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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.

The optimal process for detecting and treating gestational diabetes mellitus (GDM) remains controversial, with wide variances in practice within and between countries. A recent pragmatic randomized controlled trial (RCT) undertaken by Hillier et al. [1] in the USA has raised renewed worldwide interest in and discussion of GDM diagnosis.

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.

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.

To assess associations of hyperglycemia in pregnancy with the risk of postpartum hemorrhage (PPH) in a prospective cohort of Indigenous and non-Indigenous women, compared with normoglycemia.Data were from 1102 (48% Indigenous) women of the Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study. Age-adjusted associations of gestational diabetes mellitus (GDM) or pre-existing type 2 diabetes mellitus (T2DM), obstetric and demographic covariables with PPH (blood loss ≥500 ml) were assessed using logistic regression. Multivariable-adjusted models included Indigenous ethnicity, diabetes type and their interaction.A higher proportion of Indigenous women developed PPH than non-Indigenous women (32% versus 22%; P 0.001). Compared with non-Indigenous women with normoglycemia, risks of PPH for Indigenous women with GDM or T2DM were higher (odds ratio [OR] 1.83, 95% confidence intervals [CI] 1.11-3.02, and OR 1.72, 95% CI 0.99-3.00 after age adjustment, OR 1.84, 95% CI 1.06-3.19, and OR 1.33, 95% CI 0.70-2.54 after adjustment for school education and delivery mode, and OR 1.62, 95% CI 0.95-2.77, and OR 0.99, 95% CI 0.53-1.86 after adjustment for birth weight). Importantly, Indigenous women without hyperglycemia in pregnancy were not at increased risk of PPH.The significantly higher rates of PPH experienced by Indigenous women compared with non-Indigenous women may be explained by a greater effect of GDM among Indigenous women that was only partly accounted for by birth weight.

Background Aboriginal and Torres Strait Islander women experience high rates of diabetes in pregnancy (DIP), contributing to health risks for mother and infant, and the intergenerational cycle of diabetes. By enhancing diabetes management during pregnancy, postpartum and the interval between pregnancies, the DIP Partnership aims to improve health outcomes and reduce risks early in the life-course. We describe a mixed methods formative study of health professional’s perspectives of antenatal and post-partum diabetes screening and management, including enablers and barriers to care. Methods Health professionals involved in providing diabetes care in pregnancy, from a range of health services across the Northern Territory, completed the survey (n = 82) and/or took part in interviews and/or focus groups (n = 62). Results Qualitative findings highlighted factors influencing the delivery of care as reported by health professionals, including: whose responsibility it is, access to care, the baby is the focus and pre-conception care. The main challenges were related to: disjointed systems and confusion around whose role it is to provide follow-up care beyond six weeks post-partum. Quantitative findings indicated that the majority of health professionals reported confidence in their own skills to manage women in the antenatal period (62%, 40/79) and slightly lower rates of confidence in the postpartum interval (57%, 33/58). Conclusion These findings regarding whose role it is to provide postpartum care, along with opportunities to improve communication pathways and follow up care have informed the design of a complex health intervention to improve health systems and the provision of DIP related care.

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 β-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.

In Australia's Northern Territory, Indigenous mothers account for 33% of births and have high rates of hyperglycemia in pregnancy. The prevalence of type 2 diabetes (T2D) in pregnancy is up to 10-fold higher in Indigenous than non-Indigenous Australian mothers, and the use of metformin is common. We assessed birth outcomes in relation to metformin use during pregnancy from a clinical register.The study included women with gestational diabetes (GDM), newly diagnosed diabetes in pregnancy (DIP), or pre-existing T2D from 2012 to 2016. Data were analyzed for metformin use in the third trimester. Regression models were adjusted for maternal age, body mass index, parity, and insulin use.Of 1649 pregnancies, 814 (49.4%) were to Indigenous women, of whom 234 (28.7%) had T2D (vs 4.6% non-Indigenous women; P 0.001). Metformin use was high in Indigenous women (84%-90% T2D, 42%-48% GDM/DIP) and increased over time in non-Indigenous women (43%-100% T2D, 14%-35% GDM/DIP). Among Indigenous women with GDM/DIP, there were no significant differences between groups with and without metformin in cesarean section (51% vs 39%; adjusted odds ratio [aOR] 1.25, 95% confidence interval [CI] 0.87-1.81), large for gestational age (24% vs 13%; aOR 1.5, 95% CI 0.9-2.5), or serious neonatal adverse events (9.4% vs 5.9%; aOR 1.32, 95% CI 0.68-2.57). Metformin use was independently associated with earlier gestational age (37.7 vs 38.5 weeks), but the risk did not remain independently higher after exclusion of women managed with medical nutrition therapy alone, and the increase in births37 weeks was not significant on multivariate analysis.We found no clear evidence of any adverse outcomes related to the use of metformin for the treatment of hyperglycemia in pregnancy.摘要: 背景 在澳大利亚北部地区, 原住民母亲的婴儿出生率占33%, 她们妊娠期间出现高血糖的风险很高。原住民母亲在妊娠期间的2型糖尿病(T2D)患病率与非原住民澳大利亚母亲相比较要高10倍, 并且经常使用二甲双胍治疗。我们利用临床登记表数据评估了妊娠期间使用二甲双胍治疗与出生结果之间的关系。 方法 这项研究从2012至2016年纳入了妊娠糖尿病(gestational diabetes, GDM)、妊娠期新诊断糖尿病(newly diagnosed diabetes in pregnancy, DIP)以及既往已经存在T2D的妇女。对妊娠晚期使用二甲双胍的数据进行了分析。根据母亲年龄、体重指数、产次以及胰岛素使用情况校正了回归模型。 结果 在1649名孕妇中有814名(49.4%)为原住民妇女, 其中234名(28.7%)为T2D(非原住民妇女T2D比例为4.6%；P 0.001)。原住民妇女的二甲双胍使用率更高(在T2D中为84%-90%, 在GDM/DIP中为42%-48%), 并且在非原住民妇女中随着时间的推移使用率在上升(在T2D中为43%-100%, 在GDM/DIP中为14%-35%)。在合并GDM/DIP的原住民妇女中, 使用二甲双胍治疗组与不使用二甲双胍治疗组之间的剖宫产率(分别为51%与39%; 校正后的odds ratio [aOR]为1.25, 95%置信区间[CI]为0.87-1.81)、出现大胎龄率(分别为24%与13%；aOR为1.5, 95% CI为0.9-2.5)、新生儿出现严重不良事件率(分别为9.4%与5.9%；aOR为1.32, 95% CI为0.68-2.57)都没有显著性差异。使用二甲双胍治疗与胎龄更小(分别为37.7与38.5周)独立相关, 但是将单独接受药物营养治疗的妇女排除之后, 这种风险没有独立地处于较高的水平, 并且多变量分析显示37周的出生率并没有显著地升高。 结论 我们没有发现任何与妊娠期间高血糖妇女使用二甲双胍治疗出现不良结果相关的明确证据。.

