A summary of the 2023 Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) hypertension in pregnancy guideline.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.

A survey of obstetric and gynaecology doctors at an Australian metropolitan tertiary hospital to understand their views, training and confidence in abortion care.

BACKGROUND: The barriers to comprehensive abortion care in Australian metropolitan tertiary hospitals are under-researched. Previous work has suggested that negative practitioner attitudes and lack of training may play a large role; however, this remains poorly understood. AIM: The aim was to survey doctors practicing obstetrics and gynaecology to better understand their views, training experience and confidence in abortion care. METHOD: The method involved a cross-sectional study via an anonymous survey at a single metropolitan tertiary hospital not providing substantive abortion services in Melbourne, Australia. Inclusion criterion was obstetric and gynaecology medical staff working at that hospital. Data were collected regarding views, training experiences and confidence in first-trimester medical and surgical abortion, and second-trimester surgical abortion. Data were analysed according to levels of training, categorised as RANZCOG (Royal Australian and New Zealand College of Obstetricians and Gynaecologists) Fellows, prevocational/vocational trainees and general practitioner specialists. RESULTS: Sixty-one valid responses were received from 90 eligible participants (response rate 68%). An overwhelming majority (96%) supported abortion services. The majority of RANZCOG Fellows felt confident performing first-trimester surgical abortion (89%) and first-trimester medical abortion (71%); however, only half felt confident performing second-trimester surgical abortion (50%). Prevocational/vocational trainees were overall less confident but overwhelmingly expressed interest in gaining further experience in abortion. CONCLUSION: Doctors are generally confident in providing first-trimester abortion services (medical or surgical) in the metropolitan tertiary setting. However, further work is required to understand ongoing barriers to comprehensive abortion care. There may also be a skills shortage for second-trimester surgical abortion, requiring significant improvements in abortion training.

Reductions in stillbirths and preterm birth in COVID-19-vaccinated women: a multicenter cohort study of vaccination uptake and perinatal outcomes.

BACKGROUND: COVID-19 infection in pregnancy is associated with a higher risk of progression to severe disease, but vaccine uptake by pregnant women is hindered by persistent safety concerns. COVID-19 vaccination in pregnancy has been shown to reduce stillbirth, but its relationship with preterm birth is uncertain. OBJECTIVE: This study aimed to measure the rate of COVID-19 vaccine uptake among women giving birth in Melbourne, Australia, and to compare perinatal outcomes by vaccination status. STUDY DESIGN: This was a retrospective multicenter cohort study conducted after the June 2021 government recommendations for messenger RNA COVID-19 vaccination during pregnancy. Routinely collected data from all 12 public maternity hospitals in Melbourne were extracted on births at ≥20 weeks' gestation from July 1, 2021 to March 31, 2022. Maternal sociodemographic characteristics were analyzed from the total birth cohort. Perinatal outcomes were compared between vaccinated and unvaccinated women for whom weeks 20 to 43 of gestation fell entirely within the 9-month data collection period. The primary outcomes were the rates of stillbirth and preterm birth (spontaneous and iatrogenic) in singleton pregnancies of at least 24 weeks' gestation, after exclusion of congenital anomalies. Secondary perinatal outcomes included the rate of congenital anomalies among infants born at ≥20 weeks' gestation and birthweight ≤third centile and newborn intensive care unit admissions among infants born without congenital anomalies at ≥24 weeks' gestation. We calculated the adjusted odds ratio of perinatal outcomes among vaccinated vs unvaccinated women using inverse propensity score-weighting regression adjustment with multiple covariates; P<.05 was considered statistically significant. RESULTS: Births from 32,536 women were analyzed: 17,365 (53.4%) were vaccinated and 15,171 (47.6%) were unvaccinated. Vaccinated women were more likely to be older, nulliparous, nonsmoking, not requiring an interpreter, of higher socioeconomic status, and vaccinated against pertussis and influenza. Vaccination status also varied by region of birth. Vaccinated women had a significantly lower rate of stillbirth compared with unvaccinated women (0.2% vs 0.8%; adjusted odds ratio, 0.18; 95% confidence interval, 0.09-0.37; P<.001). Vaccination was associated with a significant reduction in total preterm births at <37 weeks (5.1% vs 9.2%; adjusted odds ratio, 0.60; 95% confidence interval, 0.51-0.71; P<.001), spontaneous preterm birth (2.4% vs 4.0%; adjusted odds ratio, 0.73; 95% confidence interval, 0.56-0.96; P=.02), and iatrogenic preterm birth (2.7% vs 5.2%; adjusted odds ratio, 0.52; 95% confidence interval, 0.41-0.65; P<.001). Infants born to vaccinated mothers also had lower rates of admission to the neonatal intensive care unit. There was no significant increase in the rate of congenital anomalies or birthweight ≤3rd centile in vaccinated women. Vaccinated women were significantly less likely to have an infant with a major congenital anomaly compared with the unvaccinated group (2.4% vs 3.0%; adjusted odds ratio, 0.72; 95% confidence interval, 0.56-0.94; P=.02). This finding remained significant even when the analysis was restricted to women vaccinated before 20 weeks' gestation. CONCLUSION: COVID-19 vaccination during pregnancy was associated with a reduction in stillbirth and preterm birth, and not associated with any adverse impact on fetal growth or development. Vaccine coverage was substantially influenced by known social determinants of health.

