'Nesting networks': Women's experiences of social network support in high-risk pregnancy.

OBJECTIVE: Social support, an individual's social relationships (both online and offline), may provide protection against adverse mental health outcomes, such as anxiety and depression, which are high in women who have been hospitalised with high-risk pregnancy. This study explored the social support available to women at higher risk of preeclampsia during pregnancy by examining personal social networks. DESIGN: Semi-structured interviews were accompanied by social network mapping using the web-based social networking tool GENIE. SETTING: England. PARTICIPANTS: Twenty-one women were recruited, of whom 18 were interviewed both during pregnancy and postnatally between April 2019 and April 2020. Nineteen women completed maps pre-natally, 17 women completed maps pre-natally and post-natally. Women were taking part in the BUMP study, a randomised 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. RESULTS: Women's social networks tightened during pregnancy. The inner network changed most dramatically postnatally with women reporting fewer network members. Interviews revealed networks were primarily 'real-life' rather than online social networks, with members providing emotional, informational, and practical support. Women with a high-risk pregnancy valued the relationships they developed with health professionals during pregnancy, and would like their midwife to have a more central role in their networks by providing informational and, where needed, emotional support. The social network mapping data supported the qualitative accounts of changing networks across high-risk pregnancy. CONCLUSION: Women with a high-risk pregnancy seek to build "nesting networks" to support them through pregnancy into motherhood. Different types of support are sought from trusted sources. Midwives can play a key role. PRACTICE IMPLICATIONS: As well as highlighting other potential needs during pregnancy and the ways in which they can be met, support from midwives has a key role. Through talking to women early in their pregnancy, signposting information and explaining ways to contact health professionals regarding informational or emotional support would fill a gap that currently is met by other aspects of their network.

Perceptions and experiences of blood pressure self-monitoring during hypertensive pregnancy: A qualitative analysis of women's and clinicians' experiences in the OPTIMUM-BP trial.

BACKGROUND: Self-monitoring of blood pressure (BP) has been shown to be effective at improving BP control in the general population. The OPTIMUM-BP feasibility study was a prospective randomised controlled trial of self-monitoring of BP (SMBP) during hypertensive pregnancy. OBJECTIVE: To explore experiences, perceptions, and use of the OPTIMUM-BP self-monitoring intervention. STUDY DESIGN: Qualitative study within the OPTIMUM-BP feasibility trial. Semi-structured interviews with a purposive sample of pregnant women with chronic hypertension (n = 24) and their clinicians (n = 8) as well as 38 ethnographic observations of antenatal visits. RESULTS: Women found self-monitoring of BP feasible and acceptable and were highly motivated and pro-active in their monitoring, reporting greater control and knowledge of BP and reassurance. Women's persistence with SMBP was driven by a perceived need to safeguard the pregnancy, particularly among those taking antihypertensive medication. Clinicians also described the intervention as acceptable, though BP variability could cause uncertainty. Clinicians used different heuristics to integrate home and clinic readings. Observations suggested close working relationships between women and clinicians were key for confident integration of self-monitoring. CONCLUSIONS: Self-monitoring of BP was acceptable both to pregnant women with hypertension and their clinicians. More research is needed to understand BP variability within pregnancy to help interpret and integrate home BP readings for improved BP management. Clinical pathways that use BP self-monitoring should aim to maintain the continuity of care and relationships that are valued and appear pivotal for the confident and safe use of self-monitoring in pregnancy.

Kidney morphology in pregnancy using T2-weighted MRI.

