Clinicians' perspectives on gestational diabetes screening during the global COVID-19 pandemic in Australia.

AIM: There is no international consensus for the screening and diagnosis of gestational diabetes mellitus (GDM). In March 2020, modified screening and diagnostic recommendations were rapidly implemented in Queensland, Australia, in response to the COVID-19 pandemic. How clinicians perceived and used these changes can provide insights to support high-quality clinical practice and provide lessons for future policy changes. The aim of this study was to understand clinicians' perceptions and use of COVID-19 changes to GDM screening and diagnostic recommendations. METHODS: Queensland healthcare professionals responsible for diagnosing or caring for women with GDM were recruited for semi-structured telephone interviews. Data analysis of transcribed interviews used inductive reflexive thematic analysis. RESULTS: Seventeen interviews were conducted with the following participants: six midwives/nurses, three endocrinologists, two general practitioners, two general practitioners/obstetricians, two diabetes educators, one dietitian and one obstetrician. Three themes emerged: communication and implementation, perceptions and value of evidence and diversity in perceptions of GDM screening. Overall, clinicians welcomed the rapid changes during the initial uncertainty of the pandemic, but as COVID-19 became less of a threat to the Queensland healthcare system, some questioned the underlying evidence base. In areas where GDM was more prevalent, clinicians more frequently worried about missed diagnoses, whereas others who felt that overdiagnosis had occurred in the past continued to support the changes. CONCLUSIONS: These findings highlight the challenges to changing policy when clinicians have diverse (and often strongly held) views.

Quantitative Proteomics by SWATH-MS Suggest an Association Between Circulating Exosomes and Maternal Metabolic Changes in Gestational Diabetes Mellitus.

Several factors including placental hormones (PH) released from the human placenta have been associated with the development of insulin resistance and gestational diabetes mellitus (GDM). However, circulating levels of PH does not correlate well with maternal insulin sensitivity across gestation, suggesting that other, previously unrecognized, mechanisms may be involved. The levels of circulating exosomes are higher in GDM compared to normal. GDM derived exosomes produce greater release of pro-inflammatory cytokines from endothelial cells compared to exosomes from normal, suggesting that their contents may differ compared to normal pregnancies. Using a quantitative, information-independent acquisition (Sequential Windowed Acquisition of All Theoretical Mass Spectra [SWATH]) approach, differentially abundant circulating exosome proteins are identified in women with normal glucose tolerance (NGT) and GDM at the time of GDM diagnosis. A total of 78 statistically significant proteins in the relative expression of exosomal proteins in GDM are compared with NGT. Bioinformatic analysis shows that the exosomal proteins in GDM target pathways are mainly associated with energy production, inflammation, and metabolism. Finally, an independent cohort of patients is used to validate some of the proteins identified by SWATH. The data obtained may be of utility in elucidating the underlying physiological mechanisms associated with insulin resistance in GDM.

Human placental exosomes in gestational diabetes mellitus carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity.

There is increasing evidence that miRNAs, which are enriched in nanovesicles called exosomes, are important regulators of gene expression. When compared with normal pregnancies, pregnancies with gestational diabetes mellitus (GDM) are associated with skeletal muscle insulin resistance as well as increased levels of circulating placental exosomes. Here we investigated whether placental exosomes in GDM carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity. Exosomes were isolated from chorionic villous (CV) explants from both women with Normal Glucose Tolerant (NGT) and GDM pregnancies. Using miRNA sequencing, we identified a specific set of miRNAs selectively enriched with exosomes and compared with their cells of origin indicating a specific packaging of miRNAs into exosomes. Gene target and ontology analysis of miRNA differentially expressed in exosomes secreted in GDM compared with NGT are associated with pathways regulating cell migration and carbohydrate metabolism. We determined the expression of a selected set of miRNAs in placenta, plasma, and skeletal muscle biopsies from NGT and GDM. Interestingly, the expression of these miRNAs varied in a consistent pattern in the placenta, in circulating exosomes, and in skeletal muscle in GDM. Placental exosomes from GDM pregnancies decreased insulin-stimulated migration and glucose uptake in primary skeletal muscle cells obtained from patients with normal insulin sensitivity. Interestingly, placental exosomes from NGT increase migration and glucose uptake in response to insulin in skeletal muscle from diabetic subjects. These findings suggest that placental exosomes might have a role in the changes on insulin sensitivity in normal and GDM pregnancies.

Effect of birth weight on adulthood renal function: A bias-adjusted meta-analytic approach.

