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.

A prospective study on the relationship between polycystic ovary syndrome and age at natural menopause.

OBJECTIVE: This study aimed to determine whether polycystic ovary syndrome (PCOS) was associated with age at menopause, compared with women without PCOS, after adjusting for potential confounders. METHODS: A total of 1,696 reproductive-aged participants from the Tehran Lipid and Glucose Study were included in this population-based prospective study with a follow-up of approximately 20 years. Of these, 348 women with PCOS based on the Rotterdam criteria and 1,348 non-PCOS controls were followed to assess the age at which they reached menopause. An accelerated failure time survival regression model was used to identify the association between PCOS and the age at natural menopause (ANM), with and without adjustment for potential confounders. RESULTS: The unadjusted accelerated failure time survival model revealed a significant positive association between PCOS and ANM; PCOS women experienced time to menopause by a factor of 1.05 than non-PCOS controls (95% confidence interval, 1.02-1.06; P < 0.001). After adjusting for age at baseline, menarche age, history of hypertension, history of type 2 diabetes mellitus, parity, oral contraceptive use, body mass index, education level, physical activity, and smoking, the results remained significant (time ratio: 1.03; 95% confidence interval, 1.01-1.06; P = 0.002). CONCLUSIONS: This study indicates that ANM is significantly associated with PCOS in women. Our study findings may have implications for the fertility and reproductive health of women with PCOS. However, further large longitudinal studies on diverse populations accounting for other relevant confounders are still needed to provide data on the actual difference in age at menopause and to elucidate the underlying mechanisms of this association.

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.

Polycystic Ovary Syndrome, Subclinical Hypothyroidism, the Cut-Off Value of Thyroid Stimulating Hormone; Is There a Link? Findings of a Population-Based Study.

Despite solid evidence regarding the association of over-hypothyroidism with polycystic ovary syndrome (PCOS), the relationship between PCOS and subclinical hypothyroidism (SCH) is still a topic of debate. In the present population-based study, we aimed to assess if there is a difference between PCOS and the control group regarding the upper reference limit of thyroid stimulating hormone (TSH). We also aimed to identify the prevalence of SCH in women with PCOS compared to controls. This study was conducted on data collected in the Iranian PCOS prevalence study and the Khuzestan PCOS prevalence study. Participants that met our eligibility criteria were categorized into two groups: PCOS (n = 207) and control (n = 644). Quantile and logistic regression models were used to explore the effect of PCOS status on TSH cut-off values and SCH, respectively. The 95 percentiles of TSH were not significantly different in the PCOS group compared to control ones (6.12 and 6.56 microU/mL, respectively). There was no statistically significant association between PCOS status and SCH (OR adjusted: 1.40; 95%CI: 0.79, 2.50; p = 0.2). The prevalence of SCH and the upper reference limit of TSH were not significantly different in PCOS and controls. Investigation of SCH in women with PCOS might be questionable.

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).

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.