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.

Risk factors for pre-eclampsia in clinical practice guidelines: Comparison with the evidence.

OBJECTIVE: To compare pre-eclampsia risk factors identified by clinical practice guidelines (CPGs) with risk factors from hierarchical evidence review, to guide pre-eclampsia prevention. DESIGN: Our search strategy provided hierarchical evidence of relationships between risk factors and pre-eclampsia using Medline (Ovid), searched from January 2010 to January 2021. SETTING: Published studies and CPGs. POPULATION: Pregnant women. METHODS: We evaluated the strength of association and quality of evidence (GRADE). CPGs (n = 15) were taken from a previous systematic review. MAIN OUTCOME MEASURE: Pre-eclampsia. RESULTS: Of 78 pre-eclampsia risk factors, 13 (16.5%) arise only during pregnancy. Strength of association was usually 'probable' (n = 40, 51.3%) and the quality of evidence was low (n = 35, 44.9%). The 'major' and 'moderate' risk factors proposed by 8/15 CPGs were not well aligned with the evidence; of the ten 'major' risk factors (alone warranting aspirin prophylaxis), associations with pre-eclampsia were definite (n = 4), probable (n = 5) or possible (n = 1), based on moderate (n = 4), low (n = 5) or very low (n = 1) quality evidence. Obesity ('moderate' risk factor) was definitely associated with pre-eclampsia (high-quality evidence). The other ten 'moderate' risk factors had probable (n = 8), possible (n = 1) or no (n = 1) association with pre-eclampsia, based on evidence of moderate (n = 1), low (n = 5) or very low (n = 4) quality. Three risk factors not identified by the CPGs had probable associations (high quality): being overweight; 'prehypertension' at booking; and blood pressure of 130-139/80-89 mmHg in early pregnancy. CONCLUSIONS: Pre-eclampsia risk factors in CPGs are poorly aligned with evidence, particularly for the strongest risk factor of obesity. There is a lack of distinction between risk factors identifiable in early pregnancy and those arising later. A refresh of the strategies advocated by CPGs is needed.

Planned delivery or expectant management in preeclampsia: an individual participant data meta-analysis.

OBJECTIVE: Pregnancy hypertension is a leading cause of maternal and perinatal mortality and morbidity. Between 34+0 and 36+6 weeks gestation, it is uncertain whether planned delivery could reduce maternal complications without serious neonatal consequences. In this individual participant data meta-analysis, we aimed to compare planned delivery to expectant management, focusing specifically on women with preeclampsia. DATA SOURCES: We performed an electronic database search using a prespecified search strategy, including trials published between January 1, 2000 and December 18, 2021. We sought individual participant-level data from all eligible trials. STUDY ELIGIBILITY CRITERIA: We included women with singleton or multifetal pregnancies with preeclampsia from 34 weeks gestation onward. METHODS: The primary maternal outcome was a composite of maternal mortality or morbidity. The primary perinatal outcome was a composite of perinatal mortality or morbidity. We analyzed all the available data for each prespecified outcome on an intention-to-treat basis. For primary individual patient data analyses, we used a 1-stage fixed effects model. RESULTS: We included 1790 participants from 6 trials in our analysis. Planned delivery from 34 weeks gestation onward significantly reduced the risk of maternal morbidity (2.6% vs 4.4%; adjusted risk ratio, 0.59; 95% confidence interval, 0.36-0.98) compared with expectant management. The primary composite perinatal outcome was increased by planned delivery (20.9% vs 17.1%; adjusted risk ratio, 1.22; 95% confidence interval, 1.01-1.47), driven by short-term neonatal respiratory morbidity. However, infants in the expectant management group were more likely to be born small for gestational age (7.8% vs 10.6%; risk ratio, 0.74; 95% confidence interval, 0.55-0.99). CONCLUSION: Planned early delivery in women with late preterm preeclampsia provides clear maternal benefits and may reduce the risk of the infant being born small for gestational age, with a possible increase in short-term neonatal respiratory morbidity. The potential benefits and risks of prolonging a pregnancy complicated by preeclampsia should be discussed with women as part of a shared decision-making process.

Two-year follow-up of infant and maternal outcomes after planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): A randomised controlled trial.

