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.

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.

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.

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.

Assessment of glucose regulation in pregnancy after gastric bypass surgery.

AIMS/HYPOTHESIS: Roux-en-Y gastric bypass (RYGB) surgery is characterised by glycaemic variability. Prospective studies of glucose metabolism in pregnancy after RYGB are not available, therefore this study aimed to evaluate physiological alterations in glucose metabolism in pregnancy following RYGB. METHODS: Sixty-three pregnant women (25 who underwent RYGB, 19 non-operated obese control women and 19 normal weight control women) were included. Frequently sampled 3 h OGTTs and 1 h IVGTTs were performed between 24 and 28 weeks of gestation and, in a subgroup, were repeated at 3-6 months after delivery. RESULTS: We observed major alterations in glucose kinetics during the OGTT, including an early increase in plasma glucose followed by hypoglycaemia in 90% of women who had previously undergone RYGB. The higher degree of glycaemic variability in this group was accompanied by increased insulin, C-peptide and glucagon concentrations after oral glucose load, whereas no differences in insulin response were observed after parenteral glucose administration (RYGB vs normal weight). IVGTT data suggested improved insulin sensitivity (mean difference 0.226 × 10-4 min-1 [pmol/l]-1 [95% CI 0.104, 0.348]; p < 0.001) and disposition index in pregnancies after RYGB when compared with obese control women. However, subtle alterations in insulin action and beta cell function were still observed when comparing women who had undergone RYGB with the normal-weight control group. Moreover, we observed that fetal growth was associated with maternal glucose nadir levels and insulin secretion in offspring of those who had previously undergone RYGB. CONCLUSIONS/INTERPRETATION: Pregnancies after RYGB are affected by altered postprandial glucose, insulin and C-peptide dynamics. Insulin sensitivity is improved by RYGB, although subtle alterations in beta cell function are observed. Longitudinal studies are needed to assess potential consequences for fetal development and pregnancy outcomes.

Altered glucose profiles and risk for hypoglycaemia during oral glucose tolerance testing in pregnancies after gastric bypass surgery.

AIMS/HYPOTHESIS: A history of gastric bypass surgery can influence the results of the OGTT recommended during pregnancy. Therefore, we compared OGTT glucose kinetics and pregnancy outcome between pregnant gastric bypass patients and BMI-matched, lean and obese controls. METHODS: Medical records were used to collect data on glucose measurements during the 2 h 75 g OGTT as well as on pregnancy and fetal outcome for 304 women (n = 76 per group, matched for age and date of delivery). RESULTS: Women after bariatric surgery had lower fasting glucose levels compared with lean, obese and BMI-matched controls, and showed altered postprandial glucose kinetics, including a rise at 60 min followed by hypoglycaemia with serum glucose of <3.34 mmol/l (which occurred in 54.8%). Moreover, their risk of pre-eclampsia or gestational hypertension was reduced, with an increased risk of delivering small for gestational age infants. CONCLUSIONS/INTERPRETATION: Alternative strategies to accurately define impaired glucose metabolism in pregnancies after bariatric surgery should be explored.

Human embryonic epidermis contains a diverse Langerhans cell precursor pool.

Despite intense efforts, the exact phenotype of the epidermal Langerhans cell (LC) precursors during human ontogeny has not been determined yet. These elusive precursors are believed to migrate into the embryonic skin and to express primitive surface markers, including CD36, but not typical LC markers such as CD1a, CD1c and CD207. The aim of this study was to further characterize the phenotype of LC precursors in human embryonic epidermis and to compare it with that of LCs in healthy adult skin. We found that epidermal leukocytes in first trimester human skin are negative for CD34 and heterogeneous with regard to the expression of CD1c, CD14 and CD36, thus contrasting the phenotypic uniformity of epidermal LCs in adult skin. These data indicate that LC precursors colonize the developing epidermis in an undifferentiated state, where they acquire the definitive LC marker profile with time. Using a human three-dimensional full-thickness skin model to mimic in vivo LC development, we found that FACS-sorted, CD207(-) cord blood-derived haematopoietic precursor cells resembling foetal LC precursors but not CD14(+)CD16(-) blood monocytes integrate into skin equivalents, and without additional exogenous cytokines give rise to cells that morphologically and phenotypically resemble LCs. Overall, it appears that CD14(-) haematopoietic precursors possess a much higher differentiation potential than CD14(+) precursor cells.

Development of Blood and Lymphatic Endothelial Cells in Embryonic and Fetal Human Skin.

Blood and lymphatic vessels provide nutrients for the skin and fulfill important homeostatic functions, such as the regulation of immunologic processes. In this study, we investigated the development of blood and lymphatic endothelial cells in prenatal human skin in situ using multicolor immunofluorescence and analyzed angiogenic molecules by protein arrays of lysates and cell culture supernatants. We found that at 8 to 10 weeks of estimated gestational age, CD144(+) vessels predominantly express the venous endothelial cell marker PAL-E, whereas CD144(+)PAL-E(-) vessels compatible with arteries only appear at the end of the first trimester. Lymphatic progenitor cells at 8 weeks of estimated gestational age express CD31, CD144, Prox1, and temporary PAL-E. At that developmental stage not all lymphatic progenitor cells express podoplanin or Lyve-1, which are acquired with advancing gestational age in a stepwise fashion. Already in second-trimester human skin, the phenotype of blood and lymphatic vessels roughly resembles the one in adult skin. The expression pattern of angiogenic molecules in lysates and cell culture supernatants of prenatal skin did not reveal the expected bent to proangiogenic molecules, indicating a complex regulation of angiogenesis during ontogeny. In summary, this study provides enticing new insights into the development and phenotypic characteristics of the vascular system in human prenatal skin.

The predictive value of sequential cervical length screening in singleton pregnancies after cerclage: a retrospective cohort study.

BACKGROUND: There are few valid predictors for preterm delivery after cerclage. Experience with a screening program that included four sequential cervical length measurements in singleton pregnancies after cerclage is reviewed. METHODS: In this retrospective cohort study, 88 singleton pregnancies after cerclage were included. Cervical length (CL) measurements were performed perioperatively and at weeks 16 + 0, 18 + 0, 20 + 0, and 22 + 0 by transvaginal ultrasound. Predictive factors for early preterm delivery included patient characteristics, obstetric history and CL measurements and were analyzed separately for women with ultrasound-indicated cerclage and those with history-indicated cerclage. Women with emergency cerclage were excluded. RESULTS: In women with delivery <35 weeks, CL declined from the 16 + 0 to the 22 + 0 weeks of gestation (p = 0.009). In univariate analysis, all CL measurements were predictive for delivery <35 weeks in women who underwent ultrasound-indicated cerclage and in women who received a history-indicated cerclage, whereas in multivariate analysis only CL three to six days after cerclage remained significant (odds ratio 0.85, 95% CI 0.73-0.98). In women with ultrasound-indicated cerclage, optimized cut-off was ≤ 20 mm (specificity 83.8%, sensitivity 84.2%). CONCLUSIONS: CL measured three to six days after cerclage placement provides the best information about the risk for delivery <35 weeks.

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.

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.

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.

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.

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.

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.

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.

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.

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.