Blood pressure cut-offs at 11-13 weeks' gestation and risk of preeclampsia.

BACKGROUND: A parallel has been drawn between first trimester placental vascular maturation and maternal cardiovascular adaptations, including blood pressure. Although 140/90 mmHg is well-accepted as the threshold for chronic hypertension in the general obstetric population in early pregnancy, a different threshold could apply to stratify risk of adverse outcomes, such as preeclampsia. This could have implications for interventions, such as the threshold for initiation of antihypertensive therapy and the target blood pressure level. OBJECTIVE: We evaluated the relationship between various blood pressure cut-offs at 11-13 weeks' gestation and development of preeclampsia, overall and according to key maternal characteristics. STUDY DESIGN: This secondary analysis was of data from a prospective non-intervention cohort study of singleton pregnancies delivering at ≥24 weeks, without major anomalies, at two UK maternity hospitals, 2006-2020. BP at 11-13 weeks' gestation was classified according to American College of Cardiology/American Heart Association categories (mmHg), as: 'Normal blood pressure' (systolic <120 and diastolic <80), 'Elevated blood pressure' (systolic ≥120 and diastolic <80), 'Stage 1 hypertension' (systolic ≥130 or diastolic 80-89), and 'Stage 2 hypertension (systolic ≥140 or diastolic ≥90). For blood pressure category thresholds and the outcome of preeclampsia, the following were calculated overall and across maternal age, body mass index, ethnicity, method of conception, and previous pregnancy history: detection rate, screen positive rate, and positive and negative likelihood ratios, with 95% confidence intervals (CIs). A p value <0.05 was considered significant. RESULTS: There were 137,458 pregnancies screened at 11-13 weeks' gestation. The population was ethnically diverse, with 15.9% of Black ethnicity, 6.7% of South or East Asian ethnicity, and 2.7% of mixed ethnicity, with the remainder of White ethnicity. Compared with 'Normal blood pressure', 'Stage 2 hypertension' was associated with both preterm preeclampsia (0.3 to 4.9%) and term PE (1.0 to 8.3%). A blood pressure threshold of 140/90 mmHg was good at identifying women at increased risk of preeclampsia, overall (positive likelihood ratio 5.61, 95% CI 5.14-6.11) and across maternal characteristics, compared with 'Elevated blood pressure' (positive likelihood ratio 1.70, 95% CI 1.63-1.77) and 'Stage 1 hypertension' (positive likelihood ratio 2.68, 95% CI 2.58-2.77). There were two exceptions: a blood pressure threshold of 130/80 mmHg was better for the 2.1% of women with body mass index <18.5kg/m2 (positive likelihood ratio 5.13, 95% CI 3.22-8.16), and a threshold of 135/85 mmHg better for the 50.4% of parous women without a history of preeclampsia (positive likelihood ratio 5.24, 95% CI 4.77-5.77). There was no blood pressure threshold below which reassurance could be provided against development of preeclampsia (all negative likelihood ratios ≥0.20). CONCLUSIONS: The traditional blood pressure threshold of 140/90 mmHg performs well to identify women at increased risk of preeclampsia. Women who are underweight or parous with no prior history of preeclampsia may be better identified by lower thresholds; however a randomised trial would be necessary to determine any benefits of such an approach if antihypertensive therapy were also administered at this threshold. No blood pressure threshold reassured against development of preeclampsia, regardless of maternal characteristics.

Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus.

BACKGROUND: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. OBJECTIVE: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique. STUDY DESIGN: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which the experts were asked to rate on a 5-point Likert scale (from "strongly disagree"=1 to "strongly agree"=5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of ≤3 were deemed to have had no consensus and were excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and nonconsensus statements were then aggregated. RESULTS: A total of 68 international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on 5 continents and have contributed to >80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, and 91% for the first, second, and third rounds, respectively, and 71% completed all 3 rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including the following: (1) although there is no agreement on the distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2-cm distance; (2) all pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; (3) when a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at approximately 32 weeks to rule out vasa previa; (4) outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; (5) asymptomatic patients with vasa previa should be delivered by scheduled cesarean delivery between 35 and 37 weeks of gestation; and (6) there was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa. CONCLUSION: Through focus group discussion and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines.

