Search

Antenatal corticosteroids (ACS) are an established intervention to improve outcomes in preterm birth. ACS are optimally timed if the administration-to-birth interval is greater than 24 h and7 days. Evidence has emerged suggesting harm associated with administration-to-birth intervals greater than seven days, or with repeated courses of ACS. Pre-eclampsia is a leading cause of iatrogenic preterm birth, as delivery of the fetus and placenta remains the only cure. This study investigated optimal ACS use in women delivering before 35 weeks' gestation in the United Kingdom with a diagnosis of preterm pre-eclampsia. Of 1,632 women with suspected pre-eclampsia, 250 delivered before 35 weeks' gestation with pre-eclampsia. 31 % (78/250) received optimally timed ACS, 49 % (122/250) received ACS more than seven days pre-delivery and 20 % (50/250) did not receive ACS. There were no significant differences in gestational age, mean birthweight, respiratory distress syndrome, neonatal unit admission or neonatal death between groups. There was a higher rate of intrauterine fetal death in the group of women who did not receive ACS (p 0.05), and a corresponding increase in vaginal delivery and reduction in caesarean section (p 0.05). Optimal ACS administration is poor in women delivering preterm with pre-eclampsia and the largest group of mistimed ACS administration were those given more than 7 days prior to birth. Clinicians should defer ACS until a decision for delivery has been made, at which point ACS should be prioritised. Judicious use of ACS may improve outcomes.

BACKGROUND: Evidence on the association between chronic hypertension and the risk of cardiovascular disease (CVD) in mothers with adverse pregnancy outcomes (APOs) is limited. We investigated the association between chronic hypertension and risk of CVD, considering the role of APOs. METHODS: We used linked electronic health records in the CALIBER platform to define a UK cohort of women with recorded births between 1997 and 2016. We conducted multivariable Cox regression to estimate the association between chronic hypertension, with and without APOs, and 12 subsequent CVD events. RESULTS: The study cohort comprised 1 784 247 births (1.2 million women); of these 12 698 (0.71%) records had chronic hypertension, and 16 499 women had incident CVD during follow-up, of which 66% occurred in women under 40 years. Chronic hypertension (versus no chronic hypertension) was associated with a 2-fold higher risk of first subsequent CVD (adjusted hazard ratios, 2.22 [95% CI, 2.03–2.42]). Compared to normotensive women without APOs, the associations were the strongest in women with chronic hypertension and APOs across the 12 CVD outcomes, varying from 9.65 (5.96–15.6) for heart failure to 2.66 (2.17–3.26) for stable angina. In women with chronic hypertension without APOs, adjusted hazard ratios varied from 5.25 (3.47–7.94) for subarachnoid hemorrhage to 1.26 (0.59–2.67) for peripheral arterial disease. In women with APOs, but without chronic hypertension, adjusted hazard ratios varied from 3.27 (2.48–4.31) for intracerebral hemorrhage to 1.33 (1.26–1.41) for stable angina. CONCLUSIONS: We found strong associations between chronic hypertension and the risk of premature CVD, with greater risk in women who additionally had APOs. Intervention programs focused on these groups might lower their risk of subsequent CVD.

Background COVID-19 vaccines are protective against disease. Pregnant women benefit from vaccination as they are at higher risk of poor maternal and neonatal outcomes following infection. Methods Following regulatory approval of two COVID-19 vaccines in the United Kingdom, a rapid national study of vaccination in pregnancy was instituted using three existing safety surveillance platforms: UKOSS, UKTIS and VIP. This preliminary report describes the data collected up to the 15th June 2021. Results There were 971 reports of COVID-19 vaccination in the UKOSS/UKTIS ( n = 493) and VIP ( n = 478) monitoring systems describing 908 individual pregnancies. Pfizer-BioNTech mRNA vaccination was most common ( n = 501, 55.2%), most women were vaccinated in their second or third trimester ( n = 566, 62.3%), and were mainly vaccinated due to occupational infection risk ( n = 577, 63.5%). Conclusion Obstetric outcome data will be obtained by December 2021. However, women should not delay vaccination whilst awaiting further safety data to emerge.

