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Summary Background Antenatal corticosteroids given to women before preterm birth improve infant survival and health. However, whether dexamethasone or betamethasone have better maternal, neonatal, and childhood health outcomes remains unclear. We therefore aimed to assess whether administration of antenatal dexamethasone to women at risk of preterm birth reduced the risk of death or neurosensory disability in their children at age 2 years compared with betamethasone. We also aimed to assess whether dexamethasone reduced neonatal morbidity, had benefits for the mother, or affected childhood body size, blood pressure, behaviour, or general health compared with betamethasone. Methods In this multicentre, double-blind, randomised controlled trial, we recruited pregnant women from 14 maternity hospitals in Australia and New Zealand that could provide care to preterm babies. Women were eligible for study inclusion if they were at risk of preterm birth before 34 weeks of gestation, had a singleton or twin pregnancy, and had no contraindications to antenatal corticosteroids. We randomly assigned women (1:1) to receive two intramuscular injections of either 12 mg dexamethasone (dexamethasone sodium phosphate) or 11·4 mg betamethasone (Celestone Chronodose), 24 h apart. The randomisation schedule used balanced, variable blocks that were stratified by hospital, gestational age, and number of fetuses (singleton or twins). We masked all participants, staff, and assessors to treatment groups. Analyses were by intention to treat. The primary outcome was death or neurosensory disability at age 2 years (corrected for prematurity). This study is registered with ANZCTR, ACTRN12608000631303. Findings Between Jan 28, 2009, and Feb 1, 2013, we randomly assigned 1346 (78%) women who were pregnant with 1509 fetuses to groups: 679 (50%) women were assigned to receive dexamethasone and 667 (50%) women were assigned to receive betamethasone. 27 (4%) fetuses, infants, or children in the dexamethasone group and 28 (4%) fetuses, infants, or children in the betamethasone group died before age 2 years. The primary outcome of death or neurosensory disability at age 2 years was determined for 603 (79%) of 763 fetuses whose mothers received dexamethasone and 591 (79%) of 746 fetuses whose mothers received betamethasone. We found a similar incidence of death or neurosensory disability in the dexamethasone (198 [33%] of 603 infants) and betamethasone groups (192 [32%] of 591 infants; adjusted relative risk [adjRR] 0·97, 95% CI 0·83 to 1·13; p=0·66). 18 (3%) of 679 women in the dexamethasone group and 28 of 667 (4%) women in the betamethasone group reported side-effects. Discomfort at the injection site, the most frequent side-effect, was less likely in the dexamethasone group than in the betamethasone group (six [1%] women vs 17 [3%] women; p=0·02). Interpretation The incidence of survival without neurosensory disability at age 2 years did not differ between dexamethasone and betamethasone treatment. Our findings indicate that either antenatal corticosteroid can be given to women before preterm birth to improve infant and child health. Funding National Health and Medical Research Council (Australia).

Barriers to women's reproductive health care access, particularly for termination of pregnancy, are increasing at the local, regional, and national levels through numerous institutional, legislative, and regulatory restrictions. Lack of access to reproductive health care has negative consequences for women's health. Twelve women's health care organizations affirm their support for access to comprehensive reproductive health care, including abortion.

Background: von Willebrand disease (vWD) is a heterogeneous hereditary bleeding disorder and is associated with risk of primary postpartum haemorrhage (PPH). Design and methods: An observational study at a tertiary referral centre in Australia of 16 women with 23 deliveries with a median age of 27.5 years (range, 21-39; IQR = 9). Median gestational age at delivery was 39 weeks (range, 35-41; IQR = 1.1). Results: All cases had type 1 vWD, apart from one case with type 2. Patients were managed in combined obstetrics and haematology clinics. PPH occurred in ten deliveries (44%). Intravenous desmopressin was administered in 6 cases, and IV human vWF was administered in 4 cases. Two cases with mild vWD had received oral tranexamic acid. The median Apgar score at 1 and 5 min was 9 (IQR = 1.0), while the median Apgar score at 10 min was 10.0 (IQR = 0.0). One case required transfusion of blood products postdelivery. There were no other significant complications observed. Conclusions: was associated with a high incidence of primary PPH. Individualised treatment to restore haemostasis, according to the severity of the disease, could achieve as possible, normal haemostasis with favourable outcomes for both mothers and their infants. Further studies to confirm our findings are warranted.