ObjectivesUsing 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.DesignPopulation-based retrospective panel.SettingA regional hospital that serves 26% of Victoria’s 6.5 million population in Australia.ParticipantsAll women experiencing live births between 2010 and 2017 were included. Women with missing body mass index (BMI) were excluded.ResultsA 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>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, pConclusionThis 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.

BackgroundThere is a high burden of gestational diabetes (GDM) and type 2 diabetes in pregnancy for Aboriginal and Torres Strait Islander women. Postpartum diabetes programs have the potential to prevent recurrent GDM and improve management of type 2 diabetes. However, data on such programs are limited, particularly in the Indigenous context. We aimed to explore Aboriginal Australian women’s and health providers’ preferences for a program to prevent and improve diabetes after pregnancy.MethodsA phenomenological methodology underpinned semi-structured in-depth interviews with eleven Aboriginal women and seven health professionals across the Northern Territory from October 2019- February 2020. Interviews were analysed using an inductive analysis framework to address the barriers and enablers of proposed diabetes prevention programs identified by participants.ResultsIdentified structural barriers to lifestyle change included: food insecurity, persuasive marketing of unhealthy food options, lack of facilities and cultural inappropriateness of previous programs. Enablers to lifestyle change included: a strong link between a healthy lifestyle and connection with Country, family and community. Suggested strategies to improve lifestyle included: co-designed cooking classes or a community kitchen, team sports and structural change (targeting the social determinants of health). Lifestyle change was preferred over metformin to prevent and manage diabetes after pregnancy by participants and health care providers.ConclusionsWe recommend individual level programs be designed alongside policies that address systemic inequalities. A postpartum lifestyle program should be co-designed with community members and grounded in Aboriginal conceptions of health to adequality address the health disparities experienced by Aboriginal people in remote communities.

Aims/hypothesis: Women with gestational diabetes mellitus (GDM) and obesity experience lower rates of breastfeeding. Little is known about breastfeeding among mothers with type 2 diabetes. Australian Indigenous women have a high prevalence of type 2 diabetes in pregnancy. We aimed to evaluate the association of hyperglycaemia, including type 2 diabetes, with breastfeeding outcomes. Methods: Indigenous (n = 495) and non-Indigenous (n = 555) participants of the Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) cohort included women without hyperglycaemia in pregnancy (n = 222), with GDM (n = 684) and with type 2 diabetes (n = 144). The associations of hyperglycaemia in pregnancy and breastfeeding at hospital discharge, 6 weeks and 6 months post-partum were evaluated with logistic regression, after adjustment for maternal obesity, ethnicity, maternal and neonatal characteristics. Results: Indigenous women were more likely to predominantly breastfeed at 6 weeks across all levels of hyperglycaemia. Compared with women with no hyperglycaemia in pregnancy, women with type 2 diabetes had lower odds for exclusive breastfeeding at discharge (adjusted OR for exclusive breastfeeding 0.4 [95% CI 0.2, 0.8] p = 0.006). At 6 weeks and 6 months, the relationship between type 2 diabetes and predominant breastfeeding was not statistically significant (6 weeks 0.7 [0.3, 1.6] p = 0.40, 6 months 0.8 [0.4, 1.6] p = 0.60). Women with gestational diabetes were as likely to achieve predominant breastfeeding at 6 weeks and 6 months as women without hyperglycaemia in pregnancy. Conclusions/interpretation: Indigenous women had high rates of breastfeeding. Women with type 2 diabetes had difficulty establishing exclusive breastfeeding at hospital discharge. Further research is needed to assess the impact on long-term breastfeeding outcomes Refereed/Peer-reviewed

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.