BackgroundPre-eclampsia is a multiorgan disease of pregnancy that has short- and long-term implications for the woman and fetus, whose immediate impact is poorly understood. We present a novel multi-system approach to MRI investigation of pre-eclampsia, with acquisition of maternal cardiac, placental, and fetal brain anatomical and functional imaging.MethodsA prospective study was carried out recruiting pregnant women with pre-eclampsia, chronic hypertension, or no medical complications, and a non-pregnant female cohort. All women underwent a cardiac MRI, and pregnant women underwent a fetal-placental MRI. Cardiac analysis for structural, morphological and flow data was undertaken; placenta and fetal brain volumetric and T2* data were obtained. All results were corrected for gestational age.ResultsSeventy-eight MRIs were obtained during pregnancy. Pregnancies affected by pre-eclampsia demonstrated lower placental and fetal brain T2*. Within the pre-eclampsia group, three placental T2* results were within the normal range, these were the only cases with normal placental histopathology. Similarly, three fetal brain T2* results were within the normal range; these cases had no evidence of cerebral redistribution on fetal Dopplers. Cardiac MRI analysis demonstrated higher left ventricular mass in pre-eclampsia with 3D modelling revealing additional specific characteristics of eccentricity and outflow track remodelling.ConclusionsWe present the first holistic assessment of the immediate implications of pre-eclampsia on the placenta, maternal heart, and fetal brain. As well as having potential clinical implications for the risk-stratification and management of women with pre-eclampsia, this gives an insight into disease mechanism.What is new?We propose a comprehensive MRI protocol for maternal cardiac and fetal-placental imaging that is safe in pregnancy and acceptable to women, and report on the largest set of functional placental MRI data in pre-eclamptic pregnanciesThe findings suggest altered oxygenation and microstructure in the placenta, which is associated with similar changes in the fetal brainThe study identifies a specific pattern of remodelling in the maternal left ventricle that is associated with pre-eclampsiaWhat are the clinical implications?We demonstrate that MRI provides maternal and fetal insights into pre-eclamptic pregnancies that cannot be obtained by other means during pregnancyFunctional placental MRI may be able to differentiate between preeclampsia disease severities, while fetal brain imaging may help refine neurodevelopmental prognostic assessment of children exposed to pre-eclampsia in uteroA specific 3D pattern of left ventricular remodelling and thickening was found to be discriminant of the presence of pre-eclampsia and may provide a basis for improved clinical risk stratification

Accurate assessment of blood pressure is fundamental to the provision of safe obstetrical care. It is simple, cost effective, and life-saving. Treatments for preeclampsia, including antihypertensive drugs, magnesium sulfate, and delivery, are available in many settings. However, the instigation of appropriate treatment relies on prompt and accurate recognition of hypertension. There are a number of different techniques for blood pressure assessment, including the auscultatory method, automated oscillometric devices, home blood pressure monitoring, ambulatory monitoring, and invasive monitoring. The auscultatory method with a mercury sphygmomanometer and the use of Korotkoff sounds was previously recommended as the gold standard technique. Mercury sphygmomanometers have been withdrawn owing to safety concerns and replaced with aneroid devices, but these are particularly prone to calibration errors and regular calibration is imperative to ensure accuracy. Automated oscillometric devices are straightforward to use, but the physiological changes in healthy pregnancy and pathologic changes in preeclampsia may affect the accuracy of a device and monitors must be validated. Validation protocols classify pregnant women as a "special population," and protocols must include 15 women in each category of normotensive pregnancy, hypertensive pregnancy, and preeclampsia. In addition to a scarcity of devices validated for pregnancy and preeclampsia, other pitfalls that cause inaccuracy include the lack of training and poor technique. Blood pressure assessment can be affected by maternal position, inappropriate cuff size, conversation, caffeine, smoking, and irregular heart rate. For home blood pressure monitoring, appropriate instruction should be given on how to use the device. The classification of hypertension and hypertensive disorders of pregnancy has recently been revised. These are classified as preeclampsia, transient gestational hypertension, gestational hypertension, white-coat hypertension, masked hypertension, chronic hypertension, and chronic hypertension with superimposed preeclampsia. Blood pressure varies across gestation and by ethnicity, but gestation-specific thresholds have not been adopted. Hypertension is defined as a sustained systolic blood pressure of ≥140 mm Hg or a sustained diastolic blood pressure of ≥90 mm Hg. In some guidelines, the threshold of diagnosis depends on the setting in which blood pressure measurement is taken, with a threshold of 140/90 mm Hg in a healthcare setting, 135/85 mm Hg at home, or a 24-hour average blood pressure on ambulatory monitoring of >126/76 mm Hg. Some differences exist among organizations with respect to the criteria for the diagnosis of preeclampsia and the correct threshold for intervention and target blood pressure once treatment has been instigated. Home blood pressure monitoring is currently a focus for research. Novel technologies, including early warning devices (such as the CRADLE Vital Signs Alert device) and telemedicine, may provide strategies that prompt earlier recognition of abnormal blood pressure and therefore improve management. The purpose of this review is to provide an update on methods to assess blood pressure in pregnancy and appropriate technique to optimize accuracy. The importance of accurate blood pressure assessment is emphasized with a discussion of preeclampsia prediction and treatment of severe hypertension. Classification of hypertensive disorders and thresholds for treatment will be discussed, including novel developments in the field.