AIM: To report the morphology of maternal kidneys captured on fetal magnetic resonance imaging (MRI) including kidney length, volume, renal pelvis diameter, and corticomedullary differentiation in pregnancy. MATERIALS AND METHODS: A retrospective study of maternal kidney morphology captured incidentally on fetal MRI. Women without chronic kidney disease, with a complete view of both kidneys and a singleton pregnancy were included. Kidney length, maximal renal pelvis diameter, kidney volume, and corticomedullary differentiation ratio were measured independently in duplicate. Associations with maternal and pregnancy variables were explored using linear regression. RESULTS: MRI images from 42 women were performed at 22-32 weeks' gestation. Serum creatinine concentrations are not checked routinely during pregnancy and were available for 15 (36%) women, with a median creatinine of 57 µmol/l (IQR: 50-63 µmol/l). Mean interpolar lengths were 10.9 and 10.4 cm for the left and right kidneys and varied with height. Mean maximal renal pelvis diameters were 9 mm and 12 mm, with upper reference intervals of 17 and 25 mm for the left and right kidneys, respectively. Renal volume in pregnancy was within the non-pregnant reference interval and varied with height and gestation. CONCLUSIONS: Maternal kidney length and volume in pregnancy are within the normal reference intervals for non-pregnant women. Renal pelvis diameter in pregnancy measured using MRI is substantially higher than described previously by ultrasound, with implications for routine reporting.

Changes to management of hypertension in pregnancy, and attitudes to self-management: An online survey of obstetricians, before and following the first wave of the COVID-19 pandemic.

OBJECTIVE: This study aimed to understand the views and practice of obstetricians regarding self-monitoring for hypertensive disorders of pregnancy (blood pressure (BP) and proteinuria), the potential for self-management (including actions taken on self-monitored parameters) and to understand the impact of the COVID-19 pandemic on such views. DESIGN: Cross-sectional online survey pre- and post- the first wave of the COVID-19 pandemic. SETTING AND SAMPLE: UK obstetricians recruited via an online portal. METHODS: A survey undertaken in two rounds: December 2019-January 2020 (pre-pandemic), and September-November 2020 (during pandemic) RESULTS: 251 responses were received across rounds one (150) and two (101). Most obstetricians considered that self-monitoring of BP and home urinalysis had a role in guiding clinical decisions and this increased significantly following the first wave of the COVID-19 pandemic (88%, (132/150) 95%CI: 83-93% first round vs 96% (95%CI: 92-94%), (97/101), second round; p = 0.039). Following the pandemic, nearly half were agreeable to women self-managing their hypertension by using their own readings to make a pre-agreed medication change themselves (47%, 47/101 (95%CI: 37-57%)). CONCLUSIONS: A substantial majority of UK obstetricians considered that self-monitoring had a role in the management of pregnancy hypertension and this increased following the pandemic. Around half are now supportive of women having a wider role in self-management of hypertensive treatment. Maximising the potential of such changes in pregnancy hypertension management requires further work to understand how to fully integrate women's own measurements into clinical care.

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a secondary analysis of the PITCHES trial.

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.

Placental growth factor in suspected preterm pre-eclampsia: a review of the evidence and practicalities of implementation.

Despite extensive research, the pathophysiology and prevention of pre-eclampsia remain elusive, diagnosis is challenging, and pre-eclampsia remains associated with adverse maternal and perinatal outcomes. 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 is increasingly being implemented in clinical practice in several countries. This review provides healthcare providers with an understanding of the evidence for PlGF-based testing and describes the practicalities and challenges to implementation. TWEETABLE ABSTRACT: Placental growth factor in pre-eclampsia: evidence and implementation of testing.

A core outcome set for pre-eclampsia research: an international consensus development study.

OBJECTIVE: To develop a core outcome set for pre-eclampsia. DESIGN: Consensus development study. SETTING: International. POPULATION: Two hundred and eight-one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. METHODS: Modified Delphi method and Modified Nominal Group Technique. RESULTS: A long-list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre-eclampsia trials with those derived from thematic analysis of 30 in-depth interviews of women with lived experience of pre-eclampsia. Forty-seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small-for-gestational-age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. CONCLUSIONS: The core outcome set for pre-eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies. TWEETABLE ABSTRACT: 281 healthcare professionals, 41 researchers and 110 women have developed #preeclampsia core outcomes @HOPEoutcomes @jamesmnduffy. [Correction added on 29 June 2020, after first online publication: the order has been corrected.].

Incidence and characteristics of pregnancy-related death across ten low- and middle-income geographical regions: secondary analysis of a cluster randomised controlled trial.

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.

Enzymatic quantification of total serum bile acids as a monitoring strategy for women with intrahepatic cholestasis of pregnancy receiving ursodeoxycholic acid treatment: a cohort study.

