Role of placental, fetal and maternal cardiovascular markers in predicting adverse outcome in women with suspected or confirmed pre-eclampsia.

OBJECTIVE: To assess the performance of placental, fetal and maternal cardiovascular markers in the prediction of adverse perinatal and maternal outcomes in women with suspected or confirmed pre-eclampsia. METHODS: This was a prospective prognostic accuracy study of women with suspected or confirmed pre-eclampsia who underwent a series of investigations to measure maternal hemodynamic indices, mean arterial pressure, augmentation index, ophthalmic artery peak systolic velocity (PSV) ratio, uterine artery pulsatility index (UtA-PI), fetal biometric and Doppler parameters, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). The performance of these markers, individually or in combination, in predicting adverse perinatal and maternal outcomes was then assessed using receiver-operating-characteristics (ROC)-curve analysis. Adverse maternal outcome was defined as one or more of severe hypertension, admission to the intensive care unit, eclampsia, placental abruption, HELLP syndrome, disseminated intravascular coagulation, platelets < 100 × 109 /L, creatinine > 90 µmol/L and alanine aminotransferase > 100 U/L. Adverse perinatal outcome was defined as one or more of preterm birth at or before 34 + 0 weeks, neonatal intensive care unit admission for > 48 h, respiratory distress syndrome, intraventricular hemorrhage, hypoxic ischemic encephalopathy, necrotizing enterocolitis, retinopathy of prematurity and confirmed fetal infection. RESULTS: We recruited 126 women with suspected (n = 31) or confirmed (n = 95) pre-eclampsia at a median gestational age of 33.9 weeks (interquartile range, 30.9-36.3 weeks). Pregnancies with adverse perinatal outcome compared to those without had a higher median UtA-PI (1.3 vs 0.8; P < 0.001), ophthalmic artery PSV ratio (0.8 vs 0.7; P = 0.01) and umbilical artery PI percentile (82.0 vs 68.5; P < 0.01) and lower median estimated fetal weight percentile (4.0 vs 43.0; P < 0.001), abdominal circumference percentile (4.0 vs 63.0; P < 0.001), middle cerebral artery PI percentile (28.0 vs 58.5; P < 0.001) and cerebroplacental ratio percentile (18.0 vs 46.5; P < 0.001). Pregnancies with adverse perinatal outcome also had a higher median sFlt-1 (8208.0 pg/mL vs 4508.0 pg/mL; P < 0.001), lower PlGF (27.2 pg/mL vs 76.3 pg/mL; P < 0.001) and a higher sFlt-1/PlGF ratio (445.4 vs 74.4; P < 0.001). The best performing individual marker for predicting adverse perinatal outcome was the sFlt-1/PlGF ratio (area under the ROC curve (AUC), 0.87 (95% CI, 0.81-0.93)), followed by estimated fetal weight (AUC, 0.81 (95% CI, 0.73-0.89)). Women who experienced adverse maternal outcome had a higher median sFlt-1 level (7471.0 pg/mL vs 5131.0 pg/mL; P < 0.001) and sFlt-1/PlGF ratio (204.3 vs 93.3; P < 0.001) and a lower PlGF level (37.0 pg/mL vs 66.1 pg/mL; P = 0.01) and estimated fetal weight percentile (16.5 vs 37.0; P = 0.04). All markers performed poorly in predicting adverse maternal outcome, with sFlt-1 (AUC, 0.69 (95% CI, 0.60-0.79)) and sFlt-1/PlGF ratio (AUC, 0.69 (95% CI, 0.59-0.78)) demonstrating the best individual performance. The addition of cardiovascular, fetal or other placental indices to the sFlt-1/PlGF ratio did not improve the prediction of adverse maternal or perinatal outcomes. CONCLUSIONS: The sFlt-1/PlGF ratio performs well in predicting adverse perinatal outcomes but is a poor predictor of adverse maternal outcomes in women with suspected or diagnosed pre-eclampsia. The addition of cardiovascular or fetal indices to the model is unlikely to improve the prognostic performance of the sFlt-1/PlGF ratio. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Stillbirth: are we making more progress than we think? A retrospective cohort study.