PRECeDe Pilot: Prevention of neonatal respiratory distress with antenatal corticosteroids before elective caesarean section in women with diabetes - a feasibility randomised trial.

OBJECTIVE: The PRECeDe Pilot Trial was designed to determine the feasibility of undertaking a multicentre, randomised controlled trial (RCT) to assess the efficacy of antenatal corticosteroids administration within 7 days before elective caesarean section (CS) in women with pre-gestational diabetes (PGDM) or gestational diabetes (GDM). DESIGN: Triple blind, parallel group, placebo-controlled, pilot RCT. SETTING: Single-centre tertiary maternity hospital in Melbourne, Australia. POPULATION: Pregnant women with PGDM (type 1 or type 2 diabetes) or GDM booked for a planned CS scheduled between 35+0 and 38+6 weeks of gestation. METHODS: Eligible participants were randomised to receive two injections of either betamethasone 11.4 mg or normal saline placebo, 24 hours apart within 7 days before CS scheduled between 35+0 and 38+6 weeks of gestation. MAIN OUTCOME MEASURE: The proportion of eligible women who consented and were randomised. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12619001475134. RESULTS: Of 537 women eligible, 182 were approached and 47 (26%) were recruited. Of these, 22 were allocated to the betamethasone group and 25 were allocated to the placebo group. There were no serious adverse events related to participation. CONCLUSION: It is feasible to undertake a triple-blind, placebo-controlled RCT investigating the efficacy of antenatal corticosteroids in preventing respiratory morbidity in infants of women with PGDM or GDM who are undergoing an elective CS between 35+0 and 38+6 weeks.

Reduction in spontaneous and iatrogenic preterm births in twin pregnancies during COVID-19 lockdown in Melbourne, Australia: a multicenter cohort study.

BACKGROUND: Melbourne, Australia, recorded one of the longest and most stringent pandemic lockdowns in 2020, which was associated with an increase in preterm stillbirths among singleton pregnancies. Twin pregnancies may be particularly susceptible to the impacts of pandemic disruptions to maternity care due to their higher background risk of adverse perinatal outcomes. METHODS: Multicenter retrospective cohort study of all twin pregnancies birthing in public maternity hospitals in Melbourne. Multivariable log-binomial regression models were used to compare perinatal outcomes between a pre-pandemic group to women in whom weeks 20+0 to 40+0 of gestation occurred entirely during one of two lockdown-exposure periods: exposure 1 from 22 March 2020 to 21 March 2021 and exposure 2 from 22 March 2021 to 27 March 2022. RESULTS: Total preterm births < 37 weeks were significantly lower in exposure 1 compared with the pre-pandemic period (63.1% vs 68.3%; adjusted risk ratio 0.92 95% CI 0.87-0.98, p = 0.01). This was mainly driven by fewer spontaneous preterm births (18.9% vs 20.3%; adjusted risk ratio 0.95 95% CI 0.90-0.99, p = 0.04). There were also lower rates of preterm birth < 34 weeks (19.9% vs 23.0%, adjusted risk ratio 0.93 95% CI 0.89-0.98 p = 0.01) and total iatrogenic births for fetal compromise (13.4% vs 20.4%; adjusted risk ratio 0.94 95% CI 0.89-0.98, p = 0.01). There were fewer special care nursery admissions (38.5% vs 43.4%; adjusted risk ratio 0.91 95% CI 0.87-0.95, p < 0.001) but no significant changes in stillbirth (1.5% vs 1.6%; adjusted risk ratio 1.00 95% CI 0.99-1.01, p = 0.82). Compared with the pre-pandemic period, there were more preterm births < 28 weeks and neonatal intensive care unit admissions in exposure 2. CONCLUSIONS: Melbourne's first lockdown-exposure period was associated with lower preterm births in twins without significant differences in adverse newborn outcomes. Our findings provide insights into the influences on preterm birth and the optimal timing of delivery for twins.