OBJECTIVE: To evaluate enzymatic total serum bile acid quantification as a monitoring strategy for women with intrahepatic cholestasis of pregnancy (ICP) treated with ursodeoxycholic acid (UDCA). DESIGN: Cohort. SETTING: One UK university hospital. POPULATION: 29 ICP cases treated with UDCA. METHODS: Serial samples were collected prospectively throughout gestation. Total serum bile acids were measured enzymatically and individual bile acids by high-performance liquid chromatography-tandem mass spectrometry. Data were log-transformed and analysed with random effects generalised least square regression. MAIN OUTCOME MEASURES: The relationship between enzymatic total bile acid measurements and individual bile acid concentrations after UDCA treatment. RESULTS: In untreated women, cholic acid was the principal bile acid (51%) and UDCA concentrations were <0.5%, whereas UDCA constituted 60% (IQR 43-69) of serum bile acids following treatment and cholic acid fell to <20%. Changes in the total bile acid measurement reflected similar alterations in the concentrations of the pathologically elevated bile acids, e.g. a two-fold increase in enzymatic total bile acids is accompanied by approximately a two-fold increase in cholic acid and chenodeoxycholic acid at most UDCA doses (P < 0.001). Most of the effects of UDCA on cholic acid occur in the first week of treatment (60% relative reduction, P = 0.025, 95% CI 0.2-0.9, from 10 micromol/l (4.7-17.6) to 3.5 micromol/l (1.4-7.5). CONCLUSION: Ursodeoxycholic acid becomes the main component of the bile acid measurement after treatment. Enzymatic total bile acid assays are good predictors of both cholic acid and chenodeoxycholic acid, the primary bile acids that are raised prior to treatment. TWEETABLE ABSTRACT: Ursodeoxycholic acid constitutes approximately 60% of the bile acid measurement and reduces pathological cholic acid in treated women.

Placental growth factor testing for suspected pre-eclampsia: a cost-effectiveness analysis.

OBJECTIVE: To calculate the cost-effectiveness of implementing PlGF testing alongside a clinical management algorithm in maternity services in the UK, compared with current standard care. DESIGN: Cost-effectiveness analysis. SETTING: Eleven maternity units participating in the PARROT stepped-wedge cluster-randomised controlled trial. POPULATION: Women presenting with suspected pre-eclampsia between 20+0 and 36+6  weeks' gestation. METHODS: Monte Carlo simulation utilising resource use data and maternal adverse outcomes. MAIN OUTCOME MEASURES: Cost per maternal adverse outcome prevented. RESULTS: Clinical care with PlGF testing costs less than current standard practice and resulted in fewer maternal adverse outcomes. There is a total cost-saving of UK£149 per patient tested, when including the cost of the test. This represents a potential cost-saving of UK£2,891,196 each year across the NHS in England. CONCLUSIONS: Clinical care with PlGF testing is associated with the potential for cost-savings per participant tested when compared with current practice via a reduction in outpatient attendances, and improves maternal outcomes. This economic analysis supports a role for implementation of PlGF testing in antenatal services for the assessment of women with suspected pre-eclampsia. TWEETABLE ABSTRACT: Placental growth factor testing for suspected pre-eclampsia is cost-saving and improves maternal outcomes.

Comparison of three commercially available placental growth factor-based tests in women with suspected preterm pre-eclampsia: the COMPARE study.

OBJECTIVE: To compare the performance of three placental growth factor (PlGF)-based tests in predicting delivery within 14 days from testing in women with suspected preterm pre-eclampsia before 35 weeks' gestation. METHODS: This was a retrospective analysis of samples collected from three prospective pregnancy cohort studies. Participants were pregnant women with suspected preterm pre-eclampsia recruited in tertiary maternity units in the UK and Ireland. Samples were analyzed simultaneously according to the manufacturers' directions. The tests compared were the DELFIA Xpress PlGF 1-2-3 test, the Triage PlGF test and the Elecsys immunoassay soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio. Areas under receiver-operating characteristics curves (AUCs) were compared. The main outcome measure was detection of a difference of 0.05 in AUC between tests for delivery within 14 days of testing. RESULTS: Plasma samples from 396 women and serum samples from 244 women were assayed. In predicting delivery within 14 days secondary to suspected pre-eclampsia prior to 35 weeks' gestation, no significant differences were observed in AUCs (P = 0.795), sensitivities (P = 0.249), positive predictive values (P = 0.765) or negative predictive values (P = 0.920) between the three tests. The specificity of the Elecsys sFlt-1/PlGF ratio test was higher than that of the other two tests (P < 0.001). CONCLUSIONS: The tests perform similarly in their prediction of need for delivery within 14 days in women with suspected pre-eclampsia. The high negative predictive values support the role of PlGF-based tests as 'rule-out' tests for pre-eclampsia. © 2018 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Longitudinal changes in vascular function parameters in pregnant women with chronic hypertension and association with adverse outcome: a cohort study.