OBJECTIVE: To quantify how the changing stillbirth risk profile of women is affecting the interpretation of the stillbirth rate. DESIGN: A retrospective, population-based cohort study from 1983 to 2018. SETTING: Victoria, Australia. POPULATION: A total of 2 419 923 births at ≥28 weeks of gestation. METHODS: Changes in maternal characteristics over time were assessed. A multivariable logistic regression model was developed for stillbirth, based on maternal characteristics in 1983-1987, and used to calculate individual predictive probabilities of stillbirth from the regression equation. The number of expected stillbirths per year as a result of the change in maternal demographics was then calculated, assuming no changes in care and in the associations between maternal characteristics and stillbirth over time. MAIN OUTCOME MEASURE: Stillbirth. RESULTS: Compared with 1983-1987, there were more women in older age groups giving birth, more nulliparous women, more indigenous women and women born in Oceania, Asia and Africa, more multiple pregnancies and more women with pre-existing diabetes in 2014-2018. Despite this, the rate of stillbirth fell from 5.42 per 1000 births in 1983 to 1.72 per 1000 births in 2018 (P < 0.001). Applying the multivariable logistic regression equation, derived from the 1983-87 data, to each year, had there been no changes in care or in the associations between maternal characteristics and stillbirth, the rate of stillbirth would have increased by 12%, from 4.94 per 1000 in 1983 to 5.54 per 1000 in 2018, as a result of the change in maternal characteristics. CONCLUSIONS: Population rates of stillbirth are falling faster than is generally appreciated. TWEETABLE ABSTRACT: Population reductions in stillbirth have been underestimated as a result of changing maternal characteristics.

Increasing obstetric intervention for fetal growth restriction is shifting birthweight centiles: a retrospective cohort study.

OBJECTIVE: To assess the impact of increasing obstetric intervention on birthweight centiles. DESIGN: Retrospective cohort study of births in five 2-year epochs: 1983-84, 1993-94, 2003-2004, 2013-2014 and 2016-2017. POPULATION: 665 205 singleton births at ≥32 weeks' gestation. SETTING: All maternity services in Victoria, Australia. METHODS: For each epoch, we calculated the birthweight cutoffs defining each birthweight centile at 34, 37 and 40 weeks' gestation. We calculated rates of iatrogenic delivery over time. We then calculated the number of babies whose birthweight would have classified them as ≥3rd centile based on 1983-84 centile definitions but as <3rd centile based on 2016-2017 centile definitions. MAIN OUTCOME MEASURES: Birthweight centile, and gestation at delivery. RESULTS: From 1983-84 to 2016-2017, the rate of iatrogenic delivery for singleton pregnancies increased at all term gestations: 1.6-6.4% at 37 weeks', 4.5-18.3% at 38 weeks', 7.6-23.9% at 39 weeks' and 18.4-25.1% at 40 weeks' (all P < 0.001). Over the same period, the birthweight cutoffs defining the 3rd, 5th and 10th centiles increased significantly at term, but not preterm, gestations. This led to increasing numbers of term births being classified as small for gestational age (SGA). Of the 2748 babies born in 2016-2017 at 37-39 weeks' gestation with a birthweight <3rd centile in that period, 1478 (53.8%) would have been classified as ≥3rd centile based on 1983-84 centile definitions. CONCLUSION: Increasing intervention is shifting the birthweight cutoffs that define birthweight centiles and thereby redefining what constitutes SGA. This undermines the use of population-derived birthweight centiles to audit clinical care. TWEETABLE ABSTRACT: Increasing obstetric intervention is shifting birthweight centiles and therefore definitions of normality.

Chronic hepatitis B infection and the risk of gestational diabetes: a cross-sectional study.

OBJECTIVE: An estimated two billion people worldwide live with hepatitis B virus (HBV) infection. Many of these are women of reproductive age. Studies that have examined pregnancy outcomes in women living with HBV have reported conflicting results in relation to the incidence of gestational diabetes (GDM). The aim of this study is to examine if gestational diabetes is more common in women with chronic HBV residing in a non-Asian country. DESIGN: Cross-sectional study. SETTING: Victoria, Australia. POPULATION: All singleton births between 2009 and 2017. METHODS: Poisson regression was performed to determine whether gestational diabetes is more common in women with HBV than in women without HBV taking into account other risk factors such as maternal age, body mass index (BMI), parity and country of birth. MAIN OUTCOME MEASURE: Gestational diabetes diagnosis in women with chronic HBV infection. RESULTS: For women with HBV, the unadjusted incidence risk ratio for GDM was 1.75 (95% CI 1.6-1.9). After adjusting for region of birth, BMI, parity, age and smoking, the adjusted incidence risk ratio was 1.2 (95% CI 1.1-1.3). The highest incidence (37.1%) of GDM was in women with HBV and a BMI of >40. CONCLUSIONS: The findings from this study confirm an association between HBV and GDM. TWEETABLE ABSTRACT: HBV is associated with GDM with an incidence risk ratio for GDM of 1.75 (95% CI 1.6-1.9).

