Repeat placental growth factor-based testing in women with suspected preterm pre-eclampsia (PARROT-2): a multicentre, parallel-group, superiority, randomised controlled trial.

BACKGROUND: Placental growth factor (PlGF)-based testing has high diagnostic accuracy for predicting pre-eclampsia needing delivery, significantly reducing time to diagnosis and severe maternal adverse outcomes. The clinical benefit of repeat PlGF-based testing is unclear. We aimed to determine whether repeat PlGF-based testing (using a clinical management algorithm and nationally recommended thresholds) reduces adverse perinatal outcomes in pregnant individuals with suspected preterm pre-eclampsia. METHODS: In this multicentre, parallel-group, superiority, randomised controlled trial, done in 22 maternity units across England, Scotland, and Wales, we recruited women aged 18 years or older with suspected pre-eclampsia between 22 weeks and 0 days of gestation and 35 weeks and 6 days of gestation. Women were randomly assigned (1:1) to revealed repeat PlGF-based testing or concealed repeat testing with usual care. The intervention was not masked to women or partners, or clinicians or data collectors, due to the nature of the trial. The trial statistician was masked to intervention allocation. The primary outcome was a perinatal composite of stillbirth, early neonatal death, or neonatal unit admission. The primary analysis was by the intention-to-treat principle, with a per-protocol analysis restricted to women managed according to their allocation group. The trial was prospectively registered with the ISRCTN registry, ISRCTN 85912420. FINDINGS: Between Dec 17, 2019, and Sept 30, 2022, 1253 pregnant women were recruited and randomly assigned treatment; one patient was excluded due to randomisation error. 625 women were allocated to revealed repeat PlGF-based testing and 627 women were allocated to usual care with concealed repeat PlGF-based testing (mean age 32·3 [SD 5·7] years; 879 [70%] white). One woman in the concealed repeat PlGF-based testing group was lost to follow-up. There was no significant difference in the primary perinatal composite outcome between the revealed repeat PlGF-based testing group (195 [31·2%]) of 625 women) compared with the concealed repeat PlGF-based testing group (174 [27·8%] of 626 women; relative risk 1·21 [95% CI 0·95-1·33]; p=0·18). The results from the per-protocol analysis were similar. There were four serious adverse events in the revealed repeat PlGF-based testing group and six in the concealed repeat PlGF-based testing group; all serious adverse events were deemed unrelated to the intervention by the site principal investigators and chief investigator. INTERPRETATION: Repeat PlGF-based testing in pregnant women with suspected pre-eclampsia was not associated with improved perinatal outcomes. In a high-income setting with a low prevalence of adverse outcomes, universal, routine repeat PlGF-based testing of all individuals with suspected pre-eclampsia is not recommended. FUNDING: Tommy's Charity, Jon Moulton Charitable Trust, and National Institute for Health and Care Research Guy's and St Thomas' Biomedical Research Centre.

Boldly going Introducing conflict management training to Starship Children's Hospital.

Conflict between health professionals and whanau (families) in paediatric hospitals is common and leads to significant distress for families and staff. The likelihood of challenges and conflict around communication and critical medical decision-making is increased where there are cultural and social complexities. Training staff to recognise and manage conflict as early as possible improves patient/whanau outcomes and staff well-being. This article describes an ongoing collaboration between Starship Children's Hospital in Auckland New Zealand (NZ) and the UK Medical Mediation Foundation (MMF) focused on educating staff in the early recognition and management of conflict using mediation skills. An evidence-based training programme and structured ongoing supervision of a small group of champions has enabled this training to be embedded into Starship clinical practice. The collaboration has included careful consideration of the New Zealand setting, ensuring that the content of the programme specifically addresses our unique cultural and social context. Mediation skills are an important step in ensuring that our patients and whanau feel heard, acknowledged, and respected, and contribute to the Starship Child Health's strategic priority of eliminating inequity and addressing institutional bias.

The assessment of blood pressure in pregnant women: pitfalls and novel approaches.

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.

The effectiveness of decision aids for pregnancy related decision-making in women with pre-pregnancy morbidity; systematic review and meta-analysis.

