Sensitivity, specificity, and diagnostic accuracy of WHO 2013 criteria for diagnosis of gestational diabetes mellitus in low risk early pregnancies: international, prospective, multicentre cohort study.

Objective: To evaluate the predictability of gestational diabetes mellitus wth a 75 g oral glucose tolerance test (OGTT) in early pregnancy, based on the 2013 criteria of the World Health Organization, and to test newly proposed cut-off values. Design: International, prospective, multicentre cohort study. Setting: Six university or cantonal departments in Austria, Germany, and Switzerland, from 1 May 2016 to 31 January 2019. Participants: Low risk cohort of 829 participants aged 18-45 years with singleton pregnancies attending first trimester screening and consenting to have an early 75 g OGTT at 12-15 weeks of gestation. Participants and healthcare providers were blinded to the results. Main outcome measures: Fasting, one hour, and two hour plasma glucose concentrations after an early 75 g OGTT (12-15 weeks of gestation) and a late 75 g OGTT (24-28 weeks of gestation). Results: Of 636 participants, 74 (12%) developed gestational diabetes mellitus, according to World Health Organization 2013 criteria, at 24-28 weeks of gestation. Applying WHO 2013 criteria to the early OGTT with at least one abnormal value gave a low sensitivity of 0.35 (95% confidence interval 0.24 to 0.47), high specificity of 0.96 (0.95 to 0.98), positive predictive value of 0.57 (0.41 to 0.71), negative predictive value of 0.92 (0.89 to 0.94), positive likelihood ratio of 10.46 (6.21 to 17.63), negative likelihood ratio of 0.65 (0.55 to 0.78), and diagnostic odds ratio of 15.98 (8.38 to 30.47). Lowering the postload glucose values (75 g OGTT cut-off values of 5.1, 8.9, and 7.8 mmol/L) improved the detection rate (53%, 95% confidence interval 41% to 64%) and negative predictive value (0.94, 0.91 to 0.95), but decreased the specificity (0.91, 0.88 to 0.93) and positive predictive value (0.42, 0.32 to 0.53) at a false positive rate of 9% (positive likelihood ratio 5.59, 4.0 to 7.81; negative likelihood ratio 0.64, 0.52 to 0.77; and diagnostic odds ratio 10.07, 6.26 to 18.31). Conclusions: The results of this prospective low risk cohort study indicated that the 75 g OGTT as a screening tool in early pregnancy is not sensitive enough when applying WHO 2013 criteria. Postload glucose values were higher in early pregnancy complicated by diabetes in pregnancy. Lowering the postload cut-off values identified a high risk group for later development of gestational diabetes mellitus or those who might benefit from earlier treatment. Results from randomised controlled trials showing a beneficial effect of early intervention are unclear. Trial registration: ClinicalTrials.gov NCT02035059.

The molecular and phenotypic makeup of fetal human skin T lymphocytes.

The adult human skin contains a vast number of T cells that are essential for skin homeostasis and pathogen defense. T cells are first observed in the skin at the early stages of gestation; however, our understanding of their contribution to early immunity has been limited by their low abundance and lack of comprehensive methodologies for their assessment. Here, we describe a new workflow for isolating and expanding significant amounts of T cells from fetal human skin. Using multiparametric flow cytometry and in situ immunofluorescence, we found a large population with a naive phenotype and small populations with a memory and regulatory phenotype. Their molecular state was characterized using single-cell transcriptomics and TCR repertoire profiling. Importantly, culture of total fetal skin biopsies facilitated T cell expansion without a substantial impact on their phenotype, a major prerequisite for subsequent functional assays. Collectively, our experimental approaches and data advance the understanding of fetal skin immunity and potential use in future therapeutic interventions.

Performance of early risk assessment tools to predict the later development of gestational diabetes.