Pregnant women with diabetes and their clinician's experience of participating in a pilot randomised controlled trial of corticosteroid administration in late pregnancy: A qualitative study.

BACKGROUND: Little research exists to support the administration of corticosteroids to pregnant women with diabetes. Pregnant women are often excluded from clinical trials due to concerns of harm to the foetus. AIM: This study aimed to understand the experiences of women and clinicians of participating in the Prevention of neonatal Respiratory distress with antenatal corticosteroids before Elective Caesarean section in women with Diabetes pilot randomised controlled trial to determine the acceptability of the study protocol. METHODS: Women and clinicians participating in the pilot trial were invited to complete a telephone interview regarding their experiences of participating. Qualitative data were collected and subsequently analysed using thematic analysis. RESULTS: A total of 13 women and nine clinicians were recruited between June 2020 and May 2022 for a telephone interview. Participating in the study was deemed acceptable by women and clinicians. Women chose to participate in the study due to the perceived low risk of harm associated with the intervention and for altruistic reasons. The high level of clinical support and information provided for the duration of the pilot trial was valued by women and clinicians. All clinicians highlighted the importance of conducting the trial to inform evidence-based practice. CONCLUSIONS: Pregnant women are more likely to participate in clinical trials when perceived risks are low and they are well-informed during decision-making. Clinicians will support clinical trials when they perceive a benefit to practice and feel assured that women receive extensive monitoring and support. Incorporating these factors into study protocols is more likely to be successful in recruiting pregnant women and maintaining the engagement of clinical staff for the duration of clinical trials. PATIENT OR PUBLIC CONTRIBUTIONS: Patients were invited to be participants in this study. A consumer has been included in the planning and oversite of the large multicentre trial.

Neonatal outcomes following antenatal corticosteroid administration prior to elective caesarean delivery in women with pre-gestational diabetes: A retrospective cohort study.

BACKGROUND: The benefit of antenatal corticosteroid (ACS) administration for the prevention of neonatal morbidity and mortality has been well described for preterm infants. Some studies have demonstrated a benefit for infants born by elective caesarean section (CS) at late preterm or term gestations. However, the neonatal benefits of ACS are not well described when given to pregnant women with diabetes. AIMS: The aim of this study was to evaluate the neonatal outcomes following ACS administration in women with pre-gestational diabetes mellitus (PGDM) when administered prior to elective CS after 36 weeks gestation. METHODS: This retrospective observational study included all women with PGDM who gave birth by elective CS between 36+0 and 38+6 weeks gestation. Neonatal outcomes for exposed participants were compared to outcomes for non-exposed participants. RESULTS: Of the 306 women identified, 65 (21.2%) were exposed to ACS within seven days prior to birth and 241 (78.8%) were not. Although not statistically significant, ACS-exposed infants born prior to 38+0 weeks were less likely to require respiratory support or neonatal nursery admission compared to those who were not exposed; however, exposed infants born after 37+0 weeks were more likely to require parenteral treatment for neonatal hypoglycaemia. CONCLUSION: This study did not demonstrate any statistically significant beneficial or harmful effects of ACS in neonates of women with PGDM who are born by elective CS. While it is plausible that ACS could reduce neonatal respiratory morbidity in this population, further prospective studies evaluating the benefits and harms are required before recommending this practice.

Variation in clinical practice guideline recommendations for medication use in pregnancy in Australia: A systematic review.