OBJECTIVE: We evaluated the best time to initiate delivery in late preterm pre-eclampsia in order to optimise long-term infant and maternal outcomes. DESIGN: Parallel-group, non-masked, randomised controlled trial. SETTING: Forty-six maternity units in the UK. POPULATION: Women with pre-eclampsia between 34+0 and 36+6  weeks of gestation, without severe disease, were randomised to planned delivery or expectant management. MAIN OUTCOME MEASURES: Infant neurodevelopmental outcome at 2 years of age, using the Parent Report of Children's Abilities - Revised (PARCA-R) composite score. RESULTS: Between 29 September 2014 and 10 December 2018, 901 women were enrolled in the trial, with 450 women allocated to planned delivery and 451 women allocated to expectant management. At the 2-year follow-up, the intention-to-treat analysis population included 276 women (290 infants) allocated to planned delivery and 251 women (256 infants) allocated to expectant management. The mean composite standardised PARCA-R scores were 89.5 (SD 18.2) in the planned delivery group and 91.9 (SD 18.4) in the expectant management group, with an adjusted mean difference of -2.4 points (95% CI -5.4 to 0.5 points). CONCLUSIONS: In infants of women with late preterm pre-eclampsia, the average neurodevelopmental assessment at 2 years lies within the normal range, regardless of whether planned delivery or expectant management was pursued. With the lower than anticipated follow-up rate there was limited power to demonstrate that these scores did not differ, but the small between-group difference in PARCA-R scores is unlikely to be clinically important.

Postnatal health and care following hypertensive disorders in pregnancy: a prospective cohort study (BPiPP study).

INTRODUCTION: One in 10 women have hypertensive disorders in pregnancy (HDP) and are at risk of adverse short- and long-term health outcomes, yet there is limited information on their postnatal health and care needs. This study aimed to look at postnatal physical and psychological morbidity in women with HDP, compared to women without HDP, and the postnatal care received in both groups. METHODS: Within a prospective cohort study, women with and without HDP were identified and recruited on the postnatal ward of 17 maternity units across England and invited to complete a short baseline questionnaire. At 3 months postpartum, women were sent a follow-up questionnaire, with reminders. The principal outcomes were the mean score at 3 months for the Edinburgh Postnatal Depression Scale (EPDS) and the EuroQol Group 5-dimension (EQ-5D) scale. RESULTS: One thousand eight hundred twenty-nine women agreed to participate. Of these, 1757 (96%) completed the baseline questionnaire: 769 (44%) women had HDP and 988 (56%) women did not. Despite a difference in health-related quality of life and symptoms of depression at baseline between the two groups, at 3 months postnatal, within the 653 women who completed their follow-up questionnaire (37.2% of those who completed the baseline questionnaire) there were no significant differences between the groups (median EQ-5D VAS: 85 in women with HDP, 85 in women without HDP, p = 0.99 and mean EPDS score 5.5 in women with HDP, 5.0 in women without HDP, p = 0.80). Overall levels of physical postnatal morbidity were high, with 89% reporting one or more morbidities. Approximately 9% of women were re-admitted within 3 months after birth, higher in the HDP group (13.1%) higher compared to women without HDP (5.5%; RR 2.41; 95% CI 1.44-4.05). CONCLUSION: Overall levels of physical and psychological morbidity were high in this postnatal population. Although there were increased needs of women with HDP in the immediate postnatal period (compared to other women), their health assessments were similar at 3 months. This study highlights the unmet needs of women in the postnatal period, in addition to a missed opportunity to influence future pregnancies and improve the longer-term health of women and their babies.

Effect of Self-monitoring of Blood Pressure on Blood Pressure Control in Pregnant Individuals With Chronic or Gestational Hypertension: The BUMP 2 Randomized Clinical Trial.