While the association between low birth weight (LBW; <2500 g) and development of adult chronic renal disease (CKD) is inconsistently reported, less information is available regarding association of high birth weight (HBW; ≥4000 g) with CKD. We undertook a systematic review and meta-analysis on studies published before 30 September 2015 and report associations between birth weight and renal function. Blood (glomerular filtration rate (GFR)) and urine (microalbuminuria/albumin excreation rate (AER)/urinary albumin creatinine ratio (ACR)) parameters were used to define CKD. Three different effect size estimates were used (odds ratio, regression coefficient and mean difference). The odds of developing CKD in the life course among those born LBW was 1.77 (95% CI: 1.42, 2.20) times and 1.68 (1.27, 2.33) times, assessed by blood and urine parameters respectively. Higher risk was also observed among Asian and Australian populations (blood: OR 2.68; urine: OR 2.28), individuals aged ≤30 years (blood: OR 2.30; urine: OR 1.26), and ≥50 years (blood: OR 3.66; urine: OR 3.10), people with diabetes (blood: OR 2.51), and aborigines (urine: OR 2.32). There was no significant association between HBW and CKD. For every 1 kg increase in BW, the estimated GFR increased by 2.09 mL/min per 1.73 m(2) (1.33-2.85), and it was negatively associated with LogACR (ß -0.07, 95% CI: -0.14, 0.00). LBW inborn had lower mean GFR -4.62 (-7.10, -2.14) compared with normal BW. Findings of this study suggest that LBW increased the risk of developing CKD, and HBW did not show any significant impact.

Reference intervals for plasma sulfate and urinary sulfate excretion in pregnancy.

BACKGROUND: Sulfate is important for fetal growth and development. During pregnancy, the fetus relies on sulfate from the maternal circulation. We report reference intervals for maternal plasma sulfate levels and fractional excretion index (FEI) for sulfate in pregnancy, as well as sulfate levels in cord blood from term pregnancies. METHODS: Plasma and urine were collected from 103 pregnant women of 10-20 weeks gestation and 106 pregnant women of 30-37 weeks gestation. Venous cord plasma was collected from 80 healthy term babies. Sulfate levels were measured by ion chromatography. Plasma and urinary creatinine levels were used to calculate FEI sulfate in pregnant women. Analyses provide reference intervals, and explored the relationship between maternal sulfate data with several prenatal factors. RESULTS: Median maternal plasma sulfate levels were 452 µmol/L and 502 µmol/L at 10-20 and 30-37 weeks gestation, respectively, and inversely correlated with FEI sulfate median values of 0.15 and 0.11. Overall reference intervals were 305-710 and 335-701 µmol/L (2.5th; 97.5th percentile; for 10-20 and 30-37 weeks gestation, respectively) for maternal plasma sulfate, and 0.06-0.31 and 0.05-0.28 for maternal FEI sulfate. Term venous cord plasma sulfate median levels were significantly (p = 0.038) higher in female babies (375 µmol/L) when compared to male babies (342 µmol/L), with an overall reference interval of 175-603 µmol/L. CONCLUSIONS: We provide the first reference intervals for maternal plasma sulfate levels and FEI sulfate, as well as cord plasma sulfate levels. These findings provide reference data for further studies of sulfate levels in both mother and child.

Changing the protocol for gestational diabetes mellitus screening.

BACKGROUND: Gestational diabetes mellitus (GDM) affects 5-8% of pregnant women in Australia and is linked to adverse maternal and neonatal outcomes. Earlier diagnosis and treatment has been suggested to improve these outcomes. AIM: To describe the experience of a change in GDM screening policy at a large tertiary hospital. MATERIALS AND METHODS: A 6-month audit was performed following a policy change involving introduction of screening for all women early in pregnancy (by either random blood glucose level (BGL) or oral glucose tolerance testing (OGTT), depending on their perceived risk of developing GDM), followed by universal OGTT at 26-28 weeks' gestation. The prevalence of GDM (including changes expected from new Australasian Diabetes in Pregnancy Society (ADIPS) criteria), maternal and neonatal outcomes and adherence to new screening policy are reported. RESULTS: The prevalence of GDM was 7.9% (1.6% early, 6.3% later diagnoses). More women with early diagnoses required insulin. Early testing with random BGL for low-risk women only identified 1.7% of those with GDM. Early OGTT for high-risk women identified 24.9% of GDM diagnoses. Adherence to the new screening protocol was generally poor, with 26% adherence at booking, 64% at 26 weeks' gestation and 27% with unknown GDM status. CONCLUSIONS: While early testing with OGTT for high-risk women may be helpful, the value of early testing with random BGL for low-risk women is questionable. The new ADIPS criteria are likely to increase the number of women diagnosed with GDM (with an emphasis on earlier diagnosis), but the absolute increase remains small.