BACKGROUND: Medication use in pregnancy is common; however, it is unknown if clinical practice guideline (CPG) prescribing recommendations referred to in Australia at the state, national and international level are consistent. AIMS: This systematic review aimed to: (1) identify sources of CPGs that inform prescribing during pregnancy in Australia; (2) assess CPG quality; and (3) evaluate variation within CPG recommendations for medication use in three common conditions in pregnancy: prophylactic antibiotics following premature rupture of membranes (PROM) at term, antidepressants in pregnancy and metformin in gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A literature search was conducted across PubMed, Scopus and EMBASE databases. Grey literature was identified through publicly available Australian policy statements. Prescribing recommendations for prophylactic antibiotics following PROM at term, antidepressants in pregnancy and metformin in GDM, were compared at the state, national and international levels. CPG quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. RESULTS: We identified 39 CPG sources that inform prescribing during pregnancy in Australia. CPG quality varied between resources. There was minor variation in recommendations for antibiotic prophylaxis in PROM at term. Recommendations regarding metformin use in GDM were also variable, with CPGs either recommending its use as a first-line agent when lifestyle modifications are not effective or when insulin therapy is not practicable. Recommendations for antidepressant use were consistent across CPGs analysed. CONCLUSION: Multiple CPGs exist to inform prescribing during pregnancy in Australia, with variation present within CPG quality and recommendations. These findings offer insight into potential sources of variation in maternal and neonatal health outcomes.

My Baby's Movements: An assessment of the effectiveness of the My Baby's Movements phone program in reducing late-gestation stillbirth rates.

BACKGROUND: Delayed reporting of decreased fetal movements (DFM) could represent a missed opportunity to prevent stillbirth. Mobile phone applications (apps) have the potential to improve maternal awareness and reporting of DFM and contribute to stillbirth prevention. AIMS: To evaluate the effectiveness of the My Baby's Movements (MBM) app on late-gestation stillbirth rates. MATERIALS AND METHODS: The MBM trial evaluated a multifaceted fetal movements awareness package across 26 maternity services in Australia and New Zealand between 2016 and 2019. In this secondary analysis, generalised linear mixed models were used to compare rates of late-gestation stillbirth, obstetric interventions, and neonatal outcomes between app users and non-app users including calendar time, cluster, primiparity and other potential confounders as fixed effects, and hospital as a random effect. RESULTS: Of 140 052 women included, app users comprised 9.8% (n = 13 780). The stillbirth rate was not significantly lower among app users (1.67/1000 vs 2.29/1000) (adjusted odds ratio (aOR) 0.79; 95% CI 0.51-1.23). App users were less likely to have a preterm birth (aOR 0.81; 0.75-0.88) or a composite adverse neonatal outcome (aOR 0.87; 0.81-0.93); however, they had higher rates of induction of labour (IOL) (aOR 1.27; 1.22-1.32) and early term birth (aOR 1.08; 1.04-1.12). CONCLUSIONS: The MBM app had low uptake and its use was not associated with stillbirth rates but was associated with some neonatal benefit, and higher rates of IOL and early term birth. Use and acceptability of tools designed to promote fetal movement awareness is an important knowledge gap. The implications of increased IOL and early term births warrant consideration in future studies.

Increase in preterm stillbirths in association with reduction in iatrogenic preterm births during COVID-19 lockdown in Australia: a multicenter cohort study.