Does public reporting of the detection of fetal growth restriction improve clinical outcomes: a retrospective cohort study.

OBJECTIVE: To assess the impact of publicly reporting a statewide fetal growth restriction (FGR) performance indicator. DESIGN: Retrospective cohort study from 2000 to 2017. SETTING: All maternity services in Victoria, Australia. POPULATION: A total of 1 231 415 singleton births at ≥32 weeks of gestation. METHODS: We performed an interrupted time-series analysis to assess the impact of publicly reporting an FGR performance indicator on the rate of detection for severe cases of small for gestational age (SGA). Rates of perinatal mortality and morbidity and obstetric intervention were assessed for severe SGA pregnancies and pregnancies delivered for suspected SGA. MAIN OUTCOME MEASURES: Gestation at delivery, obstetric management and perinatal outcome. RESULTS: The public reporting of a statewide FGR performance indicator was associated with a steeper reduction per quarter in the percentage of severe SGA undelivered by 40 weeks of gestation, from 0.13 to 0.51% (P = 0.001), and a decrease in the stillbirth rate by 3.3 per 1000 births among those babies (P = 0.01). Of babies delivered for suspected SGA, the percentage with birthweights ≥ 10th centile increased from 41.4% (n = 307) in 2000 to 53.3% (n = 1597) in 2017 (P < 0.001). Admissions to a neonatal intensive care unit for babies delivered for suspected SGA but with a birthweight ≥ 10th centile increased from 0.8 to 2.0% (P < 0.001). CONCLUSIONS: The public reporting of an FGR performance indicator has been associated with the improved detection of severe SGA and a decrease in the rate of stillbirth among those babies, but with an increase in the rate of iatrogenic birth for babies with normal growth. TWEETABLE ABSTRACT: The public reporting of hospital performance is associated with a reduction in stillbirth, but also with unintended interventions.

Impact of different glycaemic treatment targets on pregnancy outcomes in gestational diabetes.

AIM: With no current randomized trials, we explored the impact of tight compared with standard treatment targets on pregnancy outcomes in gestational diabetes mellitus (GDM). METHODS: This cohort study of singleton births ≥ 28 weeks' gestation was conducted at two major Australian maternity services (2009-2013). Standardized maternal, neonatal and birth outcomes were examined using routine healthcare data and compared for women with GDM at Service One (n = 2885) and Service Two (n = 1887). Services applied different treatment targets: Service One (standard targets, reference group) fasting < 5.5 mmol/l, 2-h postprandial < 7.0 mmol/l; Service Two (tight targets) fasting < 5.0 mmol/l, 2-h postprandial < 6.7 mmol/l. Multivariable regression with propensity score adjustment was used to examine associations between targets and outcomes. RESULTS: GDM prevalence and insulin use were 7.9% and 31% at Service One, and 5.7% and 46% at Service Two. There were no differences in primary outcomes: birthweight > 90th centile [adjusted odds ratio (OR) 1.06, 95% confidence interval (CI) 0.87-1.30] and < 10th centile (OR 0.84, 95% CI 0.70-1.01), or secondary outcomes gestational hypertension, pre-eclampsia, shoulder dystocia or a perinatal composite. Service Two with tight targets had increased induction of labour (OR 3.63, 95% CI 3.17-4.16), elective Caesarean section (OR 1.75, 95% CI 1.37-2.23) and Apgar scores < 7 at 5 min (OR 1.54, 95% CI 1.05-2.25), decreased hypoglycaemia (OR 0.76, 95% CI 0.61-0.94]), jaundice (OR 0.47, 95% CI 0.35-0.63) and respiratory distress (OR 0.68, 95% CI 0.47-0.98). CONCLUSIONS: Tight GDM treatment targets were associated with greater insulin use and no difference in primary birthweight outcomes. The service with tight targets had higher obstetric intervention, lower rates of reported hypoglycaemia, jaundice, respiratory distress and lower Apgar scores. High-quality interventional data are required before tight treatment targets can be implemented.