OBJECTIVES: Raised vascular function measures are associated with adverse maternal and perinatal outcomes in low-risk pregnancy. This study aimed to evaluate the association between longitudinal vascular function parameters and adverse outcome in pregnant women with chronic hypertension, and to assess whether these measures vary according to baseline parameters such as black ethnicity. METHODS: This was a nested cohort study of women with chronic hypertension and a singleton pregnancy recruited to the PANDA (Pregnancy And chronic hypertension: NifeDipine vs lAbetalol as antihypertensive treatment) study at one of three UK maternity units. Women had serial pulse-wave analyses performed using the Arteriograph®, while in a sitting position, from 12 weeks' gestation onwards. Statistical analysis was performed using random-effects logistic regression models. Longitudinal vascular parameters were compared between women who developed superimposed pre-eclampsia (SPE) and those who did not, between women who delivered a small-for-gestational-age (SGA) infant (birth weight < 10th centile) and those who delivered an infant with birth weight ≥ 10th centile and between women of black ethnicity and those of non-black ethnicity. RESULTS: The cohort included 97 women with chronic hypertension and a singleton pregnancy, of whom 90% (n = 87) were randomized to antihypertensive treatment and 57% (n = 55) were of black ethnicity, with up to six (mean, three) longitudinal vascular function assessments. SPE was diagnosed in 18% (n = 17) of women and 30% (n = 29) of infants were SGA. In women who developed subsequent SPE, compared with those who did not, mean brachial systolic blood pressure (SBP) (148 mmHg vs 139 mmHg; P = 0.002), mean diastolic blood pressure (DBP) (87 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (139 mmHg vs 128 mmHg; P = 0.001) and mean augmentation index (AIx-75) (29% vs 22%; P = 0.01) were significantly higher across gestation. In women who delivered a SGA infant compared to those who delivered an infant with birth weight ≥ 10th centile, mean brachial SBP (146 mmHg vs 138 mmHg; P = 0.001), mean DBP (86 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (137 mmHg vs 127 mmHg; P < 0.0001) and mean pulse-wave velocity (9.1 m/s vs 8.5 m/s; P = 0.02) were higher across gestation. No longitudinal differences were found in vascular function parameters in women of black ethnicity compared with those of non-black ethnicity. CONCLUSION: There were persistent differences in vascular function parameters and brachial blood pressure throughout pregnancy in women with chronic hypertension who later developed adverse maternal or perinatal outcome. Further investigation into the possible clinical use of these findings is warranted. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Impact of ethnicity on adverse perinatal outcome in women with chronic hypertension: a cohort study.

