There is a paucity of strong evidence associated with adverse pregnancy outcomes and thrombophilia in pregnancy. These problems include both early (recurrent miscarriage) and late placental vascular-mediated problems (fetal loss, pre-eclampsia, placental abruption and intra-uterine growth restriction). Due to poor quality case-control and cohort study designs, there is often an increase in the relative risk of these complications associated with thrombophilia, particularly recurrent early pregnancy loss, late fetal loss and pre-eclampsia, but the absolute risk remains very small. It appears that low-molecular weight heparin has other benefits on the placental vascular system besides its anticoagulant properties. Its use is in the context of antiphospholipid syndrome and recurrent pregnancy loss and also in women with implantation failure to improve live birth rates. There is currently no role for low-molecular weight heparin to prevent late placental-mediated complications in patients with inherited thrombophilia and this may be due to small patient numbers in the studies involved in summarising the evidence. There is potential for low-molecular weight heparin to improve pregnancy outcomes in women with prior severe vascular complications of pregnancy such as early-onset intra-uterine growth restriction and pre-eclampsia but further high quality randomised controlled trials are required to answer this question.

Key pointsVenous thromboembolism (VTE) in pregnancy remains a leading cause of direct maternal mortality in the developed world and identifiable risk factors are increasing in incidence.VTE is approximately 10-times more common in the pregnant population (compared with non-pregnant women) with an incidence of 1 in 1000 and the highest risk in the postnatal period.If pulmonary imaging is required, ventilation perfusion scanning is usually the preferred initial test to detect pulmonary embolism within pregnancy. Treatment should be commenced on clinical suspicion and not be withheld until an objective diagnosis is obtained.The mainstay of treatment for pulmonary thromboembolism in pregnancy is anticoagulation with low molecular weight heparin for a minimum of 3 months in total duration and until at least 6 weeks postnatal. Low molecular weight heparin is safe, effective and has a low associated bleeding risk.Educational aimsTo inform readers about the current guidance for diagnosis and management of pulmonary thromboembolism in pregnancy.To highlight the risks of venous thromboembolism during pregnancy.To introduce the issues surrounding management of pulmonary thromboembolism around labour and delivery

Chronic hypertension in pregnancy is associated with significant adverse pregnancy outcomes, increasing the risk of pre-eclampsia, fetal growth restriction and preterm birth. Dietary nitrate, abundant in green leafy vegetables and beetroot, is reduced in vivo to nitrite and subsequently nitric oxide, and has been demonstrated to lower blood pressure, improve vascular compliance and enhance blood flow in non-pregnant humans and animals. The primary aims of this study were to determine the acceptability and efficacy of dietary nitrate supplementation, in the form of beetroot juice, to lower blood pressure in hypertensive pregnant women. In this double-blind, placebo-controlled feasibility trial, 40 pregnant women received either daily nitrate supplementation (70 mL beetroot juice, n = 20) or placebo (70 mL nitrate-depleted beetroot juice, n = 20) for 8 days. Blood pressure, cardiovascular function and uteroplacental blood flow was assessed at baseline and following acute (3 h) and prolonged (8 days) supplementation. Plasma and salivary samples were collected for analysis of nitrate and nitrite concentrations and acceptability of this dietary intervention was assessed based on questionnaire feedback. Dietary nitrate significantly increased plasma and salivary nitrate/nitrite concentrations compared with placebo juice (p < 0.001), with marked variation between women. Compared with placebo, there was no overall reduction in blood pressure in the nitrate-treated group; however there was a highly significant correlation between changes in plasma nitrite concentrations and changes in diastolic blood pressure in the nitrate-treated arm only (r = -0.6481; p = 0.0042). Beetroot juice supplementation was an acceptable dietary intervention to 97% of women. This trial confirms acceptability and potential efficacy of dietary nitrate supplementation in pregnant women. Conversion of nitrate to nitrite critically involves oral bacterial nitrate reductase activities. We speculate that differences in efficacy of nitrate supplementation relate to differences in the oral microbiome, which will be investigated in future studies.