Hypertensive disorders of pregnancy and long-term cardiovascular health: FIGO Best Practice Advice.

Hypertensive disorders of pregnancy (HDP) are the most common causes of maternal and perinatal morbidity and mortality. They are responsible for 16% of maternal deaths in high-income countries and approximately 25% in low- and middle-income countries. The impact of HDP can be lifelong as they are a recognized risk factor for future cardiovascular disease. During pregnancy, the cardiovascular system undergoes significant adaptive changes that ensure adequate uteroplacental blood flow and exchange of oxygen and nutrients to nurture and accommodate the developing fetus. Failure to achieve normal cardiovascular adaptation is associated with the development of HDP. Hemodynamic alterations in women with a history of HDP can persist for years and predispose to long-term cardiovascular morbidity and mortality. Therefore, pregnancy and the postpartum period are an opportunity to identify women with underlying, often unrecognized, cardiovascular risk factors. It is important to develop strategies with lifestyle and therapeutic interventions to reduce the risk of future cardiovascular disease in those who have a history of HDP.

Management of obesity across women's life course: FIGO Best Practice Advice.

Obesity is a chronic, progressive, relapsing, and treatable multifactorial, neurobehavioral disease. According to the World Health Organization, obesity affects 15% of women and has long-term effects on women's health. The focus of care in patients with obesity should be on optimizing health outcomes rather than on weight loss. Appropriate and common language, considering cultural sensitivity and trauma-informed care, is needed to discuss obesity. Pregnancy is a time of significant physiological change. Pre-, ante-, and postpartum clinical encounters provide opportunities for health optimization for parents with obesity in terms of, but not limited to, fertility and breastfeeding. Pre-existing conditions may also be identified and managed. Beyond pregnancy, women with obesity are at an increased risk for gastrointestinal and liver diseases, impaired kidney function, obstructive sleep apnea, and venous thromboembolism. Gynecological and reproductive health of women living with obesity cannot be dismissed, with accommodations needed for preventive health screenings and consideration of increased risk for gynecologic malignancies. Mental wellness, specifically depression, should be screened and managed appropriately. Obesity is a complex condition and is increasing in prevalence with failure of public health interventions to achieve significant decrease. Future research efforts should focus on interprofessional care and discovering effective interventions for health optimization.

Using FIGO Nutrition Checklist counselling in pregnancy: A review to support healthcare professionals.

The period before and during pregnancy is increasingly recognized as an important stage for addressing malnutrition. This can help to reduce the risk of noncommunicable diseases in mothers and passage of risk to their infants. The FIGO Nutrition Checklist is a tool designed to address these issues. The checklist contains questions on specific dietary requirements, body mass index, diet quality, and micronutrients. Through answering these questions, awareness is generated, potential risks are identified, and information is collected that can inform health-promoting conversations between women and their healthcare professionals. The tool can be used across a range of health settings, regions, and life stages. The aim of this review is to summarize nutritional recommendations related to the FIGO Nutrition Checklist to support healthcare providers using it in practice. Included is a selection of global dietary recommendations for each of the components of the checklist and practical insights from countries that have used it. Implementation of the FIGO Nutrition Checklist will help identify potential nutritional deficiencies in women so that they can be addressed by healthcare providers. This has potential longstanding benefits for mothers and their children, across generations.

Pregnancy as an opportunity to prevent type 2 diabetes mellitus: FIGO Best Practice Advice.

Gestational diabetes (GDM) impacts approximately 17 million pregnancies worldwide. Women with a history of GDM have an 8-10-fold higher risk of developing type 2 diabetes and a 2-fold higher risk of developing cardiovascular disease (CVD) compared with women without prior GDM. Although it is possible to prevent and/or delay progression of GDM to type 2 diabetes, this is not widely undertaken. Considering the increasing global rates of type 2 diabetes and CVD in women, it is essential to utilize pregnancy as an opportunity to identify women at risk and initiate preventive intervention. This article reviews existing clinical guidelines for postpartum identification and management of women with previous GDM and identifies key recommendations for the prevention and/or delayed progression to type 2 diabetes for global clinical practice.

Major risk factors for stillbirth in high-income countries: a systematic review and meta-analysis.