Machine learning-enabled maternal risk assessment for women with pre-eclampsia (the PIERS-ML model): a modelling study.

BACKGROUND: Affecting 2-4% of pregnancies, pre-eclampsia is a leading cause of maternal death and morbidity worldwide. Using routinely available data, we aimed to develop and validate a novel machine learning-based and clinical setting-responsive time-of-disease model to rule out and rule in adverse maternal outcomes in women presenting with pre-eclampsia. METHODS: We used health system, demographic, and clinical data from the day of first assessment with pre-eclampsia to predict a Delphi-derived composite outcome of maternal mortality or severe morbidity within 2 days. Machine learning methods, multiple imputation, and ten-fold cross-validation were used to fit models on a development dataset (75% of combined published data of 8843 patients from 11 low-income, middle-income, and high-income countries). Validation was undertaken on the unseen 25%, and an additional external validation was performed in 2901 inpatient women admitted with pre-eclampsia to two hospitals in south-east England. Predictive risk accuracy was determined by area-under-the-receiver-operator characteristic (AUROC), and risk categories were data-driven and defined by negative (-LR) and positive (+LR) likelihood ratios. FINDINGS: Of 8843 participants, 590 (6·7%) developed the composite adverse maternal outcome within 2 days, 813 (9·2%) within 7 days, and 1083 (12·2%) at any time. An 18-variable random forest-based prediction model, PIERS-ML, was accurate (AUROC 0·80 [95% CI 0·76-0·84] vs the currently used logistic regression model, fullPIERS: AUROC 0·68 [0·63-0·74]) and categorised women into very low risk (-LR <0·1; eight [0·7%] of 1103 women), low risk (-LR 0·1 to 0·2; 321 [29·1%] women), moderate risk (-LR >0·2 and +LR <5·0; 676 [61·3%] women), high risk (+LR 5·0 to 10·0, 87 [7·9%] women), and very high risk (+LR >10·0; 11 [1·0%] women). Adverse maternal event rates were 0% for very low risk, 2% for low risk, 5% for moderate risk, 26% for high risk, and 91% for very high risk within 48 h. The 2901 women in the external validation dataset were accurately classified as being at very low risk (0% with outcomes), low risk (1%), moderate risk (4%), high risk (33%), or very high risk (67%). INTERPRETATION: The PIERS-ML model improves identification of women with pre-eclampsia who are at lowest and greatest risk of severe adverse maternal outcomes within 2 days of assessment, and can support provision of accurate guidance to women, their families, and their maternity care providers. FUNDING: University of Strathclyde Diversity in Data Linkage Centre for Doctoral Training, the Fetal Medicine Foundation, The Canadian Institutes of Health Research, and the Bill & Melinda Gates Foundation.

Pregnancy-An Ideal Period to Identify Women at Risk for Chronic Hypertension.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in women. Pregnancy is an ideal period to implement cardiovascular prevention strategies as women seek medical help. We aimed to develop a predictive model to identify women at increased risk for chronic hypertension (CH) based on information collected in the index pregnancy. METHODS: Cohort of 26 511 women seen in 2 consecutive pregnancies. Included were women without CH, with information on maternal characteristics and blood pressure at 11 to 13 weeks' gestation, and the development of preeclampsia or gestational hypertension (GH) in the index pregnancy. Logistic regression models were fitted for the prediction of the development of future CH by the 20th week of the subsequent pregnancy. The performance of screening and risk calibration of the model were assessed. RESULTS: In this study 1560 (5.9%) women developed preeclampsia or GH (index pregnancy), and 215 (0.8%) developed future CH, with a median of 3.0 years later. Predictors of development of future CH were maternal age, weight, and blood pressure; Black and South Asian ethnicity; family history of preeclampsia; parity; and development of preeclampsia or GH. Preeclampsia or GH detected 52.1% (45.2%-58.9%) of future CH. At a screen-positive rate of 10%, a model including maternal characteristics, early pregnancy blood pressure, and development of preeclampsia or GH detected 73.5% (67.1-79.3) of future CH. CONCLUSIONS: Early pregnancy maternal characteristics, blood pressure, and development of preeclampsia or GH identify three-fourths of women at risk for future CH. Our results offer an important preventative strategy for identifying women at increased risk of future CH, which is applicable worldwide.

