A systematic review of the effects of maternal obesity on neonatal outcomes in women with gestational diabetes.

Maternal obesity and gestational diabetes mellitus (GDM) prevalence are increasing, with both conditions associated with adverse neonatal outcomes. This review aimed to determine the risk of adverse outcomes in women with obesity and GDM, compared with women with obesity alone. A systematic search identified 28 eligible articles. Meta-analysis was conducted using a random effects model, to generate pooled estimates (odds ratios, OR, or mean difference, MD). Compared with normal-weight controls, women with obesity had increased risks of large for gestational age (LGA, OR 1.98, 95% CI: 1.56, 2.52) and macrosomia (OR 2.93, 95% CI: 1.71, 5.03); the latter's risk almost double in women with obesity than GDM. Birth weight (MD 113 g, 95% CI: 69, 156) and shoulder dystocia (OR 1.23, 95% CI: 0.85, 1.78) risk was also higher. GDM significantly amplified neonatal risk in women with obesity, with a three- to four-fold risk of LGA (OR 3.22, 95% CI: 2.17, 4.79) and macrosomia (OR 3.71, 95% CI: 2.76, 4.98), as well as higher birth weights (MD 176 g, 95% CI: 89, 263), preterm delivery (OR 1.49, 95% CI: 1.25, 1.77), and shoulder dystocia (OR 1.99, 95% CI: 1.31, 3.03), when compared with normal-weight controls. Our findings demonstrate that maternal obesity increases serious neonatal adverse risk, magnified by the presence of GDM. Effective strategies are needed to safeguard against neonatal complications associated with maternal obesity, regardless of GDM status.

Therapeutic Potential for Beta-3 Adrenoreceptor Agonists in Peripheral Arterial Disease and Diabetic Foot Ulcers.

Annually, peripheral arterial disease is estimated to cost over USD 21 billion and diabetic foot disease an estimated at USD 9-13 billion. Mirabegron is a TGA-approved beta-3 adrenoreceptor agonist, shown to be safe and effective in the treatment of overactive bladder syndrome by stimulating bladder smooth muscle relaxation. In this review, we discuss the potential use of beta-3 adrenoreceptor agonists as therapeutic agents repurposed for peripheral arterial disease and diabetic foot ulcers. The development of both conditions is underpinned by the upregulation of oxidative stress pathways and consequential inflammation and hypoxia. In oxidative stress, there is an imbalance of reactive oxygen species and nitric oxide. Endothelial nitric oxide synthase becomes uncoupled in disease states, producing superoxide and worsening oxidative stress. Agonist stimulation of the beta-3 adrenoreceptor recouples and activates endothelial nitric oxide synthase, increasing the production of nitric oxide. This reduces circulating reactive oxygen species, thus decreasing redox modification and dysregulation of cellular proteins, causing downstream smooth muscle relaxation, improved endothelial function and increased angiogenesis. These mechanisms lead to endothelial repair in peripheral arterial disease and an enhanced perfusion in hypoxic tissue, which will likely improve the healing of chronic ulcers.

Maternal Weight Management to Prevent the Developmental Programming of MAFLD in Offspring of Obese Mothers.

The global surge of obesity amongst women of reproductive age has raised concerns surrounding the health consequences for their offspring as there is a formidable link between an obesogenic maternal environment and the developmental programming of metabolic dysfunction in the offspring. Specifically, the offspring of mothers with obesity have a three-fold higher risk of developing metabolic-associated fatty liver disease (MAFLD) compared to the offspring of healthy-weight mothers. Given the burgeoning burden of obesity and its comorbidities, it is essential to focus research efforts on methods to alleviate the intergenerational onset of obesity and MAFLD. This review summarizes the current research surrounding the developmental programming of MAFLD in the offspring of mothers with obesity and examines the potential for weight interventions to prevent such metabolic dysfunction in the offspring. It focuses on the benefits of pre-pregnancy interventional strategies, including dietary and exercise intervention, to ameliorate adverse liver health outcomes in the offspring. The utility and translation of these interventions for humans may be difficult for prospective mothers with obesity, thus the use of pre-pregnancy therapeutic weight loss aids, such as glucagon-like peptide-1 receptor agonists, is also discussed.

