Pregnancy-associated gynecological cancer in New South Wales, Australia 1994-2013: A population-based historical cohort study.

INTRODUCTION: Pregnancy-associated gynecological cancer (PAGC) refers to cancers of the ovary, uterus, fallopian tube, cervix, vagina, and vulva diagnosed during pregnancy or within 12 months postpartum. We aimed to describe the incidence of, and perinatal outcomes associated with, invasive pregnancy-associated gynecological cancer. MATERIAL AND METHODS: We conducted a population-based historical cohort study using linked data from New South Wales, Australia. We included all women who gave birth between 1994 and 2013, with a follow-up period extending to September 30, 2018. Three groups were analyzed: a gestational PAGC group (women diagnosed during pregnancy), a postpartum PAGC group (women diagnosed within 1 year of giving birth), and a control group (women with control diagnosis during pregnancy or within 1 year of giving birth). We used generalized estimation equations to compare perinatal outcomes between study groups. RESULTS: There were 1 786 137 deliveries during the study period; 70 women were diagnosed with gestational PAGC and 191 with postpartum PAGC. The incidence of PAGC was 14.6/100 000 deliveries and did not change during the study period. Women with gestational PAGC (adjusted odds ratio [aAOR] 6.81, 95% confidence interval [CI] 2.97-15.62) and with postpartum PAGC (aOR 2.65, 95% CI 1.25-5.61) had significantly increased odds of a severe maternal morbidity outcome compared with the control group. Babies born to women with gestational PAGC were more likely to be born preterm (aOR 3.11, 95% CI 1.47-6.59) and were at increased odds of severe neonatal complications (aOR 3.47, 95% CI 1.45-8.31) compared with babies born to women without PAC. CONCLUSIONS: The incidence of PAGC has not increased over time perhaps reflecting, in part, the effectiveness of cervical screening and early impacts of human papillomavirus vaccination programs in Australia. The higher rate of preterm birth among the gestational PAGC group is associated with adverse outcomes in babies born to these women.

Cardiac disease in pregnancy and the first year postpartum: a story of mental health, identity and connection.

BACKGROUND: Women with cardiac disease in pregnancy and the first year postpartum often face uncertainty about their condition and the trajectory of their recovery. Cardiac disease is a leading cause of serious maternal morbidity and mortality, and the prevalence is increasing. Affected women are at risk of worsening cardiac disease, chronic illness, mental illness and trauma. This compounded risk may lead to significant and long-term negative outcomes. The aim of this study is to correct the lack of visibility and information on the experiences of women with cardiac disease in pregnancy and the first year postpartum. METHODS: A qualitative study using in-depth semi-structured interviews with twenty-five women who had acquired, congenital or genetic cardiac disease during pregnancy or the first year postpartum. Data were analysed and interpreted using a thematic analysis framework. RESULTS: Analysis of the interviews produced three major themes: 1) Ground zero: index events and their emotional and psychological impact, 2) Self-perception, identity and worthiness, and 3) On the road alone; isolation and connection. There was a narrative consistency across the interviews despite the women being diverse in age, cardiac diagnosis and cardiac health status, parity and timing of diagnosis. The thread prevailing over the temporal and clinical differences was one of distress, biographical disruption, identity, isolation, a necessitated re-imagining of their lives, and the process of multi-layered healing. CONCLUSION: Acknowledging and understanding the breadth, complexity and depth of women's experiences is fundamental to improving outcomes. Our findings provide unique insights into women's experiences and challenges across a spectrum of diseases. Most women did not report an isolated trauma or distressing event, rather there was a layering and persistence of psychological distress necessitating enhanced assessment, management and continuity of care beyond the routine 6-week postpartum check. Further research is required to understand long-term outcomes and to refine the findings for specific disease cohorts to be able to respond effectively.

Quality of life and mental health of women who had cardiac disease in pregnancy and postpartum.