Using medico-legal claims for quality improvement in maternity care: application and revision of an NHSLA coding taxonomy.

OBJECTIVE: To validate the NHSLA maternity claims taxonomy at the level of a single maternity service and assess its ability to direct quality improvement. DESIGN: Qualitative descriptive study. SETTING: Medico-legal claims between 1 January 2000 and 31 December 2016 from a maternity service in metropolitan Melbourne, Australia. POPULATION: All obstetric claims and incident notifications occurring within the date range were included for analysis. METHODS: De-identified claims and notifications data were derived from the files of the insurer of Victorian public health services. Data included claim date, incident date and summary, and claim cost. All reported issues were coded using the NHSLA taxonomy and the lead issue identified. MAIN OUTCOME MEASURES: Rate of claims and notifications, relative frequency of issues, a revised taxonomy. RESULTS: A combined total of 265 claims and incidents were reported during the 6 years. Of these 59 were excluded, leaving 198 medico-legal events for analysis (1.66 events/1000 births). The costs for all claims was $46.7 million. The most common claim issues were related to management of labour (n = 63, $17.7 million), cardiotocographic interpretation (n = 43, $24.4 million), and stillbirth (n = 35, $656,750). The original NHSLA classification was not sufficiently detailed to inform care improvement programmes. A revised taxonomy and coding flowchart is presented. CONCLUSIONS: Systematic analysis of obstetric medico-legal claims data can potentially be used to inform quality and safety improvement. TWEETABLE ABSTRACT: New taxonomy to target health improvement from maternity claims based on NHSLA Ten Years of Maternity Claims.

Maternal creatine in pregnancy: a retrospective cohort study.

OBJECTIVE: To estimate creatine concentrations in maternal plasma and urine, and establish relationships with maternal characteristics, diet and fetal growth. DESIGN: Retrospective cohort study. SETTING: Lyell McEwin Hospital, Adelaide, Australia. POPULATION: A biobank of plasma and urine samples collected at 13, 18, 30 and 36 weeks' gestation from 287 pregnant women from a prospective cohort of asthmatic and non-asthmatic women. METHODS: Creatine was measured by enzymatic analysis. Change in creatine over pregnancy was assessed using the Friedman test. Linear mixed models regression was used to determine associations between maternal factors and diet with creatine across pregnancy and between creatine with indices of fetal growth at birth. MAIN OUTCOME MEASURES: Maternal creatine concentrations, associations between maternal factors and creatine and between creatine and fetal growth parameters. RESULTS: Maternal smoking, body mass index, asthma and socio-economic status were positively and parity negatively associated with maternal plasma and/or urine creatine. Maternal urine creatine concentration was positively associated with birthweight centile and birth length. After adjustment, each µmol/l increase in maternal urinary creatine was associated with a 1.23 (95% CI 0.44-2.02) unit increase in birthweight centile and a 0.11-cm (95% CI 0.03-0.2) increase in birth length. CONCLUSIONS: Maternal factors and fetal growth measures are associated with maternal plasma and urine creatine concentrations. TWEETABLE ABSTRACT: Maternal creatine is altered by pregnancy; fetal growth measures are associated with maternal creatine concentrations.

Combination gefitinib and methotrexate treatment for non-tubal ectopic pregnancies: a case series.