OBJECTIVE: To assess the impact of maternal ethnicity on the risk of adverse perinatal outcome in pregnant women with chronic hypertension. METHODS: Demographic and delivery data were collated of women with chronic hypertension and singleton pregnancy who delivered at one of three UK obstetric units between 2000 and 2014. Multivariable logistic regression models were used to calculate risk ratios (RR), according to ethnic group, for adverse perinatal outcome, adjusted for other maternal characteristics including age, parity, body mass index, smoking status, deprivation index and year of delivery. The impact of maternal ethnicity on birth-weight centile calculation was investigated by comparing the birth-weight centile chart customized for ethnicity (Gestation Related Optimal Weight; GROW) with a birth-weight centile calculator that does not adjust for that factor (INTERGROWTH-21st ). RESULTS: The study cohort included 4481 pregnancies (4045 women) with chronic hypertension. Women of white ethnicity accounted for 47% (n = 2122) of the cohort and 36% (n = 1601) were of black, 8.5% (n = 379) of Asian and 8.5% (n = 379) of other ethnicity. The overall incidence of stillbirth was 1.6%, that of preterm birth < 37 weeks was 16% and that of fetal growth restriction (birth weight < 3rd centile) was 11%. Black women, compared with white women, had the highest risk for all adverse perinatal outcomes, with stillbirth occurring in 3.1% vs 0.6% of pregnancies (adjusted RR (aRR), 5.56 (95% CI, 2.79-11.09)), preterm birth < 37 weeks in 21% vs 11% (aRR, 1.70 (95% CI, 1.43-2.01)) and birth weight < 3rd centile in 15% vs 7.4% (aRR, 2.07 (95% CI, 1.71-2.51)). Asian women, compared with white women, were also at increased risk of adverse perinatal outcome, with stillbirth occurring in 1.6% vs 0.6% (aRR, 3.03 (95% CI, 1.11-8.28)), preterm birth < 37 weeks in 20% vs 11% (aRR, 1.82 (95% CI, 1.41-2.35)) and birth weight < 3rd centile in 12% vs 7.4% (aRR, 1.69 (95% CI, 1.24-2.30)). The sensitivity and specificity for prediction of infants requiring neonatal unit admission were 40% and 93%, respectively, for those with birth weight < 3rd centile according to GROW charts, compared with 16% and 96%, respectively, for those with birth weight < 3rd centile according to INTERGROWTH-21st charts. CONCLUSIONS: Black ethnicity, compared with white, is associated with the greatest risk of adverse perinatal outcome in women with chronic hypertension, even after adjusting for other maternal characteristics. Women of Asian ethnicity are also at increased risk, but to a lesser extent. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of pre-eclampsia: review of reviews.