PURPOSE: Cardiac disease is a leading cause of maternal morbidity and mortality yet there is limited research on women's experiences and quality of life (QoL) outcomes. The aim of this study is to explore the general and health-related QoL (HRQoL) and mental health outcomes for women who have experienced cardiac disease in pregnancy and the first 12 months postpartum (CDPP). METHODS: This exploratory descriptive study recruited 43 women with acquired, genetic and congenital CDPP. Patient reported outcomes measures (PROMs) used were: WHOQoL-Bref, a Kansas City Cardiac Questionnaire (KCCQ), the Depression, Anxiety and Stress Scales-21 (DASS-21), the Cardiac Anxiety Questionnaire (CAQ) plus newly developed questions. RESULTS: Women reported low health satisfaction (51.7/100), physical health (55.2/100) and low HRQoL (63.1/100). Women had clinically significant scores for depression (24%), anxiety (22%) and stress (19.5%) (DASS-21) and 44.5% scored at least moderate anxiety on the CAQ. Most women (83.7%) were advised to avoid pregnancy which 88.9% found "upsetting" to "devastating"; 10.0% were offered counselling. Most women were concerned about reduced longevity (88.1%), offspring developing a cardiac condition (73.8%), and the limitations on enjoyment of life (57.1%). Women missed medical appointments due to cost (25.03%) and difficulty arranging childcare (45.5%). CONCLUSION: The majority of women reported inadequate information and counselling support, with women with CDPP having sustained impaired QoL and mental health outcomes. The new and modified questions relating to mothering and children reflected the primacy of mothering to women's identity and needs.

The healthcare experiences of women with cardiac disease in pregnancy and postpartum: A qualitative study.

INTRODUCTION: Cardiac disease affects an estimated 1%-4% of all pregnancies and is a leading cause of maternal morbidity and mortality. There is a lack of data on the healthcare experiences of affected women to inform health service delivery and person-centred care. This study sought to explore and understand the healthcare experiences of women with cardiac disease in pregnancy and postpartum. METHODS: This qualitative study used semi-structured interviews with women who had cardiac disease in pregnancy or the first 12 months postpartum. Data were analysed using thematic analysis. RESULTS: Participants were 25 women with pre-existing or newly diagnosed acquired, genetic and congenital cardiac disease. Analysis of the interviews highlighted the discrepancy between care aspirations and experiences. The participants had a wide range of cardiac diseases and timing of diagnoses, but had similar healthcare experiences of being dismissed, not receiving the information they required, lack of continuity of care and clinical guidelines and of feeling out of place within a healthcare system that did not accommodate their combined needs as a mother and a cardiac patient. CONCLUSION: This study identified a lack of person-centred care and responsiveness of the healthcare system in providing fit-for-purpose healthcare for women with complex disease who are pregnant or new mothers. In particular, cardiac and maternity care providers have an opportunity to listen to women who are the experts on their emergent healthcare needs, contributing to development of the knowledge base on the healthcare experiences of having cardiac disease in pregnancy and postpartum. PATIENT OR PUBLIC CONTRIBUTION: Public and patient input into the value and design of the study was gained through NSW Heart Foundation forums, including the Heart Foundation's women's patient group.

The Spectrum, Severity and Outcomes of Rheumatic Mitral Valve Disease in Pregnant Women in Australia and New Zealand.

BACKGROUND: Rheumatic heart disease (RHD) poses significant perinatal risks. We aimed to describe the spectrum, severity and outcomes of rheumatic mitral valve disease in pregnancy in Australia and New Zealand. METHODS: A prospective, population-based cohort study of pregnant women with RHD recruited 2013-14 through the hospital-based Australasian Maternity Outcomes Surveillance System. Outcome measures included maternal and perinatal morbidity and mortality. Univariable and multivariable logistic regression analyses were undertaken to test for predictors of adverse maternal and perinatal outcomes. RESULTS: Of 274 pregnant women identified with RHD, 124 (45.3%) had mitral stenosis (MS) and 150 (54.7%) had isolated mitral regurgitation (MR). One woman with mild MS/moderate MR died. There were six (2.2%) stillbirths and two (0.7%) neonatal deaths. Babies born to women with MS were twice as likely to be small-for-gestational-age (22.7% vs 11.4%, p=0.013). In women with MS, use of cardiac medication (AOR 7.42) and having severe stenosis (AOR 16.35) were independently associated with adverse cardiac outcomes, while New York Heart Association (NYHA) class >1 (AOR 3.94) was an independent predictor of adverse perinatal events. In women with isolated MR, use of cardiac medications (AOR 7.03) and use of anticoagulants (AOR 6.05) were independently associated with adverse cardiac outcomes. CONCLUSIONS: Careful monitoring and specialist care for women with RHD in pregnancy is required, particularly for women with severe MS, those on cardiac medication, and those on anticoagulation, as these are associated with increased risk of adverse maternal cardiac outcomes. In the context of pregnancy, contraception and preconception planning are important for young women diagnosed with RHD.