Importance: Inadequate management of elevated blood pressure is a significant contributing factor to maternal deaths. The role of blood pressure self-monitoring in pregnancy in improving clinical outcomes for the pregnant individual and infant is unclear. Objective: To evaluate the effect of blood pressure self-monitoring, compared with usual care alone, on blood pressure control and other related maternal and infant outcomes, in individuals with pregnancy hypertension. Design, Setting, and Participants: Unblinded, randomized clinical trial that recruited between November 2018 and September 2019 in 15 hospital maternity units in England. Individuals with chronic hypertension (enrolled up to 37 weeks' gestation) or with gestational hypertension (enrolled between 20 and 37 weeks' gestation). Final follow-up was in May 2020. Interventions: Participants were randomized to either blood pressure self-monitoring using a validated monitor and a secure telemonitoring system in addition to usual care (n = 430) or to usual care alone (n = 420). Usual care comprised blood pressure measured by health care professionals at regular antenatal clinics. Main Outcomes and Measures: The primary maternal outcome was the difference in mean systolic blood pressure recorded by health care professionals between randomization and birth. Results: Among 454 participants with chronic hypertension (mean age, 36 years; mean gestation at entry, 20 weeks) and 396 with gestational hypertension (mean age, 34 years; mean gestation at entry, 33 weeks) who were randomized, primary outcome data were available from 444 (97.8%) and 377 (95.2%), respectively. In the chronic hypertension cohort, there was no statistically significant difference in mean systolic blood pressure for the self-monitoring groups vs the usual care group (133.8 mm Hg vs 133.6 mm Hg, respectively; adjusted mean difference, 0.03 mm Hg [95% CI, -1.73 to 1.79]). In the gestational hypertension cohort, there was also no significant difference in mean systolic blood pressure (137.6 mm Hg compared with 137.2 mm Hg; adjusted mean difference, -0.03 mm Hg [95% CI, -2.29 to 2.24]). There were 8 serious adverse events in the self-monitoring group (4 in each cohort) and 3 in the usual care group (2 in the chronic hypertension cohort and 1 in the gestational hypertension cohort). Conclusions and Relevance: Among pregnant individuals with chronic or gestational hypertension, blood pressure self-monitoring with telemonitoring, compared with usual care, did not lead to significantly improved clinic-based blood pressure control. Trial Registration: ClinicalTrials.gov Identifier: NCT03334149.

Effect of Self-monitoring of Blood Pressure on Diagnosis of Hypertension During Higher-Risk Pregnancy: The BUMP 1 Randomized Clinical Trial.

Importance: Inadequate management of elevated blood pressure (BP) is a significant contributing factor to maternal deaths. Self-monitoring of BP in the general population has been shown to improve the diagnosis and management of hypertension; however, little is known about its use in pregnancy. Objective: To determine whether self-monitoring of BP in higher-risk pregnancies leads to earlier detection of pregnancy hypertension. Design, Setting, and Participants: Unblinded, randomized clinical trial that included 2441 pregnant individuals at higher risk of preeclampsia and recruited at a mean of 20 weeks' gestation from 15 hospital maternity units in England between November 2018 and October 2019. Final follow-up was completed in April 2020. Interventions: Participating individuals were randomized to either BP self-monitoring with telemonitoring (n = 1223) plus usual care or usual antenatal care alone (n = 1218) without access to telemonitored BP. Main Outcomes and Measures: The primary outcome was time to first recorded hypertension measured by a health care professional. Results: Among 2441 participants who were randomized (mean [SD] age, 33 [5.6] years; mean gestation, 20 [1.6] weeks), 2346 (96%) completed the trial. The time from randomization to clinic recording of hypertension was not significantly different between individuals in the self-monitoring group (mean [SD], 104.3 [32.6] days) vs in the usual care group (mean [SD], 106.2 [32.0] days) (mean difference, -1.6 days [95% CI, -8.1 to 4.9]; P = .64). Eighteen serious adverse events were reported during the trial with none judged as related to the intervention (12 [1%] in the self-monitoring group vs 6 [0.5%] in the usual care group). Conclusions and Relevance: Among pregnant individuals at higher risk of preeclampsia, blood pressure self-monitoring with telemonitoring, compared with usual care, did not lead to significantly earlier clinic-based detection of hypertension. Trial Registration: ClinicalTrials.gov Identifier: NCT03334149.

Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial.