BACKGROUND: Several prognostic models for gestational diabetes mellitus (GDM) are provided in the literature; however, their clinical significance has not been thoroughly evaluated, especially with regard to application at early gestation and in accordance with the most recent diagnostic criteria. This external validation study aimed to assess the predictive accuracy of published risk estimation models for the later development of GDM at early pregnancy. METHODS: In this cohort study, we prospectively included 1132 pregnant women. Risk evaluation was performed before 16 + 0 weeks of gestation including a routine laboratory examination. Study participants were followed-up until delivery to assess GDM status according to the IADPSG 2010 diagnostic criteria. Fifteen clinical prediction models were calculated according to the published literature. RESULTS: Gestational diabetes mellitus was diagnosed in 239 women, that is 21.1% of the study participants. Discrimination was assessed by the area under the ROC curve and ranged between 60.7% and 76.9%, corresponding to an acceptable accuracy. With some exceptions, calibration performance was poor as most models were developed based on older diagnostic criteria with lower prevalence and therefore tended to underestimate the risk of GDM. The highest variable importance scores were observed for history of GDM and routine laboratory parameters. CONCLUSIONS: Most prediction models showed acceptable accuracy in terms of discrimination but lacked in calibration, which was strongly dependent on study settings. Simple biochemical variables such as fasting glucose, HbA1c and triglycerides can improve risk prediction. One model consisting of clinical and laboratory parameters showed satisfactory accuracy and could be used for further investigations.

Correlative SEM-Raman microscopy to reveal nanoplastics in complex environments.

Nowadays "microplastics" (MPs) is an already well-known term and results of micro-sized particles found in consumer products or environments are regularly reported. However, studies of native MPs smaller than 1 µm, often referred to as nanoplastics (NPs), in analytically challenging environments are rare. In this study, a correlative approach between scanning electron microscopy and Raman microscopy is tested to meet the challenges of finding and identifying NPs in the 100 nm range in various environments, ranging from ideal (distilled water) to challenging (sea salt, human amniotic fluid). To test the viability of this approach in principle, standardized polystyrene beads (Ø 200 nm) are mixed into the various environments in different concentrations. Promising detection limits of 2 10-3 µg/L (distilled water), 20 µg/L (sea salt) and 200 µg/L (human amniotic fluid) are found. To test the approach in practices both sea salt and amniotic fluid are analysed for native NPs as well. Interestingly a nylon-NP was found in the amniotic fluid, maybe originating from the sampling device. However, the practical test reveals limitations, especially with regard to the reliable identification of unknown NPs by Raman microscopy, due to strong background signals from the environments. We conclude from this in combination with the excellent performance in distilled water that a combination of this approach with an advanced sample preparation technique would yield a powerful tool for the analysis of NPs in various environments.

αßγδ T cells play a vital role in fetal human skin development and immunity.

T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αß and γδ T cell receptors (TCRs) that was enriched in fetal skin and intestine but not detected in other fetal organs and peripheral blood. TCR sequencing data revealed that double-positive (DP) αßγδ T cells displayed little overlap of CDR3 sequences with single-positive αß T cells. Gene signatures, cytokine profiles and in silico receptor-ligand interaction studies indicate their contribution to early skin development. DP αßγδ T cells were phosphoantigen responsive, suggesting their participation in the protection of the fetus against pathogens in intrauterine infections. Together, our analyses unveil a unique cutaneous T cell type within the native skin microenvironment and point to fundamental differences in the immune surveillance between fetal and adult human skin.

Association between maternal triglycerides and disturbed glucose metabolism in pregnancy.

AIMS: Dyslipidemia in pregnancy is associated with adverse pregnancy outcomes as elevated triglycerides might be considered as a risk factor for hyperglycemia and gestational diabetes. As only a few studies have addressed the association between maternal triglycerides and glucose metabolism, we aimed to explore the pathophysiologic associations of moderate hypertriglyceridemia and maternal glucose metabolism in pregnancy. METHODS: Sixty-seven pregnant women received a detailed metabolic characterization at 12+0-22+6 weeks of gestation by an extended 2h-75g OGTT (oral glucose tolerance test); with measurements of glucose, insulin and C-peptide at fasting and every 30 min after ingestion and assessment of triglycerides at fasting state. All examinations were repeated at 24+0-27+6 weeks of gestation. RESULTS: Elevated triglycerides in early gestation were associated with insulin resistance and ß-cell dysfunction. Mean glucose concentrations during the OGTT in early pregnancy were already higher in women with hypertriglyceridemia as compared to women with triglycerides in the normal range. A higher degree of insulin resistance and increased OGTT glucose levels were also observed when metabolic assessments were repeated between 24 and 28 weeks of gestation. Of note, elevated triglycerides at early gestation were associated with development of gestational diabetes by logistic regression (odds ratio: 1.16, 95%CI: 1.03-1.34, p=0.022 for an increase of 10 mg/dl). CONCLUSIONS: Hypertriglyceridemia at the start of pregnancy is closely related to impaired insulin action and ß-cell function. Women with hypertriglyceridemia have higher mean glucose levels in early- and mid-gestation. Pregnant women with elevated triglycerides in early pregnancy are at increased risk of developing gestational diabetes.