Heart Disease and Pregnancy: The Need for a Twenty-First Century Approach to Care .

Pregnancy and childbirth present a specific challenge to the maternal cardiovascular system. Pre-existing cardiac diseases, or cardiac diseases that occur during pregnancy, are associated with a significant risk of morbidity and mortality for both mother and baby. In recent decades, cardiac disease has emerged as a leading cause of maternal death in most high income countries, including Australia and New Zealand. The burden of cardiac disease in pregnancy is likely to be growing due to an increase in adult survivors with congenital heart disease embarking on pregnancy coupled with demographic shifts in the age and cardiovascular risk factors of women giving birth and the persisting high incidence of acute rheumatic fever in First Nations women. There is widespread consensus that the best obstetric and neonatal outcomes in women with cardiac disease are delivered by a strategy of carefully coordinated multidisciplinary care. Australia and New Zealand currently lack nationally agreed strategies for clinical practice and service delivery for women with heart disease in pregnancy. This state-of-the-art review summarises some of the key issues faced in relation to prevention, diagnosis, treatment and health service delivery in this patient group and concludes with suggested priorities for policy and research.

Having a baby in your 40s with assisted reproductive technology: The reproductive dilemma of autologous versus donor oocytes.

BACKGROUND: Increasing numbers of women ≥40 years old are accessing assisted reproductive technology (ART) due to age-related infertility. There is limited population-based evidence about the impact on the cumulative live birth rate (CLBR) of women aged ≥40 years using their own oocytes, compared to women of a similar age, using donor oocytes. AIMS: To compare the CLBR for women ≥40 years undergoing ART using autologous oocytes and women of similar age using donor oocytes. MATERIALS AND METHODS: This population-based retrospective cohort study used data from all women aged ≥40 years undergoing ART with donated (n = 987) or autologous oocytes (n = 19 170) in Victoria, Australia between 2009 and 2016. A discrete-time survival model was used to evaluate the CLBR following ART with donor or autologous oocytes. The odds ratio, adjusted for woman's age; male age; parity; cause of infertility; and the associated 95% confidence intervals (CI), were calculated. The numbers needed to be exposed (NNEs) were calculated from the adjusted odds ratio (aOR) and the CLBR in the autologous group. RESULTS: The CLBR ranged from 28.6 to 42.5% in the donor group and from 12.5% to 1.4% in the autologous group. The discrete-time survival analysis with 95% CI demonstrated significant aOR on CLBR across all ages (range aOR: 2.56, 95% CI: 1.62-4.01 to aOR: 15.40, 95% CI: 9.10-26.04). CONCLUSIONS: Women aged ≥40 years, using donor oocytes had a significantly higher CLBR than women using autologous oocytes. The findings can be used when counselling women ≥40 years about their ART treatment options and to inform public policy.

Eclampsia in Australia and New Zealand: A prospective population-based study.

BACKGROUND: Eclampsia is a serious consequence of pre-eclampsia. There are limited data from Australia and New Zealand (ANZ) on eclampsia. AIM: To determine the incidence, management and perinatal outcomes of women with eclampsia in ANZ. MATERIALS AND METHODS: A two-year population-based descriptive study, using the Australasian Maternity Outcomes Surveillance System (AMOSS), carried out in 263 sites in Australia, and all 24 New Zealand maternity units, during a staggered implementation over 2010-2011. Eclampsia was defined as one or more seizures during pregnancy or postpartum (up to 14 days) in any woman with clinical evidence of pre-eclampsia. RESULTS: Of 136 women with eclampsia, 111 (83%) were in Australia and 25 (17%) in New Zealand. The estimated incidence of eclampsia was 2.2 (95% confidence interval (CI) 1.9-2.7) per 10 000 women giving birth. Aboriginal and Torres Strait Islander women were over-represented in Australia (n = 9; 8.1%). Women with antepartum eclampsia (n = 58, 42.6%) were more likely to have a preterm birth (P = 0.04). Sixty-three (47.4%) women had pre-eclampsia diagnosed prior to their first eclamptic seizure of whom 19 (30.2%) received magnesium sulphate prior to the first seizure. Nearly all women (n = 128; 95.5%) received magnesium sulphate post-seizure. No woman received prophylactic aspirin during pregnancy. Five women had a cerebrovascular haemorrhage, and there were five known perinatal deaths. CONCLUSIONS: Eclampsia is an uncommon consequence of pre-eclampsia in ANZ. There is scope to reduce the incidence of this condition, associated with often catastrophic morbidity, through the use of low-dose aspirin and magnesium sulphate in women at higher risk.