BACKGROUND: In women with late preterm pre-eclampsia, the optimal time to initiate delivery is unclear because limitation of maternal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of neonatal or infant outcomes, compared with expectant management (usual care) in women with late preterm pre-eclampsia. METHODS: In this parallel-group, non-masked, multicentre, randomised controlled trial done in 46 maternity units across England and Wales, we compared planned delivery versus expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia from 34 to less than 37 weeks' gestation and a singleton or dichorionic diamniotic twin pregnancy. The co-primary maternal outcome was a composite of maternal morbidity or recorded systolic blood pressure of at least 160 mm Hg with a superiority hypothesis. The co-primary perinatal outcome was a composite of perinatal deaths or neonatal unit admission up to infant hospital discharge with a non-inferiority hypothesis (non-inferiority margin of 10% difference in incidence). Analyses were by intention to treat, together with a per-protocol analysis for the perinatal outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN01879376. The trial is closed to recruitment but follow-up is ongoing. FINDINGS: Between Sept 29, 2014, and Dec 10, 2018, 901 women were recruited. 450 women (448 women and 471 infants analysed) were allocated to planned delivery and 451 women (451 women and 475 infants analysed) to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group (289 [65%] women) compared with the expectant management group (338 [75%] women; adjusted relative risk 0·86, 95% CI 0·79-0·94; p=0·0005). The incidence of the co-primary perinatal outcome by intention to treat was significantly higher in the planned delivery group (196 [42%] infants) compared with the expectant management group (159 [34%] infants; 1·26, 1·08-1·47; p=0·0034). The results from the per-protocol analysis were similar. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group. INTERPRETATION: There is strong evidence to suggest that planned delivery reduces maternal morbidity and severe hypertension compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater neonatal morbidity. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. METHODS: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. RESULTS: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. CONCLUSIONS: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. TRIAL REGISTRATION: PROSPERO ID: CRD42015029349 .

The Effect of Delayed Injection of Leukocyte-Rich Platelet-Rich Plasma Following Rotator Cuff Repair on Patient Function: A Randomized Double-Blind Controlled Trial.

PURPOSE: To investigate the effect of delayed application of leukocyte-rich platelet-rich plasma (PRP) on rotator cuff repair results as assessed by outcome scores and imaging at one year. METHODS: Patients with a symptomatic rotator cuff tear awaiting arthroscopic repair were approached to take part in the study. Final eligibility for the study was confirmed at the time of surgery. A total of 97 patients were randomized to an ultrasound guided injection of leukocyte-rich PRP or normal saline between 10 and 14 days postsurgery. A total of 87 patients completed clinical evaluation and underwent magnetic resonance imaging imaging at 1 year. Outcome scores included the American Shoulder and Elbow Score, Constant score, Western Ontario Rotator Cuff Index, and the Disabilities of the Arm, Shoulder and Hand Score. Structural integrity of the repair was assessed according to the Sugaya grading. Muscle fatty infiltration was assessed on magnetic resonance imaging using the Goutallier classification. RESULTS: At 1 year postsurgery, there was no significant difference between the treatment groups on any of the patient-reported outcome measures or Constant score. On postoperative imaging analysis, there was no difference in the retear rates (Sugaya 4 and 5) between the groups (21% in control group vs 15.3% in PRP group). Fatty infiltration on postoperative imaging was found to be significantly higher in the normal saline group compared with the PRP group (Kendall's tau-b P = .032). CONCLUSIONS: The delayed application of PRP postrotator cuff repair did not improve function as measured by patient-reported outcome measures and Constant score at 1 year postoperatively. LEVEL OF EVIDENCE: Level II, prospective randomized therapeutic trial.

Using self-monitoring to detect and manage raised blood pressure and pre-eclampsia during pregnancy: the BUMP research programme and its impact.

Raised blood pressure affects around ten percent of pregnancies worldwide, causing maternal and perinatal morbidity and mortality. Self-monitoring of blood pressure during higher-risk or hypertensive pregnancy has been shown to be feasible, acceptable, safe, and no more expensive than usual care alone. Additionally, self-testing for proteinuria has been shown to be just as accurate as healthcare professional testing, creating the potential for monitoring of multiple indicators through pregnancy. The work suggests however, that an organisational shift is needed to properly use and see benefits from self-monitored readings. This paper describes the findings from a large programme of work examining the use of self-monitoring in pregnancy, summarising the findings in the context of the wider literature and current clinical context. The BUMP Research Programme developed and tested self-monitoring and self-testing interventions for pregnancy. The work showed that self-monitoring during pregnancy was feasible, acceptable, safe, and no more expensive, but did not improve the detection or control of hypertension.

Detection and Control of Pregnancy Hypertension Using Self-Monitoring of Blood Pressure With Automated Telemonitoring: Cost Analyses of the BUMP Randomized Trials.