Aims: To determine among First Nations and Europid pregnant women the cumulative incidence and predictors of postpartum type 2 diabetes and prediabetes and describe postpartum cardiovascular disease (CVD) risk profiles. Methods: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Ethnic-specific rates of postpartum type 2 diabetes and prediabetes were reported for women with diabetes in pregnancy (DIP), gestational diabetes (GDM) or normoglycaemia in pregnancy over a short follow-up of 2.5 years (n = 325). Pregnancy characteristics and CVD risk profiles according to glycaemic status, and factors associated with postpartum diabetes/prediabetes were examined in First Nations women. Results: The cumulative incidence of postpartum type 2 diabetes among women with DIP or GDM were higher for First Nations women (48%, 13/27, women with DIP, 13%, 11/82, GDM), compared to Europid women (nil DIP or GDM p < 0.001). Characteristics associated with type 2 diabetes/prediabetes among First Nations women with GDM/DIP included, older age, multiparity, family history of diabetes, higher glucose values, insulin use and body mass index (BMI). Conclusions: First Nations women experience a high incidence of postpartum type 2 diabetes after GDM/DIP, highlighting the need for culturally responsive policies at an individual and systems level, to prevent diabetes and its complications. Refereed/Peer-reviewed

The purpose of this study was to examine the association of parental pre-pregnancy weight and body mass index (BMI) on offspring weight and BMI change from childhood to adulthood.

Pre‐eclampsia (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 low‐resource countries are at a higher risk of developing PE compared with those in high‐resource countries. Although a complete understanding of the pathogenesis of PE remains unclear, the current theory suggests a two‐stage 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 new‐onset 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 (thrombocytopenia–platelet count

Summary Background and objectives Parental body mass index (BMI) is strongly linked with the development of offspring overweight and obesity. However, there are a limited number of studies focusing on the association of parental body mass index before pregnancy on offspring growth and body composition in early life, particularly in developing countries. Methods Data from the University Sains Malaysia (USM) Pregnancy Cohort which consists of 153 mother-offspring pairs were used. Data were collected using interview-administered questionnaires and anthropometric measurements were also obtained. Multiple linear regression and generalised equation estimation (GEE) were used to examine the direction and impact of the association between parental BMI and child growth and body composition (weight for age, height for age, body mass index for age, weight for height and fat mass at age 2m, 6m, and 12m). Potential confounders, including validated measures of maternal diets and physical activity during pregnancy, were considered. Results Of 153 parents, one-quarter of the mothers and 42.2% of the fathers, respectively, were overweight or obese before pregnancy. A significant association was found between maternal BMI and child's weight for height z -score (WHZ) and body mass index for age z -score (BAZ). Conclusions Having high pre-pregnancy BMI may increase BMI and WAZ of offspring in early life. Findings from this study emphasise the importance of monitoring maternal weight status, particularly before and during pregnancy and early life of offspring among Malaysians.

OBJECTIVE To study effects of lifestyle intervention on metabolic and clinical outcomes in obese women fulfilling the World Health Organization (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) in early gestation. RESEARCH DESIGN AND METHODS Secondary analysis of data from the Lifestyle in Pregnancy (LiP) study, a lifestyle randomized controlled trial in 304 pregnant women with BMI ≥30 kg/m2. Early GDM (week 12–15) was diagnosed according to modified WHO 2013 GDM criteria: fasting venous plasma glucose ≥5.1 mmol/L and/or 2-h capillary blood glucose (CBG) ≥8.5 mmol/L (75-g oral glucose tolerance test [OGTT]). Women with treated GDM fulfilling local Danish GDM criteria (2-h CBG ≥9.0 mmol/L) (n = 16) and women with normal OGTT (n = 198) were excluded. RESULTS Of 90 women with early GDM, 36 received lifestyle intervention and 54 standard care. All were Caucasian, and median age was 29 years (interquartile range 27–33) and BMI 34.5 kg/m2 (32.3–38.1). All baseline characteristics were similar in the lifestyle intervention and standard care groups. At gestational week 28–30, the women in the lifestyle intervention group had significantly higher fasting total cholesterol and fasting LDL. All other metabolic parameters including measurements of glucose, insulin, and HOMA of insulin resistance were similar. There were more planned cesarean sections in the lifestyle intervention group (22.2 vs. 5.6%), but all other obstetric outcomes were similar. CONCLUSIONS Lifestyle intervention in obese women fulfilling WHO 2013 GDM criteria in early pregnancy was not effective in improving obstetric or metabolic outcomes. Future studies should focus on interventions starting prepregnancy.