BACKGROUND: The COVID-19 pandemic has been associated with a worsening of perinatal outcomes in many regions around the world. Melbourne, Australia, had one of the longest and most stringent lockdowns worldwide in 2020 while recording only rare instances of COVID-19 infection in pregnant women. OBJECTIVE: This study aimed to compare the stillbirth and preterm birth rates in women who were exposed or unexposed to lockdown restrictions during pregnancy. STUDY DESIGN: This was a retrospective, multicenter cohort study of perinatal outcomes in Melbourne before and during the COVID-19 lockdown. The lockdown period was defined as the period from March 23, 2020 to March 14, 2021. Routinely-collected maternity data on singleton pregnancies ≥24 weeks gestation without congenital anomalies were obtained from all the 12 public hospitals in Melbourne. We defined the lockdown-exposed cohort as those women for whom weeks 20 to 40 of gestation occurred during the lockdown and the unexposed control group as women from the corresponding calendar periods 12 and 24 months before. The main outcome measures were stillbirth, preterm birth, fetal growth restriction (birthweight < third centile), and iatrogenic preterm birth for fetal compromise. We performed multivariable logistic regression analysis to compare the odds of stillbirth, preterm birth, fetal growth restriction, and iatrogenic preterm birth for fetal compromise, adjusting for multiple covariates. RESULTS: There were 24,817 births in the exposed group and 50,017 births in the control group. There was a significantly higher risk of preterm stillbirth in the exposed group than the control group (0.26% vs 0.18%; adjusted odds ratio, 1.49; 95% confidence interval, 1.08-2.05; P=.015). There was also a significant reduction in the preterm birth of live infants <37 weeks (5.68% vs 6.07%; adjusted odds ratio, 0.93; 95% confidence interval, 0.87-0.99; P=.02), which was largely mediated by a significant reduction in iatrogenic preterm birth (3.01% vs 3.27%; adjusted odds ratio, 0.91; 95% confidence interval, 0.83-0.99; P=.03), including iatrogenic preterm birth for fetal compromise (1.25% vs 1.51%; adjusted odds ratio, 0.82; 95% confidence interval, 0.71-0.93; P=.003). There were also significant reductions in special care nursery admissions during lockdown (11.53% vs 12.51%; adjusted odds ratio, 0.90; 95% confidence interval, 0.86-0.95; P<.0001). There was a trend to fewer spontaneous preterm births <37 weeks in the exposed group of a similar magnitude to that reported in other countries (2.69% vs 2.82%; adjusted odds ratio, 0.95; 95% confidence interval, 0.87-1.05; P=.32). CONCLUSION: Lockdown restrictions in Melbourne, Australia were associated with a significant reduction in iatrogenic preterm birth for fetal compromise and a significant increase in preterm stillbirths. This raises concerns that pandemic conditions in 2020 may have led to a failure to identify and appropriately care for pregnant women at an increased risk of antepartum stillbirth. Further research is required to understand the relationship between these 2 findings and to inform our ongoing responses to the pandemic.

The role of Australian clinical quality registries in pregnancy care: A scoping review.

BACKGROUND: Pregnancy represents a time of increased morbidity and mortality for women and their infants. Clinical quality registries (CQRs) collect, analyse and report key healthcare quality indicators for patient cohorts to improve patient care. There are limited data regarding existing CQRs in pregnancy. This scoping review aimed to: (1) identify Australian CQRs specific to pregnancy care and describe their general characteristics; and (2) outline their aims and measured outcomes METHODS: The scoping review was undertaken according to Joanna Briggs Institute guidelines. CQRs were identified using a systematic approach from publications (Ovid MEDLINE, PubMed, Google Scholar), peer consultation, the Australian register of clinical registries and web searches. Details surrounding general characteristics, aims and outcomes were collated. RESULTS: We identified two primary sources of information about pregnancy care. (1) Six CQRs are specific to pregnancy (Australia and New Zealand twin-twin transfusion syndrome registry, Australian Pregnancy Register for women with epilepsy and those taking anti-epileptic drugs, National Register of Antipsychotic Medication in Pregnancy, Australasian Maternity Outcomes Surveillance System, Neonatal Alloimmune Thrombocytopaenia Registry and the Diabetes in Pregnancy clinical register). (2) Fourteen observational cohort studies were facilitated by non-pregnancy-specific CQRs where a subsection of patients underwent pregnancy. CONCLUSIONS: Australian CQRs currently report varied information regarding some selected conditions during pregnancy and offer therapeutic and epidemiological insight into their care. Further research into their effectiveness is warranted. We note the lack of a CQR spanning the common problems of pregnancy in general, where significant health, service and economic gains are possible.

Circulating mRNAs are differentially expressed in pregnancies with severe placental insufficiency and at high risk of stillbirth.