Intrahepatic cholestasis of pregnancy (ICP) is associated with poor perinatal outcomes in some women such as preterm delivery and fetal demise. Ursodeoxycholic acid (UDCA) is the main therapeutic agent for ICP, but recent evidence failed to show an impact on most perinatal outcomes. Our objective is to summarize the latest evidence in the management of ICP, with a focus on perinatal outcome. We propose a practical approach that combines pharmacotherapy with biochemical and fetal testing, as well as delivery planning.

No abstract

Background Women whose pregnancies are affected by hypertensive disorders of pregnancy, in particular preterm pre-eclampsia, are at increased risk of long-term cardiovascular morbidity and mortality. Objectives To investigate the hypothesis that prolongation of a pregnancy affected by preterm pre-eclampsia managed by expectant management compared with planned early delivery would result in worse cardiovascular function 6 months postpartum. Design A randomised controlled trial. Setting 28 maternity hospitals in England and Wales. Participants Women who were eligible for the Pre-eclampsia in HOspital: Early iNductIon or eXpectant management (PHOENIX) study were approached and recruited for the PHOEBE study. The PHOENIX (Pre-eclampsia in HOspital: Early iNductIon or eXpectant management) study was a parallel-group, non-masked, multicentre, randomised controlled trial that was carried out in 46 maternity units across England and Wales. This study compared planned early delivery with expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia who were 34 weeks’ gestation to less than 37 weeks’ gestation and having a singleton or dichorionic diamniotic twin pregnancy. Interventions Postpartum follow-up included medical history, blood pressure assessment and echocardiography. All women had blood sampling performed on at least two time points from recruitment to the 6-month follow-up for assessment of cardiac necrosis markers. Main outcome measures Primary outcome was a composite of systolic and/or diastolic dysfunction (originally by 2009 guidelines then updated by 2016 guidelines, with an amended definition of diastolic dysfunction). Analyses were by intention to treat, together with a per-protocol analysis for the primary and secondary outcomes. Results Between 27 April 2016 and 30 November 2018, 623 women were found to be eligible, of whom 420 (67%) were recruited across 28 maternity units in England and Wales. A total of 133 women were allocated to planned delivery, 137 women were allocated to expectant management and a further 150 received non-randomised expectant management within usual care. The mean time from enrolment to delivery was 2.5 (standard deviation 1.9) days in the planned delivery group compared with 6.8 (standard deviation 5.3) days in the expectant management group. There were no differences in the primary outcome between women in the planned delivery group and those in the expectant management group using either the 2009 (risk ratio 1.06, 95% confidence interval 0.80 to 1.40) or the 2016 definition (risk ratio 0.78, 95% confidence interval 0.33 to 1.86). Overall, 10% (31/321) of women had a left ventricular ejection fraction 2, 95% confidence interval 1.12 to 1.59 per 5 kg/m2) and maternal age (adjusted odds ratio 2.16, 95% confidence interval 1.44 to 3.22 per 10 years). Limitations include changing definitions regarding systolic and/or diastolic dysfunction. Conclusions Preterm pre-eclampsia results in persistence of hypertension in the majority of women with late preterm pre-eclampsia at 6 months postpartum and systolic dysfunction in 10%. Pre-eclampsia should not be considered a self-limiting disease of pregnancy alone. Future work Interventions aimed at reducing cardiovascular dysfunction. Trial registration Current Controlled Trials ISRCTN01879376. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 12. See the NIHR Journals Library website for further project information.

BACKGROUND: Many women with chronic hypertension are conflicted about antihypertensive medication during pregnancy and some are non-adherent to prescribed medication. OBJECTIVES: Codesign, implement and evaluate a novel shared decision-making (SDM) intervention for use with pregnant women with chronic hypertension. SETTING AND PARTICIPANTS: Pregnant women with chronic hypertension and their principal healthcare professionals (obstetricians, midwives, and physicians), at three National Health Service hospital trusts with different models of care. MAIN OUTCOME MEASURES: The RE-AIM framework guided the evaluation. Primary: Decisional conflict scale, medication intention survey and women's acceptability. Secondary: Healthcare professionals' acceptability and the barriers and facilitators to SDM implementation with pregnant women with chronic hypertension. RESULTS: Fifty women participated. Nearly half (46 %; n = 23) of women were from Black and Asian backgrounds. The SDM intervention was effective at reducing decisional conflict (mean reduction from baseline 42 %, 95 % CI 35-49, p ≤ 0.05). In 36 women (72 %), the reduction was of clinical importance. 24 women (48 %) were uncertain about or planned not to take antihypertensives prior to the SDM intervention, compared to two women (4 %) after the intervention. The intervention was acceptable to women and healthcare professionals. 10 of 14 healthcare professionals felt that the in-consultation aid facilitated SDM in current antenatal contexts, a similar proportion (10/14) felt the length of consultations hindered SDM. CONCLUSION: A novel codesigned SDM intervention reduced decisional conflict and increased women's intention to take antihypertensive agents during pregnancy. This intervention could be adopted into practice for women making pregnancy decisions where there is uncertainty around the medication management option.