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).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.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.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.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 Journal of Gynecology and Obstetrics regrets that, in the above article, an error appeared in the 5.3.4 Measurement of uterine artery pulsatility index section on page 17, 5th paragraph, second last sentence: The first-trimester abnormal UTPI is defined as less than the 90th percentile, achieving a detection rate of 48%, at 8% false-positive rate, for the identification of early-onset PE. should have been: The first-trimester abnormal UTPI is defined as greater than the 90th percentile, achieving a detection rate of 48%, at 8% false-positive rate, for the identification of early-onset PE. Affiliation of the author, Mary D'Alton has been corrected to the following: Obstetrician and Gynecologist in-Chief, Columbia University Irving Medical Center, NewYork-Presbyterian The online version is corrected with the above changes after first online publication. We apologize for the inconvenience caused.

Prenatal exposure to alcohol has adverse ramifications on foetal development resulting in developmental abnormalities and major congenital anomalies. Experimental studies have documented effects on kidney structure and function among offspring exposed to alcohol during foetal life; however, human evidence is scarce. Thus, the present study aimed to determine the development of CKD among a cohort of 30-year-old Australian offspring whose mothers reported consumption of alcohol during pregnancy. The study sample comprised 1626 offspring of the birth the Australia cohort study (MUSP) who serum creatinine was assessed at 30 years old and CKD was categorised from stage 1 to stage 5 based on their level of eGFR following the CKD-EPI definition. Seven percent (n = 111) of offspring had mild to moderate (stage 2 and 3) CKD at 30 years. The overall adjusted odds of CKD were 2.01 (95% CI 0.97 to 4.13) for offspring of moderate to heavy drinking mothers in late pregnancy, 1.60 (0.70 to 3.37) for early pregnancy and 1.18 (0.72 to 1.94) for pre-pregnancy. The association was higher for female offspring-2.69 (1.02 to 7.14) for late pregnancy and 2.95 (1.12 to 7.80) for early pregnancy. Higher but insignificant odds were found for male offspring at late pregnancy 1.44 (0.46 to 4.47) only. Maternal alcohol exposure during early and late pregnancy is associated with development of mild to moderate CKD in their offspring at 30 years. This association is stronger for female than male offspring.

Despite recent attempts at building consensus, an internationally consistent definition of gestational diabetes mellitus (GDM) remains elusive. Within and between countries, there is disagreement between obstetric, medical, and endocrine groups as to the diagnosis and management of GDM. The current article aims to discuss the background to the controversy of GDM diagnosis and to address issues related to the detection and treatment of GDM in low-, middle-, and high-resource settings. The criteria recommended by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG), the American Diabetes Association (ADA), and the World Health Organization (WHO) are endorsed. We also wish to put into perspective the importance of GDM, both during and after pregnancy, in terms of its relationship to overall women's health.

Aims. To develop a program to support behaviour changes for women with a history of Gestational Diabetes Mellitus (GDM) and a Body Mass Index (BMI) > 25 kg/m2to delay or prevent Type 2 Diabetes Mellitus.Methods. Women diagnosed with GDM in the previous 6 to 24 months and BMI > 25 kg/m2were randomized to an intervention (I) (n=16) or a control (C) (n=15) group. The intervention was a pedometer program combined with nutrition coaching, with the primary outcome increased weight loss in the intervention group. Secondary outcomes included decreased waist and hip measurements, improved insulin sensitivity and body composition, increased physical activity, and improved self-efficacy in eating behaviours.Results. Median (IQR) results were as follows: weight: I −2.5 (2.3) kg versus C +0.2 (1.6) kg (P=0.009), waist: I −3.6 (4.5) cm versus C −0.1 (3.6) cm (P=0.07), and hip: I −5.0 (3.3) cm versus C −0.2 (2.6) cm (P=0.002). There was clinical improvement in physical activity and eating behaviours and no significant changes in glucose metabolism or body composition.Conclusion. A pedometer program and nutrition coaching proved effective in supporting weight loss, waist circumference, physical activity, and eating behaviours in women with previous GDM.

It is unclear whether any breastfeeding or a certain duration of breastfeeding is protective against the development of diabetes in adult offspring.We followed a sub-sample of 3,595 offspring born in the Mater Hospital in Brisbane, Australia between 1981 and 1983 and for whom we had doctor diagnosed self-reported diabetes at age 21 years and maternal reported duration of breastfeeding at 6-month post-natal follow-up. Multiple logistic regression was used to examine the independent associations of duration of breastfeeding (never breastfeed, breastfed4 months and breastfed ≥4 months) with offspring diabetes by age 21 years.Of 3,595 young adults, 45 (1.25 %) developed diabetes by age 21 years. The odds ratio of experiencing diabetes was 0.58 (95 % CI 0.29, 1.16) for offspring who were breastfed4 months, and it was 0.29 (95 % CI 0.13, 0.63), for offspring who were breastfed at least 4 months compared to the never breastfed offspring. Adjusting for potential confounding and mediating factors including maternal age, education, pre-pregnancy body mass index (BMI), smoking, offspring sports, TV and their BMI at 21 years did not substantially alter this association.Findings of this study suggest that infants who are breastfed for longer than 4 months have a substantial protective effect against the development of diabetes in young adulthood, which is independent of current BMI. Promoting breastfeeding for a minimum of 4 months may be a useful strategy for the prevention of diabetes among young adults.