INTRODUCTION: Women with pre-existing morbidity arising from medical conditions or previous caesarean section are at higher risk of adverse pregnancy outcomes compared to women without such morbidity. Women often face complex pregnancy-related decision-making that may be characterized by conflicting maternal and perinatal priorities. The aim of this systematic review and meta-analysis was to assess randomised controlled trials of decision aids to evaluate whether they are effective at reducing decisional conflict scores and to evaluate what type of decision aids are most effective for women with pre-existing morbidity in pregnancy. METHODS: We searched Medline (via Ovid), Embase (via Ovid), CINAHL (via EBSCO) from the earliest entries until September 2021. We selected randomised controlled trials comparing patient decision aids for women with pre-existing morbidity with usual clinical practice or a control intervention. Study characteristics and Jadad risk of bias was recorded. Meta-analysis by pre-existing morbidity type was performed using Stata 17 and the data was presented with a Forest Plot. Random effects models were used to calculate summary estimates if there was substantial clinical or statistical heterogeneity and post mean DCS scores were described in a sensitivity analysis and presented as a line graph, to improve clinical interpretation of results.. A narrative synthesis of the selected studies evaluated what type of decision aid works and for in what circumstances. RESULTS: Ten randomised controlled trials, which reported data from 4028 women, were included. Patient decision aids were evaluated in women with pre-existing morbidity who were undertaking pregnancy-related decision-making. Patient decision aids reduced decisional conflict scale scores by an additional - 3.7, 95% Confidence Interval - 5.9% to - 1.6%) compared to the control group. Women with pre-existing medical conditions were more conflicted at baseline and had greater reductions in decisional conflict scale score (mean difference vs. control group: - 6.6%; 95% CI - 9.8% to - 3.3%), in contrast to those with previous caesarean section (mean difference - 2.4%; 95% CI - 4.8% to - 0.1%). There was limited evidence on the effect of decision aids on health outcomes. Decision aids reduced unwanted variation in decision-making support across maternity settings. CONCLUSION: Patient decision aids are effective tools to support personalised care planning and informed decision-making in women with pre-existing morbidity. Women with pre-existing medical morbidity were more conflicted at baseline and were more likely to benefit from decision aids. Adoption of aids in this population may lead to improve adherence and health outcomes, warranting further research.

Genetic Correlates of Psychological Responses to the COVID-19 Crisis in Young Adult Twins in Great Britain.

We investigated how the COVID-19 crisis and the extraordinary experience of lockdown affected young adults in England and Wales psychologically. One month after lockdown commenced (T2), we assessed 30 psychological and behavioural traits in more than 4000 twins in their mid-twenties and compared their responses to the same traits assessed in 2018 (T1). Mean changes from T1 to T2 were modest and inconsistent. Contrary to the hypothesis that major environmental changes related to COVID-19 would result in increased variance in psychological and behavioural traits, we found that the magnitude of individual differences did not change from T1 to T2. Twin analyses revealed that while genetic factors accounted for about half of the reliable variance at T1 and T2, they only accounted for ~ 15% of individual differences in change from T1 to T2, and that nonshared environmental factors played a major role in psychological and behavioural changes. Shared environmental influences had negligible impact on T1, T2 or T2 change. Genetic factors correlated on average .86 between T1 and T2 and accounted for over half of the phenotypic stability, as would be expected for a 2-year interval even without the major disruption of lockdown. We conclude that the first month of lockdown has not resulted in major psychological or attitudinal shifts in young adults, nor in major changes in the genetic and environmental origins of these traits. Genetic influences on the modest psychological and behavioural changes are likely to be the result of gene-environment correlation not interaction.

The impact of chronic kidney disease Stages 3-5 on pregnancy 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 <10% of pre-pregnancy concentrations. Women with a urinary protein:creatinine ratio >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 <10% of pre-pregnancy concentrations. At 1 year post-partum, 46% (58/126) of women had lost ≥25% of their pre-pregnancy eGFR or required RRT. Most women with renal transplants had CKD Stage 3 and more stable renal function prior to pregnancy. Renal transplantation was not independently associated with adverse obstetric or renal outcomes. CONCLUSIONS: Contemporary pregnancies in women with CKD Stages 3-5 are complicated by preterm delivery, low birthweight and loss of maternal renal function. Chronic hypertension, pre- or early pregnancy proteinuria and a gestational fall in serum creatinine of <10% of pre-pregnancy values are more important predictors of adverse obstetric and renal outcome than CKD Stages 3-5. Pregnancy in women with CKD Stages 3-5 advances the need for dialysis or transplantation by 2.5 years.