Background Gestational diabetes mellitus (GDM) is associated with life-long increased risk of type 2 diabetes: affected women are advised to undergo oral glucose tolerance testing (OGTT) at 6–12 weeks postpartum, then glucose screening every 1–3 years. Aims We investigated whether in women with GDM, antenatal clinical factors predicted postpartum abnormal glucose tolerance and compliance with screening. Materials and methods In women with GDM delivering 2007 to mid-2009 in a single hospital, antenatal/obstetric data and glucose tests at 6–12 weeks postpartum and during 5.5 years post-pregnancy were retrospectively collected. Predictors of return for testing and abnormal glucose tolerance were identified using multivariate analysis. Results Of 165 women, 117 (70.9%) returned for 6–12 week postpartum OGTT: 23 (19.6%) were abnormal. Smoking and parity, independent of socioeconomic status, were associated with non-return for testing. Fasting glucose ≥5.4 mmol/L on pregnancy OGTT predicted both non-return for testing and abnormal OGTT. During 5.5 years post-pregnancy, 148 (89.7%) women accessed glucose screening: nine (6.1%) developed diabetes, 33 (22.3%) had impaired fasting glucose / impaired glucose tolerance. Predictors of abnormal glucose tolerance were fasting glucose ≥5.4 mmol/L and 2-h glucose ≥9.3 mmol/L on pregnancy OGTT (~2.5-fold increased risk), and polycystic ovary syndrome (~3.4 fold increased risk). Risk score calculation, based on combined antenatal factors, did not improve predictions. Conclusions Antenatal clinical factors were modestly predictive of return for testing and abnormal glucose tolerance post-pregnancy in women with GDM. Risk score calculations were ineffective in predicting outcomes: risk scores developed in other populations require validation. Ongoing glucose screening is indicated for all women with GDM.

CONTEXT Miscarriage care can safely and effectively be offered in appropriately equipped offices and emergency departments. However, it is often treated in the operating room, which limits access to timely, cost-effective and high-quality care. METHODS Between May 2013 and January 2014, in-depth interviews were conducted with 30 staff holding diverse roles at 15 medical offices and emergency departments with the aim of exploring barriers to and facilitators of offering miscarriage care, and identifying methods for expanding care. On-site observations were also conducted at four facilities. All data were transcribed, iteratively coded and analyzed using qualitative techniques. RESULTS Similar barriers to and facilitators of providing miscarriage care were identified across facility types. Barriers were physician preference for providing care in the operating room, the similarity of miscarriage management and abortion procedures, the limited availability of support staff, difficulties integrating miscarriage management into patient scheduling and flow, and uncertainty about responding to women's emotional needs. Facilitators were a commitment to evidence-based medicine, insurance coverage of miscarriage, offering other procedures of similar complexity and the minimal resources needed for miscarriage care. Resources needed to expand miscarriage services included a medically trained “champion,” best practices for implementing services, persistence and patience, training, clear protocols, and systems for tracking equipment and supplies. CONCLUSIONS Miscarriage care was viewed as neither resource-intensive nor technically complex to provide. Although it may be emotionally and politically challenging to offer, effective strategies are available for expanding the scope of miscarriage care offered in multiple settings.