Non-tubal ectopic pregnancies are a rare subgroup of ectopic pregnancies implanted at sites other than the Fallopian tube. Mortality from non-tubal ectopic pregnancies is higher compared with that for tubal ectopic pregnancies, and they are becoming more common, partly due to the rising incidence of Caesarean sections and use of assisted reproductive technologies. Non-tubal ectopic pregnancies can be especially difficult to treat. Surgical treatment is complex, and follow-up after medical treatment is usually protracted. There is therefore a need for more effective medical therapies to resolve non-tubal ectopic pregnancies and reduce operative intervention. We have recently reported successful use of combination gefitinib (an orally available epidermal growth factor receptor inhibitor) and methotrexate for treatment of tubal pregnancies. To our knowledge, this combination has not been used to treat non-tubal pregnancies. Here we report the use of combination gefitinib and methotrexate to treat eight women with stable, non-tubal ectopic pregnancies at two tertiary academic teaching hospitals (Edinburgh, UK and Melbourne, Australia); five interstitial and three Caesarean section scar ectopic pregnancies. Pretreatment serum hCG levels ranged from 2458 to 48 550 IU/l, and six women had pretreatment hCG levels >5000 IU/l. The women were co-administered 1-2 doses of i.m. methotrexate (50 mg/m² on Day 1, ± Day 4 or Day 7) with seven once daily doses of oral gefitinib (250 mg). The women were monitored until complete resolution of the ectopic pregnancy, defined as a serum hCG <15 IU/l. Time to resolution (days from first methotrexate dose until serum hCG <15 IU/l), safety and tolerability, complication rates and subsequent fertility outcomes were also recorded. All eight women were successfully treated with combination gefitinib and methotrexate. The most common side effects were transient acne/rash and diarrhoea, known side effects of gefitinib. All women promptly resumed menstruation and importantly, three women subsequently conceived spontaneously. Two have delivered a healthy infant at term and the third is currently in her second trimester of pregnancy. Hence, our case series supports a future clinical trial to determine the efficacy of combination gefitinib and methotrexate to treat non-tubal ectopic pregnancies.

Antioxidant therapies: a potential role in perinatal medicine.

Pregnancies complicated by impaired placentation, acute severe reductions in oxygen supply to the fetus, or intrauterine infection are associated with oxidative stress to the mother and developing baby. Such oxidative stress is characterized as an upregulation in the production of oxidative or nitrative free radicals and a concomitant decrease in the availability of antioxidant species, thereby creating a state of fetoplacental oxidative imbalance. Recently, there has been a good deal of interest in the potential for the use of antioxidant therapies in the perinatal period to protect the fetus, particularly the developing brain, against oxidative stress in complications of pregnancy and birth. This review will examine why the immature brain is particularly susceptible to oxidative imbalance and will provide discussion on antioxidant treatments currently receiving attention in the adult and perinatal literature - allopurinol, melatonin, α-lipoic acid, and vitamins C and E. In addition, we aim to address the interaction between oxidative stress and the fetal inflammatory response, an interaction that may be vital when proposing antioxidant or other neuroprotective strategies.

Glucocorticoid treatment does not alter early cardiac adaptations to growth restriction in preterm sheep fetuses.

OBJECTIVE: To study the consequences of glucocorticoid treatment in fetal growth restriction (FGR) on cardiac function. SETTING: Laboratory. SAMPLE: Sheep. METHODS: Growth restriction was induced in sheep fetuses using single umbilical artery ligation (SUAL) on days 105-110 of gestation (term 147). Control fetuses were not ligated. Betamethasone (BM) (11.4 mg intramuscularly) or saline was administered to ewes on days 5 and 6 after surgery. Ewes were anaesthetised on day 7, the fetuses were removed, and their hearts were mounted on a Langendorff apparatus. Balloon catheters were inserted into the right and left ventricles. OUTCOME MEASURES: Ventricular contractile function and infarct area following ischaemia/reperfusion. RESULTS: The SUAL resulted in FGR (body weight 77% of control). The FGR was associated with increases in basal left ventricular pressure development and rates of contraction and relaxation. Right ventricular contraction was unaffected. Following brief ischaemia/reperfusion, the infarct area in FGR hearts was increased four-fold compared with controls. Antenatal BM resulted in a proportional increase in heart size and coronary flow, especially in FGR fetuses, and left ventricular pressure and heart rate responses to ß-adrenoceptor activation were increased. CONCLUSIONS: Fetal hearts rapidly adapt to FGR to maintain substrate delivery to the brain and heart. The FGR greatly enhanced the area of ischaemia, with implications for susceptibility in postnatal life. Antenatal BM treatment does not interfere with these cardiac changes but appears to increase left ventricle ß-adrenoceptor responsiveness, which may render the offspring vulnerable to subsequent cardiac dysfunction.

Decline in ßhCG levels between days 0 and 4 after a single dose of methotrexate for ectopic pregnancy predicts treatment success: a retrospective cohort study.