BACKGROUND: Pregnancy hypertension continues to cause maternal and perinatal morbidity. Two linked UK randomized trials showed adding self-monitoring of blood pressure (SMBP) with automated telemonitoring to usual antenatal care did not result in earlier detection or better control of pregnancy hypertension. This article reports the trials' integrated cost analyses. METHODS: Two cost analyses. SMBP with usual care was compared with usual care alone in pregnant individuals at risk of hypertension (BUMP 1 trial [Blood Pressure Monitoring in High Risk Pregnancy to Improve the Detection and Monitoring of Hypertension], n=2441) and with hypertension (BUMP 2 trial, n=850). Clinical notes review identified participant-level antenatal, intrapartum, and postnatal care and these were costed. Comparisons between trial arms used means and 95% CIs. Within BUMP 2, chronic and gestational hypertension cohorts were analyzed separately. Telemonitoring system costs were reported separately. RESULTS: In BUMP 1, mean (SE) total costs with SMBP and with usual care were £7200 (£323) and £7063 (£245), respectively, mean difference (95% CI), £151 (-£633 to £936). For the BUMP 2 chronic hypertension cohort, corresponding figures were £13 384 (£1230), £12 614 (£1081), mean difference £323 (-£2904 to £3549) and for the gestational hypertension cohort were £11 456 (£901), £11 145 (£959), mean difference £41 (-£2486 to £2567). The per-person cost of telemonitoring was £6 in BUMP 1 and £29 in BUMP 2. CONCLUSIONS: SMBP was not associated with changes in the cost of health care contacts for individuals at risk of, or with, pregnancy hypertension. This is reassuring as SMBP in pregnancy is widely prevalent, particularly because of the COVID-19 pandemic. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03334149.

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.

Self-monitoring blood pressure in Pregnancy: Evaluation of health professional experiences of the BUMP trials.

BACKGROUND: The BUMP trials evaluated a self-monitoring of blood pressure intervention in addition to usual care, testing whether they improved detection or control of hypertension for women at risk of hypertension or with hypertension during pregnancy. This process evaluation aimed to understand healthcare professionals' perspectives and experiences of the BUMP trials of self-monitoring of blood pressure during pregnancy. METHODS: Twenty-two in-depth qualitative interviews and an online survey with 328 healthcare professionals providing care for pregnant people in the BUMP trials were carried out across five maternity units in England. RESULTS: Analysis used Normalisation Process Theory to identify factors required for successful implementation and integration into routine practice. Healthcare professionals felt self-monitoring of blood pressure did not over-medicalise pregnancy for women with, or at risk of, hypertension. Most said self-monitored readings positively affected their clinical encounters and professional roles, provided additive information on which to base decisions and enriched their relationships with pregnant people. Self-monitoring of blood pressure shifts responsibilities. Some healthcare professionals felt women having responsibility to decide on timing of monitoring and whether to act on self-monitored readings was unduly burdensome, and resulted in healthcare professionals taking additional responsibility for supporting them. CONCLUSIONS: Despite healthcare professionals' early concerns that self-monitoring of blood pressure might over-medicalise pregnancy, our analysis shows the opposite was the case when used in the care of pregnant people with, or at higher risk of, hypertension. While professionals retained ultimate clinical responsibility, they viewed self-monitoring of blood pressure as a means of sharing responsibility and empowering women to understand their bodies, to make judgements and decisions, and to contribute to their care.

Hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP) are one of the most commonly occurring complications of pregnancy and include chronic hypertension, gestational hypertension, and pre-eclampsia. New developments in early pregnancy screening to identify women at high risk for pre-eclampsia combined with targeted aspirin prophylaxis could greatly reduce the number of affected pregnancies. Furthermore, recent advances in the diagnosis of pre-eclampsia, such as placental growth factor based testing, have been shown to improve the identification of those pregnancies at highest risk of severe complications. Evidence from trials has refined the target blood pressure and timing of delivery to manage chronic hypertension and pre-eclampsia with non-severe features, respectively. Importantly, a wealth of epidemiological data now links HDP to future cardiovascular disease and diabetes decades after an affected pregnancy. This review discusses the current guidelines and research data on the prevention, diagnosis, management, and postnatal follow-up of HDP. It also discusses the gap in knowledge regarding the long term risks for cardiovascular disease following HDP and illustrates the importance of improving adherence to postnatal guidelines to monitor hypertension and the need for more research focused on primary prevention of future cardiovascular disease in women identified as being at high risk because of HDP.