OBJECTIVE: Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to review published systematic reviews to collate evidence on the ability of available tests to predict pre-eclampsia, to identify high-value avenues for future research and to minimize future research waste in this field. METHODS: MEDLINE, EMBASE and The Cochrane Library including DARE (Database of Abstracts of Reviews of Effects) databases, from database inception to March 2017, and bibliographies of relevant articles were searched, without language restrictions, for systematic reviews and meta-analyses on the prediction of pre-eclampsia. The quality of the included reviews was assessed using the AMSTAR tool and a modified version of the QUIPS tool. We evaluated the comprehensiveness of search, sample size, tests and outcomes evaluated, data synthesis methods, predictive ability estimates, risk of bias related to the population studied, measurement of predictors and outcomes, study attrition and adjustment for confounding. RESULTS: From 2444 citations identified, 126 reviews were included, reporting on over 90 predictors and 52 prediction models for pre-eclampsia. Around a third (n = 37 (29.4%)) of all reviews investigated solely biochemical markers for predicting pre-eclampsia, 31 (24.6%) investigated genetic associations with pre-eclampsia, 46 (36.5%) reported on clinical characteristics, four (3.2%) evaluated only ultrasound markers and six (4.8%) studied a combination of tests; two (1.6%) additional reviews evaluated primary studies investigating any screening test for pre-eclampsia. Reviews included between two and 265 primary studies, including up to 25 356 688 women in the largest review. Only approximately half (n = 67 (53.2%)) of the reviews assessed the quality of the included studies. There was a high risk of bias in many of the included reviews, particularly in relation to population representativeness and study attrition. Over 80% (n = 106 (84.1%)) summarized the findings using meta-analysis. Thirty-two (25.4%) studies lacked a formal statement on funding. The predictors with the best test performance were body mass index (BMI) > 35 kg/m2 , with a specificity of 92% (95% CI, 89-95%) and a sensitivity of 21% (95% CI, 12-31%); BMI > 25 kg/m2 , with a specificity of 73% (95% CI, 64-83%) and a sensitivity of 47% (95% CI, 33-61%); first-trimester uterine artery pulsatility index or resistance index > 90th centile (specificity 93% (95% CI, 90-96%) and sensitivity 26% (95% CI, 23-31%)); placental growth factor (specificity 89% (95% CI, 89-89%) and sensitivity 65% (95% CI, 63-67%)); and placental protein 13 (specificity 88% (95% CI, 87-89%) and sensitivity 37% (95% CI, 33-41%)). No single marker had a test performance suitable for routine clinical use. Models combining markers showed promise, but none had undergone external validation. CONCLUSIONS: This review of reviews calls into question the need for further aggregate meta-analysis in this area given the large number of published reviews subject to the common limitations of primary predictive studies. Prospective, well-designed studies of predictive markers, preferably randomized intervention studies, and combined through individual-patient data meta-analysis are needed to develop and validate new prediction models to facilitate the prediction of pre-eclampsia and minimize further research waste in this field. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Predicción de la preeclampsia: revisión de revisiones OBJETIVO: Los estudios primarios y las revisiones sistemáticas proporcionan estimaciones de precisión variable para diferentes factores en la predicción de la preeclampsia. El objetivo de este estudio fue revisar las revisiones sistemáticas publicadas para recopilar evidencia sobre la capacidad de las pruebas disponibles para predecir la preeclampsia, identificar avenidas de investigación futura valiosas y minimizar el desperdicio futuro de investigación en este campo. MÉTODOS: Se realizaron búsquedas de artículos relevantes en bibliografías sobre el tema y en las bases de datos MEDLINE, EMBASE y The Cochrane Library, incluida DARE (Database of Abstracts of Reviews of Effects), desde el inicio de cada base de datos hasta marzo de 2017, sin restricciones de idioma, para obtener revisiones sistemáticas y metaanálisis sobre la predicción de la preeclampsia. La calidad de las revisiones incluidas se evaluó utilizando la herramienta AMSTAR y una versión modificada de la herramienta QUIPS. Se evaluó la amplitud de la búsqueda, el tamaño de la muestra, las pruebas y los resultados evaluados, los métodos de síntesis de datos, las estimaciones de la capacidad de predicción, el riesgo de sesgo relacionado con la población estudiada, la medición de los predictores y los resultados, la deserción del estudio y el ajuste por confusión. RESULTADOS: De las 2444 citas identificadas, se incluyeron 126 revisiones, que informaron sobre más de 90 predictores y 52 modelos de predicción para la preeclampsia. Alrededor de un tercio (n=37 (29,4%)) de todas las revisiones investigaron únicamente marcadores bioquímicos para predecir la preeclampsia, 31 (24,6%) investigaron asociaciones genéticas con la preeclampsia, 46 (36,5%) informaron sobre las características clínicas, cuatro (3,2%) evaluaron sólo marcadores ecográficos y seis (4,8%) estudiaron una combinación de pruebas; dos (1,6%) revisiones adicionales evaluaron los estudios primarios que investigaron cualquier prueba de diagnóstico de la preeclampsia. Las revisiones incluyeron entre dos y 265 estudios primarios, que incluyeron hasta 25 356 688 mujeres en la revisión más grande. Sólo aproximadamente la mitad (n=67 (53,2%)) de las revisiones evaluaron la calidad de los estudios incluidos. En muchas de las revisiones incluidas hubo un alto riesgo de sesgo, particularmente en relación con la representatividad de la población y la deserción de los estudios. Más del 80% (n=106 (84,1%)) resumió los hallazgos utilizando el metaanálisis. Treinta y dos (25,4%) estudios carecían de una declaración formal sobre la financiación. Los predictores con el mejor rendimiento de la prueba fueron el índice de masa corporal (IMC) >35 kg.m-2 , con una especificidad del 92% (IC 95%, 89-95%) y una sensibilidad del 21% (IC 95%, 12-31%); IMC >25 kg.m-2 , con una especificidad del 73% (IC 95%: 64-83%) y una sensibilidad del 47% (IC 95%: 33-61%); índice de pulsatilidad de la arteria uterina en el primer trimestre o índice de resistencia >90° percentil (especificidad del 93% (IC 95%: 90-96%) y sensibilidad del 26% (IC 95%: 23-31%)); factor de crecimiento placentario (especificidad 89% (IC 95%, 89-89%) y sensibilidad 65% (IC 95%, 63-67%)); y proteína placentaria 13 (especificidad 88% (IC 95%, 87-89%) y sensibilidad 37% (IC 95%, 33-41%)). Ningún marcador por sí solo tuvo un rendimiento de la prueba adecuado para el uso clínico rutinario. Los modelos que combinan marcadores son prometedores, pero ninguno fue sometido a una validación externa. CONCLUSIONES: Esta revisión de revisiones ha puesto en duda la necesidad de un metaanálisis agregado adicional en esta área, dado el gran número de revisiones publicadas sujetas a las limitaciones comunes de los estudios predictivos primarios. Se necesitan estudios prospectivos bien diseñados de marcadores predictivos, preferiblemente en estudios de intervención aleatorios, y combinados mediante el metaanálisis de datos de pacientes individuales, para desarrollar y validar nuevos modelos predictivos que faciliten la predicción de la preeclampsia y minimicen el desperdicio de investigación adicional en este campo.

