Gestational diabetes mellitus (GDM) is a common complication of pregnancy; its rising incidence is a result of increased maternal obesity and older maternal age together with altered diagnostic criteria identifying a greater proportion of pregnant women with GDM. Its consequences are far-reaching, associated with poorer maternal and neonatal outcomes compared to non-GDM pregnancies, and GDM has implications for metabolic health in both mother and offspring. Objective markers to identify women at high risk for the development of GDM are useful to target therapy and potentially prevent its development. Established clinical risk factors for GDM include overweight/obesity, age, ethnicity, and family history of diabetes, though they lack specificity for its development. The addition of biomarkers to predictive models of GDM may improve the ability to identify women at risk of GDM prior to its development. These biomarkers reflect the pathophysiologic mechanisms of GDM involving insulin resistance, chronic inflammation, and altered placental function. In addition, the role of epigenetic changes in GDM pathogenesis highlights the complex interplay between genetic and environmental factors, potentially offering further refinement of the prediction of GDM risk. In this review, we will discuss the clinical challenges associated with the diagnosis of GDM and its current pathophysiologic basis, giving rise to potential biomarkers that may aid in its identification. While not yet validated for clinical use, we explore the possible clinical role of biomarkers in the future. We also explore novel diagnostic tools, including high throughput methodologies, that may have potential future application in the identification of women with GDM.

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.

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.

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.

Background: The placenta stands at the maternal–fetal interface and is a key organ regulating the intrauterine environment. In pregnancies exposed to obesity, placental function, signaling, and nutrient handling are adversely altered. Pre-conception weight loss is a potential intervention to alter an obesogenic milieu of pregnancy, which we investigated in a mouse model of maternal obesity using diet or administration of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. Methods: Pre-pregnancy weight loss in C57BL/6 high-fat diet (HFD)-fed dams was induced in the pre-pregnancy period by switching diet from HFD to chow diet or administering liraglutide (0.3 mg/kg/day subcutaneously for 4 weeks) whilst continuing HFD. In addition, a group of HFD-fed dams were switched to chow diet post-conception. The metabolomic profile and gene expression within the placenta was compared at day 18–20 of gestation. Results: ¹H NMR spectroscopy metabolomic analysis of placenta of HFD mice showed an altered amino acid metabolomic profile, with lower aspartate, glutamate, and glutamine levels compared to the placenta of chow-fed mice (p < 0.05). Meanwhile, gene expression analysis identified both oxidative stress and inflammation in the placentas of HFD-fed dams. Whilst dietary modification alone was sufficient to reduce markers of oxidative stress and inflammation, liraglutide treatment modulated pathological changes, including placental metabolic stress but not inflammation. Conclusions: These findings highlight the importance of dietary or pharmacological interventions in the pre- or immediate post-conception period, with pre-conception offering a critical window to reduce aberrant placental changes induced by obesity.

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. Abstract 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.