Gestational diabetes in a rural, regional centre in south Western Australia: predictors of risk.

INTRODUCTION: Gestational diabetes mellitus (GDM) is the most common antenatal complication in Western Australia. Rural areas may be at greater risk due to poorer socioeconomic status, reduced healthcare access, increased obesity and greater Aboriginal population. This paper reviews the prevalence and risk factors of GDM and outcomes for pregnancies in a regional rural centre, with a view to predicting the risk of GDM in this population, given factors identified early in the pregnancy. METHODS: Retrospective logistic regression analysis of all deliveries at Bunbury Regional Hospital (BRH) from February 2009 to March 2011 was used to produce a risk score for development of GDM. RESULTS: Of 1645 women delivered at BRH in the study period, nine had pre-existing diabetes and were excluded. A further 73 (4.46%) developed GDM in the current pregnancy. Logistic regression showed GDM to be strongly associated with maternal obesity (adjusted odds ratio 2.48; 95% CI 1.62-3.82), age (2.21; 1.57-3.09) lowest socioeconomic quintile (2.34; 1.23-4.22) and Asian ethnicity (3.47; 1.25-8.26). A cut-off value of 0.4 for the scoring system predicted the absence of GDM in 97.75% of women with a sensitivity of 69.9% and a predicted risk of 20.7% for GDM. Maternal outcomes showed that GDM was associated with an increased caesarean section rate (48.0% vs 30.8%; p=0.0066), lower spontaneous vaginal birth rate (37.7% vs 56.6%; p=0.048), postpartum haemorrhage (28.8% vs 17.7%; p=0.028) and longer median hospital stay (3 vs 2 days; p=0.0001). Neonatal outcomes showed a threefold increase in shoulder dystocia (10.5% vs 3.5%; p=0.025). CONCLUSIONS: These results confirm the known association of GDM with age; obesity, lower socioeconomic quintile and Asian ethnicity are also present in the rural population. The absence of association with Aboriginal ethnicity was not expected and is discussed.

Recommendations for the prevention of pregnancy-associated venous thromboembolism.

Pregnancy is a risk factor for venous thromboembolism (VTE), an important cause of maternal morbidity and mortality. Although there is a 4-5-fold increased risk compared to that of nonpregnant women of the same age, the absolute risk is low at no more than two episodes of VTE per 1000 pregnancies. There is uncertainty about which women require thromboprophylaxis during pregnancy or postpartum because of a lack of data from appropriate clinical trials. For this reason, recommendations for prophylaxis should be made only after explaining the available evidence to the patient and taking into account her perception of the balance of risk and benefit in thromboprophylaxis. The aim of these recommendations is to provide clinicians with practical advice to assist in decisions regarding thromboprophylaxis in women considered to be at risk of VTE during pregnancy and the postpartum. The authors are clinicians from across New Zealand and Australia representing the fields of haematology, obstetric medicine, anaesthesiology, maternal-fetal medicine and obstetrics. Authors were invited to review the relevant literature and then worked collaboratively to devise recommendations and resolve areas of controversy. The recommendations contained herein were reached by consensus and represent the opinion of the panel. The absence of randomised clinical trials in this area limits the strength of evidence that can be used, and it is acknowledged that they represent level C evidence. The panel advocates for appropriate clinical studies to be carried out in this patient population to address the inadequacy of present evidence.

Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period.

Venous thromboembolism (VTE) in pregnancy and the postpartum is an important cause of maternal morbidity and mortality; yet, there are few robust data from clinical trials to inform an approach to diagnosis and management. Failure to investigate symptoms suggestive of pulmonary embolism (PE) is a consistent finding in maternal death enquiries, and clinical symptoms should not be relied on to exclude or diagnose VTE. In this consensus statement, we present our recommendations for the diagnosis and management of acute deep venous thrombosis (DVT) and PE. All women with suspected DVT in pregnancy should be investigated with whole leg compression ultrasonography. If the scan is negative and significant clinical suspicion remains, then further imaging for iliofemoral DVT maybe required. Imaging should be undertaken in all women with suspected PE, as the fetal radiation exposure with both ventilation/perfusion scans and CT pulmonary angiography is within safe limits. Low-molecular-weight heparin (LMWH) is the preferred therapy for acute VTE that occur during pregnancy. In observational cohort studies, using once-daily regimens appears adequate, in particular with the LMWH tinzaparin; however, pharmacokinetic data support twice-daily therapy with other LMWH and is recommended, at least initially, for PE or iliofemoral DVT in pregnancy. Treatment should continue for a minimum duration of six months, and until at least six weeks postpartum. Induction of labour or planned caesarean section maybe required to allow an appropriate transition to unfractionated heparin to avoid delivery in women in therapeutic doses of anticoagulation.