Maternal Overweight vs. Polycystic Ovary Syndrome: Disentangling Their Impact on Insulin Action in Pregnancy-A Prospective Study.

BACKGROUND: To investigate insulin sensitivity and glucose metabolism in pregnant lean and overweight polycystic ovary syndrome (PCOS) patients vs. lean and overweight controls without PCOS. METHODS: Prospective cohort study on 67 pregnant women (31 with PCOS and 36 controls, subdivided into overweight or obese and normal weight). All women underwent a 2h-OGTT including glucose, insulin, and C-peptide in early- and mid-gestation and were followed-up until delivery. RESULTS: Insulin sensitivity and glucometabolic parameters were comparable between PCOS patients and controls, whereas marked differences were observed between overweight/obese and lean mothers. Impaired whole-body insulin sensitivity at early pregnancy is mainly a consequence of higher BMI (body mass index; p < 0.001) compared to PCOS (p = 0.216), whereby no interaction between overweight/obesity and PCOS was observed (p = 0.194). Moreover, overweight was significantly associated with gestational diabetes (p = 0.0003), whereas there were no differences between women with and without PCOS (p = 0.51). Birth weight was inversely related to whole-body insulin sensitivity (rho = -0.33, p = 0.014) and positively associated with higher pregestational BMI (rho = 0.33, p = 0.012), whereas there was no association with PCOS. CONCLUSIONS: Impaired insulin action was mainly a consequence of overweight rather than PCOS. Our data suggest that overweight is more relevant than PCOS for the effects on insulin sensitivity and impaired glucose metabolism.

Carotid intima-media thickness in polycystic ovary syndrome and its association with hormone and lipid profiles.

OBJECTIVE: Polycystic ovary syndrome (PCOS) has been associated with an increased risk of metabolic disturbances and cardiovascular disease. Intima-media thickness of the common carotid artery (CIMT) represents a valid surrogate marker of early systemic atherosclerosis. This study aimed to investigate if CIMT is increased in PCOS patients compared to healthy controls and if there is an association with hormone and metabolic profiles. METHODS: In this prospective cross-sectional study, past medical history, anthropometrical measurements and hormonal, lipidemic and glycemic parameters were obtained in 41 PCOS patients and 43 age-matched healthy controls of similar body mass index (BMI) and frequency of smokers. B-mode ultrasound enabled CIMT measurement at the far wall of the left and right common carotid artery. RESULTS: Patients with PCOS showed significantly increased CIMT values compared to healthy controls (0.49±0.04mm vs. 0.37±0.04mm respectively, P<0.001). They featured a generally increased cardiovascular risk profile. Correlation analysis showed a positive association between CIMT and the adverse metabolic risk profile. The diagnosis of PCOS was the strongest predictor of CIMT, even after multiple adjustments for BMI, age and smoking status (ß = 0.797, P<0.001, R2 = 0.73). A model among oligomenorrhoic patients revealed a relationship between CIMT and the suspected duration of disease (ß = 0.373, P = 0.021, R2 = 0.14). CONCLUSIONS: PCOS patients are likely to feature signs of premature systemic atherosclerosis at a young age. Early exposure to adverse cardiovascular risk factors may possibly have long-term consequences on the vascular system. An early vessel screening might thus already be beneficial in these patients at a younger age.

Novel Indices of Glucose Homeostasis Derived from Principal Component Analysis: Application for Metabolic Assessment in Pregnancy.