In current protocols for the medical management of ectopic pregnancies, the first indication of treatment response is obtained no sooner than day 7. We examined whether human chorionic gonadotrophin (ßhCG) trends between days 0 and 4 after methotrexate provide an earlier indication of the likely outcome. Of 33 patients where serum ßhCG dropped between days 0 and 4 after methotrexate, the ectopic pregnancy was resolved in 88% of cases without further treatment. Of 12 women where serum ßhCG rose between days 0 and 4, only 42% had treatment success. A fall in ßhCG between days 0 and 4 after treatment with methotrexate for ectopic pregnancy predicts a high likelihood of treatment success.

Sulforaphane Bioavailability and Effects on Blood Pressure in Women with Pregnancy Hypertension.

Sulforaphane, an isothiocyanate found in cruciferous vegetables such as broccoli, shows promise as an adjuvant therapy for preeclampsia. To inform future clinical trials, we set out to determine the bioavailability of sulforaphane in non-pregnant and preeclamptic women. In six healthy female volunteers, we performed a crossover trial to compare the bioavailability of sulforaphane and metabolites afforded by an activated and non-activated broccoli extract preparation. We then undertook a dose escalation study of the activated broccoli extract in 12 women with pregnancy hypertension. In non-pregnant women, an equivalent dose of activated broccoli extract gave higher levels of sulforaphane and metabolites than a non-activated extract (p < 0.0001) and greater area under the curve (AUC) (3559 nM vs. 2172 nM, p = 0.03). Compared to non-pregnant women, in women with preeclampsia, the same dose of activated extract gave lower levels of total metabolites (p < 0.000) and AUC (3559 nM vs. 1653 nM, p = 0.007). Doubling the dose of the activated extract in women with preeclampsia doubled levels of sulforaphane and metabolites (p = 0.02) and AUC (1653 nM vs. 3333 nM, p = 0.02). In women with preeclampsia, activated broccoli extract was associated with modest decreases in diastolic blood pressure (p = 0.05) and circulating levels of sFlt-1 (p = 0.0002). A myrosinase-activated sulforaphane formulation affords better sulforaphane bioavailability than a non-activated formulation. Higher doses of sulforaphane are required to achieve likely effective doses in pregnant women than in non-pregnant women. Sulforaphane may improve endothelial function and blood pressure in women with pregnancy hypertension.

Identification of a novel member in the family Albulidae (bonefishes).

A novel Caribbean species Albula sp. cf. vulpes in the family Albulidae (bonefishes) was diagnosed through genetic and morphometric study. Phylogenies derived from 16S rRNA sequences revealed deeply separated lineages among Caribbean bonefishes. Mitochondrial DNA sequence divergences indicated a separation between 3.0 and 5.2 million years before present (b.p.). Cytochrome b phylogenies further supported the classification of A. sp. cf. vulpes as a novel albulid. Morphological variability revealed several differences between A. sp. cf. vulpes and other Caribbean species. A microsatellite library was developed to discern hybridization rates among the species. Microsatellite analyses revealed low levels of hybridization between some members in the complex. One instance of backcrossing was found between A. vulpesxA. sp. B and a pure A. sp. B, indicating that hybrids may have reduced fitness or may be reproductively isolated due to temporal-spatial spawning habitat differences.

Sulforaphane improves vascular reactivity in mouse and human arteries after "preeclamptic-like" injury.