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA).

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

A Randomized Trial of Autologous Chondrocyte Implantation Versus Alternative Forms of Surgical Cartilage Management in Patients With a Failed Primary Treatment for Chondral or Osteochondral Defects in the Knee.

BACKGROUND: There are limited randomized controlled trials with long-term outcomes comparing autologous chondrocyte implantation (ACI) versus alternative forms of surgical cartilage management within the knee. PURPOSE: To determine at 5 years after surgery whether ACI was superior to alternative forms of cartilage management in patients after a failed previous treatment for chondral or osteochondral defects in the knee. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In total, 390 participants were randomly assigned to receive either ACI or alternative management. Patients aged 18 to 55 years with one or two symptomatic cartilage defects who had failed 1 previous therapeutic surgical procedure in excess of 6 months prior were included. Dual primary outcome measures were used: (1) patient-completed Lysholm knee score and (2) time from surgery to cessation of treatment benefit. Secondary outcome measures included International Knee Documentation Committee and Cincinnati Knee Rating System scores, as well as number of serious adverse events. Analysis was performed on an intention-to-treat basis. RESULTS: Lysholm scores were improved by 1 year in both groups (15.4 points [95% CI, 11.9 to 18.8] and 15.2 points [95% CI, 11.6 to 18.9]) for ACI and alternative, with this improvement sustained over the duration of the trial. However, no evidence of a difference was found between the groups at 5 years (2.9 points; 95% CI, -1.8 to 7.5; P = .46). Approximately half of the participants (55%; 95% CI, 47% to 64% with ACI) were still experiencing benefit at 5 years, with time to cessation of treatment benefit similar in both groups (hazard ratio, 0.97; 95% CI, 0.72 to 1.32; P > .99). There was a differential effect on Lysholm scores in patients without previous marrow stimulation compared with those with marrow stimulation (P = .03; 6.4 points in favor of ACI; 95% CI, -0.4 to 13.1). More participants experienced a serious adverse event with ACI (P = .02). CONCLUSION: Over 5 years, there was no evidence of a difference in Lysholm scores between ACI and alternative management in patients who had previously failed treatment. Previous marrow stimulation had a detrimental effect on the outcome of ACI. REGISTRATION: International Standard Randomised Controlled Trial Number: 48911177.

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.

Labor induction information leaflets-Do women receive evidence-based information about the benefits and harms of labor induction?

Objectives: To determine the extent to which a sample of NHS labor induction leaflets reflects evidence on labor induction. Setting: Audit of labor induction patient information leaflets-local from WILL trial (When to Induce Labor to Limit risk in pregnancy hypertension) internal pilot sites or national-level available online. Methods: Descriptive analysis [n = 21 leaflets, 19 (one shared) in 20 WILL internal pilot sites and 2 NHS online] according to NHS "Protocol on the Production of Patient Information" criteria: general information (including indications), why and how induction is offered (including success and alternatives), and potential benefits and harms. Results: All leaflets described an induction indication. Most leaflets (n = 18) mentioned induction location and 16 the potential for delays due to delivery suite workloads and competing clinical priorities. While 19 leaflets discussed membrane sweeping (17 as an induction alternative), only 4 leaflets mentioned balloon catheter as another mechanical method. Induction success (onset of active labor) was presented by a minority of leaflets (n = 7, 33%), as "frequent" or in the "majority", with "rare" or "occasional" failures. Benefits, harms and outcomes following induction were not compared with expectant care, but rather with spontaneous labor, such as for pain (n = 14, with nine stating more pain with induction). Potential benefits of induction were seldom described [n = 7; including avoiding stillbirth (n = 4)], but deemed to be likely. No leaflet stated vaginal birth was more likely following induction, but most stated Cesarean was not increased (n = 12); one leaflet stated that Cesarean risks were increased following induction. Women's satisfaction was rarely presented (n = 2). Conclusion: Information provided to pregnant women regarding labor induction could be improved to better reflect women's choice between induction and expectant care, and the evidence upon which treatment recommendations are based. A multiple stakeholder-involved and evidence-informed process to update guidance is required.