The experiences of women from culturally and linguistically diverse backgrounds with gestational diabetes mellitus: A mixed methods systematic review.

BACKGROUND: Gestational diabetes mellitus (GDM) is experienced at a higher rate in women from culturally and linguistically diverse (CALD) backgrounds. The aim of this systematic review is to describe the experiences of women with GDM from CALD backgrounds and compare their experiences to women with GDM from non-CALD backgrounds. MATERIALS AND METHODS: MEDLINE, EMBASE, PsycINFO, Scopus, WOS and CINAHL databases were searched for qualitative and quantitative studies which included data on the experiences of CALD background women with GDM during all stages of pregnancy. Quality appraisal utilized checklists for analytical cross-sectional studies and qualitative research. Thematic analysis was performed using nVivo software. RESULTS: Of the 3054 studies identified, 24 studies met the inclusion criteria. Data synthesis produced five key themes: (1) Response to diagnosis, (2) Experiences with self-management, (3) Interactions with the healthcare system, (4) Mental health challenges and (5) Facilitators and barriers to support. Women with GDM from CALD and non-CALD backgrounds similarly expressed mental health challenges, feeling burdened by recommendations, and challenges interacting with healthcare professionals (HCP). The major difference in experience was the cultural relevance of recommendations, especially related to diet recommendations. CONCLUSION: Gestational diabetes mellitus is a burdensome diagnosis for CALD and non-CALD women, with CALD women uniquely experiencing a lack of culturally relevant recommendations for self-management. The similarities and differences in experience call for optimisation of GDM management and support for women with GDM.

Fasting Glucose Level on the Oral Glucose Tolerance Test Is Associated with the Need for Pharmacotherapy in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) has a rapidly increasing prevalence, which poses challenges to obstetric care and service provision, with known serious long-term impacts on the metabolic health of the mother and the affected offspring. The aim of this study was to evaluate the association between glucose levels on the 75 g oral glucose tolerance test and GDM treatment and outcomes. We performed a retrospective cohort study of women with GDM attending a tertiary Australian hospital obstetric clinic between 2013 and 2017, investigating the relationship between the 75 g oral glucose tolerance test (OGTT) glucose values, and obstetric (timing of delivery, caesarean section, preterm birth, preeclampsia), and neonatal (hypoglycaemia, jaundice, respiratory distress and NICU admission) outcomes. This time frame encompassed a change in diagnostic criteria for gestational diabetes, due to changes in international consensus guidelines. Our results showed that, based on the diagnostic 75 g OGTT, fasting hyperglycaemia, either alone or in combination with elevated 1 or 2 h glucose levels, was associated with the need for pharmacotherapy with either metformin and/or insulin (p < 0.0001; HR 4.02, 95% CI 2.88-5.61), as compared to women with isolated hyperglycaemia at the 1 or 2 h post-glucose load timepoints. Fasting hyperglycaemia on the OGTT was more likely in women with higher BMI (p < 0.0001). There was an increased risk of early term birth in women with mixed fasting and post-glucose hyperglycaemia (adjusted HR 1.72, 95% CI 1.09-2.71). There were no significant differences in rates of neonatal complications such as macrosomia or NICU admission. Fasting hyperglycaemia, either alone or in combination with post-glucose elevations on the OGTT, is a strong indicator of the need for pharmacotherapy in pregnant women with GDM, with significant ramifications for obstetric interventions and their timing.

Maternal Weight Intervention in the Perinatal Period Improves Liver Health in the Offspring of Mothers with Obesity.

Early-life exposure to maternal obesity predisposes offspring to metabolic-associated fatty liver disease (MAFLD). This study aimed to determine if peripartum weight loss, either through dietary intervention or pharmacological intervention, improved adverse liver health outcomes in the offspring of mothers with obesity. C57Bl/6 dams were fed a chow diet or a high-fat diet (HFD) for 8 weeks. HFD-fed mice either continued HFD, transitioned to a chow diet, or were administered liraglutide for 4 weeks. Pregnancy was induced following a one-week washout of liraglutide during which all animals remained on their respective diets. A proportion of HFD-fed mice transitioned to a chow diet during pregnancy. All offspring were weaned to the HFD. Offspring anthropometric, metabolic, and hepatic outcomes were assessed at postnatal week 12. The offspring of mothers with obesity had phenotypic changes consistent with MAFLD. The offspring of mothers that had weight loss with perinatal dietary intervention had reduced insulin resistance (p < 0.001) and hepatic expression of markers of inflammation (p < 0.001), oxidative stress (p < 0.05), and fibrosis (p < 0.05). A similar phenotype was observed in the offspring of mothers with pre-pregnancy weight loss via liraglutide despite ongoing consumption of the HFD during pregnancy. All methods and timing of maternal weight intervention were effective at ameliorating adverse liver effects in the offspring.