Highlights • Chronic hypertension and gestational hypertension groups had good adherence to self monitoring of blood pressure (SMBP). • There was no evidence of adherence varying in different socio-demographic groups. • The differences between SMBP and clinic BP readings were small., Objectives To assess adherence to self-monitoring of blood pressure (SMBP), and differences between SMBP and clinic readings, in a self-monitoring intervention for managing pregnancy hypertension. Study design OPTIMUM-BP was an unmasked randomised controlled clinical trial. 154 women with pregnancy hypertension from four maternity units in England were recruited and randomised to SMBP or usual care. This secondary analysis included 91 women randomised to self-monitoring who provided BP readings. Trial instructions were for daily SMBP. Main outcome measures Adherence was calculated as proportion of days on which SMBP readings were taken. Proportion of weeks in which at least 4 and at least 2 SMBP readings were taken was also calculated. Mean differences between clinic and SMBP measurements were calculated. Results Self-monitored BP data were available for 49 women with chronic hypertension and 42 women with gestational hypertension. Median percentage of days with SMBP readings was 77% (IQR 51, 89) in the chronic hypertension group and 85% (IQR 52, 95) in the gestational hypertension group. Adherence did not vary by different socio-demographic groups. Mean difference (95% CI) between clinic and SMBP for systolic BP was 0.99 mmHg (−1.44, 3.41; chronic hypertension) and 3.76 mmHg (0.75, 6.78; gestational hypertension) and for diastolic BP was 3.03 mmHg (0.93, 5.12; chronic hypertension) and 3.27 mmHg (0.56, 5.98; gestational hypertension). Conclusions Adherence to self-monitoring was good and differences between SMBP and clinic readings were small. These findings offer reassurance about the use of self-monitoring at a time when it is being increasingly implemented in maternity settings.

PURPOSE To provide a new approach to jointly assess microstructural and molecular properties of the human placenta in vivo fast and efficiently and to present initial evidence in cohorts of healthy pregnancies and those affected by pre-eclampsia. METHODS Slice and diffusion preparation shuffling, built on the previously proposed ZEBRA method, is presented as a robust and fast way to obtain T1 and apparent diffusivity coefficient (ADC) values. Joint modeling and evaluation is performed on a cohort of healthy and pre-eclamptic participants at 3T. RESULTS The datasets show the ability to obtain robust and fast T1 -ADC measurements. Significant decay over gestation in T1 (-11 ms/week, P

Background: Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. Methods: In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 μmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. Findings: The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67·8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0·7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0·6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1·04, 95% CI 0·35–3·07; p=0·95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0·29, 95% CI 0·04–2·42; p=0·25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1·28, 95% CI 0·86–1·91; p=0·22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0·60, 0·39–0·91; p=0·016). Interpretation: Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. Funding: Tommy's, the Wellcome Trust, ICP Support, and the National Institute for Health Research.

This secondary analysis of the PHOENIX trial (evaluating planned delivery against expectant management in late preterm preeclampsia) demonstrates that in women who started induction of labour, 63% of women delivered vaginally (56% at 34 weeks’ gestation). Compared to expectant management, planned delivery was associated with higher rates of neonatal unit admission for prematurity (but lower proportions of infants small-for-gestational age infants); length of neonatal unit stay and neonatal morbidity (including respiratory support) were similar across both intervention groups at all gestational windows. Neonatal unit admission was increased by earlier gestation at delivery, development of severe preeclampsia, and being small-for-gestational age.

Objective To evaluate how English maternity units implemented self-monitoring of blood pressure (SMBP) in pregnancy in response to the COVID-19 pandemic. Design Mixed methods including surveys, anonymised patient data and in-depth interviews with women. Setting Maternity units across England. Participants 45 maternity units completed a survey about the implementation of SMBP (supported by the provision of guidance and blood pressure monitors) during the pandemic, 166 women completed a survey about their experiences of SMBP, and 23 women took part in in-depth interviews. Clinical data from 627 women undertaking SMBP were available from 13 maternity units. Results SMBP was predominantly used to provide additional BP monitoring for hypertensive or high-risk pregnant women. Overall maternity units and women were positive about its use in terms of reducing the need for additional face-to-face contacts and giving women more control and insight into their own BP. However, there were challenges in setting up SMBP services rapidly and embedding them within existing care pathways, particularly around interpreting readings and managing the provision of monitors. Conclusions A considerable proportion of maternity units in England commenced a SMBP service for hypertensive or high-risk women from March 2020. There is a need for further research into appropriate care pathways, including guidance around white coat or masked hypertension and the use of SMBP postnatally.