BACKGROUND: Fetuses affected by placental insufficiency do not receive adequate nutrients and oxygenation, become growth restricted and acidemic, and can demise. Preterm fetal growth restriction is a severe form of placental insufficiency with a high risk of stillbirth. We set out to identify maternal circulating mRNA transcripts that are differentially expressed in preterm pregnancies complicated by very severe placental insufficiency, in utero fetal acidemia, and are at very high risk of stillbirth. METHODS: We performed a cohort study across six hospitals in Australia and New Zealand, prospectively collecting blood from 128 pregnancies complicated by preterm fetal growth restriction (delivery < 34 weeks' gestation) and 42 controls. RNA-sequencing was done on all samples to discover circulating mRNAs associated with preterm fetal growth restriction and fetal acidemia in utero. We used RT-PCR to validate the associations between five lead candidate biomarkers of placental insufficiency in an independent cohort from Europe (46 with preterm fetal growth restriction) and in a third cohort of pregnancies ending in stillbirth. RESULTS: In the Australia and New Zealand cohort, we identified five mRNAs that were highly differentially expressed among pregnancies with preterm fetal growth restriction: NR4A2, EMP1, PGM5, SKIL, and UGT2B1. Combining three yielded an area under the receiver operative curve (AUC) of 0.95. Circulating NR4A2 and RCBTB2 in the maternal blood were dysregulated in the presence of fetal acidemia in utero. We validated the association between preterm fetal growth restriction and circulating EMP1, NR4A2, and PGM5 mRNA in a cohort from Europe. Combining EMP1 and PGM5 identified fetal growth restriction with an AUC of 0.92. Several of these genes were differentially expressed in the presence of ultrasound parameters that reflect placental insufficiency. Circulating NR4A2, EMP1, and RCBTB2 mRNA were differentially regulated in another cohort destined for stillbirth, compared to ongoing pregnancies. EMP1 mRNA appeared to have the most consistent association with placental insufficiency in all cohorts. CONCLUSIONS: Measuring circulating mRNA offers potential as a test to identify pregnancies with severe placental insufficiency and at very high risk of stillbirth. Circulating mRNA EMP1 may be promising as a biomarker of severe placental insufficiency.

Controversies in antenatal corticosteroid treatment.

Antenatal corticosteroids are now established as one of the cornerstones of therapy in the prevention of neonatal morbidity and mortality prior to preterm birth. Although this practice is widely accepted, a significant number of controversies exist. This review explores the knowledge gaps regarding the use of antenatal corticosteroids in the preterm, late preterm and term populations. Furthermore, the role of antenatal corticosteroids in special populations, such as diabetes, multiple pregnancies and periviable gestations, where high-quality data from randomized controlled trials are lacking, is also considered.

Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial Cells.

OBJECTIVE: Biglycan (BGN) has reduced expression in placentae from pregnancies complicated by fetal growth restriction (FGR). We used first trimester placental samples from pregnancies with later small for gestational age (SGA) infants as a surrogate for FGR. The functional consequences of reduced BGN and the downstream targets of BGN were determined. Furthermore, the expression of targets was validated in primary placental endothelial cells isolated from FGR or control pregnancies. APPROACH AND RESULTS: BGN expression was determined using real-time polymerase chain reaction in placental tissues collected during chorionic villous sampling performed at 10 to 12 weeks' gestation from pregnancies that had known clinical outcomes, including SGA. Short-interference RNA reduced BGN expression in telomerase-immortalized microvascular endothelial cells, and the effect on proliferation, angiogenesis, and thrombin generation was determined. An angiogenesis array identified downstream targets of BGN, and their expression in control and FGR primary placental endothelial cells was validated using real-time polymerase chain reaction. Reduced BGN expression was observed in SGA placental tissues. BGN reduction decreased network formation of telomerase-immortalized microvascular endothelial cells but did not affect thrombin generation or cellular proliferation. The array identified target genes, which were further validated: angiopoetin 4 (ANGPT4), platelet-derived growth factor receptor α (PDGFRA), tumor necrosis factor superfamily member 15 (TNFSF15), angiogenin (ANG), serpin family C member 1 (SERPIN1), angiopoietin 2 (ANGPT2), and CXC motif chemokine 12 (CXCL12) in telomerase-immortalized microvascular endothelial cells and primary placental endothelial cells obtained from control and FGR pregnancies. CONCLUSIONS: This study reports a temporal relationship between altered placental BGN expression and subsequent development of SGA. Reduction of BGN in vascular endothelial cells leads to disrupted network formation and alterations in the expression of genes involved in angiogenesis. Therefore, differential expression of these may contribute to aberrant angiogenesis in SGA pregnancies.

Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a history: a randomized trial.