Improving women's experiences with gestational diabetes from culturally and linguistically diverse backgrounds in Australia: a qualitative study.

Introduction: Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes in many countries worldwide, including Australia. Although studies have explored the experiences of women with GDM from ethnic minority groups, few have compared their experiences with women from Anglosphere backgrounds. Objective: To investigate the responses to diagnosis, the management of GDM, and the experiences of healthcare services among women with GDM from different culturally and linguistically diverse (CALD) backgrounds. Methods: Participants were recruited via convenience sampling by advertisement posted around antenatal clinics of three hospitals in NSLHD: Royal North Shore, Hornsby, and Manly Hospitals. The interviews were semi-structured, one-on-one, and in-person conducted by a trained female volunteer. The interviews were audio-recorded, transcribed into text. The data was analyzed via an inductive and descriptive coding approach. The codes were then categorized into main themes and sub-themes. Results: 30 women (7 Australian-born, 11 Chinese, 8 Indians, and 4 Koreans) partook the semi-structured interviews and 5 themes were identified: (1) Reaction to diagnosis; (2) Management issues; (3) Roles of friends and family; (4) Information access; and (5) Experience with healthcare services. The lack of culturally tailored dietary information, social support and language barriers were the main factors underpinning the differences in GDM experiences among women from CALD backgrounds versus Australian-born. Conclusion: Healthcare models should provide more emotional support upon diagnosis, culturally tailored guidelines for lifestyle modifications, and involve friends and family in care and management to enhance the experience of GDM for women from CALD backgrounds.

A case series and literature review of necrobiosis lipoidica.

Summary: Necrobiosis lipoidica (NL) is a rare and chronic disease characterised by yellow-brown, atrophic, telangiectatic plaques usually located on the lower extremities, with pathological features of collagen necrobiosis and dermal inflammation. Most cases are seen in those with diabetes mellitus, particularly type 1 diabetes (T1DM), and many without diabetes have evidence of abnormal glucose tolerance or family history of autoimmune disease. In this study, we describe four patients with NL and T1DM. A common theme is late identification and delay in diagnosis. Hence, we discuss the clinical features, need for clinicopathological correlation, and the management and prognostic implications for this distinctive entity. While most remain relatively asymptomatic, others progress to debilitating disease with pruritus, dysesthesia, and pain. Pain is often intense in the presence of ulcerated plaques, a morbid complication of NL. Diagnosis requires the integration of both clinical and histopathological findings. NL has proven a challenging condition to treat, and despite the numerous therapeutic modalities available, there is no standard of care. Hence, in this study, we provide an overview of current management strategies available for NL. Learning points: Necrobiosis lipoidica (NL) is classically seen in patients with type 1 diabetes. Koebner phenomenon, defined as the appearance of new skin lesions on previously unaffected skin secondary to trauma, is a well-recognised feature in NL. Background skin phototype contributes to variable yellow appearance of lesions in NL. Diagnosis of NL requires careful clinicopathological correlation. NL is a chronic disease often refractory to treatment leading to significant morbidity for the patient and a management conundrum for the multidisciplinary healthcare team. No standard therapeutic regimen has been established for the management of NL.

Diet Modification before or during Pregnancy on Maternal and Foetal Outcomes in Rodent Models of Maternal Obesity.