Risk factors, management, and outcomes of amniotic fluid embolism: A multicountry, population-based cohort and nested case-control study.

BACKGROUND: Amniotic fluid embolism (AFE) remains one of the principal reported causes of direct maternal mortality in high-income countries. However, obtaining robust information about the condition is challenging because of its rarity and its difficulty to diagnose. This study aimed to pool data from multiple countries in order to describe risk factors, management, and outcomes of AFE and to explore the impact on the findings of considering United Kingdom, international, and United States AFE case definitions. METHODS AND FINDINGS: A population-based cohort and nested case-control study was conducted using the International Network of Obstetric Survey Systems (INOSS). Secondary data on women with AFE (n = 99-218, depending on case definition) collected prospectively in population-based studies conducted in Australia, France, the Netherlands, Slovakia, and the UK were pooled along with secondary data on a sample of control women (n = 4,938) collected in Australia and the UK. Risk factors for AFE were investigated by comparing the women with AFE in Australia and the UK with the control women identified in these countries using logistic regression. Factors associated with poor maternal outcomes (fatality and composite of fatality or permanent neurological injury) amongst women with AFE from each of the countries were investigated using logistic regression or Wilcoxon rank-sum test. The estimated incidence of AFE ranged from 0.8-1.8 per 100,000 maternities, and the proportion of women with AFE who died or had permanent neurological injury ranged from 30%-41%, depending on the case definition. However, applying different case definitions did not materially alter findings regarding risk factors for AFE and factors associated with poor maternal outcomes amongst women with AFE. Using the most liberal case definition (UK) and adjusting for the severity of presentation when appropriate, women who died were more likely than those who survived to present with cardiac arrest (89% versus 40%, adjusted odds ratio [aOR] 10.58, 95% confidence interval [CI] 3.93-28.48, p < 0.001) and less likely to have a source of concentrated fibrinogen (40% versus 56%, aOR 0.44, 95% CI 0.21-0.92, p = 0.029) or platelets given (24% versus 49%, aOR 0.23, 95% CI 0.10-0.52, p < 0.001). They also had a lower dose of tranexamic acid (median dose 0.7 g versus 2 g, p = 0.035) and were less likely to have had an obstetrician and/or anaesthetist present at the time of the AFE (61% versus 75%, aOR 0.38, 95% CI 0.16-0.90, p = 0.027). Limitations of the study include limited statistical power to examine factors associated with poor maternal outcome and the potential for residual confounding or confounding by indication. CONCLUSIONS: The findings of our study suggest that when an AFE is suspected, initial supportive obstetric care is important, but having an obstetrician and/or anaesthetist present at the time of the AFE event and use of interventions to correct coagulopathy, including the administration of an adequate dose of tranexamic acid, may be important to improve maternal outcome. Future research should focus on early detection of the coagulation deficiencies seen in AFE alongside the role of tranexamic acid and other coagulopathy management strategies.

In utero exposure to breast cancer treatment: a population-based perinatal outcome study.

Chemotherapy during a viable pregnancy may be associated with adverse perinatal outcomes. We conducted a prospective cohort study to examine the perinatal outcomes of babies born following in utero exposure to chemotherapy in Australia and New Zealand. Over 18 months we identified 24 births, of >400 g and/or >20-weeks' gestation, to women diagnosed with breast cancer in the first or second trimesters. Eighteen babies were exposed in utero to chemotherapy. Chemotherapy commenced at a median of 20 weeks gestation, for a mean duration of 10 weeks. Twelve exposed infants were born preterm with 11 by induced labour or pre-labour caesarean section. There were no perinatal deaths or congenital malformations. Our findings show that breast cancer diagnosed during mid-pregnancy is often treated with chemotherapy. Other than induced preterm births, there were no serious adverse perinatal outcomes.