Objective: There is a need for emerging Australian data on emergency peripartum hysterectomy (EPH) especially in rural areas due to the associated high maternal morbidity and mortality. The aim of this study is to review the incidence and complications of EPH in the northern region of Tasmania. Design: A retrospective cohort study at a single health care institution during a 10 year period. Setting: Launceston General Hospital, the main maternity referral centre for the northern region of Tasmania. Participants: Case notes of women coded with hysterectomy during childbirth were included and analysed. Main outcome measures: Primary outcomes were maternal and neonatal morbidity and mortality. Results: Eighteen women were identified, giving an incidence of 1.01 per 1000 births. Indications for surgery were abnormal placentation, uterine atony and uterine rupture. Maternal morbidity was high, and included intensive care admissions (55%), disseminated intravascular coagulopathy (50%), hypovolemic shock (38%), febrile illness (27%) and urinary tract injuries (22%). The mean estimated total blood loss was 4091.6 mL, and 88% of women received blood transfusions. All women received prophylactic antibiotics. Women with morbidly adherent placenta were likely to experience more complications and transfusions. There were no maternal or neonatal deaths identified. Conclusion: The rate of peripartum hysterectomy in rural Tasmania is higher compared with other Australian tertiary-level hospitals, suggesting that Australian women birthing in rural and regional areas might be at greater risk. Maternal morbidity associated with abnormal placentation is high; hence, better diagnostic modalities and multidisciplinary antenatal management are required to improve maternal outcomes.

Pregnancy is a hypercoagulable state associated with an increased risk of venous thromboembolic disease (VTE). We retrospectively studied 38 Caucasian pregnant women with thrombophilia risk and compared their obstetric outcomes with a matched cohort without known thrombophilia risk during the period between January 2007 and December 2010. There were (2) cases with factor V Leiden, (6) prothrombin gene mutation, (1) antithrombin III deficiency, (2) protein C deficiency, (3) protein S deficiency, (10) MTHFR mutation, (7) anti-cardiolipin antibodies, and (1) lupus anticoagulant. Patients without thrombophilia who presented with recurrent unprovoked VTE were considered as high risk (6 cases). Most patients received anticoagulation (34/38) with aspirin only (6), enoxaparin (27), and warfarin (1). Twenty-six out of thirty-eight pregnant women (68.4%) with an increased risk of thrombophilia experienced one or more obstetric complications defined as hypertension, preeclampsia, placenta abruptio, VTE, and oligohydramnios, compared with 15 out of 40 (37.5%) pregnant women in the control group (OR 3.6; 95% CI 1.42, 9.21,P<0.001). The incidence of obstetric complications was significantly higher in the thrombophilia group compared to the controls. However, these complications were the lowest among patients who received full-dose anticoagulation. Our study suggests that strict application of anticoagulation therapy for thrombophilia of pregnancy is associated with an improved pregnancy outcome. The study was registered in the Australian and New Zealand Clinical Trials Registry underACTRN12612001094864.

Cancers are initiated as a result of changes that occur in the genome. Identification of gains and losses in the structure and expression of tumor-suppressor genes and oncogenes lies at the root of the understanding of cancer cell biology. Here, we show that the mitogen–activated protein kinase (MAPK) MKK3 suppresses the growth of breast cancer, in which it varies in copy number. A pervasive loss of MKK3 gene copy number in patients with breast cancer is associated with an impairment of MKK3 expression and protein level in malignant tissues. To assess the functional role of MKK3 in breast cancer, we showed in an animal model that MKK3 activity is required for suppression of tumor growth. Active MKK3 enhanced expression of the cyclin-dependent kinase inhibitors p21Cip1/Waf1 and p27Kip1, leading to increased cell-cycle arrest in G1 phase of the cell cycle. Our results reveal the functional significance of MKK3 as a tumor suppressor and improve understanding of the dynamic role of the MAPK pathway in tumor progression. Cancer Res; 74(1); 162–72. ©2013 AACR.

