Boundary layer convective-like activity at Dome Concordia, Antarctica

The paper presents the micro-meteorological field experiment carried out at the plateau station of Dome Concordia (3300 m a.s.l.) during the Antarctic summer of 1997. The experiment dealt with the study of the trends of boundary layer features and the characteristics of the surface energy and momentum exchanges. A monostatic Doppler sodar, fast-response sensors and radiometers were used for this study. The experiment was part of a program that aims to assess the role of the continental polar regions in shaping the surface circulation over Antarctica. In spite of the markedly stable conditions found throughout the investigated period, some convective-like activity was detected during the warmer hours of the day

Maternal thyroid function and offspring birth anthropometrics in women with polycystic ovary syndrome

ObjectivesPolycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within the normal range may influence fetal growth. Our aim was to investigate whether maternal thyroid function is associated with newborn anthropometrics in PCOS and explore the potential modifying effect of metformin.MethodsPost-hoc analyses of two RCTs in which pregnant women with PCOS were randomized to metformin or placebo, from first trimester to delivery. Maternal serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at gestational weeks (gw) 5–12, 19, 32 and 36 in 309 singleton pregnancies. The mean z-scores of birthweight, birth length, and head circumference were estimated in the offspring. Associations of maternal thyroid parameters with offspring anthropometrics and the outcomes large for gestational age (LGA) and small for gestational age (SGA) were studied using linear and logistic regression models, with adjustment for body mass index (BMI) when relevant.ResultsMaternal fT4 at baseline was negatively associated with birth length (b= -0.09, p=0.048). Furthermore, ΔfT4 during pregnancy correlated positively to z-score of both birth weight and length (b=0.10, p=0.017 and b=0.10, p=0.047 respectively), independently of treatment group. TSH at baseline and gw19 was inversely associated with LGA (OR 0.47, p=0.012 and OR 0.58, p=0.042), while ΔTSH was positively associated with LGA (OR 1.99, p=0.023). There were inverse associations between TSH at baseline and SGA (OR 0.32, p=0.005) and between ΔfT4 and SGA (OR 0.59, p=0.005) in the metformin group only. There were no associations between maternal thyroid function and head circumference of the newborns.ConclusionIn women with PCOS, a higher maternal fT4 in early pregnancy and a greater decrease in fT4 during pregnancy was associated with a lower offspring birthweight and shorter birth length. Higher TSH by mid-gestation and smaller increase in TSH during pregnancy was associated with less risk of LGA. Subclinical variations in maternal thyroid function might play a role for birth anthropometrics of PCOS offspring

Metformin exposure, maternal PCOS status and fetal venous liver circulation: A randomized, placebo-controlled study

Background: Metformin is prescribed to women with polycystic ovary syndrome (PCOS) to prevent pregnancy complications. Children exposed to metformin vs. placebo in utero, have increased head circumference at birth and are more overweight and obese at 8 years of age. Also, maternal PCOS-status seems to alter the long-term cardio-metabolic health of offspring. We hypothesized that the long-term effects of metformin-exposure and/or maternal PCOS may be mediated by circulatory adaptations during fetal life. Material and methods: This is a sub-study of a larger double-blinded, placebo-controlled trial, where women with PCOS were randomized to metformin (2g/day) or placebo in pregnancy, a total of 487 women. A sub-group of participants (N = 58) took part in this sub-study and had an extended ultrasound examination at gestational week 32, including blood flow velocity and diameter measurements of the umbilical vein (UV), the ductus venosus (DV) and the portal vein (PV). Blood flow volume was calculated and adjusted for estimated fetal weight (EFW) (normalized flow). Metformin exposed fetuses were compared to placebo exposed fetuses. Fetuses of mothers with PCOS (metformin [n = 30] and placebo [n = 28]) were compared to a low-risk reference population (N = 160) by z-score statistics. Results: There was no difference in fetal liver flow between metformin vs. placebo-exposed fetuses. Fetuses of mothers with PCOS had higher EFW (0.63 [95% CI 0.44–0.83] p<0.001), lower normalized UV, DV, PV, and lower total venous liver blood flows than the reference population. Conclusion: Metformin during pregnancy did not affect fetal liver blood-flow. In our population, maternal PCOS-status was associated with reduced total venous liver blood-flow, which may explain altered growth and metabolism later in life.publishedVersio

High-intensity interval training in polycystic ovary syndrome : A two-center, three-armed randomized