There is currently limited evidence on the costs associated with late preterm pre-eclampsia beyond antenatal care and post-natal discharge from hospital. The aim of this analysis is to evaluate the 24-month cost-utility of planned delivery for women with late preterm pre-eclampsia at 34Women between 34A total of 450 women were randomised to planned delivery, 451 to expectant management: 187 and 170 women, respectively, had complete data at 24 months. Planned delivery resulted in a significantly lower mean cost per woman and infant(s) over 24 months (- £2711, 95% confidence interval (CI) - 4840 to - 637), with a mean incremental difference in QALYs of 0.019 (95% CI - 0.039 to 0.063). Short-term and 24-month infant costs were not significantly different between the intervention arms. There is a 99% probability that planned delivery is cost-effective at all thresholds below £37,000 per QALY gained.There is a high probability that planned delivery is cost-effective compared to expectant management. These results need to be considered alongside clinical outcomes and in the wider context of maternity care.ISRCTN registry ISRCTN01879376. Registered 25 November 2013.

OBJECTIVE: To understand the current prevalence of, and attitudes to, self-monitoring of blood pressure (BP) during pregnancy. METHODS: 5555 pregnant women from antenatal clinics in 16 hospitals in England were invited to complete a survey. MAIN OUTCOME MEASURES: The primary outcome was the proportion of women currently BP self-monitoring. Secondary outcomes included self-monitoring schedules and women’s interactions with clinicians regarding self-monitoring. Population characteristics including risk factors for pre-eclampsia, ethnicity and deprivation level were considered. RESULTS: Completed surveys were received and analysed from 5181 pregnant women (93% response rate). Comparison to hospital demographic data suggests that respondents were representative of the UK population. 983/5181 (19%) of women were currently self-monitoring their BP, comprising 189/389 (49%) hypertensive women and 794/4792 (17%) normotensive women. However, only 482/983 (49%) reported ever sharing this information with antenatal care teams. Of those who self-monitored, 68% (668/983) were able to provide a previous BP reading, compared to 1% (67/5181) of those who did not self-monitor. CONCLUSION: Many women are now choosing to self-monitor their BP during pregnancy and clinicians should enquire about this proactively and consider providing better information on BP monitoring. Those who self-monitor appear to have better knowledge about their blood pressure. If these findings were replicated nationwide, around 125,000 pregnant women would be currently self-monitoring BP in the UK, yet only half of these women may communicate their readings to their antenatal care teams, suggesting a missed opportunity for enhanced care. Current trials will make the place of self-monitoring in pregnancy clearer.

Introduction We aimed to explore the use of magnetic resonance imaging (MRI) in vivo as a tool to elucidate the placental phenotype in women with chronic hypertension. Methods In case-control study, women with chronic hypertension and those with uncomplicated pregnancies were imaged using either a 3T Achieva or 1.5T Ingenia scanner. T2-weighted images, diffusion weighted and T1/T2* relaxometry data was acquired. Placental T2*, T1 and apparent diffusion coefficient (ADC) maps were calculated. Results 129 women (43 with chronic hypertension and 86 uncomplicated pregnancies) were imaged at a median of 27.7 weeks’ gestation (interquartile range (IQR) 23.9–32.1) and 28.9 (IQR 26.1–32.9) respectively. Visual analysis of T2-weighted imaging demonstrated placentae to be either appropriate for gestation or to have advanced lobulation in women with chronic hypertension, resulting in a greater range of placental mean T2* values for a given gestation, compared to gestation-matched controls. Both skew and kurtosis (derived from histograms of T2* values across the whole placenta) increased with advancing gestational age at imaging in healthy pregnancies; women with chronic hypertension had values overlapping those in the control group range. Upon visual assessment, the mean ADC declined in the third trimester, with a corresponding decline in placental mean T2* values and showed an overlap of values between women with chronic hypertension and the control group. Discussion A combined placental MR examination including T2 weighted imaging, T2*, T1 mapping and diffusion imaging demonstrates varying placental phenotypes in a cohort of women with chronic hypertension, showing overlap with the control group., Highlights • MRI enables evaluation of the placental contribution of adverse pregnancy outcomes. • Placental MRI examination was undertaken in women with chronic hypertension. • T2-weighted imaging showed varied placental visual appearance compared to controls. • Overlap in mean T2*, T1, ADC and T2* histogram derived measures was noted. • MRI may elucidate placental dysfunction and development of adverse outcomes.