BACKGROUND: Stillbirth rates in high-income countries have shown little or no improvement over the past two decades. Prevention strategies that target risk factors could be important in rate reduction. This systematic review and meta-analysis was done to identify priority areas for stillbirth prevention relevant to those countries. METHODS: Population-based studies addressing risk factors for stillbirth were identified through database searches. The factors most frequently reported were identified and selected according to whether they could potentially be reduced through lifestyle or medical intervention. The numbers attributable to modifiable risk factors were calculated from data relating to the five high-income countries with the highest numbers of stillbirths and where all the data required for analysis were available. Odds ratios were calculated for selected risk factors, from which population-attributable risk (PAR) values were calculated. FINDINGS: Of 6963 studies initially identified, 96 population-based studies were included. Maternal overweight and obesity (body-mass index >25 kg/m(2)) was the highest ranking modifiable risk factor, with PARs of 8-18% across the five countries and contributing to around 8000 stillbirths (≥22 weeks' gestation) annually across all high-income countries. Advanced maternal age (>35 years) and maternal smoking yielded PARs of 7-11% and 4-7%, respectively, and each year contribute to more than 4200 and 2800 stillbirths, respectively, across all high-income countries. In disadvantaged populations maternal smoking could contribute to 20% of stillbirths. Primiparity contributes to around 15% of stillbirths. Of the pregnancy disorders, small size for gestational age and abruption are the highest PARs (23% and 15%, respectively), which highlights the notable role of placental pathology in stillbirth. Pre-existing diabetes and hypertension remain important contributors to stillbirth in such countries. INTERPRETATION: The raising of awareness and implementation of effective interventions for modifiable risk factors, such as overweight, obesity, maternal age, and smoking, are priorities for stillbirth prevention in high-income countries. FUNDING: The Stillbirth Foundation Australia, the Department of Health and Ageing, Canberra, Australia, and the Mater Foundation, Brisbane, Australia.

Cost-effectiveness of gestational diabetes screening including prevention of type 2 diabetes: application of the GeDiForCE model in Australia.

AIMS: Gestational diabetes mellitus (GDM) is associated with an increased risk of perinatal complications and of developing type 2 diabetes mellitus (T2DM). A strategy including universal screening following new evidence-based thresholds recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) combined with antenatal care and postpartum lifestyle management could reduce these risks. This new strategy has been endorsed by the Australasian Diabetes in Pregnancy Society (ADIPS) following evidence that showed previous diagnostic thresholds were too high to prevent perinatal adverse events (PAEs) and subsequent T2DM. This study therefore aimed to assess the cost-effectiveness of the new ADIPS GDM strategy in Australia. METHODS: A decision tree model (GeDiForCE) was applied in this study. Our analysis modifies the model and optimizes resource use and cost parameters, to reflect real costs within the Australian context. Data on Australian GDM and T2DM epidemiology, intervention costs and literature were used to estimate model parameters. Costs (in AUD $), averted disability-adjusted life years (DALYs) and net cost per DALY averted during life-time horizon were calculated. Sensitivity analyses were also conducted, by testing the impact of variations in key input variables. RESULTS: Compared to the previous criteria, the new ADIPS strategy costs AUD $20,671 (USD $15,839) per DALY averted in the base case, however sensitivity analyses reveal it is dominant in over half of cases and has a 86% chance of being dominant and/or cost-effective according to WTP threshold of $151,200 international dollars ($I) or $AUD 217,576 per DALY averted (equal to three times per capita GDP). Compared with no screening or treatment, the new ADIPS strategy saves AUD $25,509 (USD $19,547) per DALY averted. CONCLUSIONS: Using local data and literature estimates, this study shows that use of the new Australian Diabetes In Pregnancy Society gestional diabetes mellitus strategy would lead to cost saving care for pregnant women in Australia when compared to a no screening scenario and is likely to be cost effective when compared to previously used criteria.

Hyperglycemia in Pregnancy and Women's Health in the 21st Century.

Hyperglycemia is the commonest medical condition affecting pregnancy and its incidence is increasing globally in parallel with the twin epidemics of diabetes and obesity. Both pre-pregnancy diabetes and gestational diabetes are associated with short term pregnancy complications, with the risk of immediate complications generally broadly rising with more severe hyperglycemia. In this article we firstly consider these risks and their optimal management during pregnancy and then broaden our scope to consider the long-term implications of hyperglycemia in pregnancy as it relates to overall maternal and offspring health in a life course perspective.

Hyperglycemia and adverse pregnancy outcomes.