Purpose Exercise training is recommended to improve cardiometabolic health and fertility in women with polycystic ovary syndrome (PCOS), yet there are few randomized controlled trials on the effects of different exercise protocols on clinical reproductive outcomes. Our aim was to determine the effect of high-intensity interval training (HIT) on menstrual frequency, as a proxy of reproductive function, in women with PCOS. Methods The IMPROV-IT study was a two-center randomized controlled trial undertaken in Norway and Australia. Women with PCOS were eligible for inclusion. After stratification for body mass index <27 or ≥27 kg·m−2 and study center, participants were randomly allocated (1:1:1) to high-volume HIT (HV-HIT), low-volume HIT (LV-HIT), or a control group. Measurements were assessed at baseline, after the 16-wk exercise intervention, and at 12-month follow-up. The primary outcome was menstrual frequency after 12 months. Secondary outcomes included markers of cardiometabolic and reproductive health, quality of life, and adherence to and enjoyment of HIT. Results We randomly allocated 64 participants to the HV-HIT (n = 20), LV-HIT (n = 21), or control group (n = 23). There were no differences in menstrual frequency at 12 months between the LV-HIT and control groups (frequency ratio, 1.02; 95% confidence interval [CI], 0.73–1.42), the HV-HIT and control groups (frequency ratio, 0.93; 95% CI, 0.67–1.29), or the LV-HIT and HV-HIT groups (frequency ratio, 1.09; 95% CI, 0.77–1.56). Menstrual frequency increased in all groups from baseline to 12 months. More participants became pregnant in the LV-HIT group (n = 5) than in the control group (n = 0, P = 0.02). Conclusions A semisupervised HIT intervention did not increase menstrual frequency in women with PCOS. Clinical Trial Registration Number:ClinicalTrials.gov (NCT02419482)

Maternal PCOS status and metformin in pregnancy: Steroid hormones in 5–10 years old children from the PregMet randomized controlled study

Objective: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with potential effects on offspring both genetically and through altered intrauterine environment. Metformin, which ameliorate hormonal disturbances in non-pregnant women with PCOS is increasingly used in pregnancy. It passes the placenta, and the evidence on potential consequences for offspring endocrine development is scarce. We explore the potential effects of maternal PCOS status and intrauterine metformin exposure on offspring steroid hormone levels. Design: This is a follow-up study of 5–10 years old children from the PregMet-study–a randomized controlled trial comparing metformin (2000 mg/day) to placebo during PCOS pregnancies. Of the 255 children invited, 117 (46%) were included. Methods: There was no intervention in this follow-up study. Outcomes were serum levels of androstenedione, testosterone, SHBG, cortisol, 17-hydroxyprogesterone, 11-deoxycortisol and calculated free testosterone converted to gender-and age adjusted z-scores from a Norwegian reference population. These were compared in i) placebo-exposed children versus children from the reference population (z-score zero) by the deviation in z-score by one-sample t-tests and ii) metformin versus placebo-exposed children by two-sample t-tests. Holm-Bonferroni adjustments were performed to account for multiple endpoints. Results: Girls of mothers with PCOS (n = 30) had higher mean z-scores of androstenedione (0.73 (95% confidence interval (CI) 0.41 to 1.06), p<0.0001), testosterone (0.76 (0.51 to 1.00), p<0.0001), and free testosterone (0.99 (0.67 to 1.32), p<0.0001) than the reference population. Metformin-exposed boys (n = 31) tended to have higher 11-deoxycortisol z-score than placebo-exposed boys (n = 24) (mean difference 0.65 (95% CI 0.14–1.17), p = 0.014). Conclusion: Maternal PCOS status was associated with elevated androgens in 5- to 10-year-old daughters, which might indicate earlier maturation and increased risk of developing PCOS. An impact of metformin in pregnancy on steroidogenesis in children born to mothers with PCOS cannot be excluded. Our findings need confirmation in studies that include participants that have entered puberty.publishedVersio

Anthropometrics of neonates born to mothers with PCOS with metformin or placebo exposure in utero