Background Contemporaneous data are required for women with chronic kidney disease (CKD) Stages 3–5 to inform pre-pregnancy counselling and institute appropriate antenatal surveillance. Methods A retrospective cohort study in women with CKD Stages 3–5 after 20 weeks’ gestation was undertaken in six UK tertiary renal centres in the UK between 2003 and 2017. Factors predicting adverse outcomes and the impact of pregnancy in accelerating the need for renal replacement therapy (RRT) were assessed. Results There were 178 pregnancies in 159 women, including 43 women with renal transplants. The live birth rate was 98%, but 56% of babies were born preterm (before 37 weeks’ gestation). Chronic hypertension was the strongest predictor of delivery before 34 weeks’ gestation. Of 121 women with known pre-pregnancy hypertension status, the incidence of delivery before 34 weeks was 32% (31/96) in women with confirmed chronic hypertension compared with 0% (0/25) in normotensive women. The risk of delivery before 34 weeks doubled in women with chronic hypertension from 20% [95% confidence interval (CI) 9–36%] to 40% (95% CI 26–56%) if the gestational fall in serum creatinine was 100 mg/mmol prior to pregnancy or before 20 weeks’ gestation had an increased risk for birthweight below the 10th centile (odds ratio 2.57, 95% CI 1.20–5.53). There was a measurable drop in estimated glomerular filtration rate (eGFR) between pre-pregnancy and post-partum values (4.5 mL/min/1.73 m2), which was greater than the annual decline in eGFR prior to pregnancy (1.8 mL/min/1.73 m2/year). The effect of pregnancy was, therefore, equivalent to 1.7, 2.1 and 4.9 years of pre-pregnancy renal disease in CKD Stages 3a, 3b and 4–5, respectively. The pregnancy-associated decline in renal function was greater in women with chronic hypertension and in those with a gestational fall in serum creatinine of, Graphical Abstract Graphical Abstract

Background: Chronic hypertension (CH) adversely impacts pregnancy. It remains unclear whether antihypertensive treatment alters these risks. We examined the role of antihypertensive treatment in the association between CH and adverse pregnancy outcomes. Methods: Electronic health records from the UK Caliber and Clinical Practice Research Datalink were used to define a cohort of women delivering between 1997 and 2016. Primary outcomes were preeclampsia, preterm birth (PTB), and fetal growth restriction (FGR). We used multivariable logistic regression to compare outcomes in women with CH to women without CH and propensity score matching to compare antihypertensive agents. Results: The study cohort consisted of 1 304 679 women and 1 894 184 births. 14 595 (0.77%) had CH, and 6786 (0.36%) were prescribed antihypertensive medications in pregnancy. Overall, women with CH (versus no CH), had higher odds of preeclampsia (adjusted odds ratio [aOR], 5.74 [95% CI, 5.44–6.07]); PTB (aOR, 2.53 [2.39–2.67]); and FGR (aOR, 2.51 [2.31–2.72]). Women with CH prescribed treatment (versus untreated women) had higher odds of preeclampsia (aOR, 1.17 [1.05–1.30]), PTB (1.25 [1.12–1.39]), and FGR (1.80 [1.51–2.14]). Women prescribed methyldopa (versus β-blockers) had higher odds of preeclampsia (aOR, 1.43 [1.19–1.73]); PTB (1.59 [1.30–1.93]), but lower odds of FGR (aOR, 0.66 [0.48–0.90]). Odds of adverse outcomes were similar in relation to calcium channel blockers (versus β-blockers) except for PTB (aOR, 1.94 [1.15–3.27]). Among women prescribed treatment, lower average blood pressure ( Conclusions: Treatment with antihypertensive agents and control of hypertension ameliorates some effects but higher risks of adverse outcomes persist. β-Blockers versus methyldopa may be associated with better pregnancy outcomes except for FGR. Powered trials are needed to inform optimal treatment of CH during pregnancy.

Background Assisted reproductive technology (ART) has emerged as a common treatment option for infertility, a problem that affects an estimated 48 million couples worldwide. Advancing maternal age with increasing prepregnancy cardiovascular risk factors, such as chronic hypertension, obesity, and diabetes, has raised concerns about pregnancy complications associated with ART. However, in‐hospital complications following pregnancies conceived by ART are poorly described. Methods and Results To assess the patient characteristics, obstetric outcomes, vascular complications and temporal trends of pregnancies conceived by ART, we analyzed hospital deliveries conceived with or without ART between January 1, 2008, and December 31, 2016, from the United States National Inpatient Sample database. We included 106 248 deliveries conceived with ART and 34 167 246 deliveries conceived without ART. Women who conceived with ART were older (35 versus 28 years; P P Conclusions Pregnancies conceived by ART have higher risks of adverse obstetric outcomes and vascular complications compared with spontaneous conception. Clinicians should have detailed discussions on the associated complications of ART in women during prepregnancy counseling.