BACKGROUND: It is controversial whether maternal hyperglycemia less severe than that in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes. METHODS: A total of 25,505 pregnant women at 15 centers in nine countries underwent 75-g oral glucose-tolerance testing at 24 to 32 weeks of gestation. Data remained blinded if the fasting plasma glucose level was 105 mg per deciliter (5.8 mmol per liter) or less and the 2-hour plasma glucose level was 200 mg per deciliter (11.1 mmol per liter) or less. Primary outcomes were birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinically diagnosed neonatal hypoglycemia, and cord-blood serum C-peptide level above the 90th percentile. Secondary outcomes were delivery before 37 weeks of gestation, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia. RESULTS: For the 23,316 participants with blinded data, we calculated adjusted odds ratios for adverse pregnancy outcomes associated with an increase in the fasting plasma glucose level of 1 SD (6.9 mg per deciliter [0.4 mmol per liter]), an increase in the 1-hour plasma glucose level of 1 SD (30.9 mg per deciliter [1.7 mmol per liter]), and an increase in the 2-hour plasma glucose level of 1 SD (23.5 mg per deciliter [1.3 mmol per liter]). For birth weight above the 90th percentile, the odds ratios were 1.38 (95% confidence interval [CI], 1.32 to 1.44), 1.46 (1.39 to 1.53), and 1.38 (1.32 to 1.44), respectively; for cord-blood serum C-peptide level above the 90th percentile, 1.55 (95% CI, 1.47 to 1.64), 1.46 (1.38 to 1.54), and 1.37 (1.30 to 1.44); for primary cesarean delivery, 1.11 (95% CI, 1.06 to 1.15), 1.10 (1.06 to 1.15), and 1.08 (1.03 to 1.12); and for neonatal hypoglycemia, 1.08 (95% CI, 0.98 to 1.19), 1.13 (1.03 to 1.26), and 1.10 (1.00 to 1.12). There were no obvious thresholds at which risks increased. Significant associations were also observed for secondary outcomes, although these tended to be weaker. CONCLUSIONS: Our results indicate strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased birth weight and increased cord-blood serum C-peptide levels.

Relationship between obesity and lower rates of breast feeding initiation in regional Victoria, Australia: an 8-year retrospective panel study.

OBJECTIVES: Using routinely collected hospital data, this study explored secular trends over time in breast feeding initiation in a large Australian sample. The association between obesity and not breast feeding was investigated utilising a generalised estimating equations logistic regression that adjusted for sociodemographics, antenatal, intrapartum and postpartum conditions, mode of delivery and infant's-related covariates. DESIGN: Population-based retrospective panel. SETTING: A regional hospital that serves 26% of Victoria's 6.5 million population in Australia. PARTICIPANTS: All women experiencing live births between 2010 and 2017 were included. Women with missing body mass index (BMI) were excluded. RESULTS: A total of 7491 women contributed to 10 234 live births. At baseline, 57.2% of the women were overweight or obese, with obesity increasing over 8 years by 12.8%, p=0.001. Although, breast feeding increased over time, observed in all socioeconomic status (SES) and BMI categories, the lowest proportions were consistently found among the obese and morbidly obese (78.9% vs 87.1% in non-obese mothers, p<0.001). In the multivariable analysis, risk of not breast feeding was associated with higher BMI, teenage motherhood, smoking, belonging to the lowest SES class, gravidity >4 and undergoing an assisted vaginal or caesarean delivery. Compared with women with a normal weight, the obese and morbidly obese were 66% (OR 1.66, 95% CI 1.40 to 1.96, p<0.001) to 2.6 times (OR 2.61, 95% CI 2.07 to 3.29, p<0.001) less likely to breast feed, respectively. The detected dose-response effect between higher BMI and lower breast feeding was not explained by any of the study covariates. CONCLUSION: This study provides evidence of increasing breast feeding proportions in regional Victoria over the past decade. However, these proportions were lowest among the obese and morbidly obese and those coming from the most disadvantaged backgrounds suggesting the need for targeted interventions to support breast feeding among these groups. The psychosocial and physiological associations between obesity and breast feeding should further be investigated.

Early life predictors of development of blood pressure from childhood to adulthood: Evidence from a 30-year longitudinal birth cohort study.