Little is known about pulse pressure (PP) during early life and its association with renal function at young adulthood. This study describes an early life course association of PP with adult renal function at 30 years from a large community-based birth cohort study in Australia.Sample comprises 1169 young adults aged 30 years from the Mater-University of Queensland Study of Pregnancy, whose blood pressure was recorded in at least three follow-ups (5, 14, 21, and 30 years) and renal function was assessed at 30 years. Estimated glomerular filtration rate was estimated to determine the stages of chronic kidney disease (CKD). A group-based trajectory modelling was developed to identify patterns of PP from childhood to adulthood. Multiple logistic regression was used to determine whether PP trajectories predict adult CKD.In total, 7% of participants (91) had mild CKD. Three PP trajectories were identified: 16% were in the high PP trajectory group characterized by substantial increase in PP over time; 58% were in the middle group who had lower PP at 5 years, which increased at 14 years and then gradually declined at 21 and 30 years, and the remaining 26% were in a lower group which remained static. In the adjusted model, significantly higher odds were found for the high [odds ratio: 2.42 (95% confidence interval: 1.02-5.74)] and middle [2.23 (1.19-4.19)] PP trajectory groups for development of mild CKD at 30 years compared with the low (static) group.Early life high and middle PP trajectories predict the risk of subclinical renal insufficiency by age 30 years.

Aims To assess outcomes of women in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) cohort with gestational diabetes mellitus (GDM) managed by lifestyle modification compared with women without hyperglycaemia in pregnancy. Methods Indigenous (n = 97) and Europid (n = 113) women managed by lifestyle modification were compared to women without hyperglycaemia (n = 235). Multivariate linear and logistic regressions assessed whether GDM-lifestyle women had poorer outcomes compared to women without hyperglycaemia. Results Women with GDM-lifestyle had higher body mass index and lower gestational weight gain than women without hyperglycaemia. On univariate analysis, gestational age at delivery was lower and induction rates were higher in women with GDM-lifestyle than without hyperglycaemia. On multivariable regression, GDM-lifestyle was associated with lower gestational age at delivery (by 0.73 weeks), lower birthweight z-score (by 0.26, p = 0.007), lower likelihood of large for gestational age (LGA) [OR (95% CI): 0.55 (0.28, 1.02), p = 0.059], and greater likelihood of labour induction [2.34 (1.49, 3.66), p Conclusion Women with GDM managed by lifestyle modification had higher induction rates and their offspring had lower birthweight z-scores, with a trend to lower LGA than those without hyperglycaemia in pregnancy. Further studies are indicated to explore reasons for higher induction rates.

ObjectiveThe 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.MethodThis 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.ResultsFemales 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 ConclusionThis study observed high prevalence of stage-2 to stage-5 renal insufficiency in Bangladeshi populations, irrespective of age, and especially among the females.

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.

Sulfate is an important nutrient for fetal growth and development. The fetus has no mechanism for producing its own sulfate and is therefore totally reliant on sulfate from the maternal circulation via placental sulfate transport. To build a model of directional sulfate transport in the placenta, we investigated the relative abundance of the 10 known sulfate transporter mRNAs in human placenta from uncomplicated term pregnancies. SLC13A4 and SLC26A2 were the most abundant sulfate transporter mRNAs, which localized to syncytiotrophoblast and cytotrophoblast cells, respectively. These findings indicate important physiological roles for SLC13A4 and SLC26A2 in human placental sulfate transport.

Pregnancy in women with type 1 diabetes mellitus (T1DM) is generally associated with increased insulin requirements.To determine the frequency and significance of declining insulin requirements in late gestation in women with T1DM.We conducted a retrospective review of 54 women seen at our institution from 2006 to 2010 with a diagnosis of T1DM pre-pregnancy and presentation for antenatal care prior to 28 weeks. Information was collected regarding patient demographics, insulin dose and pregnancy outcome. A 15% difference in weight-adjusted basal insulin from 30 weeks gestation to delivery was considered significant.Five women (9.3%) had a fall of 15% or more and 23 (42.5%) had a rise of 15% or more rise in insulin requirements. There were fewer neonatal intensive care admissions but more infants with an APGAR8 at 5 min in women with a fall in insulin requirements. These differences were not evident when the data were re-analysed by quartiles of change.In most women with T1DM, insulin requirements show little change from 30 weeks gestation until delivery. Almost 10% of women had a significant fall in insulin requirements which did not correlate with adverse neonatal outcome. These results require validation in a larger, prospective trial.

The global epidemic of obesity has led to an increasing number of obese women of reproductive age. Obesity is associated with reduced fertility, and pregnancies complicated by maternal obesity are associated with adverse outcomes, including increased risk of gestational diabetes, pre-eclampsia, preterm birth, instrumental and caesarean births, infections, and post-partum haemorrhage. The medical and obstetric management of obese women is focused on identifying, addressing, and preventing some of these associated complications, and is a daunting challenge given the high percentage of patients with obesity and few therapeutic options proven to improve outcomes in this population. The UK’s National Institute for Health and Care Excellence guidelines and the American College of Obstetricians and Gynecologists recommend that all pregnant women follow a healthy diet, and consider at least half an hour of moderate physical activity per day during pregnancy. However, although obese women are often directed to seek the advice of a nutritionist and to limit gestational weight gain, guidelines for the management of pregnancy and delivery in this high-risk group are lacking. The post-partum period represents an important opportunity to optimise maternal health before the next pregnancy. As many of the physiological changes of pregnancy associated with maternal obesity are present from early pregnancy onward, reducing maternal obesity before conception is probably the best strategy to decrease the health burden associated with maternal obesity.