Scientists and regulators in Europe and the United States continue to seek methods and strategies to improve knowledge on rational use of medicines for pregnant and breastfeeding populations, an important subset of women’s health. Regulatory agencies have made strides toward improvement, but much more is needed. Recognizing the importance of international collaboration, we have begun to consider how to address these important public health issues more globally. The health of the child begins with the health of the mother.

Objective To evaluate whether a particular group of women with intrahepatic cholestasis of pregnancy (ICP), based on their presenting characteristics, would benefit from treatment with ursodeoxycholic acid (UDCA). Design Secondary analysis of the PITCHES trial (ISRCTN91918806). Setting United Kingdom. Population or Sample 527 women with ICP. Methods Subgroup analyses were performed to determine whether baseline bile acid concentrations or baseline itch scores moderated a woman’s response to treatment with UDCA. Main outcome measures Bile acid concentration and itch score. Results In women with baseline bile acid concentrations less than 40 μmol/l, treatment with UDCA resulted in increased post‐randomisation bile acid concentrations (geometric mean ratio 1.19, 95% CI 1.00–1.41, P = 0.048). A test of interaction showed no significance (P = 0.647). A small, clinically insignificant difference was seen in itch response in women with a high baseline itch score (–6.0 mm, 95% CI −11.80 to −0.21, P = 0.042), with a test of interaction not showing significance (P = 0.640). Further subgroup analyses showed no significance. Across all women there was a weak relationship between bile acid concentrations and itch severity. Conclusions There was no subgroup of women with ICP in whom a beneficial effect of treatment with UDCA on bile acid concentration or itch score could be identified. This confirms that its routine use in women with this condition for improvement of bile acid concentration or itch score should be reconsidered. Tweetable abstract PITCHES: No group of women with ICP has been found in whom UDCA reduces bile acid concentrations or pruritus., Tweetable abstract PITCHES: No group of women with ICP has been found in whom UDCA reduces bile acid concentrations or pruritus.

Background: Lopinavir–ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir–ritonavir improves outcomes in patients admitted to hospital with COVID-19. Methods: In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir–ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir–ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir–ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91–1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91–1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99–1·20; p=0·092). Interpretation: In patients admitted to hospital with COVID-19, lopinavir–ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir–ritonavir for treatment of patients admitted to hospital with COVID-19. Funding: Medical Research Council and National Institute for Health Research.

Recent evidence supports the use of an early, short course of glucocorticoids in patients with COVID-19 who require mechanical ventilation or oxygen support. As the number of coronavirus disease 2019 (COVID-19) cases continues to increase, the number of pregnant women with the disease is very likely to increase as well. Because pregnant women are at increased risk for hospitalization, intensive care unit admission, and mechanical ventilation support, obstetricians will be facing the dilemma of initiating maternal corticosteroid therapy while weighing its potential adverse effects on the fetus (or neonate if the patient is postpartum and breastfeeding). Our objective is to summarize the current evidence supporting steroid therapy in the management of patients with acute respiratory distress syndrome and COVID-19 and to elaborate on key modifications for the pregnant patient.

Objective The aim of this article is to describe the incidence and characteristics of pregnancy-related death in low- and middle-resource settings, in relation to the availability of key obstetric resources. Design This is a secondary analysis of a stepped-wedge cluster randomised controlled trial. Setting This trial was undertaken at ten sites across eight low- and middle-income countries in sub-Saharan Africa, India and Haiti. Population Institutional-level consent was obtained and all women presenting for maternity care were eligible for inclusion. Methods Pregnancy-related deaths were collected prospectively from routine data sources and active case searching. Main outcome measures Pregnancy-related death, place, timing and age of maternal death, and neonatal outcomes in women with this outcome. Results Over 20 months, in 536 233 deliveries there were 998 maternal deaths (18.6/10 000, range 28/10 000-630/10 000). The leading causes of death were obstetric haemorrhage (36.0%, n = 359), hypertensive disorders of pregnancy (20.6%, n = 206), sepsis (14.1%, n = 141) and other (26.5%, n = 264). Approximately a quarter of deaths occurred prior to delivery (28.4%, n = 283), 35.7% (n = 356) occurred on the day of delivery and 35.9% (n = 359) occurred after delivery. Half of maternal deaths (50.6%; n = 505) occurred in women aged 20-29 years, 10.3% (n = 103) occurred in women aged under 20 years, 34.5% (n = 344) occurred in women aged 30-39 years and 4.6% (n = 46) occurred in women aged ≥40 years. There was no measured association between the availability of key obstetric resources and the rate of pregnancy-related death. Conclusions The large variation in the rate of pregnancy-related death, irrespective of resource availability, emphasises that inequality and inequity in health care persists. Tweetable abstract Inequality and inequity in pregnancy-related death persists globally, irrespective of resource availability.