AIMS: This study is aimed at assessing the association of previously developed indices of glucose homeostasis derived from principal component analysis (PCA) with parameters of insulin action, secretion, and beta cell function during pregnancy. METHODS: In this prospective longitudinal study, an oral glucose tolerance test was performed in sixty-seven pregnant women at two prepartum (12+0 to 22+6 and 24+0 to 28+6) and one postpartum (2 to 11 months) visits. Three principal component scores (PCS) were calculated based on measurements of glucose, insulin, C-peptide, age, and BMI to assess their association with fasting and dynamic indices of insulin action, secretion, and ß-cell function. RESULTS: PCS1 was positively associated with fasting and dynamic parameters of insulin sensitivity (Matsuda index: r = 0.93, p < 0.001), whereas a strong negative association was observed for early, late, and total insulin response. PCS2 was associated with higher mean glucose but negatively related to parameters of insulin secretion. PCS3 was significantly associated with fasting indices of insulin sensitivity. PCS1 to 3 assessed at early pregnancy were also associated with development of GDM, whereby random forest analysis revealed the highest variable importance for PCS1. PCS1 to 3 were significantly related to the oral disposition index explaining 49.0% of its variance. CONCLUSIONS: PCS1 to 3 behaved similarly as compared to previous observations in nonpregnant women and were furthermore associated with the development of GDM. These findings support our hypothesis that PCS1 to 3 could be used as novel indices of glucose disposal during pregnancy.

Effects of gum chewing on glycaemic control in women with gestational diabetes mellitus: A randomized controlled trial. Impact of chewing on hyperglycaemia in women with GDM.

BACKGROUND: The amount of chewing might be relevant in reducing hyperglycaemia in diabetic patients. The study assessed the impact of enhanced chewing on glycaemic control in women with gestational diabetes mellitus (GDM). METHODS: As an open-label, mono-centre randomized controlled trial, 59 women with recent diagnosis of GDM were included. They received either routine care or additional chewing gum intervention. SMBG was performed for five days. RESULTS: No significant impact on mean values of postprandial glucose levels were observed. The estimated mean differences (intervention vs. control group) were: 4.9 mg/dl, 98.4 %CI -7.2-17.1 (breakfast); -4.5 mg/dl, 98.4 %CI -15.1-6.0 (lunch); -3.8 mg/dl, 98.4 %CI -15.9 to 8.4 (dinner). OGTT levels at 60 and 120 min. were associated with glucose levels after breakfast. CONCLUSION: In conclusion, no significant differences in blood glucose levels were observed between the groups and therefore major effects of chewing on hyperglycaemia in women with GDM could be excluded. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03961542, Date of registration: 20.01.2019. Retrospectively registered.

Bariatric Surgery Impacts Levels of Serum Lipids during Pregnancy.

INTRODUCTION: Bariatric surgery confers a high risk for nutritional deficiencies that could affect physiologic adaptation of lipids during pregnancy. We aimed to evaluate differences in serum lipids in pregnant women after bariatric surgery compared to obese and lean mothers. METHODS: 25 women with a history of Roux-en-Y gastric bypass (RYGB), 19 obese and 19 normal-weight controls were included at the 24th-28th gestational week for determination of fasting lipids with follow-up in a subgroup after delivery. Data on neonatal biometry were additionally assessed. RESULTS: Women after RYGB showed lower total-cholesterol (TC), low-density lipoprotein C (LDL-C), non-high-density lipoprotein C (non-HDL-C) and triglycerides (TG) compared to obese mothers. Despite their higher BMI, women after RYGB showed lower TC, LDL-C and non-HDL-C than normal-weight mothers. Ultrasensitive C-reactive protein was lower in RYGB mothers than in obese ones, reaching values of lean controls. Differences remained unchanged in BMI-matched comparison. Birth weight percentiles of RYGB offspring were associated with maternal TC (r = 0.59, p = 0.021), LDL-C (r = 0.71, p = 0.003), non-HDL (r = 0.59, p = 0.021) but not HDL-C or TG. After delivery, lipids decreased in all women; however, TC and LDL-C showed more attenuated decline in mothers after RYGB than control women. CONCLUSION: Pregnancies after RYGB show alterations of physiologic patterns in lipid profile. Further studies are required to evaluate whether imbalances in maternal lipids constitute a risk for abnormal fetal growth in this special cohort.

Trajectories of Fetal Adipose Tissue Thickness in Pregnancies After Gastric Bypass Surgery.

