Obstetrics and Gynaecology - Research Publications
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ItemPrevalence of diabetic retinopathy in women with pregestational diabetes during pregnancy and the postpartum(WILEY, 2022-09)BACKGROUND: Diabetic retinopathy (DR) may be affected by pregnancy. The majority of prevalence data regarding DR in pregnancy predate the advent of contemporary guidelines for diabetes management during pregnancy. This study reports DR prevalence and associated risk factors in women with pregestational diabetes during pregnancy and the postpartum in Australia. METHODS: A total of 172 pregnant women with type 1 (T1DM) or type 2 diabetes diagnosed pre-pregnancy were prospectively recruited from two obstetrics hospitals in Melbourne (November 2017-March 2020). Eye examinations were scheduled in each trimester, at 3-, 6-, and 12-months postpartum. DR severity was graded from two-field fundus photographs by an independent grader utilising the Airlie House Classification. Sight-threatening DR (STDR) was defined as the presence of diabetic macular oedema or proliferative DR. RESULTS: Overall, 146 (84.9%) women had at least one eye examination during pregnancy. The mean age was 33.8 years (range 19-51), median diabetes duration was 7.0 years (IQR 3.0-17.0), 71 women (48.6%) had T1DM. DR and STDR prevalence during pregnancy per 100 eyes was 24.3 (95% CI 19.7-29.6) and 9.0 (95% CI 6.1-12.9); while prevalence in the postpartum was 22.2 (95% CI 16.5-29.3) and 10.0 (95% CI 5.4-17.9), respectively. T1DM, longer diabetes duration, higher HbA1c in early pregnancy, and pre-existing nephropathy were significant risk factors. CONCLUSIONS: The prevalence of DR in pregnant women was similar to the non-pregnant diabetic population in Australia. One in nine participants had STDR during pregnancy and the postpartum, highlighting the need to optimise DR management guidelines in pregnancy given the significant risk of vision loss.
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ItemObstetric and perinatal outcomes for women with pre-existing diabetes in rural compared to metropolitan settings in Victoria, Australia(WILEY, 2021-06)BACKGROUND: Pre-existing diabetes in pregnancy is associated with an increased risk of complications. Likewise, living in rural, regional and remote Victoria, Australia, is also associated with poorer health outcomes. There is a gap in the literature with regard to whether Victorian women with pre-existing diabetes experience a greater risk of adverse pregnancy outcomes compared to their metropolitan counterparts. AIM: Our objective is to compare obstetric and perinatal outcomes for women with pre-existing diabetes delivering in rural vs metropolitan hospitals in Victoria, Australia. MATERIALS AND METHODS: Retrospective population-based study using routinely collected state-based data of singleton births to women with type 1 and type 2 diabetes who delivered in metropolitan (n = 3233) and rural hospitals (n = 693) in Victoria, Australia, between 2006-2015. Pearson's χ2 test, Fisher's exact test and MannWhitney U-test were used to compare obstetric and perinatal outcomes between metropolitan and rural locations. RESULTS: Delivery in a rural hospital was associated with higher rates of stillbirth (2.3% vs 1.1%, P = 0.027), macrosomia (25.9% vs 16.9%, P < 0.001), shoulder dystocia (8.4% vs 3.5%, P < 0.001) and admission to the neonatal intensive care unit/special care nursery (73.2% vs 59.3%, P < 0.001). Smoking (18.0% vs 8.9%, P < 0.001), overweight/obesity (P = 0.047) and socioeconomic disadvantage (P < 0.001) were more common in rural women. CONCLUSIONS: Women with pre-existing diabetes who deliver in rural hospitals experience a greater risk of adverse perinatal outcomes and present with increased maternal risk factors. These results suggest a need to improve care for women with pre-existing diabetes in rural Victoria.