Standardizing clinical care measures of rheumatic heart disease in pregnancy: A qualitative synthesis.

BACKGROUND: Rheumatic heart disease (RHD) is a preventable cardiac condition that escalates risk in pregnancy. Models of care informed by evidence-based clinical guidelines are essential to optimal health outcomes. There are no published reviews that systematically explore approaches to care provision for pregnant women with RHD and examine reported measures. The review objective was to improve understanding of how attributes of care for these women are reported and how they align with guidelines. METHODS: A search of 13 databases was supported by hand-searching. Papers that met inclusion criteria were appraised using CASP/JBI checklists. A content analysis of extracted data from the findings sections of included papers was undertaken, informed by attributes of quality care identified previously from existing guidelines. RESULTS: The 43 included studies were predominantly conducted in tertiary care centers of low-income and middle-income countries. Cardiac guidelines were referred to in 25 of 43 studies. Poorer outcomes were associated with higher risk scores (detailed in 36 of 41 quantitative studies). Indicators associated with increased risk include anticoagulation during pregnancy (28 of 41 reported) and late booking (gestation documented in 15 of 41 studies). Limited access to cardiac interventions was discussed (19 of 43) in the context of poorer outcomes. Conversely, early assessment and access to regular multidisciplinary care were emphasized in promoting optimal outcomes for women and their babies. CONCLUSIONS: Despite often complex care requirements in challenging environments, pregnancy provides an opportunity to strengthen health system responses and address whole-of-life health for women with RHD. A standard set of core indicators is proposed to more accurately benchmark care pathways, outcomes, and burden.

Novel DLX3 variants in amelogenesis imperfecta with attenuated tricho-dento-osseous syndrome.

OBJECTIVES: Variants in DLX3 cause tricho-dento-osseous syndrome (TDO, MIM #190320), a systemic condition with hair, nail and bony changes, taurodontism and amelogenesis imperfecta (AI), inherited in an autosomal dominant fashion. Different variants found within this gene are associated with different phenotypic presentations. To date, six different DLX3 variants have been reported in TDO. The aim of this paper was to explore and discuss three recently uncovered new variants in DLX3. SUBJECTS AND METHODS: Whole-exome sequencing identified a new DLX3 variant in one family, recruited as part of an ongoing study of genetic variants associated with AI. Targeted clinical exome sequencing of two further families revealed another new variant of DLX3 and complete heterozygous deletion of DLX3. For all three families, the phenotypes were shown to consist of AI and taurodontism, together with other attenuated features of TDO. RESULTS: c.574delG p.(E192Rfs*66), c.476G>T (p.R159L) and a heterozygous deletion of the entire DLX3 coding region were identified in our families. CONCLUSION: These previously unreported variants add to the growing literature surrounding AI, allowing for more accurate genetic testing and better understanding of the associated clinical consequences.

Obstetric anal sphincter injuries among women with gestational diabetes and women without gestational diabetes: A NSW population-based cohort study.

BACKGROUND: Obstetric anal sphincter injuries (OASIs) are associated with maternal morbidity; however, it is uncertain whether gestational diabetes (GDM) is an independent risk factor when considering birthweight mode of birth and episiotomy. AIMS: To compare rates of OASIs between women with GDM and women without GDM by mode of birth and birthweight. To investigate the association between episiotomy, mode of birth and the risk of OASIs. METHODS: A population-based cohort study of women who gave birth vaginally in NSW, from 2007 to 2013. Rates of OASIs were compared between women with and without GDM, stratified by mode of birth, birthweight and a multi-categorical variable of mode of birth and episiotomy. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated by multivariable logistic regression. RESULTS: The rate of OASIs was 3.6% (95% CI: 2.6-2.7) vs 2.6% (95% CI: 3.4-2.8; P < 0.001) among women with and without GDM, respectively. Women with GDM and a macrosomic baby (birthweight ≥ 4000 g) had a higher risk of OASIs with forceps (aOR 1.76, 95% CI: 1.08-2.86, P = 0.02) or vacuum (aOR 1.89, 95% CI: 1.17-3.04, P = 0.01), compared with those without GDM. For primiparous women with GDM and all women without GDM, an episiotomy with forceps was associated with lower odds of OASIs than forceps only (primiparous GDM, forceps-episiotomy aOR 2.49, 95% CI: 2.00-3.11, forceps aOR 5.30, 95% CI: 3.72-7.54), (primiparous without GDM, forceps-episiotomy aOR 2.71, 95% CI: 2.55-2.89, forceps aOR 5.95, 95% CI: 5.41-6.55) and (multiparous without GDM, forceps-episiotomy aOR 3.75, 95% CI: 3.12-4.50, forceps aOR 6.20, 95% CI: 4.96-7.74). CONCLUSION: Women with GDM and a macrosomic baby should be counselled about the increased risk of OASIs with both vacuum and forceps. With forceps birth, this risk can be partially mitigated by performing a concomitant episiotomy.

