. OBJECTIVE: This study aimed to investigate the relationship between EEE with fracture incidence by longitudinal design in a community-based study. METHODS: A total of 5269 eligible postmenarcheal women, including 2411 premenopausal and 2858 menopausal women, were recruited from among the Tehran Lipid and Glucose Study. Cox proportional hazards regression model with adjustment of potential confounders was performed to assess the relationship between duration of EEE and incident of any hospitalized fractures. RESULTS: A total of 26.7% (1409/5269) women were menopausal at the baseline, and 2858 of the remaining participants reached menopause at the end of follow-up. Results of the unadjusted model demonstrated that the EEE z-score was negatively associated with fracture incidence [unadjusted hazard ratio (HR) 0.81, 95% CI 0.68-0.96] in postmenarchal women, indicating that per 1-SD increase of EEE z-score, the hazard of fracture reduced by 19%. Results remained statistically unchanged after adjustment for potential confounders (adjusted HR 0.70, 95% CI 0.58-0.86). CONCLUSION: The findings of this cohort study suggest that a longer duration of EEE has a protective effect on fracture incidence; a point that needs to be considered in fracture risk assessment.

Investigating the Clinical Utility of the Anti-Mullerian Hormone Testing for the Prediction of Age at Menopause and Assessment of Functional Ovarian Reserve: A Practical Approach and Recent Updates.

Low ovarian reserve is a serious condition, leading to sterility in up to 10% of women in their mid-thirties. According to current knowledge, serum anti-Müllerian hormone (AMH) levels for age are the best available marker for the screening the quantity of a woman's functional ovarian reserve, better than age alone or other reproductive markers. This review summarizes recent findings, clinical utility and limitations in the application of serum AMH testing as an accurate marker for the screening of functional ovarian reserves and predicting age at menopause. AMH assessment hold promise in helping women make informed decisions about their future fertility and desired family size. However, screening of the functional ovarian reserve could be offered to all women at 26 years of age or older who seek to assess future fertility or in case of personal request, ovarian reserve screening may be considered beyond 30 years; however, it has never been advocated beyond 35 years, since it is not advisable to delay childbearing beyond this age. In this respect, an age-specific serum AMH levels lower than the 10th percentile may be used as a threshold for the identification of a low functional ovarian reserve in an individual woman. Its level should be interpreted with caution in the adolescent and young women aged below 25 years (since AMH levels peak at this age); recent users of hormonal contraceptives (since AMH levels transiently decrease until two months after discontinuation); and women with PCOS (which dramatically increases AMH levels). However, the ability of AMH levels to predict the time to menopause is promising but requires further investigation and routine AMH testing for the purposes of predicting the time to menopause is not recommended.

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.

The Prevalence of Polycystic Ovary Syndrome, Its Phenotypes and Cardio-Metabolic Features in a Community Sample of Iranian Population: Tehran Lipid and Glucose Study.