Using clinical symptoms to predict adverse maternal and perinatal outcomes in women with preeclampsia: data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study.

OBJECTIVES: Preeclampsia is a leading cause of maternal morbidity. The clinical challenge lies in predicting which women with preeclampsia will suffer adverse outcomes and would benefit from treatment, while minimizing potentially harmful interventions. Our aim was to determine the ability of maternal symptoms (i.e., severe nausea or vomiting, headache, visual disturbance, right upper quadrant pain or epigastric pain, abdominal pain or vaginal bleeding, and chest pain or dyspnea) to predict adverse maternal or perinatal outcomes. METHODS: We used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a multicentre, prospective cohort study designed to investigate the maternal risks associated with preeclampsia. Relative risks and receiver operating characteristic (ROC) curves were assessed for each preeclampsia symptom and outcome pair. RESULTS: Of 2023 women who underwent assessment, 52% experienced at least one preeclampsia symptom, with 5.2% and 5.3% respectively experiencing an adverse maternal or perinatal outcome. No symptom and outcome pair, in either of the maternal or perinatal groups, achieved an area under the ROC curve value > 0.7, which would be necessary to demonstrate a discriminatory predictive value. CONCLUSION: Maternal symptoms of preeclampsia are not independently valid predictors of maternal adverse outcome. Caution should be used when making clinical decisions on the basis of symptoms alone in the preeclamptic patient.

PIERS proteinuria: relationship with adverse maternal and perinatal outcome.

OBJECTIVE: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. METHODS: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments. RESULTS: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. CONCLUSION: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.

Preeclamptic angina--a pathognomonic symptom of preeclampsia.

AIM: To describe an important symptom of preeclampsia previously not defined. METHODS: Individual clinician experience case series collected and recorded prospectively. RESULTS: Little attention has been given to symptoms in the diagnosis of preeclampsia. Although "epigastric pain" is often mentioned, there is no accurate description in the literature of the specific diagnostic attributes that distinguish the upper abdominal pain of preeclampsia from that of other causes. The symptom is described herein and defined as "preeclamptic angina" (PEA). It is associated strongly with severe preeclampsia but often not recognized, particularly when it is not accompanied by usual features of preeclampsia. It is experienced typically as a severe pain that begins at night, usually maximal in the low retrosternum or epigastrium, constant and unremitting for 1-6 h. It may radiate or be confined to the right hypochondrium or back. The liver is tender on palpation. The pain may precede the diagnosis of preeclampsia by 7 days or more and may be the only abnormality on presentation such that preeclampsia is not suspected. It is of ominous prognosis and is associated with a high rate of maternal and fetal complications. Laboratory and clinical abnormalities of preeclampsia are ultimately manifest in all cases, but their absence at the time of presentation may lead to erroneous alternative diagnoses. Recognition of this characteristic symptom will lead to earlier diagnosis of preeclampsia in atypical cases, with the potential to avoid maternal and perinatal morbidity and mortality.

Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model.

BACKGROUND: Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. METHODS: We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. FINDINGS: 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 [5%] within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84-0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. INTERPRETATION: The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. FUNDING: Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute.

Sepsis in pregnancy and early goal-directed therapy.

Sepsis is a major cause of serious morbidity and mortality in pregnant women and their babies. Conventional management has evolved over many years. Improved understanding of the underlying pathophysiology and randomized clinical trials have led to recommendations for the formalization and standardization of the management of severe sepsis in non-pregnant patients. Most of these recommendations are applicable to pregnancy. The Surviving Sepsis Campaign and Early Goal Directed Therapy have relevance to the care of pregnant women with serious infection and are reviewed here.