Policy Impacts of the Australian National Perinatal Depression Initiative: Psychiatric Admission in the First Postnatal Year.

This paper helps to quantify the impact of the Australian National Perinatal Depression Initiative (NPDI) on postnatal inpatient psychiatric hospitalisation. Based on individual hospital admissions data from New South Wales and Western Australia, we found that the NPDI reduced inpatient psychiatric hospital admission by up to 50% [0.9% point reduction (95% CI 0.70-1.22)] in the first postnatal year. The greatest reduction was observed for adjustment disorders. The NPDI appears to be associated with fewer post-birth psychiatric disorders hospital admissions; this suggests earlier detection of psychiatric disorders resulting in early care of women at risk during their perinatal period.

Gestational age-specific perinatal mortality rates for assisted reproductive technology (ART) and other births.

STUDY QUESTION: Is perinatal mortality rate higher among births born following assisted reproductive technology (ART) compared to non-ART births? SUMMARY ANSWER: Overall perinatal mortality rates in ART births was higher compared to non-ART births, but gestational age-specific perinatal mortality rate of ART births was lower for very preterm and moderate to late preterm births. WHAT IS KNOWN ALREADY: Births born following ART are reported to have higher risk of adverse perinatal outcomes compared to non-ART births. STUDY DESIGN, SIZE, DURATION: This population-based retrospective cohort study included 407 368 babies (391 952 non-ART and 15 416 ART)-393 491 singletons and 10 877 twins or high order multiples. PARTICIPANTS/MATERIALS, SETTING, METHODS: All births (≥20 weeks of gestation and/or ≥400 g of birthweight) in five states and territories in Australia during the period 2007-2009 were included in the study, using National Perinatal Data Collection (NPDC). Primary outcome measures were rates of stillbirth, neonatal and perinatal deaths. Adjusted odds ratio (AOR) and 95% confidence interval (CI) were used to estimate the likelihood of perinatal death. MAIN RESULTS AND THE ROLE OF CHANCE: Rates of multiple birth and low birthweight were significantly higher in ART group compared to the non-ART group (P < 0.01). Overall perinatal mortality rate was significantly higher for ART births (16.5 per 1000 births, 95% CI 14.5-18.6), compared to non-ART births (11.3 per 1000 births, 95% CI 11.0-11.6) (AOR 1.45, 95% CI 1.26-1.68). However, gestational age-specific perinatal mortality rate of ART births (including both singletons and multiples) was lower for very preterm (<32 weeks' gestation) and moderate to late preterm births (32-36 weeks' gestation) (AOR 0.61, 95% CI 0.53-0.70 and AOR 0.61, 95% CI 0.53-0.70, respectively) compared to non-ART births. Congenital abnormality and spontaneous preterm were the most common causes of neonatal deaths in both ART and non-ART group. LIMITATIONS, REASONS FOR CAUTION: Due to different cut-off limit for perinatal period in Australia, the results of this study should be interpreted with cautions for other countries. Australian definition of perinatal period commences at 20 completed weeks (140 days) of gestation and ends 27 completed days after birth which is different from the definition by World Health Organisation (commences at 22 completed weeks (154 days) of gestation and ends seven completed days after birth) and by Centers for Disease Control and Prevention (includes infant deaths under age 7 days and fetal deaths at 28 weeks of gestation or more). WIDER IMPLICATIONS OF THE FINDINGS: Preterm birth is the single most important contributing factor to increased risk of perinatal mortality among ART singletons compared to non-ART singletons. Further research on reducing early preterm delivery, with the aim of reducing the perinatal mortality among ART births is needed. Couples who access ART treatment should be fully informed regarding the risk of preterm birth and subsequent risk of perinatal death. STUDY FUNDING/COMPETING INTEREST(S): There was no funding associated with this study. No conflict of interest was declared.