Diagnostic accuracy of repeat placental growth factor measurements in women with suspected preeclampsia: A case series study.

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 <100 pg/mL had a high sensitivity (87.5%, 95% confidence interval [CI] 67.6%-97.3%) and a negative predictive value (97.7%, 95% CI 93.5%-99.5%) at the initial test (receiver operating characteristic [ROC] area 0.79, 95% CI 0.68-0.89). Similar test performance was seen for PlGF <100 pg/mL when undertaken as a repeat test (sensitivity 90.7%, 95% CI 85.2%-95.9%, negative predictive value 92.2%, 95% CI 85.3-96.6%). Overall, 25.6% of women changed PlGF category between the first and second PlGF tests. For each PlGF category, determination of time to delivery was similar for first and second tests. 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.

Chronic hypertension in pregnancy: impact of ethnicity and superimposed preeclampsia on placental, endothelial, and renal biomarkers.

Black ethnicity is associated with worse pregnancy outcomes in women with chronic hypertension. Preexisting endothelial and renal dysfunction and poor placentation may contribute, but pathophysiological mechanisms underpinning increased risk are poorly understood. This cohort study aimed to investigate the relationship between ethnicity, superimposed preeclampsia, and longitudinal changes in markers of endothelial, renal, and placental dysfunction in women with chronic hypertension. Plasma concentrations of placental growth factor (PlGF), syndecan-1, renin, and aldosterone and urinary angiotensinogen-to-creatinine ratio (AGTCR), protein-to-creatinine ratio (PCR), and albumin-to-creatinine ratio (ACR) were quantified during pregnancy and postpartum in women with chronic hypertension. Comparisons of longitudinal biomarker concentrations were made using log-transformation and random effects logistic regression allowing for gestation. Of 117 women, superimposed preeclampsia was diagnosed in 21% ( n = 25), with 24% ( n = 6) having an additional diagnosis of diabetes. The cohort included 63 (54%) women who self-identified as being of black ethnicity. PlGF concentrations were 67% lower [95% confidence interval (CI) -79 to -48%] and AGTCR, PCR, and ACR were higher over gestation, in women with subsequent superimposed preeclampsia (compared with those without superimposed preeclampsia). PlGF <100 pg/ml at 20-23.9 wk of gestation predicted subsequent birth weight <3rd percentile with 88% sensitivity (95% CI 47-100%) and 83% specificity (95% CI 70-92%). Black women had 43% lower renin (95% CI -58 to -23%) and 41% lower aldosterone (95%CI -45 to -15%) concentrations over gestation. Changes in placental (PlGF) and renal (AGTCR/PCR/ACR) biomarkers predated adverse pregnancy outcome. Ethnic variation in the renin-angiotensin-aldosterone system exists in women with chronic hypertension in pregnancy and may be important in treatment selection.

Adverse maternal and perinatal outcomes in pregnant women with sickle cell disease: systematic review and meta-analysis.

A systematic review and meta-analysis of observational studies were conducted to quantify the association between sickle cell disease in pregnancy and adverse maternal and perinatal outcomes. Data sources (Medline, Embase, Maternity and Infant care, Cochrane, Web of Science, Popline) were searched for publications to June 2014. Eligibility criteria included observational studies reporting maternal and perinatal health outcomes in pregnant women with sickle cell disease against a comparative group of pregnant women without sickle cell disease. Twenty-one studies (including 26,349 women with sickle cell disease; 26,151,746 women without sickle cell disease) were eligible for inclusion. Pregnancies in women with HbSS genotype, compared with women without sickle cell disease, were at increased risk of maternal mortality (relative risk [RR], 5.98; 95% confidence interval [CI], 1.94-18.44), preeclampsia (RR, 2.43; 95% CI, 1.75-3.39), stillbirth (RR, 3.94; 95% CI, 2.60-5.96), preterm delivery (RR, 2.21; 95% CI, 1.47-3.31), and small for gestational age infants (RR, 3.72; 95% CI, 2.32-5.98). Meta-regression demonstrated that genotype (HbSS vs HbSC), low gross national income, and high study quality were associated with increased RRs. Despite advances in the management of sickle cell disease, obstetrics, and neonatal medicine, pregnancies complicated by the disease remain associated with increased risk of adverse maternal and perinatal outcomes.