Introduction: Fetal growth may be affected by both maternal polycystic ovary syndrome (PCOS) and metformin therapy. Here, we explore the effect of intrauterine metformin exposure on birth anthropometrics of infants born to women with PCOS. We also investigated whether the effect of metformin on birth anthropometrics is modified by maternal pre-pregnancy body mass index, PCOS hyperandrogenic phenotype, serum androgen levels, preconception use of metformin and offspring sex. Additionally, we assessed newborn anthropometrics in relation to a national reference population. Material and methods: Individual data from three randomized controlled triasl were pooled. The randomized controlled trials investigated the effects of metformin in pregnant women with PCOS. In all, 397 and 403 were randomized to the metformin and placebo groups, respectively. A Scandinavian growth reference was used to calculate sex and gestational age adjusted z-scores. Linear regression models were used to estimate the effect of metformin on offspring z-scores of head circumference, birth length, birthweight, placental weight, body mass index, ponderal index and birthweight:placental weight ratio. S-testosterone, s-androstenedione, and s-sex-hormone binding globulin from four timepoints in pregnancy were analyzed. Results: Compared with the PCOS-placebo group, newborns in the PCOS-metformin group had larger head circumference (head circumference z-score: mean difference = 0.25, 95% CI = 0.11– 0.40). This effect of metformin on head circumference z-score was particularly observed among offspring of overweight/obese mothers and mothers with hyperandrogenic PCOS-phenotype. We observed no difference in other anthropometric measures between the metformin and placebo groups or any clear interaction between maternal androgen levels and metformin. Newborns in the PCOS-placebo group were shorter than in the reference population (birth length z-score: mean = −0.04, 95% CI = –0.05 to −0.03), but head circumference and birthweight were similar. Conclusions: Larger head circumference was observed at birth in metformin-exposed offspring of mothers with PCOS. PCOS-offspring were also shorter, with a similar birthweight to the reference population, indirectly indicating higher weight-to-height ratio at birth.publishedVersio

Normo- and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life

Objective: To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life. Design: Case-control study. Setting: Not applicable. Patient(s): In all, 1,550 women with normoandrogenic (n = 686) or hyperandrogenic (n = 842) PCOS and 447 control women were divided into three age groups: 39 years). Interventions(s): None. Main Outcome Measure(s): Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein. Result(s): Both normo- and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, low-density lipoprotein, and total cholesterol, higher blood pressure, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two-to fivefold higher in women with PCOS compared with control women, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. Conclusion(s): When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from early adulthood on. (C) 2016 by American Society for Reproductive Medicine.Peer reviewe

Higher blood pressure in normal weight women with PCOS compared to controls

Objective: Obesity is considered to be the strongest predictive factor for cardio-metabolic risk in women with polycystic ovary syndrome (PCOS). The aim of the study was to compare blood pressure (BP) in normal weight women with PCOS and controls matched for age and BMI. Methods: From a Nordic cross-sectional base of 2615 individuals of Nordic ethnicity, we studied a sub cohort of 793 normal weight women with BMI = 140/90 mmHg was 11.1% (57/ 512) in women with PCOS vs 1.8% (5/281) in controls, P = 35 years the prevalence of BP >= 140/90 mmHg was comparable in women with PCOS and controls (12.7% vs 9.8%, P = 0.6). Using multiple regression analyses, the strongest association with BP was found for age, waist circumference, and total cholesterol in women with PCOS. Conclusions: Normal weight women with PCOS have higher BP than controls. BP and metabolic screening are relevant also in young normal weight women with PCOS.Peer reviewe

Awareness of polycystic ovary syndrome among obstetrician-gynecologists and endocrinologists in Northern Europe

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Metformin in Pregnancy Study (MiPS): Protocol for a systematic review with individual patient data meta-analysis

AbstractIntroduction Gestational diabetes mellitus (GDM) is a common disorder of pregnancy and contributes to adverse pregnancy outcomes. Metformin is often used for the prevention and management of GDM; however, its use in pregnancy continues to be debated. The Metformin in Pregnancy Study aims to use individual patient data (IPD) meta-analysis to clarify the efficacy and safety of metformin use in pregnancy and to identify relevant knowledge gaps.Methods and analysis MEDLINE, EMBASE and all Evidence-Based Medicine will be systematically searched for randomised controlled trials (RCT) testing the efficacy of metformin compared with placebo, usual care or other interventions in pregnant women. Two independent reviewers will assess eligibility using prespecified criteria and will conduct data extraction and quality appraisal of eligible studies. Authors of included trials will be contacted and asked to contribute IPD. Primary outcomes include maternal glycaemic parameters and GDM, as well as neonatal hypoglycaemia, anthropometry and gestational age at delivery. Other adverse maternal, birth and neonatal outcomes will be assessed as secondary outcomes. IPD from these RCTs will be harmonised and a two-step meta-analytic approach will be used to determine the efficacy and safety of metformin in pregnancy, with a priori adjustment for covariates and subgroups to examine effect moderators of treatment outcomes. Sensitivity analyses will assess heterogeneity, risk of bias and the impact of trials which have not provided IPD.Ethics and disseminationAll IPD will be deidentified and studies contributing IPD will have ethical approval from their respective local ethics committees. This study will provide robust evidence regarding the efficacy and safety of metformin use in pregnancy, and may identify subgroups of patients who may benefit most from this treatment modality. Findings will be published in peer-reviewed journals and disseminated at scientific meetings, providing much needed evidence to inform clinical and public health actions in this area.</p