Incidence and causes of perinatal death in prenatally diagnosed vasa previa: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to estimate the perinatal mortality associated with prenatally diagnosed vasa previa and to determine what proportion of those perinatal deaths are directly attributable to vasa previa. DATA SOURCES: The following databases have been searched from January 1, 1987, to January 1, 2023: PubMed, Scopus, Web of Science, and Embase. STUDY ELIGIBILITY CRITERIA: Our study included all studies (cohort studies and case series or reports) that had patients in which a prenatal diagnosis of vasa previa was made. Case series or reports were excluded from the meta-analysis. All cases in which prenatal diagnosis was not made were excluded from the study. METHODS: The programming language software R (version 4.2.2) was used to conduct the meta-analysis. The data were logit transformed and pooled using the fixed effects model. The between-study heterogeneity was reported by I2. The publication bias was evaluated using a funnel plot and the Peters regression test. The Newcastle-Ottawa scale was used to assess the risk of bias. RESULTS: Overall, 113 studies with a cumulative sample size of 1297 pregnant individuals were included. This study included 25 cohort studies with 1167 pregnancies and 88 case series or reports with 130 pregnancies. Moreover, 13 perinatal deaths occurred among these pregnancies, consisting of 2 stillbirths and 11 neonatal deaths. Among the cohort studies, the overall perinatal mortality was 0.94% (95% confidence interval, 0.52-1.70; I2=0.0%). The pooled perinatal mortality attributed to vasa previa was 0.51% (95% confidence interval, 0.23-1.14; I2=0.0%). Stillbirth and neonatal death were reported in 0.20% (95% confidence interval, 0.05-0.80; I2=0.0%) and 0.77% (95% confidence interval, 0.40-1.48; I2=0.0%) of pregnancies, respectively. CONCLUSION: Perinatal death is uncommon after a prenatal diagnosis of vasa previa. Approximately half of the cases of perinatal mortality are not directly attributable to vasa previa. This information will help in guiding physicians in counseling and will provide reassurance to pregnant individuals with a prenatal diagnosis of vasa previa.

Maternal and neonatal complications in pregnancies with and without pre-gestational diabetes mellitus.

OBJECTIVES: To compare pregnancy complications in pregnancies with and without pre-gestational diabetes mellitus (DM) managed in a multidisciplinary high-risk diabetes antenatal clinic. METHODS: This screening cohort study was undertaken at a large maternity unit in the United Kingdom between January 2010 and December 2022. We included singleton pregnancies that booked at our unit at 11-13 weeks' gestation. Univariate and multivariate logistic regression analysis was carried out to determine risks of complications in pregnancies with type 1 and type 2 DM after adjusting for maternal and pregnancy characteristics. Effect sizes were expressed as absolute risks (AR) and odds ratio (OR) (95 % confidence intervals [CI]). RESULTS: The study population included 53,649 singleton pregnancies, including 509 (1.0 %) with pre-existing DM and 49,122 (99.0 %) without diabetes. Multivariate logistic regression analysis demonstrated that there was a significant contribution from pre-existing DM in prediction of adverse outcomes, including antenatal complications such as fetal defects, stillbirth, preterm delivery, polyhydramnios, preeclampsia and delivery of large for gestational age (LGA) neonates; intrapartum complications such as caesarean delivery (CS) and post-partum haemorrhage; and neonatal complications including admission to neonatal intensive care unit, hypoglycaemia, jaundice and hypoxic ischaemic encephalopathy (HIE). In particular, there was a 5-fold increased risk of stillbirth and HIE. CONCLUSIONS: The maternal and neonatal complications in pregnancies with pre-existing DM are significantly increased compared to those without DM despite a decade of intensive multidisciplinary antenatal care. Further research is required to investigate strategies and interventions to prevent morbidity and mortality in pregnancies with pre-gestational DM.

Placental growth factor testing at 19-23 weeks of gestation as a guide to subsequent care in pregnancy: A prospective observational study.