Repeat Placental Growth Factor-Based Testing in Women With Suspected Preterm Preeclampsia: A Stratified Analysis of the PARROT-2 Trial.

BACKGROUND: PlGF (placental growth factor)-based testing reduces severe maternal adverse outcomes. Repeat PlGF-based testing is not associated with improved perinatal or maternal outcomes. This planned secondary analysis aimed to determine whether there is a subgroup of women who benefit from repeat testing. METHODS: Pregnant individuals with suspected preterm preeclampsia were randomized to repeat revealed PlGF-based testing, compared with usual care where testing was concealed. Perinatal and maternal outcomes were stratified by trial group, by initial PlGF-based test result, and by PlGF-based test type (PlGF or sFlt-1 [soluble fms-like tyrosine kinase-1]/PlGF ratio). RESULTS: A total of 1252 pregnant individuals were included. Abnormal initial PlGF-based test identified a more severe phenotype of preeclampsia, at increased risk of adverse maternal and perinatal outcomes. Repeat testing was not significantly associated with clinical benefit in women with abnormal initial results. Of women with a normal initial result, 20% developed preeclampsia, with the majority at least 3 to 4 weeks after initial presentation. Repeat test results were more likely to change from normal to abnormal in symptomatic women (112/415; 27%) compared with asymptomatic women (163/890; 18%). A higher proportion of symptomatic women who changed from normal to abnormal were diagnosed with preeclampsia, compared with asymptomatic women. CONCLUSIONS: Our results do not demonstrate evidence of the clinical benefit of repeating PlGF-based testing if the initial result is abnormal. Judicious use of repeat PlGF-based testing to stratify risk may be considered at least 2 weeks after a normal initial test result, particularly in women who have symptoms or signs of preeclampsia. REGISTRATION: URL: https://www.isrctn.com/ISRCTN85912420; Unique identifier: ISRCTN85912420.

Rule-in and rule-out of pre-eclampsia using DELFIA Xpress PlGF 1-2-3 and sFlt-1: PlGF ratio.

OBJECTIVES: The objective of this study was to explore and validate thresholds for Placental growth factor (PlGF) and soluble fms-like tyrosine-kinase 1 (s-Flt-1) (as s-Flt-1: PlGF ratio), to rule-in and rule-out disease in women with suspected pre-eclampsia, using DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays. STUDY DESIGN: 369 samples from women with suspected or confirmed pre-eclampsia were analysed from a prospective cohort study. MAIN OUTCOME MEASURES: Serum PlGF and sFlt-1: PlGF were quantified using DELFIA® Xpress PlGF1-2-3 and DELFIA® Xpress sFlt-1 tests. Performances were evaluated at established and exploratory thresholds. Low PlGF concentration and sFlt-1: PlGF AUROC were compared. RESULTS: PlGF 1-2-3 concentration thresholds were confirmed to have high performance for rule-in (<50 pg/ml) and rule-out (≥150 pg/ml) pre-eclampsia within seven days (20-33+6 Weeks <50 pg/ml: Negative predictive value (NPV) 90.7% (95% CI 83.9, 95.3); ≥150 pg/ml: NPV 94.8% (95% CI 88.4, 98.3)) and 28 days (20-33+6 Weeks <50 pg/ml: Negative predictive value (NPV) 83.9% (95% CI 76.0, 90.0); ≥150 pg/ml: NPV 92.8% (95% CI 85.7, 97.0)). Optimal sFlt-1: PlGF thresholds for rule-in were ≥ 70 before 34 weeks and ≥ 90 after 34 weeks, and <50 to rule-out pre-eclampsia. Low PlGF alone had comparable performance to sFlt-1: PlGF, but test performance for both was reduced in women with Kidney Disease. CONCLUSIONS: DELFIA® Xpress PlGF1-2-3 and sFlt-1 assays for pre-eclampsia rule-in and rule-out have comparable performance to other established assays, and could be an alternative for clinical use. Performance was not enhanced by use of sFlt-1: PlGF ratio, suggesting that PlGF alone could provide a cheaper alternative to dual biomarker testing.