BACKGROUND AND AIMS: The early life predictors of changes in the blood pressures of offspring between childhood and young adulthood have not been well defined. Thus, this study aimed to determine the life course association of offspring's blood pressure with prenatal and early infancy lifestyle, and other factors taking advantage of a large community-based, longitudinal study of a birth cohort in Australia - the MUSP study. METHODS: The systolic and diastolic blood pressure (SBP, DBP) was measured for 3793, 3782, 2628 and 1780 offspring of the Australian longitudinal cohort study at 5, 14, 21 and 30 years of their age, respectively. Individual PP and mean arterial pressure (MAP) was equated, and Generalized Estimating Equations with time (age) and predictor interaction modelling were performed. RESULTS: Blood pressures of the offspring increased significantly between 5 and 30 years. Early life factors such as pre-pregnancy overweight/obesity, and hypertensive disorder in pregnancy were significantly positively associated, and duration of gestation and pre-pregnancy thinness of the mothers negatively associated with this life course increase in the offspring's blood pressure. Rapid increase in body weight from birth to 5 years had a strong association with increasing blood pressures components throughout their life course. CONCLUSIONS: Several maternal pre-pregnancy and pregnancy factors along with the early life growth characteristics of offspring are important predictors of increase in blood pressure of the offspring from their childhood to adulthood.

Type 2 Diabetes in Pregnancy.

Hyperglycemia is common during pregnancy, involving multisystem adaptations. Pregnancy-induced metabolic changes increase insulin resistance. Pregnancy-induced insulin resistance adds to preexisting insulin resistance. Preexisting pancreatic ß-cell defect compromises the ability to enhance insulin secretion, leading to hyperglycemia. Women with type 2 DM have similar rates of major congenital malformations, stillbirth, and neonatal mortality, but an even higher risk of perinatal mortality. In utero type 2 DM exposure confers greater risk and reduces time to development of type 2 DM in offspring. Preconception care to improve metabolic control in women with type 2 diabetes is critical.

Renal insufficiency among urban populations in Bangladesh: A decade of laboratory-based observations.

OBJECTIVE: The objective of this study was to describe the age and sex-specific prevalence of renal insufficiency, and observe its trends over a decade at an urban Bangladesh setup. METHOD: This was a cross-sectional study, in which we observed the Estimated Glomerular Filtration Rate (eGFR) of 218,888 adults, aged ≥19 years, who had submitted their blood specimen to the Clinical Biochemistry Laboratory of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) during the years 2006-2015. We applied CKD-EPI definition in estimating eGFR using their age-and sex-specific serum creatinine concentrations. Based on the eGFR, we classified the population into five stages of renal insufficiency (stage-1 to stage-5), at age intervals of five-years. Data were analysed using the Linear Regression and Multinomial Logistic Regression models. RESULTS: Females constituted 43% (n = 94,931) of the study population; and 34% (n = 42,576) of the males and 31% (n = 29,830) of the females had their serum creatinine concentrations above the upper limit of the laboratory reference cut-off. The overall prevalence of stage-2 to stage-5 renal insufficiency were 24% (n = 52,126), 17% (n = 38,539), 8% (n = 16,504) and 6% (n = 12,665) respectively; the prevalence were 23% (n = 1,890), 19% (n = 1,579), 9% (n = 769) and 9% (n = 770) respectively in 2006, and 24% (n = 10,062), 17% (n = 6,903), 6% (n = 2,537) and 5% (n = 1,924) respectively in 2015. The prevalence was higher among the females. At least 2% of the adults, younger than <44 years, had stage-4 and stage-5 in 2015. The age-adjusted eGFR was significantly lower among the post-menopausal females (aged ≥46 y) compared to the same age group males (64.08±10.83 vs. 66.83±10.41 mL/min/1.73 m2; p<0.001). Compared to 2006, the number of individuals with renal insufficiency (stage 2 and above) had increased at least two times, irrespective of age, in 2015. A single year of increase in the age was significantly associated with 1.32 unit reductions in the eGFR; and the reductions were higher for females who also had higher odds of renal insufficiency stages-2 and beyond. CONCLUSION: This study observed high prevalence of stage-2 to stage-5 renal insufficiency in Bangladeshi populations, irrespective of age, and especially among the females.

Adipose Tissue Exosomal Proteomic Profile Reveals a Role on Placenta Glucose Metabolism in Gestational Diabetes Mellitus.