Most women with type 1 diabetes mellitus (T1DM) have increased insulin requirements during pregnancy. However, a minority of women have a fall in insulin requirements. When this occurs in late gestation, it often provokes concern regarding possible compromise of the feto-placental unit. In some centres, this is considered as an indication for delivery, including premature delivery. There are, however, many other factors that affect insulin requirements in pregnancy in women with type 1 diabetes mellitus and the decline in insulin requirements may represent a variant of normal pregnancy. If there is no underlying pathological process, expedited delivery in these women is not warranted and confers increased risks to the newborn. We will explore the factors affecting insulin requirements in gestation in this review. We will also discuss some novel concepts regarding beta-cell function in pregnancy.

Diabet. Med. 29, e199e204 (2012) Abstract Aims To assess associations between maternal serum vitamin D concentration and glucose metabolism in a cohort of pregnant women living in an Australian subtropical environment. Methods Cross-sectional assessment of 25-hydroxy vitamin D concentrations in 399 Hyperglycemia and Adverse Pregnancy Outcome ancillary study participants, treated at an obstetric teaching hospital in Brisbane, Australia. All patients underwent a blinded 75-g oral glucose tolerance test at 2432 (target 28) weeks gestation. Results The mean (+/- standard deviation) fasting plasma glucose was 4.5 +/- 0.4 mmol/l. Mean (+/- standard deviation) serum 25-hydroxy vitamin D was 132.5 +/- 44.0 nmol/l. A difference of one standard deviation in maternal 25-hydroxy vitamin D was inversely related to fasting glucose (fasting glucose lower by 0.047 mmol/l, P = 0.012) when assessed with multiple linear regression after adjusting for confounders. Maternal 25-hydroxy vitamin D correlated with beta-cell function as estimated by the log-transformed homeostasis model assessment beta-cell function equation (r = 0.131, P = 0.009), but not with the homeostasis model assessment of insulin resistance. Conclusions An association between mid-gestational 25-hydroxy vitamin D and fasting glucose was confirmed in a largely normoglycaemic and vitamin D-replete pregnant population. The correlation between 25-hydroxy vitamin D and beta-cell function suggests that vitamin D may influence glucose metabolism through this mechanism. Intervention studies are required to determine causality and the role of vitamin D replacement in deficient individuals.

Summary 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.

The purpose of this research was to assess the ability of ductus venosus (DV) Doppler velocimetry to predict adverse perinatal outcome in pregnancies complicated by pre-existing diabetes mellitus.This was a prospective study conducted at a tertiary referral obstetric facility in Brisbane, Australia. The study group included women with pregestational diabetes mellitus who delivered in the hospital between 1 January 1995 and 31 December 2006. The DV Doppler index was defined as abnormal if the DV peak velocity index for veins (PVIV) was equal to or greater than the 95(th) percentile for gestation. Adverse perinatal outcome included one or more of the following criteria: small-for-gestational-age infant; Cesarean section for non-reassuring fetal status; fetal acidemia at delivery; a 1-min Apgar score ofor= 3; a 5-min Apgar score of7; hypoxic ischemic encephalopathy; and stillbirth or neonatal death. The maternal characteristics and perinatal outcomes of pregnancies with normal or abnormal DV Doppler indices were compared.Eighty-two pregestational diabetic pregnancies were studied and an abnormal DV-PVIV was identified in 25 (30.5%). Adverse perinatal outcome was identified in eight of 25 (32.0%) pregnancies with an abnormal DV-PVIV compared to seven of 57 (12.3%) pregnancies with a normal DV-PVIV (P0.05). The sensitivity of the DV-PVIV in predicting adverse perinatal outcomes in pregestational diabetic pregnancies was 53.3%, the specificity was 74.6%, the positive predictive value was 32.0% and the negative predictive value was 87.7%.It may be useful to include DV-PVIV in the antenatal screening of pregnancies complicated by pregestational diabetes.

OBJECTIVE To determine if glucose and C-peptide values obtained as part of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study could be used to estimate insulin sensitivity during late pregnancy. RESEARCH DESIGN AND METHODS A total of 78 women enrolled in the HAPO study were recruited for this ancillary study. Venous plasma samples were drawn after an 8- to 10-h fast (time 0) and at 30, 60, 90, and 120 min after a 75-g glucose challenge, which was performed at 24–32 weeks' gestation. Samples were analyzed for plasma glucose, insulin, and C-peptide. Insulin sensitivity was estimated using the established Matsuda and DeFronzo insulin sensitivity index for oral glucose tolerance tests (ISOGTT). Insulin sensitivity was also calculated from two other commonly used indexes of insulin sensitivity (that for homeostasis model assessment [ISHOMA] and that for quantitative insulin sensitivity check index [ISQUICKI]). A new insulin sensitivity index was calculated using the glucose and C-peptide concentrations at 0 and 60 min to derive ISHOMA C-pep, ISQUICKI C-pep, and ISOGTT C-pep. These indexes were then correlated with insulin sensitivity estimated from the ISOGTT. RESULTS The strongest correlation with the ISOGTT was obtained for ISOGTT C-pep (r = 0.792, P < 0.001). Further, the correlations of ISHOMA C-pep and ISQUICKI C-pep with ISOGTT were also significant (r = 0.676, P < 0.001 and r = 0.707, P < 0.001, respectively). CONCLUSIONS These data suggest that calculated ISOGTT C-pep is an excellent predictor of insulin sensitivity in pregnancy and can be used to estimate insulin sensitivity in over 25,000 women participating in the HAPO study.