The obesity epidemic has serious implications for women of reproductive age; its rising incidence is associated not just with health implications for the mother but also has transgenerational ramifications for the offspring. Increased incidence of diabetes, cardiovascular disease, obesity, and kidney disease are seen in both the mothers and the offspring. Animal models, such as rodent studies, are fundamental to studying maternal obesity and its impact on maternal and offspring health, as human studies lack rigorous controlled experimental design. Furthermore, the short and prolific reproductive potential of rodents enables examination across multiple generations and facilitates the exploration of interventional strategies to mitigate the impact of maternal obesity, both before and during pregnancy. Given that obesity is a major public health concern, it is important to obtain a greater understanding of its pathophysiology and interaction with reproductive health, placental physiology, and foetal development. This narrative review focuses on the known effects of maternal obesity on the mother and the offspring, and the benefits of interventional strategies, including dietary intervention, before or during pregnancy on maternal and foetal outcomes. It further examines the contribution of rodent models of maternal obesity to elucidating pathophysiological pathways of disease development, as well as methods to reduce the impact of obesity on the mothers and the developing foetus. The translation of these findings into the human experience will also be discussed.

Low-dose hydralazine reduces albuminuria and glomerulosclerosis in a mouse model of obesity-related chronic kidney disease.

AIM: To determine, using a mouse model of obesity, whether low-dose hydralazine prevents obesity-related chronic kidney disease (CKD). METHODS: From 8 weeks of age, male C57BL/6 mice received a high-fat diet (HFD) or chow, with or without low-dose hydralazine (25 mg/L) in drinking water, for 24 weeks. Biometric and metabolic variables, renal function and structural changes, renal global DNA methylation, DNA methylation profile and markers of renal fibrosis, injury, inflammation and oxidative stress were assessed. RESULTS: The HFD-fed mice developed obesity, with glucose intolerance, hyperinsulinaemia and dyslipidaemia. Obesity increased albuminuria and glomerulosclerosis, which were significantly ameliorated by low-dose hydralazine in the absence of a blood pressure-lowering effect. Obesity increased renal global DNA methylation and this was attenuated by low-dose hydralazine. HFD-induced changes in methylation of individual loci were also significantly reversed by low-dose hydralazine. Obese mice demonstrated increased markers of kidney fibrosis, inflammation and oxidative stress, but these markers were not significantly improved by hydralazine. CONCLUSION: Low-dose hydralazine ameliorated HFD-induced albuminuria and glomerulosclerosis, independent of alterations in biometric and metabolic variables or blood pressure regulation. Although the precise mechanism of renoprotection in obesity is unclear, an epigenetic basis may be implicated. These data support repurposing hydralazine as a novel therapy to prevent CKD progression in obese patients.

Obesity Class Impacts Adverse Maternal and Neonatal Outcomes Independent of Diabetes.

Introduction: Obesity in pregnancy is a known risk factor for adverse maternal and neonatal outcomes. Few studies have compared adverse pregnancy-related outcomes according to obesity severity. Hence, we aimed to examine the impact of obesity class on maternal and perinatal outcomes. Methods: We retrospectively analysed data from all singleton births from mothers with obesity from 2013-2017 in Northern Sydney Local Health District in Sydney, Australia. Women were categorised into obesity class I (BMI 30-34.9kg/m2), class II (BMI 35-39.9 kg/m2) or class III (BMI 40+ kg/m2). Across BMI classes, we compared maternal outcomes including mode of delivery, gestational diabetes mellitus (GDM), and preeclampsia, and neonatal outcomes including large- and small-for-gestational age (SGA, LGA), neonatal hypoglycaemia, birth defects and timing of birth. Logistic analyses were performed to explore the impact of maternal obesity class on these outcomes, adjusting for maternal age, country of birth, parity, diabetes (both pre-existing and gestational) and hypertension. Results: There were 2466 births to women with obesity, class (69.1%), class II (21.8%), and class III (9.2%). 42.5% delivered by Caesarean section, 22.3% developed GDM and 11.2% had a hypertensive disorder in pregnancy, and Caesarean section and GDM were more common in women with higher class obesity. LGA occurred in 27.3% and SGA occurred in 4.0% of women across all classes of obesity. LGA rates were 49% more likely in women with class III compared to women with class I obesity (OR=1.49, CI 1.06-2.09, p=0.02). The presence of diabetes in the index pregnancy did not significantly impact risk of neonatal LGA between maternal obesity classes. Other neonatal adverse outcomes such as stillbirth and birth defects were more common in women with higher class obesity. SGA, neonatal hypoglycaemia, gestational age at delivery, APGAR 5-minute score and NICU admissions were similar across obesity classes, after adjustment for covariates. Conclusions: Obesity class increases the risk of many adverse maternal and neonatal outcomes. Obesity class is independently associated with LGA incidence in the neonate, independent of maternal factors including GDM. Ongoing efforts must be made to reduce obesity incidence in women of reproductive age to circumvent the adverse perinatal outcomes associated with obesity.