CONTEXT: Molecules produced by adipose tissue (AT) function as an endocrine link between maternal AT and fetal growth by regulating placental function in normal women and women with gestational diabetes mellitus (GDM). OBJECTIVE: We hypothesized that AT-derived exosomes (exo-AT) from women with GDM would carry a specific set of proteins that influences glucose metabolism in the placenta. DESIGN: Exosomes were isolated from omental AT-conditioned media from normal glucose tolerant (NGT) pregnant women (n = 65) and pregnant women with GDM (n = 82). Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry was used to construct a small ion library from AT and exosomal proteins, followed by ingenuity pathway analysis to determine the canonical pathways and biofunctions. The effect of exosomes on human placental cells was determined using a Human Glucose Metabolism RT2 Profiler PCR array. RESULTS: The number of exosomes (vesicles/µg of tissue/24 hours) was substantially (1.7-fold) greater in GDM than in NGT, and the number of exosomes correlated positively with the birthweight Z score. Ingenuity pathway analysis of the exosomal proteins revealed differential expression of the proteins targeting the sirtuin signaling pathway, oxidative phosphorylation, and mechanistic target of rapamycin signaling pathway in GDM compared with NGT. GDM exo-AT increased the expression of genes associated with glycolysis and gluconeogenesis in placental cells compared with the effect of NGT exo-AT. CONCLUSIONS: Our findings are consistent with the possibility that AT exosomes play an important role in mediating the changes in placental function in GDM and might be responsible for some of the adverse consequences in this pregnancy complication, such as fetal overgrowth.

The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention.