INTRODUCTION: The widespread maternal endothelial dysfunction that underlies the manifestations of preeclampsia is thought to arise from excessive placental production of antiangiogenic factors and enhanced oxidative stress. Therefore, we assessed whether the natural antioxidant sulforaphane could improve vascular function. METHODS: Cell viability of human umbilical vein endothelial cells (HUVECs) was assessed after 24 or 48 h in normoxia (20% O2) or hypoxia (1% O2) with or without sulforaphane. To model vascular dysfunction associated with preeclampsia, mouse mesenteric arteries were incubated in trophoblast conditioned media (TCM), and human omental arteries incubated in preeclamptic explant media (PEM) with or without sulforaphane. Both media are rich in antiangiogenic compounds associated with preeclampsia. TCM was generated from primary cytotrophoblast cells from term placentae of normotensive, while PEM was generated from explants from preeclamptic women. Reactivity was assessed by wire myography. sulforaphane's actions as a vasodilator were also investigated. RESULTS: Under conditions of hypoxia, sulforaphane improved HUVEC viability. In mouse mesenteric arteries, sulforaphane reduced contraction evoked by potassium (p < 0.001), phenylephrine and endothelin 1 (all p < 0.001). Sulforaphane also inhibited Ca2+-induced contraction (p = 0.014). Sulforaphane prevented TCM-induced augmentation of phenylephrine and angiotensin II-mediated contraction of mouse mesenteric arteries. In human omental arteries, sulforaphane induced vasodilation (p < 0.001), and prevented PEM-induced endothelial dysfunction by restoring arterial sensitivity to the endothelium-dependent vasodilator bradykinin (p = 0.008). DISCUSSION: Sulforaphane causes relaxation in arteries and protects against arterial dysfunction induced by placental-derived antiangiogenic factors, which are known to contribute to the preeclampsia.

Sulforaphane improves syncytiotrophoblast mitochondrial function after in vitro hypoxic and superoxide injury.

INTRODUCTION: Placental mitochondrial dysfunction contributes to the oxidative stress that underlies preeclampsia. Here, we assessed whether sulforaphane (SFN) could improve syncytiotrophoblast mitochondrial function after in vitro hypoxic and superoxide injury. METHODS: Placental cytotrophoblasts were isolated from healthy term placentae (n = 12) and incubated for 48 h in 8% O2 ± 1 µM SFN before acute (4hrs) or chronic (24hrs) hypoxic (1% O2), or superoxide (xanthine/xanthine oxidase) injury. Cytotrophoblasts were also isolated from preeclamptic placentae (n = 5) and cultured in 8% O2 ± 1 µM SFN. Mitochondrial respiration was measured using the Seahorse MitoStress XF assay. Cells were stained with mitotracker red to assess mitochondrial membrane health and mitochondrial gene expression assessed using RT-qPCR. RESULTS: SFN prevented significant reductions in syncytiotrophoblast mitochondrial maximal respiration, spare respiratory capacity, basal respiration and ATP production following acute hypoxia. Chronic hypoxia only reduced maximal and spare respiratory capacity. SFN prevented these negative changes and increased respiration overall. Alternatively, acute superoxide injury significantly increased mitochondrial maximal respiration and spare respiratory capacity. SFN treatment further increased basal respiration following superoxide injury and prevented significant decreases in ATP production and coupling efficiency. In preeclamptic placentae, SFN significantly increased mitochondrial maximal respiration, spare respiratory capacity, basal respiration and ATP production, and decreased proton leak. SFN up-regulated mRNA expression of mitochondrial complexes and corrected an up-regulation in fission gene expression observed after hypoxic-superoxide injury. Finally, preliminary results suggest SFN prevented hypoxia-induced impairment of mitochondrial membrane structure. DISCUSSION: SFN mitigated hypoxia and superoxide induced changes to syncytiotrophoblast mitochondrial function in vitro, and improved mitochondrial respiration in trophoblast cells from preeclamptic placentae.

Survey of Australian maternity hospitals to inform development and implementation of a stillbirth prevention 'bundle of care'.

BACKGROUND: 'Bundles of care' are being implemented to improve key practice gaps in perinatal care. As part of our development of a stillbirth prevention bundle, we consulted with Australian maternity care providers. OBJECTIVE: To gain the insights of Australian maternity care providers to inform the development and implementation of a bundle of care for stillbirth prevention. METHODS: A 2018 on-line survey of hospitals providing maternity services included 55 questions incorporating multiple choice, Likert items and open text. A senior clinician at each site completed the survey. The survey asked questions about practices related to fetal growth restriction, decreased fetal movements, smoking cessation, intrapartum fetal monitoring, maternal sleep position and perinatal mortality audit. The objectives were to assess which elements of care were most valued; best practice frequency; and, barriers and enablers to implementation. RESULTS: 227 hospitals were invited with 83 (37%) responding. All proposed elements were perceived as important. Hospitals were least likely to follow best practice recommendations "all the time" for smoking cessation support (<50%), risk assessment for fetal growth restriction (<40%) and advice on sleep position (<20%). Time constraints, absence of clear guidelines and lack of continuity of carer were recognised as barriers to implementation across care practices. CONCLUSIONS: Areas for practice improvement were evident. All elements of care were valued, with increasing awareness of safe sleeping position perceived as less important. There is strong support from maternity care providers across Australia for a bundle of care to reduce stillbirth.