Preconception weight loss improves fertility and maternal outcomes in obese mice.

Women with obesity have higher incidences of infertility, with longer time to conception and increased risk of pregnancy complications compared to women with normal body weight. There is a lack of evidence demonstrating the benefit of preconception maternal weight loss on fertility and pregnancy outcomes. We aimed to determine if preconception weight loss, either with diet modification or glucose-like peptide 1 receptor agonist liraglutide, improves maternal weight, fertility, and pregnancy outcomes. C57BL/6 female mice were fed either a high-fat diet (HFD) or chow for 8 weeks. HFD-fed dams were administered liraglutide (0.3 mg/kg, s.c., for 4 weeks) or switched to chow to induce weight loss. Prior to mating, liraglutide was ceased and mice continued on HFD. Mice in the 'diet switch' group continued on chow. Pregnancy rates were recorded. Maternal anthropometry and glucose tolerance were measured before and after the intervention and at late gestation. Offspring outcomes were assessed. Liraglutide or diet switch led to weight reduction, improved insulin resistance (P< 0.001), and enhanced fertility, particularly in the liraglutide group (P< 0.005). Liraglutide-treated mice had significantly higher gestational weight gain (GWG) compared to the diet switch group (P< 0.05), with similar weight and glucose tolerance in late gestation to HFD mice. In contrast, diet switch maintained similar weight and glucose tolerance in late gestation to control mice. Pre-pregnancy weight intervention with liraglutide was effective at restoring fertility. Diet modification also improved fertility and avoided catch up weight gain in pregnancy. Liraglutide may be a therapeutic strategy for weight loss to prepare for pregnancy. However, our study provides caution about the potential for excessive GWG without diet intervention in pregnancy.

Universal Subsidized Continuous Glucose Monitoring Funding for Young People With Type 1 Diabetes: Uptake and Outcomes Over 2 Years, a Population-Based Study.

OBJECTIVE: Continuous glucose monitoring (CGM) is increasingly used in type 1 diabetes management; however, funding models vary. This study determined the uptake rate and glycemic outcomes following a change in national health policy to introduce universal subsidized CGM funding for people with type 1 diabetes aged <21 years. RESEARCH DESIGN AND METHODS: Longitudinal data from 12 months before the subsidy until 24 months after were analyzed. Measures and outcomes included age, diabetes duration, HbA1c, episodes of diabetic ketoacidosis and severe hypoglycemia, insulin regimen, CGM uptake, and percentage CGM use. Two data sources were used: the Australasian Diabetes Database Network (ADDN) registry (a prospective diabetes database) and the National Diabetes Service Scheme (NDSS) registry that includes almost all individuals with type 1 diabetes nationally. RESULTS: CGM uptake increased from 5% presubsidy to 79% after 2 years. After CGM introduction, the odds ratio (OR) of achieving the HbA1c target of <7.0% improved at 12 months (OR 2.5, P < 0.001) and was maintained at 24 months (OR 2.3, P < 0.001). The OR for suboptimal glycemic control (HbA1c ≥9.0%) decreased to 0.34 (P < 0.001) at 24 months. Of CGM users, 65% used CGM >75% of time, and had a lower HbA1c at 24 months compared with those with usage <25% (7.8 ± 1.3% vs. 8.6 ± 1.8%, respectively, P < 0.001). Diabetic ketoacidosis was also reduced in this group (incidence rate ratio 0.49, 95% CI 0.33-0.74, P < 0.001). CONCLUSIONS: Following the national subsidy, CGM use was high and associated with sustained improvement in glycemic control. This information will inform economic analyses and future policy and serve as a model of evaluation diabetes technologies.

Novel Role of Gestational Hydralazine in Limiting Maternal and Dietary Obesity-Related Chronic Kidney Disease.