OBJECTIVE: To determine whether serum placental growth factor (PlGF) at 19-23 weeks of gestation can improve the identification of risk for adverse outcomes. DESIGN: Prospective observational cohort study. SETTING: Two English maternity units. POPULATION: Unselected singleton pregnancies attending routine ultrasound at 19-23 weeks of gestation. METHODS: Outcomes ascertained by health record review. Diagnostic test properties evaluated clinical risk factors for pre-eclampsia (according to National Institute of Care Excellence) or fetal growth restriction (according to Royal College of Obstetricians and Gynaecologists), low PlGF at 19-23 weeks of gestation (<5th percentile) or both. MAIN OUTCOME MEASURES: Pre-eclampsia, gestational hypertension, stillbirth, birthweight below third percentile or neonatal intensive care unit (NICU) admission for ≥48 h. RESULTS: In 30 013 pregnancies, risk factors were present in 9941 (33.1%), low PlGF was present in 1501 (5.0%) and both ('two-stage' screening) were present in 547 (1.8%) pregnancies. Risk factors detected 41.7%-54.7% of adverse outcomes, and could not meaningfully revise the risk (all positive likelihood ratios, +LR, <5.0; all negative likelihood ratios, -LR, ≥0.2). Low PlGF detected 8.5%-17.4% of adverse outcomes, but meaningfully increased risks (other than NICU admission) associated with delivery <37 weeks of gestation (+LR = 5.03-15.55); all -LRs were ≥0.2. 'Two-stage' screening detected 4.2%-8.9% of adverse outcomes, with meaningful +LRs (6.28-18.61) at <37 weeks of gestation, except for NICU admission of ≥48 h, which had an +LR of 7.56 at <34 weeks of gestation; all -LRs were ≥0.2. No screening strategy meaningfully increased or decreased the detection of adverse outcome risk at term. CONCLUSIONS: Clinical risk factor screening has a high screen-positive rate and a poor detection of adverse outcomes. False positives cannot be reduced by PlGF testing at 19-23 weeks of gestation; therefore, this cannot be recommended as a useful strategy on its own.

Relation of antepartum stillbirth to birthweight and gestational age: Prospective cohort study.

OBJECTIVES: To investigate the incidence of antepartum stillbirth in relation to the distribution of neonatal/fetal weight for different gestational ages. DESIGN: Prospective observational cohort study. SETTING: Obstetric ultrasound departments in two UK maternity hospitals. POPULATION: 168 966 women with singleton pregnancies attending for routine antenatal care. METHODS: We examined the incidence of antepartum stillbirths, within different birthweight and fetal weight percentile subgroups, conditioning for gestational age. MAIN OUTCOME MEASURES: Incidence of antepartum stillbirth. RESULTS: The risk of stillbirth progressively increased for lower birthweight. Considering the 25-75th percentile as the reference category, the relative risks for stillbirth at <37 weeks' gestation were 7.6 (95% confidence interval [CI] 5.7-10.2) <1st percentile, 2.6 (95% CI 1.8-3.7) 1 to 10th percentile, 1.4 (95% CI 0.9-2.1) 10 to 25th percentile, 0.8 (95% CI 0.4-1.5) 75 to 90th percentile, 0.8 (95% CI 0.4-1.7) 90 to 99th percentile, 0.9 (95% CI 0.3-2.5) >99th percentile. The respective values for births at ≥37 weeks' gestation were 5.0 (95% CI 2.9-8.9), 2.1 (95% CI 1.4-3.3), 1.4 (95% CI 0.9-2.1), 1.2 (95% CI 0.7-1.8), 1.0 (95% CI 0.6-1.8) and 4.0 (95% CI 1.8-9.3). The incidence of stillbirth in ongoing low-risk singleton pregnancies gradually increases for smaller fetuses at any gestational point. The higher incidence (5.56%) was evident for fetal weight <1st percentile between 24 and 28 weeks' gestation. CONCLUSION: Fetal weight and the weight of the stillborn have a continuous association with the incidence of antepartum stillbirth which is affected by gestational age.

Gestational Diabetes Mellitus: Association with Maternal and Neonatal Complications.