It is estimated that women with CKD are ten times more likely to develop preeclampsia than women without CKD, with preeclampsia affecting up to 40% of pregnancies in women with CKD. However, the shared phenotype of hypertension, proteinuria, and impaired excretory kidney function complicates the diagnosis of superimposed preeclampsia in women with CKD who have hypertension and/or proteinuria that predates pregnancy. This article outlines the diagnoses of preeclampsia and superimposed preeclampsia. It discusses the pathogenesis of preeclampsia, including abnormal placentation and angiogenic dysfunction. The clinical use of angiogenic markers as diagnostic adjuncts for women with suspected preeclampsia is described, and the limited data on the use of these markers in women with CKD are presented. The role of kidney biopsy in pregnancy is examined. The management of preeclampsia is outlined, including important advances and controversies in aspirin prophylaxis, BP treatment targets, and the timing of delivery.

Objective: To estimate normal ranges for maternal vital signs throughout pregnancy, which have not been well defined in a large contemporary population. Methods: We conducted a three-center, prospective, longitudinal cohort study in the United Kingdom from August 2012 to September 2017. We recruited women at less than 20 weeks of gestation without significant comorbidities with accurately dated singleton pregnancies. We measured participants' blood pressure (BP), heart rate, respiratory rate, oxygen saturation and temperature following standardized operating procedures at 4–6 weekly intervals throughout pregnancy. Results: We screened 4,279 pregnant women, 1,041 met eligibility criteria and chose to take part. Systolic and diastolic BP decreased slightly from 12 weeks of gestation: median or 50th centile (3rd–97th centile) 114 (95–138); 70 (56–87) mm Hg to reach minimums of 113 (95–136); 69 (55–86) mm Hg at 18.6 and 19.2 weeks of gestation, respectively, a change (95% CI) of −1.0 (−2 to 0); −1 (−2 to −1) mm Hg. Systolic and diastolic BP then rose to a maximum median (3rd–97th centile) of 121 (102–144); 78 (62–95) mm Hg at 40 weeks of gestation, a difference (95% CI) of 7 (6–9) and9 (8–10) mm Hg, respectively. The median (3rd–97th centile) heart rate was lowest at 12 weeks of gestation: 82 (63–105) beats per minute (bpm), rising progressively to a maximum of 91 (68–115) bpm at 34.1 weeks. SpO2 decreased from 12 weeks of gestation: median (3rd–97th centile) 98% (94–99%) to 97% (93–99%) at 40 weeks. The median (3rd–97th centile) respiratory rate at 12 weeks of gestation was 15 (9–22), which did not change with gestation. The median (3rd–97th centile) temperature at 12 weeks of gestation was 36.7 (35.6–37.5)°C, decreasing to a minimum of 36.5 (35.3–37.3)°C at 33.4 weeks. Conclusion: We present widely relevant, gestation-specific reference ranges for detecting abnormal BP, heart rate, respiratory rate, oxygen saturation and temperature during pregnancy. Our findings refute the existence of a clinically significant BP drop from 12 weeks of gestation. Clinical Trial Registration: ISRCTN, ISRCTN10838017.

INTRODUCTION: Preeclampsia affects about 3% of singleton pregnancies and is characterized by placental dysfunction. It is associated with significant maternal and perinatal morbidity and mortality. The diagnosis of preeclampsia remains a challenge, and the clinical course can develop for weeks before a diagnosis is confirmed. National guidelines have approved placental growth factor (PlGF) testing to rule out suspected preeclampsia, but the utility of repeated PlGF measurement is unknown. The aim of this case series analysis was to evaluate the test performance of repeated PlGF sampling in women presenting with suspected preeclampsia, and to describe relevant clinical outcomes.MATERIAL AND METHODS: Women who presented to maternity services with suspected preeclampsia between 20 +0 and 36 +6 weeks' gestation who underwent repeat PlGF sampling with a minimum test interval of 7 days were assessed. The outcomes were delivery for preeclampsia within 14 days of sampling, the proportion changing PlGF categories, and time to delivery. RESULTS: In total, 289 women with suspected preeclampsia undergoing repeat PlGF sampling were included. PlGF CONCLUSIONS: Repeat PlGF measurement demonstrates high negative predictive value for determining preeclampsia requiring delivery in 14 days. Repeat testing may be clinically useful to risk stratify women with ongoing symptoms of disease. Confirmation of the impact of these findings is required in further studies.