Hypertensive disease in pregnancy is associated with future cardiovascular disease and, therefore, provides an opportunity to identify women who could benefit from targeted interventions aimed at reducing cardiovascular morbidity. This study focused on the highest-risk group, women with preterm preeclampsia, who have an 8-fold risk of death from future cardiovascular disease. We performed a single-center feasibility randomized controlled trial of 6 months’ treatment with enalapril to improve postnatal cardiovascular function. Echocardiography and hemodynamic measurements were performed at baseline (<3 days), 6 weeks, and 6 months postdelivery on 60 women. At randomization, 88% of women had diastolic dysfunction, and 68% had concentric remodeling/hypertrophy. No difference was seen in total vascular resistance ( P =0.59) or systolic function (global longitudinal strain: P =0.14) between groups at 6 months. However, women treated with enalapril had echocardiographic measurements consistent with improved diastolic function (E/E′[the ratio of early mitral inflow velocity and early mitral annular diastolic velocity]: P =0.04) and left ventricular remodeling (relative wall thickness: P =0.01; left ventricular mass index: P =0.03) at 6 months, compared with placebo. Urinary enalapril was detectable in 85% and 63% of women in the enalapril arm at 6 weeks and 6 months, respectively. All women responded positively to taking enalapril in the future. Our study confirmed acceptability and feasibility of the study protocol with a recruitment to completion rate of 2.2 women per month. Importantly, postnatal enalapril treatment was associated with improved echocardiographic measurements; these early improvements have the potential to reduce long-term cardiovascular disease risk. A definitive, multicenter randomized controlled trial is now required to confirm these findings. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03466333.

The endogenous anticoagulants, activated protein C (APC) and its vitamin K-dependent cofactor protein S, are reduced in pregnancy. 4-6 Fibrinolysis is reduced in pregnancy largely due to placenta-derived PAI-2; however, this normalises rapidly post-delivery. 7 As pregnancy advances, tissue factor-dependent thrombin generation increases, along with Factors VII, VIII, IX, fibrinogen, prothrombin fragment 1+2 and

Abnormal maternal serum biomarkers (AMSB), identified through the aneuploidy screening programme, are frequent incidental findings in pregnancy. They are associated with fetal growth restriction (FGR), but previous studies have not examined whether this association is with early-onset (< 34 weeks) or late-onset (> 34 weeks) FGR; as a result there is no consensus on management. The aims of this study were to determine the prevalence and phenotype of FGR in women with AMSB and test the predictive value of placental sonographic screening to predict early-onset FGR. 1196 pregnant women with AMSB underwent a 21–24 week “placental screen” comprising fetal and placental size, and uterine artery Doppler. Multivariable regression was used to calculate a predictive model for early-onset FGR (birthweight centile < 3rd/< 10th with absent umbilical end-diastolic flow, < 34 weeks). FGR prevalence was high (10.3%), however early-onset FGR was uncommon (2.3%). Placental screening effectively identified early-onset (area under the curve (AUC) 0.93, 95% confidence interval (CI) 0.87–1.00), but not late-onset FGR (AUC 0.70, 95% CI 0.64–0.75). Internal validation demonstrated robust performance for detection/exclusion of early-onset FGR. In this cohort, utilisation of our proposed algorithm with targeted fetal growth and Doppler surveillance, compared with universal comprehensive surveillance would have avoided 1044 scans, potentiating significant cost-saving for maternity services.

Our evaluation confirms the value of PlGF as a diagnostic tool for placental dysfunction. However, low PlGF in isolation should not trigger iatrogenic delivery. Further research linking placental pathology, maternal disease and maternal PlGF levels is urgently needed before this test can be implemented in routine clinical practice.

Clinicians increasingly investigate women for thrombophilias due to their associations with venous thromboembolism and placenta-mediated pregnancy complication. These associations, however, are modest and based largely on retrospective data from studies with heterogeneous classifications and populations, leading to discordance between evidence and guidelines. Current evidence suggests a contributory rather than causative role for thrombophilia in placenta-mediated pregnancy complication and venous thromboembolism. With little evidence of benefit from antithrombotic therapy in placenta-mediated pregnancy complication, thrombophilia screening remains controversial. Given the low absolute risk of placenta-mediated pregnancy complication and gestational venous thromboembolism with heritable thrombophilia, universal screening is inappropriate. Selective screening for antiphospholipid syndrome is supported by robust evidence of benefit. Conversely, selective screening for heritable thrombophilia has not been shown to effectively manage placenta-mediated pregnancy complication. Therefore, at present heritable thrombophilia screening is not warranted for placenta-mediated pregnancy complication. Until we have better evidence from better stratified patient groups, caution should remain if we wish to practice evidence-based medicine.