PURPOSE: Recent studies showed that women after surgery are at higher risk of delivering small-for-gestational infants. Thus, this study aims to investigate longitudinal changes of fetal subcutaneous adipose tissue thickness (FSCTT) of fetuses conceived after gastric bypass surgery as compared to BMI-matched controls. METHODS: Retrospective cohort study measuring ultrasound-derived longitudinal trajectories of abdominal FSCTT in 41 singleton pregnancies after gastric bypass surgery compared to 41 BMI-matched controls and 64 obese mothers. RESULTS: FSCTT was significantly lower in fetuses of women after GB as compared to BMI-matched controls in the second (mean difference 1.38 mm, p < 0.001) and third trimester of gestation (mean difference 3.37 mm, p < 0.001). Longitudinal analysis revealed significant differences in mean FSCTT trajectories between offspring's in GB mothers, BMI-matched, or obese controls. The ratio of FSCTT and abdominal circumference remained constant in the BMI-matched control group whereas it significantly decreased in fetuses of women after GB. Despite remarkable differences were observed in longitudinally assessed FSCTT, further analyses in the GB subgroup revealed that FSCTT were not influenced by OGTT mean or 120 min glucose values, biochemically hypoglycemia, time since bariatric surgery, or weight loss since surgery. CONCLUSION: In fetuses of mothers with history of bariatric surgery, abdominal FSCTT was markedly reduced. While the underlying mechanisms are not fully understood, a multifactorial genesis including nutritional deficiencies and altered metabolism after bariatric surgery is assumed.

Intrauterine Fetal Growth Delay During Late Pregnancy After Maternal Gastric Bypass Surgery.

PURPOSE: To investigate intrauterine fetal growth development and birth anthropometry of fetuses conceived after maternal gastric bypass surgery. MATERIALS AND METHODS: Longitudinal cohort study describing longitudinal growth estimated by ultrasound on 43 singleton pregnancies after gastric bypass compared to 43 BMI-matched controls. RESULTS: In fetuses after maternal gastric bypass surgery, growth percentiles decreased markedly from the beginning of the second trimester until the end of the third trimester (decrease of 3.1 fetal abdomen circumference percentiles (95 %CI 0.9-5.3, p = 0.007) per four gestational weeks). While in the second trimester, fetal anthropometric measures did not differ between the groups, the mean abdomen circumference percentiles appeared significantly smaller during the third trimester in offspring of mothers after gastric bypass (mean difference 25.1 percentiles, p < 0.001). Similar tendencies have been observed in estimated fetal weight resulting in significantly more SGA offspring at delivery in the gastric bypass group. In children born after maternal gastric bypass surgery, weight percentiles (32.12th vs. 55.86th percentile, p < 0.001) as well as placental weight (525.2 g vs. 635.7 g, p < 0.001) were significantly reduced compared to controls. CONCLUSION: In fetuses conceived after maternal gastric bypass, intrauterine fetal growth distinctively declined in the second and third trimester, most prominently observed in fetal abdomen circumferences. Birth weight and placental weight at birth was significantly lower compared to BMI-matched controls, possibly due to altered maternal metabolic factors and comparable to mothers experiencing chronic hunger episodes.

Early Assessment of the Risk for Gestational Diabetes Mellitus: Can Fasting Parameters of Glucose Metabolism Contribute to Risk Prediction?

BACKGROUND: An early identification of the risk groups might be beneficial in reducing morbidities in patients with gestational diabetes mellitus (GDM). Therefore, this study aimed to assess the biochemical predictors of glycemic conditions, in addition to fasting indices of glucose disposal, to predict the development of GDM in later stage and the need of glucose-lowering medication. METHODS: A total of 574 pregnant females (103 with GDM and 471 with normal glucose tolerance [NGT]) were included. A metabolic characterization was performed before 15⁺6 weeks of gestation by assessing fasting plasma glucose (FPG), fasting insulin (FI), fasting C-peptide (FCP), and glycosylated hemoglobin (HbA1c). Thereafter, the patients were followed-up until the delivery. RESULTS: Females with NGT had lower levels of FPG, FI, FCP, or HbA1c at the early stage of pregnancy, and therefore, showed an improved insulin action as compared to that in females who developed GDM. Higher fasting levels of FPG and FCP were associated with a higher risk of developing GDM. Moreover, the predictive accuracy of this metabolic profiling was also good to distinguish the patients who required glucose-lowering medications. Indices of glucose disposal based on C-peptide improved the predictive accuracy compared to that based on insulin. A modified quantitative insulin sensitivity check index (QUICKIc) showed the best differentiation in terms of predicting GDM (area under the receiver operating characteristics curve [ROC-AUC], 72.1%) or need for pharmacotherapy (ROC-AUC, 83.7%). CONCLUSION: Fasting measurements of glucose and C-peptide as well as the surrogate indices of glycemic condition could be used for stratifying pregnant females with higher risk of GDM at the beginning of pregnancy.