Background: Metformin is increasingly accepted as an alternative to insulin therapy in gestational diabetes mellitus (GDM). The Metformin in Gestational Diabetes (MiG) trial reported similar pregnancy outcomes for metformin versus insulin; however, supplemental insulin was required in 46% of women on metformin. Aims: We aimed to identify predictors of response to metformin monotherapy in women with GDM attending a general hospital antenatal clinic. Methods We offered extended-release metformin to women diagnosed with GDM (ADIPS 1998 criteria) at ≥24 weeks of gestation. If glucose targets were not achieved (≤5.0 mmol/L fasting, ≤6.7 mmol/L two-h post-meal), women were changed to insulin. We carried out an audit to determine characteristics of metformin responders versus nonresponders. Results: Twenty-five women chose initial metformin therapy; 16 (64%) achieved satisfactory glycaemic control (responders). Nine women (36%) were changed to insulin: seven due to inadequate control (nonresponders) and two had metformin intolerance. Fasting glucose at oral glucose tolerance test (OGTT) was significantly lower in metformin responders versus nonresponders; two-h glucose and BMI did not differ. Ninety-three percent of women with fasting glucose ≤5.2 mmol/L responded to metformin: conversely, at fasting glucose >5.2 mmol/L, 33% responded ( P = 0.005). Neonatal outcomes were similar in metformin responders and nonresponders, women who chose initial insulin therapy ( n = 25), or were diet-controlled ( n = 21). Conclusions: In women with GDM, fasting glucose on OGTT predicted response to metformin: at fasting glucose ≤5.2 mmol/L, the probability of response was 93%. Antenatal clinics should determine locally relevant predictors of response to metformin in women with GDM.

Introduction: Aboriginal and Torres Strait Islander women are at increased risk of maternal morbidity and mortality as compared to non-Aboriginals. Similarly, aboriginal babies are at increased risk of low birth weight and infant mortality. Aim: To investigate the independent association of aboriginality with Tasmanian maternal and neonatal morbidity. Materials and Methods: A retrospective analysis of all the births (gestation more than 20 weeks) from June 2013 to May 2014 was conducted at the Launceston General Hospital, Tasmania. The study compared 66 Aboriginal (4.2% of the total births) to 1477 non-aboriginal births for maternal and neonatal morbidity. Comparisons were made using logistic regression. The outcome measures were maternal and neonatal morbidity. Results: Significantly higher number of aboriginal women (49% vs 19%; OR 4.15 90%CI 2.52- 6.85) smoked and used illicit drugs (15% vs 2%; OR 9.24; 95%CI 4.28-19.96) than the non-aboriginal women (both p

Nutritional iron-deficiency anaemia (IDA) is the most common disorder in the world, affecting more than two billion people. The World Health Organization’s global database on anaemia has estimated a prevalence of 14% based on a regression-based analysis. Recent data show that the prevalence of IDA in pregnant women in industrialized countries is 17.4% while the incidence of IDA in developing countries increases significantly up to 56%. Although oral iron supplementation is widely used for the treatment of IDA, not all patients respond adequately to oral iron therapy. This is due to several factors including the side effects of oral iron which lead to poor compliance and lack of efficacy. The side effects, predominantly gastrointestinal discomfort, occur in a large cohort of patients taking oral iron preparations. Previously, the use of intravenous iron had been associated with undesirable and sometimes serious side effects and therefore was underutilised. However, in recent years, new type II and III iron complexes have been developed, which offer better compliance and toleration as well as high efficacy with a good safety profile. In summary, intravenous iron can be used safely for a rapid repletion of iron stores and correction of anaemia during and after pregnancy.

Background Provision of emergency contraceptive pills (ECPs) is widely recognized as the standard of care to prevent pregnancy after a sexual assault. However, previous research has shown that hospitals do not routinely counsel sexual assault patients about or provide sexual assault survivors with ECPs or accurate referrals. Methods We undertook a mixed methods study to assess policies and practices regarding the provision of ECPs for sexual assault survivors in South Carolina. The study includes four components: An analysis of the South Carolina Victims' Rights Amendment, in-depth interviews with rape crisis agency and state agency representatives, a survey of hospital emergency department staff, and a survey of hospital emergency department administrators. Findings Our findings indicate that hospital policies and practices regarding ECP-related services for sexual assault patients are generally consistent with the standard of care. According to hospital staff and administrators, requiring a police report and/or undergoing a rape kit examination before providing ECPs do not seem to be significant access barriers. However, hospitals that do not conduct rape kit examinations transfer patients to other facilities, and these initial hospitals do not routinely provide patients with ECPs before transfer. Conclusion Our findings suggest that further research to document whether transfer practices and reporting requirements impede access to ECPs is warranted. Furthermore, our results support the recommendation that any woman reporting sexual assault should be immediately offered dedicated, progestin-only ECPs. Last, our results suggest that key stakeholders in the sexual assault community could be engaged to improve sexual assault and ECP-related services in South Carolina.