Predicting delivery of a small-for-gestational-age infant and adverse perinatal outcome in women with suspected pre-eclampsia.

OBJECTIVE: To evaluate the test performance of 47 biomarkers and ultrasound parameters for the prediction of delivery of a small-for-gestational-age (SGA) infant and adverse perinatal outcome in women presenting with suspected pre-eclampsia. METHODS: This was a prospective, multicenter observational study in which 47 biomarkers and ultrasound parameters were measured in 397 women with a singleton pregnancy presenting with suspected preterm pre-eclampsia between 20 + 0 and 36 + 6 weeks' gestation, with the objective of evaluating them as predictors of subsequent delivery of a SGA infant and adverse perinatal outcome. Women with confirmed pre-eclampsia at enrollment were excluded. Factor analysis and stepwise logistic regression were performed in two prespecified groups stratified according to gestational age at enrollment. The primary outcome was delivery of a SGA infant with a birth weight < 3rd customized centile (SGA-3), and secondary outcomes were a SGA infant with a birth weight < 10th customized centile and adverse perinatal outcome. RESULTS: In 274 women presenting at 20 + 0 to 34 + 6 weeks' gestation, 96 (35%) delivered a SGA-3 infant. For prediction of SGA-3, low maternal placental growth factor (PlGF) concentration had a sensitivity of 93% (95% CI, 84-98%) and negative predictive value (NPV) of 90% (95% CI, 76-97%) compared with a sensitivity of 71% (95% CI, 58-82%) and a NPV of 79% (95% CI, 68-87%) for ultrasound parameters (estimated fetal weight or abdominal circumference < 10th centile). No individual biomarker evaluated had a better performance than did PlGF, and marker combinations made only small improvements to the test performance. Similar results were found in 123 women presenting between 35 + 0 and 36 + 6 weeks' gestation. CONCLUSION: In women presenting with suspected preterm pre-eclampsia, measurement of PlGF offers a useful adjunct for identifying those at high risk of delivering a SGA infant, allowing appropriate surveillance and timely intervention. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic accuracy of placental growth factor and ultrasound parameters to predict the small-for-gestational-age infant in women presenting with reduced symphysis-fundus height.

OBJECTIVES: To assess the diagnostic accuracy of placental growth factor (PlGF) and ultrasound parameters to predict delivery of a small-for-gestational-age (SGA) infant in women presenting with reduced symphysis-fundus height (SFH). METHODS: This was a multicenter prospective observational study recruiting 601 women with a singleton pregnancy and reduced SFH between 24 and 37 weeks' gestation across 11 sites in the UK and Canada. Plasma PlGF concentration < 5(th) centile, estimated fetal weight (EFW) < 10(th) centile, umbilical artery Doppler pulsatility index > 95(th) centile and oligohydramnios (amniotic fluid index < 5 cm) were compared as predictors for a SGA infant < 3(rd) customized birth-weight centile and adverse perinatal outcome. Test performance statistics were calculated for all parameters in isolation and in combination. RESULTS: Of the 601 women recruited, 592 were analyzed. For predicting delivery of SGA < 3(rd) centile (n = 78), EFW < 10(th) centile had 58% sensitivity (95% CI, 46-69%) and 93% negative predictive value (NPV) (95% CI, 90-95%), PlGF had 37% sensitivity (95% CI, 27-49%) and 90% NPV (95% CI, 87-93%); in combination, PlGF and EFW < 10(th) centile had 69% sensitivity (95% CI, 55-81%) and 93% NPV (95% CI, 89-96%). The equivalent receiver-operating characteristics (ROC) curve areas were 0.79 (95% CI, 0.74-0.84) for EFW < 10(th) centile, 0.70 (95% CI, 0.63-0.77) for low PlGF and 0.82 (95% CI, 0.77-0.86) in combination. CONCLUSIONS: For women presenting with reduced SFH, ultrasound parameters had modest test performance for predicting delivery of SGA < 3(rd) centile. PlGF performed no better than EFW < 10(th) centile in determining delivery of a SGA infant.