Pregnancy and Medicine: sine qua non or non sequitur?

Pregnancy is intrinsically imperfect, with high rates of complications for mothers and babies. A minority of pregnancies is entirely uncomplicated. Medical disorders are frequent contributors to morbidity for mothers and babies, and have become the major source of maternal mortality. For these reasons, Medicine plays a central role in the care of pregnant women. Provision of resources to maternity services must recognise the changing demographics and clinical characteristics of pregnant women in Australia, and their increased medical risk status in recent years.

The Australasian Diabetes in Pregnancy Society consensus guidelines for the management of type 1 and type 2 diabetes in relation to pregnancy.

Strict control of blood glucose levels should be pursued before conception and maintained throughout the pregnancy (glycohaemoglobin [HbA(1c)] level as close as possible to the reference range). Before conception: high-dose (5 mg daily) folate supplementation should be commenced; oral hypoglycaemic agents should be ceased; and diabetes complications screening should take place. Management should be by a multidisciplinary team experienced in the management of diabetes in pregnancy. Blood glucose monitoring is mandatory during pregnancy, and targets are: fasting 4.0-5.5 mmol/L; postprandial < 8.0 mmol/L at 1 hour; < 7 mmol/L at 2 hours. A first trimester nuchal translucency (possibly with first trimester biochemical screening with pregnancy-associated plasma protein A and beta-human chorionic gonadotropin) should be offered. Ultrasound should be performed for fetal morphology at 18-20 weeks, if required, for cardiac views at 24 weeks and for fetal growth at 28-30 and 34-36 weeks. Induction of labour or operative delivery should be based on obstetric and/or fetal indications. Level 3 neonatal nursing facilities may be required and should be anticipated when birth occurs before 36 weeks, or if there has been poor glycaemic control. Insulin requirements fall rapidly during labour and in the puerperium. At this time, close monitoring and adjustment of insulin therapy is necessary.

Factors predisposing to pre-eclampsia in women with gestational diabetes.

BACKGROUND: Lipid abnormalities occur before the onset of pre-eclampsia but their role in its pathogenesis is unclear. We tested the hypothesis that lipid abnormalities precede and contribute to the development of pre-eclampsia using women with gestational diabetes (GDM) as a focus population. METHODS: One hundred and eighty-four women with a diagnosis of GDM were studied. Anthropometry, blood pressure, fasting lipids, glucose homeostasis, markers of inflammation and endothelial damage were measured and family history of disease was assessed to determine those measures at diagnosis of GDM that best predicted the development of pre-eclampsia. RESULTS: Twelve percent of women with GDM developed pre-eclampsia. At diagnosis of GDM, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were not different in women who subsequently developed pre-eclampsia (GDM-PE). GDM-PE had elevated body mass index, blood pressure, fasting glucose, insulin, uric acid, and C-reactive protein (CRP), which have all been linked with the 'metabolic syndrome'. They had a greater degree of microalbuminuria and more frequently reported a family history of hypertension and maternal gestational diabetes. In logistic regression, the significant independent predictors for developing pre-eclampsia were fasting glucose, CRP, a family history of hypertension and the proband's mother having gestational diabetes. CONCLUSION: The results suggest that, in GDM, increased severity of insulin resistance and related features of the 'metabolic syndrome', rather than lipid abnormalities, are precursors to the development of pre-eclampsia and hence are likely to be implicated in the pathophysiology of this disorder. Moreover, these women are likely to be at particularly high risk of long-term cardiovascular disease and Type 2 diabetes.

Metformin therapy and diabetes in pregnancy.

No adverse pregnancy outcomes with metformin use have been reported, except in one unmatched study. Otherwise, the studies are small and non-randomised, with the exception of one prospective, randomised controlled trial, currently under way, comparing metformin with insulin in women with gestational diabetes mellitus (the MiG trial). No long-term follow-up data for offspring of mothers receiving metformin have been published. Any woman with diabetes should be as close to euglycaemia as possible before pregnancy. In some circumstances (eg, severe insulin resistance), metformin therapy during pregnancy may be warranted. When metformin treatment is being considered, the individual risks and benefits need to be discussed with the patient so that an appropriate decision can be reached.