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ItemRisk factors for pregnancy outcomes in Type 1 and Type 2 diabetes(WILEY, 2021-01)BACKGROUND: Understanding the risk factors and pregnancy outcomes in women affected by Type 1 and Type 2 diabetes is important for pre-pregnancy counselling. AIM: To explore differences in pregnancy outcomes between women with Type 1 and Type 2 diabetes, and healthy controls, and to examine the relationships between potential adverse risk factors and pregnancy outcomes in this cohort of women. METHODS: This is a 10-year retrospective study of women with Type 1 diabetes (n = 92), Type 2 diabetes (n = 106) and healthy women without diabetes (controls) (n = 119) from a tertiary obstetric centre. Clinical and biochemical characteristics of women with Type 1 and Type 2 diabetes were determined and related to major obstetric outcomes using univariate analysis. RESULTS: Women with pre-existing diabetes had higher adverse pregnancy outcomes (preeclampsia, emergency caesarean section, preterm birth <32 and 37 weeks, large for gestational age, neonatal jaundice, Apgar score < 7 at 5 min, neonatal intensive care admission and neonatal hypoglycaemia) compared to controls. A higher birth weight gestational centile (97.4% vs 72.4%, P = 0.001) and large for gestational age rate (63.4% vs 35.8%, P = 0.001) were observed in Type 1 diabetes compared to Type 2 diabetes. There were no differences in other outcomes between women with Type 1 and 2 diabetes. CONCLUSION: In this exploratory study, risk factors for maternal adverse outcomes differ between Type 1 and Type 2 diabetes. Maternal and foetal adverse outcomes were higher in pregnancies affected by diabetes compared to healthy women but occurred with similar frequency in women with Type 1 and Type 2 diabetes.
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ItemExtracellular vesicle-associated miRNAs are an adaptive response to gestational diabetes mellitus(BMC, 2021-08-20)BACKGROUND: Gestational diabetes mellitus (GDM) is a serious public health issue affecting 9-15% of all pregnancies worldwide. Recently, it has been suggested that extracellular vesicles (EVs) play a role throughout gestation, including mediating a placental response to hyperglycaemia. Here, we investigated the EV-associated miRNA profile across gestation in GDM, assessed their utility in developing accurate, multivariate classification models, and determined the signaling pathways in skeletal muscle proteome associated with the changes in the EV miRNA profile. METHODS: Discovery: A retrospective, case-control study design was used to identify EV-associated miRNAs that vary across pregnancy and clinical status (i.e. GDM or Normal Glucose Tolerance, NGT). EVs were isolated from maternal plasma obtained at early, mid and late gestation (n = 29) and small RNA sequencing was performed. Validation: A longitudinal study design was used to quantify expression of selected miRNAs. EV miRNAs were quantified by real-time PCR (cases = 8, control = 14, samples at three times during pregnancy) and their individual and combined classification efficiencies were evaluated. Quantitative, data-independent acquisition mass spectrometry was use to establish the protein profile in skeletal muscle biopsies from normal and GDM. RESULTS: A total of 2822 miRNAs were analyzed using a small RNA library, and a total of 563 miRNAs that significantly changed (p < 0.05) across gestation and 101 miRNAs were significantly changed between NGT and GDM. Analysis of the miRNA changes in NGT and GDM separately identified a total of 256 (NGT-group), and 302 (GDM-group) miRNAs that change across gestation. A multivariate classification model was developed, based on the quantitative expression of EV-associated miRNAs, and the accuracy to correctly assign samples was > 90%. We identified a set of proteins in skeletal muscle biopsies from women with GDM associated with JAK-STAT signaling which could be targeted by the miRNA-92a-3p within circulating EVs. Interestingly, overexpression of miRNA-92a-3p in primary skeletal muscle cells increase insulin-stimulated glucose uptake. CONCLUSIONS: During early pregnancy, differently-expressed, EV-associated miRNAs may be of clinical utility in identifying presymptomatic women who will subsequently develop GDM later in gestation. We suggest that miRNA-92a-3p within EVs might be a protected mechanism to increase skeletal muscle insulin sensitivity in GDM.
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ItemA prospective review of perinatal mortality at Hospital Nacional Guido Valadares (HNGV)(WILEY, 2020-02)BACKGROUND: Timor-Leste has one of the highest perinatal mortality rates in the Asia-Pacific region. Consistent and accurate data collection improves understanding of perinatal outcomes and facilitates the development of interventions to reduce stillbirths and early neonatal deaths. AIMS: (1) To identify changes in the rates of stillbirth and early neonatal deaths from previous published data. (2) To determine if prospective data collection and the application of the simplified Causes Of Death and Associated Conditions (CODAC) classification allows better identification of perinatal deaths in Timor-Leste. METHODS: A prospective audit of perinatal deaths of women delivering at Hospital Nacional Guido Valadares (HNGV) was undertaken from January to June 2016 inclusive. The hospital birth registry, maternal and neonatal records were reviewed to determine the most likely aetiology and classification of perinatal deaths using the simplified CODAC system. RESULTS: One hundred and ten stillbirths and 28 early neonatal deaths were identified. Fifty-four percent of perinatal deaths occurred antepartum, 26% intrapartum and 20% were early neonatal deaths. Cause of death among stillbirths could not be ascertained in 40% of cases. Intrapartum asphyxia was the commonest identified aetiology of intrapartum and early neonatal deaths. CONCLUSION: There has been limited improvement in the rate of stillbirths and early neonatal deaths at HNGV. Intrapartum hypoxia and maternal hypertensive conditions were the most common identified aetiologies highlighting areas where targeted interventions may help reduce high perinatal mortality rates. Aetiology of perinatal deaths, particularly antepartum stillbirths was difficult to discern even when well-tested classification systems are used.
