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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ItemManagement of monoamniotic twins: the question is not 'where?', but 'how?'(WILEY, 2019-02)Linked Comment: Ultrasound Obstet Gynecol 2019; 53: 175–183
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ItemPregnancy outcomes for women with pre-pregnancy diabetes mellitus in Australian populations, rural and metropolitan: A review(WILEY, 2019-04)BACKGROUND: Historically, pre-pregnancy diabetes (PPDM) is a recognised risk factor for poor pregnancy outcome. Co-existing pathology and adverse social determinants including rural-metropolitan inequities in health and healthcare access may confer additional risks. Multidisciplinary care before, during and after pregnancy can improve outcomes for women with PPDM and their infants. The extent to which rural Australian women and their families share in improved outcomes is unknown. We aimed to summarise maternal characteristics and pregnancy outcomes for women with PPDM, including women in rural settings and examine applications of existing clinical guidelines to rural Australian practice. METHODS: We sought English language population and cohort studies about PPDM using Medline, Embase, PubMed, Australian epidemiological and international clinical practice guidelines. RESULTS: Women with PPDM are changing: older, more obese, of lower parity, less likely to smoke, more likely to have type 2 rather than type 1 diabetes and shorter duration of PPDM. Women with PPDM continue to experience excess adverse pregnancy outcomes, including maternal morbidity, complicated birth, perinatal loss, congenital anomalies and mother-infant separation. On face value, clinical guidelines appear relevant to women living in rural settings but there are only a few, conflicting outcome studies for rural women with PPDM. CONCLUSIONS: PPDM is changing. A significant minority live in rural locations, and although perinatal mortality/morbidity seems to be improving, it is unclear if this is also true for rural women due to a lack of recent Australian studies. Further research is necessary to achieve excellence everywhere for women with PPDM and their babies.
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ItemTiming of diagnosis of gestational diabetes and pregnancy outcomes: A retrospective cohort(WILEY, 2019-02)BACKGROUND: Recent guidelines suggest screening high-risk women in early pregnancy for gestational diabetes (GDM); however, there is little evidence to support this. AIMS: To compare pregnancy outcomes associated with diabetes for women with risk factors for GDM according to gestation of diagnosis. Early GDM was defined as a positive test before 20 weeks gestation, late GDM as a positive test at 20 or more weeks and no GDM when both tests were negative. MATERIALS AND METHODS: Retrospective analysis in an Australian tertiary hospital of women who underwent a glucose tolerance test in pregnancy prior to 20 weeks gestation, and a repeat test after 20 weeks gestation if the initial test was negative. Results were adjusted for maternal demographics. RESULTS: Women with early GDM (n = 170) were no more likely to experience the obstetric composite outcome than women with late GDM (n = 171) or no GDM (n = 547) (early odds ratio (OR) 1.16, 95%CI 0.79-1.71; late OR 0.78, 95%CI 0.53-1.12). Infants of women with early GDM, but not late GDM, were more likely (early OR 1.8, 95%CI 1.15-2.92; late OR 1.4, 95%CI 0.90-2.23) to have the neonatal composite outcome than infants of women without GDM, predominantly due to an increase in neonatal hypoglycaemia. CONCLUSIONS: This result may be due to careful management of GDM, or because, after adjustment for maternal demographics, the early diagnosis of GDM does not substantially increase rates of adverse outcomes compared to GDM diagnosed in later pregnancy or no GDM in women with risk factors for GDM.
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ItemDiabetes and pregnancy(WILEY, 2020-12)