Pre­eclampsia (PE) is a multisystem disorder that typically affects 2%­5% of pregnant women and is one of the leading causes of maternal and perinatal morbidity and mortality, especially when the condition is of early onset. Globally, 76 000 women and 500 000 babies die each year from this disorder. Furthermore, women in low­resource countries are at a higher risk of developing PE compared with those in high­resource countries. Although a complete understanding of the pathogenesis of PE remains unclear, the current theory suggests a two­stage process. The first stage is caused by shallow invasion of the trophoblast, resulting in inadequate remodeling of the spiral arteries. This is presumed to lead to the second stage, which involves the maternal response to endothelial dysfunction and imbalance between angiogenic and antiangiogenic factors, resulting in the clinical features of the disorder. Accurate prediction and uniform prevention continue to elude us. The quest to effectively predict PE in the first trimester of pregnancy is fueled by the desire to identify women who are at high risk of developing PE, so that necessary measures can be initiated early enough to improve placentation and thus prevent or at least reduce the frequency of its occurrence. Furthermore, identification of an "at risk" group will allow tailored prenatal surveillance to anticipate and recognize the onset of the clinical syndrome and manage it promptly. PE has been previously defined as the onset of hypertension accompanied by significant proteinuria after 20 weeks of gestation. Recently, the definition of PE has been broadened. Now the internationally agreed definition of PE is the one proposed by the International Society for the Study of Hypertension in Pregnancy (ISSHP). According to the ISSHP, PE is defined as systolic blood pressure at ≥140 mm Hg and/or diastolic blood pressure at ≥90 mm Hg on at least two occasions measured 4 hours apart in previously normotensive women and is accompanied by one or more of the following new­onset conditions at or after 20 weeks of gestation: 1.Proteinuria (i.e. ≥30 mg/mol protein:creatinine ratio; ≥300 mg/24 hour; or ≥2 + dipstick); 2.Evidence of other maternal organ dysfunction, including: acute kidney injury (creatinine ≥90 µmol/L; 1 mg/dL); liver involvement (elevated transaminases, e.g. alanine aminotransferase or aspartate aminotransferase >40 IU/L) with or without right upper quadrant or epigastric abdominal pain; neurological complications (e.g. eclampsia, altered mental status, blindness, stroke, clonus, severe headaches, and persistent visual scotomata); or hematological complications (thrombocytopenia­platelet count <150 000/µL, disseminated intravascular coagulation, hemolysis); or 3.Uteroplacental dysfunction (such as fetal growth restriction, abnormal umbilical artery Doppler waveform analysis, or stillbirth). It is well established that a number of maternal risk factors are associated with the development of PE: advanced maternal age; nulliparity; previous history of PE; short and long interpregnancy interval; use of assisted reproductive technologies; family history of PE; obesity; Afro­Caribbean and South Asian racial origin; co­morbid medical conditions including hyperglycemia in pregnancy; pre­existing chronic hypertension; renal disease; and autoimmune diseases, such as systemic lupus erythematosus and antiphospholipid syndrome. These risk factors have been described by various professional organizations for the identification of women at risk of PE; however, this approach to screening is inadequate for effective prediction of PE. PE can be subclassified into: 1.Early­onset PE (with delivery at <34+0 weeks of gestation); 2.Preterm PE (with delivery at <37+0 weeks of gestation); 3.Late­onset PE (with delivery at ≥34+0 weeks of gestation); 4.Term PE (with delivery at ≥37+0 weeks of gestation). These subclassifications are not mutually exclusive. Early­onset PE is associated with a much higher risk of short­ and long­term maternal and perinatal morbidity and mortality. Obstetricians managing women with preterm PE are faced with the challenge of balancing the need to achieve fetal maturation in utero with the risks to the mother and fetus of continuing the pregnancy longer. These risks include progression to eclampsia, development of placental abruption and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. On the other hand, preterm delivery is associated with higher infant mortality rates and increased morbidity resulting from small for gestational age (SGA), thrombocytopenia, bronchopulmonary dysplasia, cerebral palsy, and an increased risk of various chronic diseases in adult life, particularly type 2 diabetes, cardiovascular disease, and obesity. Women who have experienced PE may also face additional health problems in later life, as the condition is associated with an increased risk of death from future cardiovascular disease, hypertension, stroke, renal impairment, metabolic syndrome, and diabetes. The life expectancy of women who developed preterm PE is reduced on average by 10 years. There is also significant impact on the infants in the long term, such as increased risks of insulin resistance, diabetes mellitus, coronary artery disease, and hypertension in infants born to pre­eclamptic women. The International Federation of Gynecology and Obstetrics (FIGO) brought together international experts to discuss and evaluate current knowledge on PE and develop a document to frame the issues and suggest key actions to address the health burden posed by PE. FIGO's objectives, as outlined in this document, are: (1) To raise awareness of the links between PE and poor maternal and perinatal outcomes, as well as to the future health risks to mother and offspring, and demand a clearly defined global health agenda to tackle this issue; and (2) To create a consensus document that provides guidance for the first­trimester screening and prevention of preterm PE, and to disseminate and encourage its use. Based on high­quality evidence, the document outlines current global standards for the first­trimester screening and prevention of preterm PE, which is in line with FIGO good clinical practice advice on first trimester screening and prevention of pre­eclampsia in singleton pregnancy.1 It provides both the best and the most pragmatic recommendations according to the level of acceptability, feasibility, and ease of implementation that have the potential to produce the most significant impact in different resource settings. Suggestions are provided for a variety of different regional and resource settings based on their financial, human, and infrastructure resources, as well as for research priorities to bridge the current knowledge and evidence gap. To deal with the issue of PE, FIGO recommends the following: Public health focus: There should be greater international attention given to PE and to the links between maternal health and noncommunicable diseases (NCDs) on the Sustainable Developmental Goals agenda. Public health measures to increase awareness, access, affordability, and acceptance of preconception counselling, and prenatal and postnatal services for women of reproductive age should be prioritized. Greater efforts are required to raise awareness of the benefits of early prenatal visits targeted at reproductive­aged women, particularly in low­resource countries. Universal screening: All pregnant women should be screened for preterm PE during early pregnancy by the first­trimester combined test with maternal risk factors and biomarkers as a one­step procedure. The risk calculator is available free of charge at https://fetalmedicine.org/research/assess/preeclampsia. FIGO encourages all countries and its member associations to adopt and promote strategies to ensure this. The best combined test is one that includes maternal risk factors, measurements of mean arterial pressure (MAP), serum placental growth factor (PLGF), and uterine artery pulsatility index (UTPI). Where it is not possible to measure PLGF and/or UTPI, the baseline screening test should be a combination of maternal risk factors with MAP, and not maternal risk factors alone. If maternal serum pregnancy­associated plasma protein A (PAPP­A) is measured for routine first­trimester screening for fetal aneuploidies, the result can be included for PE risk assessment. Variations to the full combined test would lead to a reduction in the performance screening. A woman is considered high risk when the risk is 1 in 100 or more based on the first­trimester combined test with maternal risk factors, MAP, PLGF, and UTPI. Contingent screening: Where resources are limited, routine screening for preterm PE by maternal factors and MAP in all pregnancies and reserving measurements of PLGF and UTPI for a subgroup of the population (selected on the basis of the risk derived from screening by maternal factors and MAP) can be considered. Prophylactic measures: Following first­trimester screening for preterm PE, women identified at high risk should receive aspirin prophylaxis commencing at 11­14+6 weeks of gestation at a dose of ~150 mg to be taken every night until 36 weeks of gestation, when delivery occurs, or when PE is diagnosed. Low­dose aspirin should not be prescribed to all pregnant women. In women with low calcium intake (<800 mg/d), either calcium replacement (≤1 g elemental calcium/d) or calcium supplementation (1.5­2 g elemental calcium/d) may reduce the burden of both early­ and late­onset PE.