Background and objectives: Gestational diabetes mellitus (GDM) is known to be associated with pregnancy complications but there is limited evidence about the strength of these associations in recent clinical practice, especially after the introduction of strict guidelines for the management of pregnancies with GDM in a multidisciplinary team setting. The objectives of our study were to first compare the rates of complications in pregnancies with GDM with those that had pre-existing diabetes mellitus and those without diabetes; and second, to derive measures of effect size expressed as odds ratios after adjustment for confounding factors to assess the independent association of GDM in prediction of these pregnancy complications. Materials and Methods: This was a prospective cohort study undertaken at a large maternity unit in the United Kingdom between January 2010 and June 2022. We included singleton pregnancies that were booked at our unit at 11-13 weeks' gestation. Multivariate regression analysis was carried out to determine the risks of complications in pregnancies with GDM after adjusting for pregnancy characteristics. Risks were expressed as odds ratio (OR) (95% confidence intervals [CI]) and expressed graphically in forest plots. Results: The study population included 53,649 singleton pregnancies including 509 (1%) with pre-existing DM, 2089 (4%) with GDM and 49,122 (95%) pregnancies without diabetes. Multivariate regression analysis demonstrated that there was a significant independent contribution from GDM in the prediction of adverse outcomes, including maternal complications such as preterm delivery, polyhydramnios, preeclampsia and delivery of large for gestational age neonates and elective caesarean section (CS); and neonatal complications including admission to neonatal intensive care unit, hypoglycaemia, jaundice and respiratory distress syndrome. Conclusions: GDM is associated with an increased rate of pregnancy complications compared to those without diabetes, even after adjustment for maternal and pregnancy characteristics. GDM does not increase the risk of stillbirth, hypoxic ischaemic encephalopathy or neonatal death.

Management of preterm labor: Clinical practice guideline and recommendation by the WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine Foundation.

This practice guideline follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation, bringing together groups and individuals throughout the world, with the goal of improving the management of preterm labor. In fact, this document provides further guidance for healthcare practitioners on the appropriate use of examinations with the aim to improve the accuracy in diagnosing preterm labor and allow timely and appropriate administration of tocolytics, antenatal corticosteroids and magnesium sulphate and avoid unnecessary or excessive interventions. Therefore, it is not intended to establish a legal standard of care. This document is based on consensus among perinatal experts throughout the world in the light of scientific literature and serves as a guideline for use in clinical practice.

Efficiency of the Cerebroplacental Ratio in Identifying High-Risk Late-Term Pregnancies.

Background and Objectives: Over the last few years, great interest has arisen in the role of the cerebroplacental ratio (CPR) to identify low-risk pregnancies at higher risk of adverse pregnancy outcomes. This study aimed to assess the predictive capacity of the CPR for adverse perinatal outcomes in all uncomplicated singleton pregnancies attending an appointment at 40-42 weeks. Materials and Methods: This is a retrospective cohort study including all consecutive singleton pregnancies undergoing a routine prenatal care appointment after 40 weeks in three maternity units in Spain and the United Kingdom from January 2017 to December 2019. The primary outcome was adverse perinatal outcomes defined as stillbirth or neonatal death, cesarean section or instrumental delivery due to fetal distress during labor, umbilical arterial cord blood pH < 7.0, umbilical venous cord blood pH < 7.1, Apgar score at 5 min < 7, and admission to the neonatal unit. Logistic mixed models and ROC curve analyses were used to analyze the data. Results: A total of 3143 pregnancies were analyzed, including 537 (17.1%) with an adverse perinatal outcome. Maternal age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01 to 1.04), body mass index (OR 1.04, 95% CI 1.03 to 1.06), racial origin (OR 2.80, 95% CI 1.90 to 4.12), parity (OR 0.36, 95% CI 0.29 to 0.45), and labor induction (OR 1.79, 95% CI 1.36 to 2.35) were significant predictors of adverse perinatal outcomes with an area under the ROC curve of 0.743 (95% CI 0.720 to 0.766). The addition of the CPR to the previous model did not improve performance. Additionally, the CPR alone achieved a detection rate of only 11.9% (95% CI 9.3 to 15) when using the 10th centile as the screen-positive cutoff. Conclusions: Our data on late-term unselected pregnancies suggest that the CPR is a poor predictor of adverse perinatal outcomes.