The parallel epidemics of obesity and Type 2 diabetes (T2DM) are progressing rapidly in Australia. The high prevalence of obesity and sedentary lifestyle in the population, compounded by later child bearing, has led to an increase in the prevalence of T2DM pre-dating pregnancy. In some centers, pregnant women with T2DM now outnumber those with type 1 diabetes (T1DM). Although there is controversy as to whether T2DM is associated with worse outcomes than T1DM in pregnancy, modern reports clearly acknowledge the seriousness of this condition. There is a clear association between obesity and adverse pregnancy outcomes (cesarean section, gestational diabetes, hypertensive disorders, birth defects and prematurity). Aside from obesity and the metabolic syndrome, additional factors may contribute to these adverse outcomes: A lack of preconception planning, a failure to achieve tight glycaemic control early in pregnancy and socio-economic disadvantage. It's likely that obesity and diabetes have compounding effects on pregnancy outcomes. In this review, we evaluate both the underlying pathogenesis of T2DM and obesity in the pregnancy context and the adverse clinical maternal and perinatal outcomes described in pregnancies complicated by maternal T2DM and obesity. We highlight the need for a comprehensive strategy to improve clinical outcomes in these pregnancies.

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.

To describe glycaemia in both breastfeeding women and artificially feeding women with Type 1 diabetes, and the changes in glycaemia induced by suckling.A blinded continuous glucose monitor was applied for up to 6 days in eight breastfeeding and eight artificially feeding women with Type 1 diabetes 2-4 months postpartum. Women recorded glucose levels, insulin dosages, oral intake and breastfeeding episodes. A standardized breakfast was consumed on 2 days. A third group (clinic controls) were identified from a historical database.Carbohydrate intake tended to be higher in breastfeeding than artificially feeding women (P = 0.09) despite similar insulin requirements. Compared with breastfeeding women, the high blood glucose index and standard deviation of glucose were higher in artificially feeding women (P = 0.02 and 0.06, respectively) and in the clinical control group (P = 0.02 and 0.05, respectively). The low blood glucose index and hypoglycaemia were similar. After suckling, the low blood glucose index increased compared with before (P0.01) and during (P0.01) suckling. Hypoglycaemia (blood glucose4.0 mmol/l) occurred within 3 h of suckling in 14% of suckling episodes, and was associated with time from last oral intake (P = 0.04) and last rapid-acting insulin (P = 0.03). After a standardized breakfast, the area under the glucose curve was positive. In breastfeeding women the area under the glucose curve was positive if suckling was avoided for 1 h after eating and negative if suckling occurred within 30 min of eating.Breastfeeding women with Type 1 diabetes had similar hypoglycaemia but lower glucose variability than artificially feeding women. Suckling reduced maternal glucose levels but did not cause hypoglycaemia in most episodes.

Clinical practice guidelines for diabetes include dietary guidelines to address the increased risk of cardiovascular disease.To identify impact of flexible insulin education with an active promotion of dietary freedom on energy and macronutrient intake and achievement of nutrient recommendations in adults with Type 1 diabetes.Dietary assessment was performed prior to and 12months following flexible insulin education. Nutrient intake and the proportion achieving the European Association for the Study of Diabetes (EASD) nutrient guidelines were compared at baseline and post course.Dietary data were available for 46 participants. Post course reductions were seen in median [IQR] energy kcal/d (1799 [1521-1931] to 1592 [1378-1940], p=0.002), fibre g/1000kcal (14 [12-16] to 13 [11-15], p=0.047), protein g/day (89 ([78-108] to 82 [74-93], p=0.001) and carbohydrate g/day (198 [172-330] to 162 [143-204], p=0.001). The proportion experiencing at least 1 severe hypoglycaemia event over 12months was significantly reduced (χ(2)=7.7, p=0.006) from baseline (n=13, 26%) to post course (n=3, 6%). Achievement of EASD guidelines was poor and did not change post course.Flexible insulin education with an active promotion of dietary freedom does not appear to 'worsen' the achievement of EASD nutrition guidelines in adults with Type 1 diabetes. On the contrary, the dietary changes observed were reductions in energy, carbohydrate and protein intake. Flexible insulin education may offer benefits in enabling reduced energy intake without increasing hypoglycaemia.