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ItemDiabetes and pregnancy(WILEY, 2020-12)
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ItemPregestational diabetes in pregnancy: Complications, management, surveillance, and mechanisms of disease-A review(WILEY, 2020-08)Diabetes is an increasingly common diagnosis among pregnant women. Pregestational diabetes is associated with an increase in many adverse pregnancy outcomes, which impact both on the woman and her fetus. The models of pregnancy care for women with diabetes are based largely on observational data or consensus opinion. Strategies for aneuploidy screening and monitoring for fetal well-being should be modified in women with diabetes. There is an increasing understanding of the mechanisms by which congenital anomalies and disorders of fetal growth occur, involving epigenetic modifications, changes in gene expression in critical developmental pathways, and oxidative stress. This knowledge may lead to pathways for improved care for these high-risk pregnancies.
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ItemAntibody mediated activation of natural killer cells in malaria exposed pregnant women(NATURE PORTFOLIO, 2021-02-18)Immune effector responses against Plasmodium falciparum include antibody-mediated activation of innate immune cells, which can induce Fc effector functions, including antibody-dependent cellular cytotoxicity, and the secretion of cytokines and chemokines. These effector functions are regulated by the composition of immunoglobulin G (IgG) Fc N-linked glycans. However, a role for antibody-mediated natural killer (NK) cells activation or Fc N-linked glycans in pregnant women with malaria has not yet been established. Herein, we studied the capacity of IgG antibodies from pregnant women, with placental malaria or non-placental malaria, to induce NK cell activation in response to placental malaria-associated antigens DBL2 and DBL3. Antibody-mediated NK cell activation was observed in pregnant women with malaria, but no differences were associated with susceptibility to placental malaria. Elevated anti-inflammatory glycosylation patterns of IgG antibodies were observed in pregnant women with or without malaria infection, which were not seen in healthy non-pregnant controls. This suggests that pregnancy-associated anti-inflammatory Fc N-linked glycans may dampen the antibody-mediated activation of NK cells in pregnant women with malaria infection. Overall, although anti-inflammatory glycans and antibody-dependent NK cell activation were detected in pregnant women with malaria, a definitive role for these antibody features in protecting against placental malaria remains to be proven.
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ItemExploring abnormal glucose metabolism in pregnancy among Australian Chinese migrants(BMJ PUBLISHING GROUP, 2020-01)OBJECTIVE: Gestational diabetes mellitus (GDM) is a metabolic disorder of pregnancy that is increasingly prevalent among Chinese women. Few studies have examined whether the migration status of Chinese women contributes to the risks of developing GDM during pregnancy. RESEARCH DESIGN AND METHODS: In this observational, cross-sectional and hospital-based study, we examined the prevalence of GDM and glycemic levels at oral glucose tolerance test (OGTT) among 491 Australian Chinese migrants (n=491) and native Chinese (n=1000). We defined GDM using the International Association of Diabetes and Pregnancy Study Groups guidelines. We collected data on maternal age, body mass index (BMI) and gestational age (GA) at booking and GA at delivery from medical records. We used multiple logistic and linear regression models to calculate the OR of having GDM and mean differences in glycemic levels in Australian Chinese migrants, relative to native Chinese. RESULTS: Age-at-booking and BMI-at-booking adjusted GDM prevalence was significantly higher in Australian Chinese migrants than native Chinese (19.7% vs 14.6%; p=0.01). After adjusting for age, BMI at booking and GA at booking, fasting glucose levels were significantly lower (β -0.08 mmol/L; 95% CI -0.14 to 0.02), while 2-hour glucose levels were significantly higher (0.22 mmol/L; 0.02 to 0.43) in Australian Chinese immigrants than native Chinese. CONCLUSIONS: Migration status may be a marker for abnormal glucose metabolism during pregnancy among Australian Chinese migrants, possibly due to socio-economic disadvantages and lifestyle changes associated with migration.