Third trimester amniocentesis for diagnosis of inherited bleeding disorders prior to delivery.

X-linked and autosomally inherited bleeding disorders confer a risk of foetal intracranial haemorrhage during delivery. Conventional prenatal diagnosis involving chorionic villus sampling or early amniocentesis is primarily aimed at offering the choice of pregnancy termination. Currently, non-invasive procedures, involving analysis of free foetal DNA in the maternal circulation, are restricted to gender determination, and are of limited value in women at risk of carrying a foetus with a bleeding disorder. These limitations, together with the rising proportion of women shown to be carrying an affected foetus, who decide to continue the pregnancy, have led to the development of prenatal mutation identification via late amniocentesis after 34 weeks of gestation, with the sole aim of directing delivery management. Although this approach has been documented in some cases of potential foetal anomaly, there are no previous reports of its use in women with heritable bleeding disorders. We report a single-centre experience of this technique in managing nine such deliveries. Of these, three showed an affected foetus, five showed an unaffected foetus and in one case no result could be obtained. In the three affected cases and the one with the inconclusive result restrictive birth plans were implemented, whereas the five unaffected cases underwent routine obstetric management; with one delivery necessitating interventions which would have been contraindicated if foetal status had not been determined. Late amniocentesis is a safe technique for guiding delivery management in women with bleeding disorders where the mutation is known.

Risk factors for small-for-gestational-age infants by customised birthweight centiles: data from an international prospective cohort study.

OBJECTIVE: To identify clinical and ultrasound variables associated with the birth of small-for-gestational-age (SGA) infants by customised centiles, subclassified according to whether their mothers were normotensive or developed hypertensive complications. DESIGN: Prospective, multicentre cohort study. SETTING: Participating centres of the Screening for Pregnancy Endpoints (SCOPE) study in Auckland, New Zealand, Adelaide, Australia, Manchester and London, UK, and Cork, Ireland. POPULATION: The 3513 nulliparous participants of the SCOPE study. METHODS: Women were interviewed at 15 ± 1 weeks, and had ultrasound growth measurements and umbilical and uterine Doppler studies at 20 ± 1 weeks. Variables associated with SGA infants were identified using logistic regression. MAIN OUTCOME MEASURES: Small for gestational age (i.e. a birthweight of less than the tenth customised centile), normotensive-SGA and hypertensive-SGA. Comparison groups for statistical analyses were non-SGA, normotensive non-SGA and hypertensive non-SGA. RESULTS: Among 376 (10.7%) SGA infants, 281 (74.7%) were normotensive-SGA and 95 (25.3%) were hypertensive-SGA. Independent risk factors for normotensive-SGA were low maternal birthweight, low fruit intake pre-pregnancy, cigarette smoking, increasing maternal age, daily vigorous exercise, being a tertiary student, head and abdominal circumference of less than the tenth centile and increasing uterine artery Doppler indices at the 20-week scan. Protective factors were: high green leafy vegetable intake pre-pregnancy, and rhesus-negative blood group. Risk factors for hypertensive-SGA were conception by in vitro fertilisation, previous early pregnancy loss and femur length of less than tenth centile at the 20-week scan. CONCLUSIONS: Risk factors for infants who are SGA by customised centiles have been identified in a cohort of healthy nulliparous women. A number of these factors are modifiable; however, further studies are needed to replicate these findings.