Incidence of vasa praevia: a systematic review and meta-analysis.

OBJECTIVES: To derive accurate estimates of the incidence of vasa praevia (VP) in a routine population of unselected pregnancies. DESIGN: Systematic review and meta-analysis. DATA SOURCES: A search of MEDLINE, EMBASE, CINAHL and the Cochrane database was performed to review relevant citations reporting outcomes in pregnancies with VP from January 2000 until 5 April 2023. ELIGIBILITY CRITERIA FOR SELECTION OF STUDIES: Prospective or retrospective cohort or population studies that provided data regarding VP cases in routine unselected pregnancies during the study period. We included studies published in the English language after the year 2000 to reflect contemporary obstetric and neonatal practice. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the retrieved citations and extracted data. The methodological quality of studies was assessed using the Newcastle-Ottawa Scale, and Preferred Reporting Items for Systematic reviews and Meta-Analyses was used to ensure standardised reporting of studies. RESULTS: A total of 3847 citations were screened and 82 full-text manuscripts were retrieved for analysis. There were 24 studies that met the inclusion criteria, of which 12 studies reported prenatal diagnosis with a systematic protocol of screening. There were 1320 pregnancies with VP in a total population of 2 278 561 pregnancies; the weighted pooled incidence of VP was 0.79 (95% CI: 0.59 to 1.01) per 1000 pregnancies, corresponding to 1 case of VP per 1271 (95% CI: 990 to 1692) pregnancies. Nested subanalysis of studies reporting screening for VP based on a specific protocol identified 395 pregnancies with VP in a population of 732 654 pregnancies with weighted pooled incidence of 0.82 (95% CI: 0.53 to 1.18) per 1000 pregnancies (1 case of VP per 1218 (95% CI: 847 to 1901) pregnancies). CONCLUSION: The incidence of VP in unselected pregnancies is 1 in 1218 pregnancies. This is higher than is previously reported and can be used as a basis to assess whether screening for this condition should be part of routine clinical practice. Incorporation of strategies to screen for VP in routine clinical practice is likely to prevent 5% of stillbirths. PROSPERO REGISTRATION NUMBER: CRD42020125495.

Preeclampsia Prevention by Timed Birth at Term.

BACKGROUND: Most preeclampsia occurs at term. There are no effective preventative strategies. We aimed to identify the optimal preeclampsia screening and timing of birth strategy for prevention of term preeclampsia. METHODS: This secondary analysis was of data from a prospective nonintervention cohort study of singleton pregnancies delivering at ≥24 weeks, without major anomalies, at 2 United Kingdom maternity hospitals. At routine visits at 11 to 13 weeks' (57 131 pregnancies screened, 1138 term preeclampsia developed) or 35 to 36 weeks' gestation (29 035 pregnancies screened, 619 term preeclampsia), with patient-specific preeclampsia risks determined by: United Kingdom National Institute for Health and Care Excellence guidance, and the Fetal Medicine Foundation competing-risks model. For each screening strategy, timing of birth for term preeclampsia prevention was evaluated at gestational time points that were fixed (37, 38, 39, 40 weeks) or dependent on preeclampsia risk by the competing-risks model at 35 to 36 weeks. Main outcomes were proportion of term preeclampsia prevented, and number-needed-to-deliver to prevent one term preeclampsia case. RESULTS: The proportion of term preeclampsia prevented was the highest, and number-needed-to-deliver lowest, for preeclampsia screening at 35 to 36 (rather than 11-13) weeks. For delivery at 37 weeks, fewer cases of preeclampsia were prevented for National Institute for Health and Care Excellence (28.8%) than the competing-risks model (59.8%), and the number-needed-to-deliver was higher (16.4 versus 6.9, respectively). The risk-stratified approach (at 35-36 weeks) had similar preeclampsia prevention (by 57.2%) and number-needed-to-deliver (8.4), but fewer women would be induced at 37 weeks (1.2% versus 8.8%). CONCLUSIONS: Risk-stratified timing of birth at term may more than halve the risk of term preeclampsia.

Personalized stratification of pregnancy care for small for gestational age neonates from biophysical markers at midgestation.