Glucagon-like peptide 1 (GLP-1) drives postprandial hyperinsulinemic hypoglycemia in pregnant women with a history of Roux-en-Y gastric bypass operation.

BACKGROUND: The influential role of incretin hormones on glucose metabolism in patients with a history of Roux-en-Y gastric bypass (RYGB) has been investigated thoroughly, but there has been little examination of the effect of incretins and ectopic lipids on altered glucose profiles, especially severe hypoglycemia in pregnant women with RYGB. METHODS: In this prospective clinical study, an oral glucose tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and continuous glucose monitoring (CGM) were conducted in 25 women with RYGB during pregnancy, 19 of normal weight (NW) and 19 with obesity (OB) between the 24th and the 28th weeks of pregnancy, and 3 to 6 months post-partum. Post-partum, the ectopic lipid content in the liver, heart, and skeletal muscle was analyzed using 1H-magnetic resonance spectroscopy (1H-MRS). RESULTS: RYGB patients presented with major fluctuations in glucose profiles, including a high occurrence of postprandial hyperglycemic spikes and hypoglycemic events during the day, as well as a high risk of hypoglycemic periods during the night (2.9 ±â€¯1.1% vs. 0.1 ±â€¯0.2% in the OB and vs. 0.8 ±â€¯0.6% in the NW groups, p < 0.001). During the extended OGTT, RYGB patients presented with exaggerated expression of GLP-1, which was the main driver of the exaggerated risk of postprandial hypoglycemia in a time-lagged correlation analysis. Basal and dynamic GLP-1 levels were not related to insulin sensitivity, insulin secretion, or beta cell function and did not differ between pregnant women with and without GDM. A lower amount of liver fat (2.34 ±â€¯5.22% vs.5.68 ±â€¯4.42%, p = 0.015), which was positively related to insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR: rho = 0.61, p = 0.002) and beta-cell function (insulinogenic index: rho = 0.65, p = 0.001), was observed in the RYGB group after delivery in comparison to the OB group. CONCLUSION: GLP-1 is mainly involved in the regulation of postprandial glucose metabolism and therefore especially in the development of postprandial hypoglycemia in pregnant RYGB patients, who are characterized by major alterations in glucose profiles, and thus in long-term regulation, multiple organ-related mechanisms, such as the lipid content in the liver, must be involved.

Pregnancy after bariatric surgery: a narrative literature review and discussion of impact on pregnancy management and outcome.

Bariatric surgery (BS) is regarded to be the most effective treatment of obesity with long lasting beneficial effects including weight loss and improvement of metabolic disorders. A considerable number of women undergoing BS are at childbearing age.Although the surgery mediated weight loss has a positive effect on pregnancy outcome, the procedures might be associated with adverse outcomes as well, for example micronutrient deficiencies, iron or B12 deficiency anemia, dumping syndrome, surgical complications such as internal hernias, and small for gestational age (SGA) offspring, possibly due to maternal undernutrition. Also, there is no international consensus concerning the ideal time to conception after BS. Hence, the present narrative review intents to summarize the available literature concerning the most common challenges which arise before and during pregnancy after BS, such as fertility related considerations, vitamin and nutritional deficiencies and their adequate compensation through supplementation, altered glucose metabolism and its implications for gestational diabetes screening, the symptoms and treatment of dumping syndrome, surgical complications and the impact of BS on pregnancy outcome. The impact of different bariatric procedures on pregnancy and fetal outcome will also be discussed, as well as general considerations concerning the monitoring and management of pregnancies after BS.Whereas BS leads to the mitigation of many obesity-related pregnancy complications, such as gestational diabetes mellitus (GDM), pregnancy induced hypertension and fetal macrosomia; those procedures pose new risks which might lead to adverse outcomes for mothers and offspring, for example nutritional deficiencies, anemia, altered maternal glucose metabolism and small for gestational age children.

To Predict the Requirement of Pharmacotherapy by OGTT Glucose Levels in Women with GDM Classified by the IADPSG Criteria.