Optimising timing of steroid administration in preterm pre-eclampsia.

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 and <7 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.

Implementation of a novel shared decision-making intervention in women with chronic hypertension in pregnancy: multiple-site multiple-method investigation.

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.

Placental growth fActor Repeat sampling for Reduction of adverse perinatal Outcomes in women with suspecTed pre-eclampsia: study protocol for a randomised controlled trial (PARROT-2).

BACKGROUND: Pre-eclampsia is a complex pregnancy disorder, characterised by new or worsening hypertension associated with multi-organ dysfunction. Adverse outcomes include eclampsia, liver rupture, stroke, pulmonary oedema, and acute kidney injury in the mother, and stillbirth, foetal growth restriction, and iatrogenic preterm delivery for the foetus. Angiogenic biomarkers, including placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1), have been identified as valuable biomarkers for preterm pre-eclampsia, accelerating diagnosis and reducing maternal adverse outcomes by risk stratification, with enhanced surveillance for high-risk women. PlGF-based testing for suspected preterm pre-eclampsia has been incorporated into national guidance. The role of repeat PlGF-based testing and its effect on maternal and perinatal adverse outcomes have yet to be evaluated. METHODS: The PARROT-2 trial is a multi-centre randomised controlled trial of repeat revealed PlGF-based testing compared to repeat concealed testing, in women presenting with suspected pre-eclampsia between 22+0 and 35+6 weeks' gestation. The primary objective is to establish whether repeat PlGF-based testing decreases a composite of perinatal severe adverse outcomes (stillbirth, early neonatal death, or neonatal unit admission). All women prior to enrolment in the trial will have an initial revealed PlGF-based test. Repeat PlGF-based tests will be performed weekly or two-weekly, depending on the initial PlGF-based test result, with results randomised to revealed or concealed. DISCUSSION: National guidance recommends that all women presenting with suspected preterm pre-eclampsia should have a single PlGF-based test when disease is first suspected, to help rule out pre-eclampsia. Clinical and cost-effectiveness of repeat PlGF-based testing has yet to be investigated. This trial aims to address whether repeat PlGF-based testing reduces severe maternal and perinatal adverse outcomes and whether repeat testing is cost-effective. TRIAL REGISTRATION: ISRCTN 85912420 . Registered on 25 November 2019.

The consequences of a year of the COVID-19 pandemic for the mental health of young adult twins in England and Wales.

BACKGROUND: The COVID-19 pandemic has affected all our lives, not only through the infection itself but also through the measures taken to control the spread of the virus (e.g. lockdown). AIMS: Here, we investigated how the COVID-19 pandemic and unprecedented lockdown affected the mental health of young adults in England and Wales. METHOD: We compared the mental health symptoms of up to 4773 twins in their mid-20s in 2018 prior to the COVID-19 pandemic (T1) and during four-wave longitudinal data collection during the pandemic in April, July and October 2020, and in March 2021 (T2-T5) using phenotypic and genetic longitudinal designs. RESULTS: The average changes in mental health were small to medium and mainly occurred from T1 to T2 (average Cohen d = 0.14). Despite the expectation of catastrophic effects of the pandemic on mental health, we did not observe trends in worsening mental health during the pandemic (T3-T5). Young people with pre-existing mental health problems were disproportionately affected at the beginning of the pandemic, but their increased problems largely subsided as the pandemic persisted. Twin analyses indicated that the aetiology of individual differences in mental health symptoms did not change during the lockdown (average heritability 33%); the average genetic correlation between T1 and T2-T5 was 0.95, indicating that genetic effects before the pandemic were substantially correlated with genetic effects up to a year later. CONCLUSIONS: We conclude that on average the mental health of young adults in England and Wales has been remarkably resilient to the effects of the pandemic and associated lockdown.

Prescribing for pregnancy: managing diabetes.

Topics for DTB review articles are selected by DTB's editorial board to provide concise overviews of medicines and other treatments to help patients get the best care. Articles include a summary of key points and a brief overview for patients. Articles may also have a series of multiple choice CME questions.

The consequences of a year of the COVID-19 pandemic for the mental health of young adult twins in England and Wales.