BACKGROUND: Antenatal identification of pregnancies at high risk of delivering small for gestational age neonates may improve the management of the condition and reduce the associated adverse perinatal outcomes. In a series of publications, we have developed a new competing-risks model for small for gestational age prediction, and we demonstrated that the new approach has a superior performance to that of the traditional methods. The next step in shaping the appropriate management of small for gestational age is the timely assessment of these high-risk pregnancies according to an antenatal stratification plan. OBJECTIVE: This study aimed to demonstrate the stratification of pregnancy care based on individual patient risk derived from the application of the competing-risks model for small for gestational age that combines maternal factors with sonographic estimated fetal weight and uterine artery pulsatility index at midgestation. STUDY DESIGN: This was a prospective observational study of 96,678 singleton pregnancies undergoing routine ultrasound examination at 19 to 24 weeks of gestation, which included recording of estimated fetal weight and measurement of uterine artery pulsatility index. The competing-risks model for small for gestational age was used to create a patient-specific stratification curve capable to define a specific timing for a repeated ultrasound examination after 24 weeks. We examined different stratification plans with the intention of detecting approximately 80%, 85%, 90%, and 95% of small for gestational age neonates with birthweight <3rd and <10th percentiles at any gestational age at delivery until 36 weeks; all pregnancies would be offered a routine ultrasound examination at 36 weeks. RESULTS: The stratification of pregnancy care for small for gestational age can be based on a patient-specific stratification curve. Factors from maternal history, low estimated fetal weight, and increased uterine artery pulsatility index shift the personalized risk curve toward higher risks. The degree of shifting defines the timing for assessment for each pregnancy. If the objective of our antenatal plan was to detect 80%, 85%, 90%, and 95% of small for gestational age neonates at any gestational age at delivery until 36 weeks, the median (range) proportions (percentages) of population examined per week would be 3.15 (1.9-3.7), 3.85 (2.7-4.5), 4.75 (4.0-5.4), and 6.45 (3.7-8.0) for small for gestational age <3rd percentile and 3.8 (2.5-4.6), 4.6 (3.6-5.4), 5.7 (3.8-6.4), and 7.35 (3.3-9.8) for small for gestational age <10th percentile, respectively. CONCLUSION: The competing-risks model provides an effective personalized continuous stratification of pregnancy care for small for gestational age which is based on individual characteristics and biophysical marker levels recorded at the midgestation scan.

Maternal and neonatal complications following Kielland's rotational forceps delivery: A systematic review and meta-analysis.

BACKGROUND: There is conflicting evidence regarding the safety of Kielland's rotational forceps delivery (KRFD) in comparison with other modes of delivery for the management of persistent fetal malposition in the second stage of labour. OBJECTIVES: To derive estimates of risks of maternal and neonatal complications following KRFD, compared with rotational ventouse delivery (RVD), non-rotational forceps delivery (NRFD) or a second-stage caesarean section (CS), from a systematic review and meta-analysis of the literature. SEARCH STRATEGY: Standard search methodology, as recommended by the Cochrane Handbook for Systematic Reviews of Interventions. SELECTION CRITERIA: Case series, prospective or retrospective cohort studies and population-based studies. DATA COLLECTION AND ANALYSIS: A meta-analysis using a random-effects model was used to derive weighted pooled estimates of maternal and neonatal complications. MAIN RESULTS: Thirteen studies were included. For postpartum haemorrhage there was no significant difference between Kielland's and ventouse delivery; the rate was lower in Kielland's delivery compared with non-rotational forceps (RR 0.79, 95% CI 0.65-0.95) and second-stage CS (RR 0.45, 95% CI 0.36-0.58). There were no differences in the rates of anal sphincter injuries or admission to neonatal intensive care. Rates of shoulder dystocia were higher with Kielland's delivery compared with ventouse delivery (RR 1.79, 95% CI 1.08-2.98), but rates of neonatal birth trauma were lower (RR 0.49, 95% CI 0.26-0.91). There were no differences seen in the rates of 5-min APGAR score < 7 between Kielland's delivery and other instrumental births, but they were lower when compared with second-stage CS (RR 0.47, 95% CI 0.23-0.97). CONCLUSIONS: Kielland's rotational forceps delivery is a safe option for the management of fetal malposition in the second stage of labour.