BACKGROUND: Maternal obesity is a risk factor for chronic kidney disease (CKD) in offspring, underpinning the theory of the developmental origins of health and disease. DNA methylation has been implicated in the programming of adult chronic disease by maternal obesity, therefore, DNA demethylating agents may mitigate offspring risk of disease. In rodent models, low-dose hydralazine has previously been shown to reduce renal fibrosis via DNA demethylation. We used mouse models of maternal obesity and offspring obesity to determine whether administration of low-dose hydralazine during gestation can prevent fetal programming of CKD in offspring. METHODS: Female C57BL/6 mice received high fat diet (HFD) or chow prior to mating, during gestation and lactation. During gestation, dams received subcutaneous hydralazine (5 mg/kg) or saline thrice-weekly. Male offspring weaned to HFD or chow, which continued until endpoint at 32 weeks. Biometric and metabolic parameters, renal global DNA methylation, renal functional and structural changes, and renal markers of fibrosis, inflammation and oxidative stress were assessed at endpoint. RESULTS: Offspring exposed to maternal obesity or diet-induced obesity had significantly increased renal global DNA methylation, together with other adverse renal effects including albuminuria, glomerulosclerosis, renal fibrosis, and oxidative stress. Offspring exposed to gestational hydralazine had significantly reduced renal global DNA methylation. In obese offspring of obese mothers, gestational hydralazine significantly decreased albuminuria, glomerulosclerosis, and serum creatinine. Obese offspring of hydralazine-treated lean mothers displayed reduced markers of renal fibrosis and oxidative stress. CONCLUSION: Gestational hydralazine decreased renal global DNA methylation and exerted renoprotective effects in offspring. This supports a potential therapeutic effect of hydralazine in preventing maternal obesity or dietary obesity-related CKD, through an epigenetic mechanism.

The Role of the Gut Microbiome in Diabetes and Obesity-Related Kidney Disease.

Diabetic kidney disease (DKD) is a progressive disorder, which is increasing globally in prevalence due to the increased incidence of obesity and diabetes mellitus. Despite optimal clinical management, a significant number of patients with diabetes develop DKD. Hence, hitherto unrecognized factors are likely to be involved in the initiation and progression of DKD. An extensive number of studies have demonstrated the role of microbiota in health and disease. Dysregulation in the microbiota resulting in a deficiency of short chain fatty acids (SCFAs) such as propionate, acetate, and butyrate, by-products of healthy gut microbiota metabolism, have been demonstrated in obesity, type 1 and type 2 diabetes. However, it is not clear to date whether such changes in the microbiota are causative or merely associated with the diseases. It is also not clear which microbiota have protective effects on humans. Few studies have investigated the centrality of reduced SCFA in DKD development and progression or the potential therapeutic effects of supplemental SCFAs on insulin resistance, inflammation, and metabolic changes. SCFA receptors are expressed in the kidneys, and emerging data have demonstrated that intestinal dysbiosis activates the renal renin-angiotensin system, which contributes to the development of DKD. In this review, we will summarize the complex relationship between the gut microbiota and the kidney, examine the evidence for the role of gut dysbiosis in diabetes and obesity-related kidney disease, and explore the mechanisms involved. In addition, we will describe the role of potential therapies that modulate the gut microbiota to prevent or reduce kidney disease progression.

Are newly introduced criteria for the diagnosis of gestational diabetes mellitus associated with improved pregnancy outcomes and/or increased interventions in New South Wales, Australia? A population-based data linkage study.