BACKGROUND: Preeclampsia and small-for-gestational-age pregnancy are major causes of maternal and perinatal morbidity and mortality. Women with a previous pregnancy affected by these conditions are at an increased risk of recurrence in a future pregnancy. Past trials evaluating the effect of low-molecular-weight heparin for the prevention of recurrence of preeclampsia and small-for-gestational-age pregnancy have shown conflicting results with high levels of heterogeneity displayed when trials were compared. OBJECTIVE: We sought to assess the effectiveness of enoxaparin in addition to high-risk care for the prevention of preeclampsia and small-for-gestational-age pregnancy in women with a history of these conditions. STUDY DESIGN: This was an open-label randomized controlled trial in 5 tertiary care centers in 3 countries. Women with a viable singleton pregnancy were invited to participate between >6+0 and <16+0 weeks if deemed to be at high risk of preeclampsia and/or small for gestational age based on their obstetric history. Eligible participants were randomly assigned in a 1-to-1 ratio to standard high-risk care or standard high-risk care plus enoxaparin 40 mg (4000 IU) by subcutaneous injection daily from recruitment until 36+0 weeks or delivery, whichever occurred sooner. Standard high-risk care was defined as care coordinated by a high-risk antenatal clinic service, aspirin 100 mg daily until 36+0 weeks, and-for women with prior preeclampsia-calcium 1000-1500 mg daily until 36+0 weeks. In a subgroup of participants serum samples were taken at recruitment and at 20 and 30 weeks' gestation and later analyzed for soluble fms-like tyrosine kinase-1, soluble endoglin, endothelin-1, placental growth factor, and soluble vascular cell adhesion molecule 1. The primary outcome was a composite of preeclampsia and/or small-for-gestational-age <5th customized birthweight percentile. All data were analyzed on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12609000699268). RESULTS: Between July 26, 2010, and Oct. 28, 2015, a total of 156 participants were enrolled and included in the analysis. In all, 149 participants were included in the outcome analysis (72 receiving standard high-risk care plus enoxaparin and 77 receiving standard high-risk care only). Seven women who miscarried <16 weeks' gestation were excluded. The majority of participants (151/156, 97%) received aspirin. The addition of enoxaparin had no effect on the rate of preeclampsia and/or small-for-gestational-age <5th customized birthweight percentile: enoxaparin 18/72 (25%) vs no enoxaparin 17/77 (22.1%) (odds ratio, 1.19; 95% confidence interval, 0.53-2.64). There was also no difference in any of the secondary outcome measures. Levels of soluble fms-like tyrosine kinase-1 and soluble endoglin increased among those who developed preeclampsia, but there was no difference in levels of these antiangiogenic factors (nor any of the other serum analytes measured) among those treated with enoxaparin compared to those receiving standard high-risk care only. CONCLUSION: The use of enoxaparin in addition to standard high-risk care does not reduce the risk of recurrence of preeclampsia and small-for-gestational-age infants in a subsequent pregnancy.

Apert syndrome: temporal lobe abnormalities on fetal brain imaging.

OBJECTIVES: Apert syndrome is characterized by craniosynostosis and complex hand and foot syndactyly, and an increased risk of brain, palate, heart, and visceral malformations, and intellectual disability. This study aims to describe the structural brain abnormalities detected by dedicated neuroimaging of fetuses with Apert syndrome. METHODS: Retrospective review of ultrasound and magnetic resonance imaging brain imaging obtained in six fetuses with a diagnosis of Apert syndrome. RESULTS: Five fetuses had attenuation of the septal leaflets, and two had corpus callosum dysgenesis. All six had temporal lobe expansion and overconvolution and temporal lobe clefts. The temporal lobe abnormalities preceded the development of cranial deformity in two fetuses. CONCLUSION: Overexpansion and overconvolution of the temporal lobe is evident antenatally and is particularly conspicuous in the fetus when the normal brain is still relatively smooth (approximately 24 to 28 weeks of gestation).

SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014.

This guideline is an evidence based, practical clinical approach to the management of Hypertensive Disorders of Pregnancy. Since the previous SOMANZ guideline published in 2008, there has been significant international progress towards harmonisation of definitions in relation to both the diagnosis and management of preeclampsia and gestational hypertension. This reflects increasing knowledge of the pathophysiology of these conditions, as well as their clinical manifestations. In addition, the guideline includes the management of chronic hypertension in pregnancy, an approach to screening, advice regarding prevention of hypertensive disorders of pregnancy, and discussion of recurrence risks and long term risk to maternal health. The literature reviewed included the previous SOMANZ Hypertensive Disorders of Pregnancy guideline from 2008 and its reference list, plus all other published National and International Guidelines on this subject. Medline, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Registry of Controlled Trials (CCRCT), National Institute for Health and Care Excellence (NICE) Evidence Search, and Database of Abstracts and Reviews of Effects (DARE) were searched for literature published between January 2007 and March, 2014.

Simplified gestational diabetes screening with a triaging fasting plasma glucose reduces the burden of oral glucose tolerance tests during pregnancy - A large tertiary comparative cohort study.