Khalafallah A, Dennis A, Bates J, Bates G, Robertson IK, Smith L, Ball MJ, Seaton D, Brain T, Rasko JEJ Launceston General Hospital (LGH), Australia; University of Tasmania, Australia; and Centenary Institute, University of Sydney, NSW, Australia) A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy. J Intern Med 2010; 268: 286–295. Background. Iron deficiency anaemia is the most common deficiency disorder in the world, affecting more than one billion people, with pregnant women at particular risk. Objectives and design. We conducted a single site, prospective, nonblinded randomized-controlled trial to compare the efficacy, safety, tolerability and compliance of standard oral daily iron versus intravenous iron Subjects. We prospectively screened 2654 pregnant women between March 2007 and January 2009 with a full blood count and iron studies, of which 461 (18%) had moderate IDA. Two hundred women matched for haemoglobin concentration and serum ferritin level were recruited. Interventions. Patients were randomized to daily oral ferrous sulphate 250 mg (elemental iron 80 mg) with or without a single intravenous iron polymaltose infusion. Results. Prior to delivery, the intravenous plus oral iron arm was superior to the oral iron only arm as measured by the increase in haemoglobin level (mean of 19.5 g/L vs. 12 g/L; P

Epilepsy is a chronic condition that is usually managed through antiepileptic drugs (AEDs). An estimated 1 million girls and women in the USA have the disorder. The stigma associated with epilepsy can impact their quality of life, including their romantic and sexual relationships and reproductive decisions. Women with epilepsy (WWE) can use contraception safely and successfully, though difficulties understanding confusing drug-drug interactions and navigating complex health systems can make obtaining appropriate contraceptive care challenging. Nonhormonal methods pose no unique issues for WWE. However, there is potential for bidirectional interactions between AEDs and hormonal contraceptives. AEDs that induce hepatic cytochrome P450 enzymes can reduce hormonal contraceptive effectiveness. Optimal contraceptive methods for women taking enzyme-inducing AEDS include any intrauterine device (IUD) or depot medroxyprogesterone acetate (DMPA, 150 mg). Recommendations for women taking no AED or non-inducing AEDs mirror those for their healthy peers. Estrogenic components of combined methods rapidly lead to large reductions in lamotrigine (LTG) levels. When combined hormonal methods are used, LTG dose adjustment is necessary in consultation with a neurologist to maintain seizure control. Accurate contraceptive guidance promotes both the reproductive and neurological health of WWE.

Background To date there is minimal data available on D-Dimer levels at different stages of pregnancy. Patients and methods We prospectively measured D-Dimer levels in 632 consecutive pregnant women from March 2007 to January 2009. The median age of the participants was 31 years (range; 18–42) with a median weight of 78 kilograms (range; 46–137). All subjects were investigated during each trimester with two different immunoturbidimetric assays; D-Dimer PLUS and INNOVANCE D-Dimer. D-Dimer levels were determined using a Sysmex® CA 1500 analyser. Results Our data demonstrate that D-Dimer levels in pregnancy show different patterns of rise within the first trimester, depending on the assay used; D-Dimer PLUS = 0.88 (SD: mean ratio), INNOVANCE D-Dimer = 0.72 (SD: mean ratio). Furthermore, the rise in mean results was greater for the INNOVANCE D-Dimer assay compared to the D-Dimer PLUS assay as shown by the ratio of third to first trimester results of 3.68 and 1.96 respectively. Both D-Dimer assays demonstrated moderate levels of intra-subject variability, with overall mean CVs of 16.5% (D-Dimer PLUS) and 16.9% (INNOVANCE D-Dimer). Furthermore, we studied the association between D-Dimer levels and occurrence of diseases of pregnancy. For both assays, there was no consistently interpretable evidence of an association between raised mean D-Dimer levels or rising D-Dimer levels and any of the diseases or conditions associated with pregnancy. Conclusion Our data suggest that the INNOVANCE D-Dimer assay increases significantly with the advancement of pregnancy, and is more sensitive than D-Dimer PLUS assay in the pregnant population.