Aims: To evaluate structured type 1 diabetes education delivered in routine practice throughout Australia. Methods: Participants attended a five-day training program in insulin dose adjustment and carbohydrate counting between April 2007 and February 2012. Using an uncontrolled before-and-after study design, we investigated: HbA1c (% and mmol/mol); severe hypoglycaemia; diabetes ketoacidosis (DKA) requiring hospitalisation, and diabetes-related distress (Problem Areas in Diabetes scale; PAID), weight (kg); body mass index. Data were collected pre-training and 6-18 months post-training. Change in outcome scores were examined overall as well as between groups stratified by baseline HbA1c quartiles. Data are mean ± SD or % (n). Results: 506 participants had data eligible for analysis. From baseline to follow-up, significant reductions were observed in the proportion of participants reporting at least one severe hypoglycaemic event (24.7% (n = 123) vs 12.1% (n = 59), p < 0.001); and severe diabetes-related distress (29.3% (n = 145) vs 12.6% (n = 60), p < 0.001). DKA requiring hospitalisation in the past year reduced from 4.1% (n = 20) to 1.2% (n = 6). For those with above target baseline HbA1c there was a small, statistically significant improvement (n = 418, 8.4 ± 1.1% (69 ± 12 mmol/mol) to 8.2 ± 1.1% (66 ± 12 mmol/mol). HbA1c improvement was clinically significant among those in the highest baseline quartile (n = 122, 9.7 ± 1.1% (82 ± 11 mmol/mol) to 9.0 ± 1.2% (75 ± 13 mmol/mol), p < 0.001). Conclusions: The proportion of participants reporting severe hypoglycaemia, DKA and severe diabetes-related distress was at least halved, and HbA1c reduced by 0.7% (7 mmol/mol) among those with highest baseline levels. Structured type 1 diabetes education delivered in routine practice offers clinically important benefits for those with greatest clinical need.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12884-015-0526-z) contains supplementary material, which is available to authorized users.

Objective: Cardiac impairment is frequently found in babies of diabetic mothers. It is still controversial whether this is due to poor glucose control. The aim of this study is to compare the cardiac function in fetuses of well- and poorly-controlled pre-gestational diabetic pregnancy in third trimester. Methods: Women with type 1 pre-gestational diabetes were enrolled at 30–32 weeks. Cardiac size and interventricular septal wall thickness were measured by M-mode at end-diastolic phase. The right and left ventricular ejection fractions were calculated. At the mitral and tricuspid valves inflow, the ratio between early ventricular filling and active atrial filling (E/A) at both atrioventricular valves were measured by Doppler echocardiography. Peak velocities of ascending aorta and pulmonary artery were assessed. The angle of isonation was kept at 6.5%) were compared with those with satisfactorily controlled diabetes (HbA1c ≤6.5%). Results: A total of 21 women with pre-gestational diabetes were recruited for this study. Eight women with well-controlled diabetes were compared with 9 women who had poorly-controlled diabetes. HbA1c in the poorly-controlled group was 7.3% and in the well-controlled group it was 5.4% (p < 0.001). There was no difference between the two groups in cardiac size, interventricular septal wall thickness, ejection fraction, aorta and pulmonary artery peak flow velocities. The right atrioventricular E/A ratio was significantly lower among the poorly-controlled diabetic pregnancies (0.71 vs. 0.54; p < 0.05). Conclusion: Fetuses of poorly-controlled diabetic mothers had a lower right atrioventricular E/A ratio. This may be due to metabolic acidosis, non-hypertrophic cardiac dysfunction or fetal polycythemia.

Objectives To assess the detection rate of congenital fetal malformations and specific problems related to routine ultrasound screening in women with pre-existing diabetes. Methods A retrospective study was carried out to assess the performance of routine ultrasound screening in women with pre-existing diabetes (Types 1 and 2) within a tertiary institution. The incidence, type and risk factors for congenital fetal malformations were determined. The detection rate of fetal anomalies for diabetic women was compared with that for the low-risk population. Factors affecting these detection rates were evaluated. Results During the study period, 12 169 low-risk pregnant women and 130 women with pre-existing diabetes had routine ultrasound screening performed within the institution. A total of 10 major anomalies (7.7%) and three minor anomalies (2.3%) were present in the fetuses of the diabetic women. Central nervous system and cardiovascular system anomalies accounted for 60% of the major anomalies. Peri-conceptional hemoglobin A 1 c of more than 9% was associated with a high prevalence of major anomalies (14311000). Women who had fetuses with major anomalies bad a significantly higher incidence of obesity (78% vs. 37%; P < 0.05). Ultrasound examination of these diabetic pregnancies showed high incidences of suboptimal image quality (37%), incomplete examinations, and repeat examinations (17%). Compared to the 'low-risk' non-diabetic population from the same institution, the relative risk for a major congenital anomaly among the diabetic women was 5.9-fold higher (95% confidence interval, 2.9-11.9). The detection rate for major fetal anomalies was significantly lower for diabetic women (30% vs. 73%; P < 0.01), and the mean body mass index for the diabetic group was significantly higher (29 vs. 23 kg/m(2); P < 0.001). Conclusion The incidence of congenital anomalies is higher in diabetic pregnancies. Unfortunately, the detection rate for fetal anomalies by antenatal ultrasound scan was significantly, worse than that for the low-risk population. This is likely to be related to the maternal body habitus and unsatisfactory examinations. Methods to overcome these difficulties are discussed.