Neonatal outcomes among twins following assisted reproductive technology: an Australian population-based retrospective cohort study.

BACKGROUND: While their incidence is on the rise, twin pregnancies are associated with risks to the mothers and their babies. This study aims to investigate the likelihood of adverse neonatal outcomes of twins following assisted reproductive technology (ART) compared to non-ART twins. METHODS: A retrospective population study using the Australian National Perinatal Data Collections (NPDC) which included 19,662 twins of ≥20 weeks gestational age or ≥ 400 g birthweight in Australia. Maternal outcomes and neonatal outcomes (preterm birth, low birth weight, resuscitation and neonatal death) were compared. Generalized Estimating Equations were used to assess the likelihood of any neonatal outcomes, with adjusted odds ratio (AOR) and 95% confidence intervals (CI) presented. Weinberg's differential rule was used to estimate monozygotic twin rate. RESULTS: ART mothers were 3.3 years older than non-ART mothers. The rates of pregnancy-induced hypertension and gestational diabetes were significantly higher for ART mothers than non-ART mothers (12.2% vs. 8.4%, p <  0.01) and (9.7% vs. 7.5%, p <  0.01) respectively. The incidence of monozygotic twins was 2.0% for ART twins and 1.1% for non-ART twins. Compared with non-ART twins, ART twins had higher rates of preterm birth (AOR 1.13, 95% CI: 1.05-1.22), low birth weight (AOR 1.13, 95% CI: 1.05-1.22), and resuscitation (AOR 1.26, 95% CI: 1.17-1.36). Liveborn ART twins had 28% (AOR 1.28, 95% CI 1.09-1.50) increased odds of having any adverse neonatal outcome compared to liveborn non-ART twins, especially for opposite-sex ART twins (AOR 1.42, 95% CI 1.11-1.82). CONCLUSION: As ART twins had higher rates of adverse outcome, special prenatal care is recommended. Couples accessing ART should be fully informed of the risk of adverse outcome of twin pregnancies.

Cesarean section and diabetes during pregnancy: An NSW population study using the Robson classification.

AIM: The aim of this study was to identify the main contributors to cesarean section (CS) among women with and without diabetes during pregnancy using the Robson classification and to compare CS rates within Robson groups. METHODS: A population-based cohort study was conducted of all women who gave birth in New South Wales, Australia, between 2002 and 2012. Women with pregestational diabetes (types 1 and 2) and gestational diabetes mellitus (GDM) were grouped using the Robson classification. Adjusted odd ratios (AOR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression. RESULTS: The total CS rate was 53.6% for women with pregestational diabetes, 36.8% for women with GDM and 28.5% for women without diabetes. Previous CS contributed the most to the total number of CS in all populations. For preterm birth, the contribution to the total was 20.5% for women with pregestational diabetes and 5.7% for women without diabetes. Compared to women without diabetes, for nulliparous with pregestational diabetes, the odds of CS was 1.4 (95% CI, 1.1-1.8) for spontaneous labor and 2.0 (95% CI, 1.7-2.3) for induction of labor. CONCLUSION: A history of CS was the main contributor to the total CS. Reducing primary CS is the first step to lowering the high rate of CS among women with diabetes. Nulliparous women were more likely to have CS if they had pregestational diabetes. This increase was also evident in all multiparous women giving birth. The high rate of preterm births and CS reflects the clinical issues for women with diabetes during pregnancy.

Exome sequencing establishes a gelsolin mutation as the cause of inherited bulbar-onset neuropathy.

INTRODUCTION: Progressive bulbar motor neuropathy is primarily caused by bulbar-onset ALS. Hereditary amyloidosis type IV also presents with a bulbar neuropathy that mimics motor neuron disease. The disease is prevalent in Finland only and is not commonly included in the differential diagnosis of ALS. METHODS: We studied 18 members of a family in which some had bulbar motor neuropathy, and we performed exome sequencing. RESULTS: Five affected family members were found to have a D187Y substitution in the GSN gene known to cause hereditary amyloidosis type IV. CONCLUSIONS: This American family presented with progressive bulbar neuropathy due to a gelsolin mutation not found in Finland. Hereditary amyloidosis type IV presents with bulbar motor neuropathy and not with peripheral neuropathy as occurs with common forms of amyloidosis. This report demonstrates the power of exome sequencing to determine the cause of rare hereditary diseases with incomplete or atypical phenotypes. Muscle Nerve 56: 1001-1005, 2017.