Introduction In the United States, ectopic pregnancies are relatively common and associated with significant maternal morbidity and mortality. The Ethical and Religious Directives for Catholic Health Care Services (the Directives ) govern the provision of care in Catholic-affiliated hospitals and prohibit the provision of abortion in almost all circumstances. Although ectopic pregnancies are not viable, some Catholic ethicists have argued that the Directives preclude physicians at Catholic hospitals from managing tubal pregnancies with methods and procedures that involve "direct" action against the embryo. Methods We undertook this qualitative study to explore the relationship between the Directives , hospital policies regarding ectopic pregnancy management, and clinical practices. We recruited participants at non-Catholic, longstanding Catholic, and recently merged facilities and conducted focused interviews with 24 physicians at 16 hospitals in 10 states. Findings Participants from three Catholic facilities reported that medical therapy with methotrexate was not offered because of their hospitals' religious affiliation. The lack of methotrexate resulted in changes in counseling and practice patterns, including managing ectopic pregnancies expectantly, providing the medication surreptitiously, and transferring patients to other facilities. Further, several physicians reported that, before initiating treatment, they were required to document nonviability through what they perceived as unnecessary paperwork, tests, and imaging studies. Conclusion Our findings suggest that some interpretations of the Directives are precluding physicians from providing women with ectopic pregnancies with information about and access to a full range of treatment options and are resulting in practices that delay care and may expose women to unnecessary risks.

Background Anal cancer is an HPV-mediated neoplasia of the squamous epithelium of the anus. A hitherto unexplained feature of anal cancer epidemiology is its much higher frequency among women, who comprise nearly two thirds of cases. Methods Cross-sectional study of women with a history of an HPV-mediated gynaecological neoplasia in Tasmania, Australia. Women presenting for follow-up gynaecological care had anal swab samples taken for anal cytology by Hologic Liquid ThinPrep and HR-HPV typing. Women with abnormal anal cytology were invited for high-resolution anoscopy (HRA). Covariates of anal outcomes evaluated by log-binomial and log-multinomial regression. Results 163 women had anal swabs taken and comprised the study sample, of whom 40.0% had abnormal cytology (28.2% high-grade). Of the 50 women with abnormal anal cytology having an HRA, 64.0% had abnormal histology (26.0% high-grade). Of the 120 women having anal HPV typing done, 31.7% had HR-HPV carriage, the most common types being 51 (11.5%) and 16 (9.2%). In addition to some known anal cancer risk factors, we found front-to-back (FTB) wiping was associated with significantly increased prevalence of cytological and histological abnormality and HR-HPV carriage, while dabbing post-toilet was significantly decreased prevalences of all anal outcomes, all robust to adjustment. Conclusions We have shown here that post-toilet wiping behaviours, specifically FTB and dabbing, significantly modulated the prevalence of anal cytological, histological and HR-HPV carriage outcomes. While the cross-sectional design precludes ascription of causality, the biological plausibility of such an autoinoculation pathway might help explain the preponderance of anal cancer among women. Conflicts of interest We have no conflicts to disclose.

Background To date, there are no data available concerning the impact of iron therapy on the long-term well-being and health-related quality of life (HRQoL) in pregnancy. Objective To assess the long-term effect of iron therapy on HRQoL in pregnancy. Design This is a follow-up study conducted between January 2010 and January 2011 of an earlier randomised open-label clinical trial of intravenous and oral iron versus oral iron for pregnancy-related iron deficiency anaemia. We used a modified version of the SF-36 questionnaire together with the original prospective HRQoL data collected during and after pregnancy. Participants and interventions Of the original evaluable 183 pregnant Caucasian women randomised to receive oral iron or a single intravenous iron polymaltose infusion followed by oral iron maintenance, 126 women completed the follow-up HRQoL study. Methods The participants were followed up 4 weeks after treatment, predelivery and postdelivery for a median period of 32 months (range, 26–42) with a well-being and HRQoL questionnaire using a modified SF-36 QoL-survey and child growth charts as set by the Australasian Paediatric Endocrine Group (APEG). Results Patients who received intravenous iron demonstrated significantly higher haemoglobin and serum ferritin levels (p