Objectives: The aim of the present study was to evaluate the prevalence of polycystic ovary syndrome (PCOS), its phenotypical and cardio-metabolic features in a community sample of the Iranian population in comparison to healthy eumenorrheic, non-hirsute women without polycystic ovaries. The second aim was to assess the cardio-metabolic characteristics of women who suffered from one criteria of PCOS compared to those healthy eumenorrheic, non-hirsute women. Methods: In this cross-sectional population-based study, a total of 1,960 eligible women, aged (18-45 years) were recruited from the Tehran-Lipid and Glucose-Study participants and were classified as the three groups of (i) women with PCOS by the Rotterdam criteria, (ii) non-PCOS women with one criteria of PCOS and (iii) healthy eumenorrheic, non-hirsute women without polycystic ovaries morphology (PCOM) as the control group. Further PCOS women were extended to four phenotypes of hyperandrogenism, oligo-anovulation, polycystic ovaries (phenotype A), hyperandrogenism, oligo/anovulation (phenotype B), hyperandrogenism, polycystic ovaries (phenotype C) and oligo-anovulation, polycystic ovaries (phenotype D). Cardio-metabolic profiles and the prevalence of comorbidities of metabolic syndrome (MetS) and lipid abnormalities were compared among these groups linear, and the median regression models adjusted for age and body mass index. Results: The prevalence of PCOS according to the diagnostic criteria of the NIH, Rotterdam and AE-PCOS Society were 13.6, 19.4, and 17.8, respectively. Among those who met the Rotterdam criteria, 23.9, 46.3, 21.6, and 8.2% had phenotypes A, B, C, and D, respectively. Among the remaining 1,580 women who did not fulfil the PCOS criteria, 108 (6.8%) suffered from only oligo/anovulation, 332 (21%) only hyperandrogenism/hyperandrogenemia, 159 (16.2%) only PCOM in ultrasound and 981 (62%) were healthy eumenorrheic, non-hirsute women without PCOM. The study revealed that some adiposity indices and lipid abnormalities in PCOS phenotypes with hyperandrogenism (A, B, and C) were worse than in healthy women. By contrast, women with phenotype D did not differ from the healthy ones in terms of adiposity and lipid abnormalities. However, the respective values for other cardio-metabolic profiles and MetS rates in different phenotypes of PCOS were similar to the healthy women. Only the prevalence of MetS in phenotype A was significantly higher than in the healthy women. There were no statistically significant differences between participants with one criteria of PCOS and healthy counterparts in terms of most adiposity indexes, cardio-metabolic factors, and comorbidity of MetS and its components. However, women with hyperandrogenism had a significantly higher level of the waist to height ratio (WHtR) and hypertriglyceridemia than their healthy counterparts. Conclusion: PCOS, mainly classical phenotypes A and B, are common among Iranian women of reproductive age. Women with PCOS who had androgen excess exhibited the worst lipid profile, and those who had full three criteria of the syndrome exhibited the higher rate of MetS. However, women with only ovulatory dysfunction and only PCOM had similar cardio-metabolic characteristics, compared to healthy subjects. These data suggest that routine screening for metabolic disturbances may be needed in the prevention of cardio-metabolic disorders in patients with more serious phenotypes of PCOS.

One-step versus two-step screening for diagnosis of gestational diabetes mellitus in Iranian population: A randomized community trial.

Objectives: There is considerable worldwide controversy regarding optimal screening and diagnostic approaches for GDM. This study aimed to compare the prevalence, maternal and neonatal outcomes of a One-step with a Two-step approach for the screening and diagnosis of GDM in a large community sample of pregnant women. Methods: We conducted a secondary analysis of a randomized community non-inferiority trial of GDM screening in Iran. For the current study, all pregnant women who met the inclusion criteria were randomized into two groups for GDM screening. The first group of women (n = 14611) was screened by a One-step screening approach [75-g 2-h oral glucose tolerance test (OGTT)] and the second group (n = 14160) by a Two-step method (the 50-g glucose challenge test followed by the 100-g OGTT). All study participants were followed up until delivery, and the adverse maternal and neonatal outcomes were recorded in detail. Results: GDM was diagnosed in 9.3% of the pregnant women who were assigned to the One-step and in 5.4% of those assigned to the Two-step approach with a statistically significant difference between them (p < 0.001). Intention-to-treat analyses showed no significant differences between the One-step and the Two-step group in the unadjusted risks of the adverse pregnancy outcomes of macrosomia, primary cesarean-section, preterm birth, hypoglycemia, hypocalcemia, hyperbilirubinemia, preeclampsia, neonatal intensive care unit admission, birth trauma, low birth weight, and intrauterine fetal death. Results remained unchanged after adjustment for potential confounder variables including gestational age at enrollment and delivery, maternal body mass index, gestational weight gain, type of delivery, treatment modality, and GDM diagnosis in the first trimester. Conclusion: We found that although the rates of GDM more than doubled with the One-step strategy, the One-step approach was similar to the Two-step approach in terms of maternal and neonatal outcomes. These findings may warn that more caution should be exercised in adopting the One-step method worldwide. Future research is needed to assess the long-term harm and benefits of those approaches to GDM screening for both mothers and their offspring. Clinical trial registration: https://www.irct.ir/trial/518, identifier (IRCT138707081281N1).

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.