The COVID-19 pandemic has impacted all our lives, not only through the infection itself, but also through the measures taken to control the virus’s spread (e.g., lockdown). Here we investigated how the COVID-19 pandemic and unprecedented lockdown affected the mental health of young adults in England and Wales. We compared the mental health symptoms of up to 4,000 twins in their mid-twenties in 2018 prior to the COVID-19 pandemic (T1) to those in a four-wave longitudinal data collection during the pandemic in April, July, and October 2020, and in March 2021 (T2-T5). The average changes in mental health were small-to-medium and mainly occurred from 2018 (T1) to March 2020 (T2, one month following the start of lockdown; average Cohen d=0.14). Despite the expectation of catastrophic effects on the pandemic on mental health of our young adults, we did not observe trends in worsening mental health during the pandemic (T3-T5). Young people with pre-existing mental health problems were adversely affected at the beginning of the pandemic, but their increased problems largely subsided as the pandemic persisted. Twin analyses indicated that the aetiology of individual differences did not change during the lockdown. The average heritability of mental health symptoms was 33% across 5 waves of assessment, and the average genetic correlation between T1 and T2-T5 was .95, indicating that genetic effects before the pandemic (T1) are substantially correlated with genetic effects up to a year later (T2-T5). We conclude that on average the mental health of young adults in England and Wales has been remarkably resilient to the effects of the pandemic and associated lockdown.

Implementation of national antenatal hypertension guidelines: a multicentre multiple methods study.

OBJECTIVE: To evaluate the implementation of National Institute for Health and Care Excellence antenatal hypertension guidelines, to identify strategies to reduce incidences of severe hypertension and associated maternal and perinatal morbidity and mortality in pregnant women with chronic hypertension. METHODS: We used a multiple method multisite approach to establish implementation of guidelines and the associated barriers and facilitators. We used a national survey of healthcare professionals (n=97), case notes review (n=55) and structured observations (n=42) to assess implementation. The barriers and facilitators to implementation were identified from semistructured qualitative interviews with healthcare professionals (n=13) and pregnant women (n=18) using inductive thematic analysis. The findings were integrated and evaluated using the Consolidated Framework for Implementation Research. SETTING AND PARTICIPANTS: Pregnant women with chronic hypertension and their principal carers (obstetricians, midwives and physicians), at three National Health Service hospital trusts with different models of care. RESULTS: We found severe hypertension to be prevalent (46% of case notes reviewed) and target blood pressure practices to be suboptimal (56% of women had an antenatal blood pressure target documented). Women were infrequently given information (52%) or offered choice (19%) regarding antihypertensives. Women (14/18) reported internal conflict in taking antihypertensives and non-adherence was prevalent (8/18). Women who were concordant with treatment recommendations described having mutual trust with professionals mediated through appropriate information, side effect management and involvement in decision making. Professionals reported needing updates and tools for target blood pressure setting and shared decision making underpinned by antihypertensive safety and effectiveness research. CONCLUSIONS: Women's non-adherence to antihypertensives is higher than anticipated. Suboptimal information provision around treatment, choice of antihypertensives and target setting practices by healthcare professionals may be contributory. Understanding the reasons for non-adherence will inform education and decision-making strategies needed to address both clinician and women's behaviour. Further research into the effectiveness and long-term safety of common antihypertensives is also required.

Genetic correlates of psychological responses to the COVID-19 crisis in young adult twins in Great Britain.

We investigated how the COVID-19 crisis and the extraordinary experience of lockdown affected young adults in England and Wales psychologically. One month after lockdown commenced (T2), we assessed 30 psychological and behavioural traits in 4,000 twins in their mid-twenties and compared their responses to the same traits assessed in 2018 (T1). Mean changes from T1 to T2 were modest and inconsistent: just as many changes were in a positive as negative direction. Twin analyses revealed that genetics accounted for about half of the reliable variance at T1 and T2. Genetic factors correlated on average .86 between T1 and T2 and accounted for over half of the phenotypic stability. Systematic environmental influences had negligible impact on T1, T2 or T2 change. Rather than the crisis fundamentally changing people psychologically, our results suggest that genetic differences between individuals play a fundamental role in shaping psychological and behavioural responses to the COVID-19 crisis.