Screening pregnant women for chlamydia: what are the predictors of infection?

OBJECTIVES: To determine the risk factors associated with chlamydial infection in pregnancy and the sensitivity and specificity of these when used for selective screening. METHODS: A prospective, cross-sectional study of pregnant women aged 16-25 years attending four major public antenatal services across Melbourne, Australia. Between October 2006 and July 2007, women were approached consecutively and asked to complete a questionnaire and to provide a first-pass urine specimen for Chlamydia trachomatis testing using PCR. RESULTS: Of 1180 eligible women, 1087 were approached and 1044 (88%) consented to participate. Among the 987 women for whom a questionnaire and a definitive diagnostic assay were available, the prevalence of chlamydia was 3.2% (95% CI 1.8 to 5.9). In a multiple logistic regression model, more than one sexual partner in the past year (AOR 11.5; 95% CI 7.1 to 18.5) was associated with chlamydia infection. The use of any antibiotic within 3 months (AOR 0.2; 95% CI 0.1 to 0.6) was associated with a decreased risk of infection. Screening restricted to women who reported more than one sexual partner in the past year would have detected 44% of infections in women aged 16-25 years and would have required only 7% of women to be screened. The addition of those women aged 20 years and under would have required 27% of women to be screened and detection of 72% of infections. CONCLUSIONS: Selective chlamydia screening of pregnant women based on risk factors can improve the yield from screening. However, the potential harm of missed infections among excluded women would need to be considered.

Reduced maternal serum concentrations of angiopoietin-2 in the first trimester precede intrauterine growth restriction associated with placental insufficiency.

The aim of this study was to investigate whether maternal serum levels of angiopoietin-2 (Ang-2) and pregnancy-associated plasma protein A (PAPP-A) are associated with subsequent intrauterine growth restriction (IUGR). Ang-2 was measured in 29 nonpregnant and 44 pregnant women at 10-13 weeks of gestation. The median concentration of Ang-2 was 26.61 ng/ml in normal pregnant women compared with 1.71 ng/ml in nonpregnant controls (P < 0.01). Women who subsequently developed severe IUGR had lower levels of Ang-2 compared with normal pregnant controls (P < 0.01). PAPP-A levels were similar in all pregnant groups. These findings suggest that Ang-2 should be evaluated for its ability to predict pregnancies that later are affected by IUGR.

Post-term surveillance and birth outcomes in South Asian-born compared with Australian-born women.

OBJECTIVE: To determine if apparently healthy post-term South Asian-born (SA) women were more likely to have abnormal post-term fetal surveillance than Australian- and New Zealand-born (AUS/NZ) women, whether those abnormalities were associated with increased rates of obstetric intervention and adverse perinatal outcomes, and whether SA women and their babies were at higher risk of adverse outcomes in the post-term period irrespective of their post-term surveillance outcomes. STUDY DESIGN: Post-term surveillance and perinatal outcomes of 145 SA and 272 AUS/NZ nulliparous women with a singleton post-term pregnancy were compared in a retrospective multicentre cohort analysis. RESULTS: Post-term SA women were not significantly more likely to have a low amniotic fluid index (AFI) than AUS/NZ women. However, they were nearly four times more likely (odds ratio 3.75; 95% CI 1.49-9.44) to have an abnormal CTG (P=0.005). Irrespective of maternal region of birth having an abnormal cardiotocography (CTG) or AFI was not associated with adverse intrapartum or perinatal outcomes. However, post-term SA women were significantly more likely than AUS/NZ women to have intrapartum fetal compromise (P=0.03) and an intrapartum cesarean section (P=0.002). Babies of SA women were more also significantly likely to be admitted to the Special Care Nursery or Neonatal Intensive Care Unit (P=0.02). CONCLUSION: Post-term SA women experience higher rates of fetal compromise (antenatal and intrapartum) and obstetric intervention than AUS/NZ women. Irrespective of maternal region of birth an abnormal CTG or AFI was not predictive of adverse outcomes.