INTRODUCTION: The incidence of gestational diabetes mellitus (GDM) is increasing in Australia, influenced by changed diagnostic criteria. We aimed to identify whether the diagnostic change was associated with improved outcomes and/or increased obstetric interventions using state-wide data in New South Wales (NSW), Australia. RESEARCH DESIGN AND METHODS: Perinatal and hospital data were linked for singleton births, 33-41 weeks' gestation, 2006-2015, NSW. An adjusted Poisson model was used to split pregnancies from 2011 onwards into those that would have been diagnosed under the old criteria ('previous GDM') and newly diagnosed cases ('additional GDM'). We compared actual rates of total and early (<39 weeks) planned births, cesareans, and maternal and neonatal adverse outcomes for GDM-diagnosed pregnancies using three predicted scenarios, where the 'additional GDM' group was assumed to have the same rates as: the 'previous GDM' group <2011 (scenario A); the 'non-GDM' group <2011 (scenario B); or the 'non-GDM' group ≥2011 (scenario C). RESULTS: GDM incidence more than doubled over the study period, with an inflection point observed at 2011. For those diagnosed with GDM since 2011, the actual incidence of interventions (planned births and cesareans) and macrosomia was consistent with scenario A, which meant higher intervention rates, but lower rates of macrosomia, than those with no GDM. Incidence of neonatal hypoglycemia was lower than scenario A and closer to the other scenarios. There was a reduction in perinatal deaths among those with GDM, lower than that predicted by all scenarios, indicating an improvement for all with GDM, not only women newly diagnosed. Incidence of maternal and neonatal morbidity indicators was within the confidence bounds for all three predicted scenarios. CONCLUSIONS: Our study suggests that the widely adopted new diagnostic criteria for GDM are associated with increased obstetric intervention rates and lower rates of macrosomic babies, but with no clear impacts on maternal or neonatal morbidity.

Complexities surrounding the diagnosis and management of hypercalcaemia in pregnancy.

SUMMARY: Hypercalcaemia in pregnancy is uncommon, with associated adverse obstetric and perinatal outcomes for both the mother and the fetus. Determination of causality is central to its management. Diagnostic imaging techniques are limited during pregnancy and the diagnosis is made more complex by physiological changes in calcium and vitamin D homeostasis in pregnancy. Further, therapeutic options are limited due to safety considerations for the pregnant woman and the developing foetus. Three cases of hypercalcaemia in pregnancy will be presented, highlighting the distinct aetiologies and management strategies for hypercalcaemia in pregnancy and the importance of early measurement of serum calcium in pregnancy screening. LEARNING POINTS: There are complex physiological changes in calcium balance in pregnancy, including increased calcium intestinal absorption and renal excretion. Hypercalcaemia in pregnancy is uncommon but has important potential maternal and foetal complications, making a compelling argument for routine antenatal, calcium screening. Identifying the cause of hypercalcaemia in pregnancy can be challenging due to the complex placental interplay in biochemical test interpretation and due to safety constraints restricting imaging and surgery. Acute medical management of hypercalcaemia must be considered in the context of both maternal and foetal well-being, along with gestational age and specific consideration for the safety of the developing fetus in late gestation.

Low-dose hydralazine during gestation reduces renal fibrosis in rodent offspring exposed to maternal high fat diet.

BACKGROUND: Maternal high fat diet (HFD) promotes chronic kidney disease (CKD) in offspring. This is in accordance with the theory of fetal programming, which suggests adverse conditions occurring in utero predispose offspring to chronic conditions later in life. DNA methylation has been proposed as a key mechanism by which fetal programming occurs and is implicated in CKD progression. DNA demethylating drugs may interrupt the fetal programming of CKD by maternal obesity. Hydralazine, an antihypertensive agent, demethylates DNA at low doses which do not reduce blood pressure. We used a mouse model of maternal obesity to determine whether gestational administration of low-dose hydralazine to mothers can prevent CKD in offspring. METHODS: C57BL/6 dams received HFD or chow from 6 weeks prior to mating and were administered subcutaneous hydralazine (5mg/kg) or saline thrice weekly during gestation. Male offspring were weaned to chow and were sacrificed at either postnatal week 9 or week 32. Biometric and metabolic parameters, renal global DNA methylation, renal structural and functional changes and markers of fibrosis, oxidative stress and inflammation were measured in offspring at weeks 9 and 32. RESULTS: In week 9 offspring, maternal HFD consumption did not significantly alter anthropometric or metabolic parameters, or renal global DNA methylation. Week 32 offspring had increased renal global DNA methylation, together with albuminuria, glomerulosclerosis, renal fibrosis and oxidative stress. Administration of low-dose hydralazine to obese mothers during gestation reduced renal global DNA methylation and renal fibrotic markers in week 32 offspring. CONCLUSION: Gestational hydralazine reduced renal global DNA methylation in offspring of obese mothers and attenuated maternal obesity-induced renal fibrosis. These data support the use of low-dose hydralazine as a demethylating agent to prevent CKD arising in offspring due to maternal HFD consumption.