Morbidity and mortality among very preterm singletons following fertility treatment in Australia and New Zealand, a population cohort study.

BACKGROUND: Due to high rates of multiple birth and preterm birth following fertility treatment, the rates of mortality and morbidity among births following fertility treatment were higher than those conceived spontaneously. However, it is unclear whether the rates of adverse neonatal outcomes remain higher for very preterm (<32 weeks gestational age) singletons born after fertility treatment. This study aims to compare adverse neonatal outcomes among very preterm singletons born after fertility treatment including assisted reproductive technology (ART) hyper-ovulution (HO) and artificial insemination (AI) to those following spontaneous conception. METHODS: The population cohort study included 24069 liveborn very preterm singletons who were admitted to Neonatal Intensive Care Unit (NICU) in Australia and New Zealand from 2000 to 2010. The in-hospital neonatal mortality and morbidity among 21753 liveborn very preterm singletons were compared by maternal mode of conceptions: spontaneous conception, HO, ART and AI. Univariate and multivariate binary logistic regression analysis was used to examine the association between mode of conception and various outcome factors. Odds ratio (OR) and adjusted odds ratio (AOR) and 95% confidence interval (CI) were calculated. RESULTS: The rate of small for gestational age was significantly higher in HO group (AOR 1.52, 95% CI 1.02-2.67) and AI group (AOR 2.98, 95% CI 1.53-5.81) than spontaneous group. The rate of birth defect was significantly higher in ART group (AOR 1.71, 95% CI 1.36-2.16) and AI group (AOR 3.01, 95% CI 1.47-6.19) compared to spontaneous group. Singletons following ART had 43% increased odds of necrotizing enterocolitis (AOR 1.43, 95% CI 1.04-1.97) and 71% increased odds of major surgery (AOR 1.71, 95% CI 1.37-2.13) compared to singletons conceived spontaneously. Other birth and NICU outcomes were not different among the comparison groups. CONCLUSIONS: Compared to the spontaneous conception group, risk of congenital abnormality significantly increases after ART and AI; the risk of morbidities increases after ART, HO and AI. Preconception planning should include comprehensive information about the benefits and risks of fertility treatment on the neonatal outcomes.

Medical termination of pregnancy in general practice in Australia: a descriptive-interpretive qualitative study.

BACKGROUND: Australian Government approval in 2012 for the use of mifepristone and misoprostol for medical termination of pregnancy (MTOP) allows general practitioners (GPs) to provide early gestation abortion in primary care settings. However, uptake of the MTOP provision by GPs appears to be low and the reasons for this have been unclear. This study investigated the provision of and referral for MTOP by GPs. METHODS: We undertook descriptive-interpretive qualitative research and selected participants for diversity using a matrix. Twenty-eight semi-structured interviews and one focus group (N = 4), were conducted with 32 GPs (8 MTOP providers, 24 non MTOP providers) in New South Wales, Australia. Interviews were recorded and transcribed verbatim. A framework to examine access to abortion services was used to develop the interview questions and emergent themes identified thematically. RESULTS: Three main themes emerged: scope of practice; MTOP demand, care and referral; and workforce needs. Many GPs saw abortion as beyond the scope of their practice (i.e. a service others provide in specialist private clinics). Some GPs had religious or moral objections; others regarded MTOP provision as complicated and difficult. While some GPs expressed interest in MTOP provision they were concerned about stigma and the impact it may have on perceptions of their practice and the views of colleagues. Despite a reported variance in demand most MTOP providers were busy but felt isolated. Difficulties in referral to a local public hospital in the case of complications or the provision of surgical abortion were noted. CONCLUSIONS: Exploring the factors which affect access to MTOP in general practice settings provides insights to assist the future planning and delivery of reproductive health services. This research identifies the need for support to increase the number of MTOP GP providers and for GPs who are currently providing MTOP. Alongside these actions provision in the public sector is required. In addition, formalised referral pathways to the public sector are required to ensure timely care in the case of complications or the provision of surgical options. Leadership and coordination across the health sector is needed to facilitate integrated abortion care particularly for rural and low income women.