The aim of this study was to assess the association between OGTT glucose levels and requirement of pharmacotherapy in GDM patients classified by the IADPSG criteria. This study included 203 GDM patients (108 managed with lifestyle modification and 95 requiring pharmacotherapy). Clinical risk factors and OGTT glucose concentrations at 0 (G0), 60 (G60), and 120 min (G120) were collected. OGTT glucose levels were significantly associated with the later requirement of pharmacotherapy (ROC-AUC: 71.1, 95% CI: 63.8-78.3). Also, the combination of clinical risk factors (age, BMI, parity, and pharmacotherapy in previous gestation) showed an acceptable predictive accuracy (ROC-AUC: 72.1, 95% CI: 65.0-79.2), which was further improved when glycemic parameters were added (ROC-AUC: 77.5, 95% CI: 71.5-83.9). Random forest analysis revealed the highest variable importance for G0, G60, and age. OGTT glucose measures in addition to clinical risk factors showed promising properties for risk stratification in GDM patients classified by the recently established IADPSG criteria.

Pre- and peripartal management of a woman with McArdle disease: a case report.

McArdle disease or glycogen storage disease (GSD) type V is a rare autosomal recessive inherited disorder in skeletal muscle metabolism leading to exercise intolerance, muscle cramps and in some cases to rhabdomyolysis and acute renal failure due to elevated serum myoglobin levels. Albeit the uterine smooth muscle is not affected, pregnancy and delivery can be physically strenuous and may require specific anesthesiologic care. However, data on pregnancy progress and outcome and on special implications linked to anesthesia in women with McArdle's disease is scarce, thus posing a challenge to pre- and peripartal management. We report a case of a pregnant woman with Morbus McArdle who was monitored during her pregnancy and delivered a healthy male via cesarean section under spinal anesthesia. Pregnancy, delivery and recovery were uneventful. Our findings, combined with a literature review, lead to the conclusion that uncomplicated pregnancy and delivery can be expected.

The Reticulum-Associated Protein RTN1A Specifically Identifies Human Dendritic Cells.

RTN1 is an endoplasmic reticulum-associated protein that was initially identified in neuronal tissues. Here we show that the main isoform RTN1A is a marker for dendritic cells. In the skin, HLA-DR+CD1ahighCD207+CD11cweak Langerhans cells were the only cells in the epidermis, and HLA-DR+CD11c+ dendritic cells were the main cells in the dermis, expressing this protein. RTN1A+ dendritic cells were also found in gingiva, trachea, tonsil, thymus, and peripheral blood. During differentiation of MUTZ-3 cells into Langerhans cells, expression of RTN1A mRNA and protein preceded established Langerhans cell markers CD1a and CD207, and RTN1A protein partially co-localized with the endoplasmic reticulum marker protein disulfide isomerase. In line with this observation, we found that RTN1A was expressed by around 80% of Langerhans cell precursors in human embryonic skin. Our findings show that RTN1A is a marker for cells of the dendritic lineage, including Langerhans cells and dermal dendritic cells. This unexpected finding will serve as a starting point for the elucidation of the, until now, elusive functional roles of RTN1A in both the immune and the nervous system.

Joint Guideline of the OEGGG, AGO, AGK and ÖGZ on the Diagnosis and Treatment of Cervical Intraepithelial Neoplasia and Appropriate Procedures When Cytological Specimens Are Unsatisfactory.

Purpose On January 1st, 2018, the ÖGZ (Austrian Society of Cytology) revised its cytological nomenclature to make it more similar to the 2015 Bethesda system. Following these changes, the Austrian Society of Gynecology and Obstetrics felt it necessary to revise the approach currently used in Austria to diagnose and treat CIN and to review the procedures to be followed when the quality of cytological specimens is unsatisfactory. It was not possible to adopt the German S3 guideline "Prevention of Cervical Cancer" in its entirety, because the Munich III gynecological cytology nomenclature used in Germany is not used in Austria. This made it necessary to compile a separate scientific opinion for Austria. Methodology The OEGGG worked together with the ÖGZ (Austrian Society for Cytology), AGO Austria (Austrian Working Group for Gynecological Oncology), the AGK (Colposcopy Working Group), and physicians representing gynecologists in private practice. The different scientific associations nominated representatives, who attended the various meetings. After an in-depth analysis of the recent literature, three meetings and numerous votes by telephone, we were able to achieve a consensus about the contents of this guideline. Recommendations The guideline provides recommendations for the diagnosis and treatment of CIN which take account of the gynecological cytology nomenclature used in Austria.