AIMS: The study aimed to evaluate the impact of a simplified screeningapproach for gestational diabetes (GDM) compared to conventional screening on OGTT rates, GDM prevalence, and perinatal outcomes. METHOD: A retrospective comparative cohort study included singleton births from 20 weeks' gestation. Pregnancies without diagnostic glucose results from 13 weeks' gestation or incomplete screenings were excluded. Simplified screening consisted of a triaging fasting plasma glucose (FPG), where only those with FPG levels between 4.7 and 5.0 mmol/L proceeded to the 2hr 75 g oral glucose tolerance test (OGTT).The study period was divided into conventional screening (1st January 2019-30th June 2020) and simplified screening (1st January 2021-31st December 2021). RESULTS: Out of 15,138 pregnancies, 12,035 met the inclusion criteria: 7385 underwent conventional and 4650 underwent simplified screening. In the simplified group, 82.9 % avoided an OGTT. The simplified screening group also had a lower GDM prevalence compared to the conventional group ((18.7 % vs. 21.7 %, p < 0.001). Perinatal outcomes, including the rate of large-for-gestational-age infants, were similar between the groups. CONCLUSION: The simplified GDM screening strategy for significantly reduced OGTTs by over 80% without impacting perinatal outcomes. It suggests that prospective studies are necessary to further evaluate this approach.

Placental syndecan expression is altered in human idiopathic fetal growth restriction.

Pregnancy represents a hypercoagulable state characterized by increased thrombin generation. However, placentas from fetal growth restriction (FGR) pregnancies are characterized by increased fibrin deposition and thrombi in the vasculature, indicative of a further increase in thrombin activation and a disturbance in coagulation in this clinical setting. The cause of the coagulation disturbance observed in FGR pregnancies is currently unknown. Anticoagulant mechanisms are crucial in the regulation of thrombin activity, and current evidence suggests that syndecans are the principal placental anticoagulant proteoglycans. The aim of this study was to determine the localization, distribution, and expression of syndecans 1 to 4 in placentas complicated by idiopathic FGR compared with gestation-matched controls. Immunohistochemistry results revealed that all of the syndecans were localized to cells located closely to the maternal and fetal circulation. The mRNA and protein expression levels of both syndecan 1 and syndecan 2 were significantly decreased in FGR samples compared with controls. This is the first study to demonstrate the differential expression of syndecans 1 to 4 in idiopathic FGR placentas compared with controls. Reduced levels of syndecan expression may result in increased placental thrombosis in the uteroplacental circulation and may therefore contribute to the pathogenesis of FGR.

Inherited thrombophilias and adverse pregnancy outcomes: a case-control study in an Australian population.

OBJECTIVE: The primary aim of this study was to examine the association between inherited thrombophilias and adverse pregnancy outcomes in an Australian population. DESIGN: Case-control study. SETTING: Two Australian tertiary level maternity hospitals. POPULATION: One hundred and fifteen cases with adverse pregnancy outcomes, comprising severe pre-eclampsia (n=45), fetal growth restriction (n=44), placental abruption (n=16) or stillbirth (n=10), and 115 controls matched for ethnicity, parity and maternal age. METHODS: Genotyping for factor V Leiden, prothrombin gene mutation, methylenetetrahydrofolate reductase 677 and 1298 and thrombomodulin polymorphism was performed using Taqman assays in an ABI prism 7700 Sequencer. Pregnancy outcome data were extracted from the medical record at the time of recruitment. MAIN OUTCOME MEASURES: Prevalence of inherited thrombophilias in women with adverse pregnancy outcomes and matched control women. RESULTS: There were no differences in baseline characteristics between cases and control women, apart from duration of gestation and neonatal birthweight. Overall, there was no significant difference in the prevalence of these inherited thrombophilia polymorphisms between cases and control women. Heterozygosity for the factor V Leiden mutation, however, was significantly associated with an increased risk of both stillbirth (odds ratio 9.33, 95% confidence interval 1.36-64.15, p=0.02) and placental abruption (odds ratio 8.62, 95% confidence interval 1.57-47.17, p=0.01). CONCLUSIONS: Overall, this study does not support a significant association between inherited thrombophilia polymorphisms and adverse pregnancy outcomes. Our two statistically significant findings should be interpreted with caution given the small number of patients in these subgroups (10 stillbirths and 16 placental abruption cases) and the wide confidence intervals.