Preterm and term pre-eclampsia: Relative burdens of maternal and perinatal complications.

OBJECTIVE: To determine the relative burdens of maternal and perinatal complications for preterm and term pre-eclampsia. DESIGN: Prospective observational cohort study. SETTING: Two English maternity units. POPULATION: Unselected women with singleton pregnancies who developed pre-eclampsia (International Society for the Study of Hypertension in Pregnancy definition). METHODS: Outcomes were ascertained by health record review and compared between pregnancies with preterm (versus term) pre-eclampsia. MAIN OUTCOME MEASURES: Severe maternal hypertension, maternal mortality or major maternal morbidity, perinatal mortality or major neonatal morbidity, neonatal unit (NNU) admission ≥48 hours, and birthweight <3rd percentile. RESULTS: Among 40 241 singleton pregnancies, 298 (0.7%, 95% confidence interval [CI] 0.66-0.83) and 1194 (3.0%, 95% CI 2.8-3.1) developed preterm and term pre-eclampsia, respectively. Women with preterm (versus term) pre-eclampsia more commonly experienced adverse maternal or perinatal events: severe hypertension 18.5% (95% CI 14.5-23.3) versus 13.6% (95% CI 11.7-15.6); maternal mortality/major morbidity 7.4% (95% CI 4.9-10.9) versus 2.2% (95% CI 1.5-3.2); perinatal mortality/major neonatal morbidity 29.5% (95% CI 24.6-34.9) versus 2.2% (95% CI 1.5-3.2); and birthweight <3rd percentile 54.4% (95% CI 48.7-59.9) versus 14.2% (95% CI 12.4-16.3). However, in absolute terms, most maternal complications occurred in women with term pre-eclampsia, as did a large proportion of perinatal complications: severe hypertension 74.7% (95% CI 68.5-80.0); maternal mortality/major morbidity 54.2% (95% CI 40.3-67.4); perinatal mortality/major neonatal morbidity 22.8% (95% CI 16.1-31.3); NNU admission ≥48 hours 38.1% (95% CI 32.4-44.1); and birthweight <3rd percentile 51.2% (95% CI 45.8-56.5). CONCLUSIONS: Although adverse event risks are greater with preterm (versus term) pre-eclampsia, term disease is associated with at least equivalent total numbers of maternal, and a significant proportion of perinatal, adverse events. Increased efforts should be made to decrease the incidence of term pre-eclampsia.

The implications of the Fetal Medicine Foundation 35- to 36-week preeclampsia prediction competing-risk model on timing of birth.

BACKGROUND: Preeclampsia is associated with increased risks of life-threatening, -altering, and -ending complications. Assessment of risk for preeclampsia at 35 to 36 weeks' gestation by the Fetal Medicine Foundation 36-week competing-risk model identifies approximately 75% of women who will develop term preeclampsia, at a 10% screen-positive rate. OBJECTIVE: This study aimed to assess whether the Fetal Medicine Foundation 36-week model can provide personalized guidance to women about the probable timing of their delivery, whether or not they develop pregnancy hypertension. STUDY DESIGN: In this prospective nonintervention screening study at 2 maternity hospitals in England, women who did not have preeclampsia (American College of Obstetricians and Gynecologists definition) and were attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation underwent assessment of risk for preeclampsia, including maternal demographic characteristics, medical history, mean arterial pressure, and serum placental growth factor and soluble fms-like tyrosine kinase-1. Fetal Medicine Foundation 36-week model risk categories for subsequent preeclampsia were defined as: A, ≥0.500; B, 0.20 to 0.499; C, 0.05 to 0.199; D, 0.020 to 0.049; and E, <0.020. Obstetrical records were examined for all women to identify their gestational age at delivery, and whether they experienced a spontaneous onset of labor (irrespective of mode of delivery) or had a medically indicated birth (either induction of labor or unlabored cesarean delivery). The cumulative incidence of delivery and risk ratios, for all deliveries and for spontaneous deliveries, was assessed. RESULTS: Among 29,035 women with singleton pregnancies, 1.0%, 2.9%, 3.3%, 5.0%, 9.9%, and 77.9% were in A, B, C, D, and E risk strata, respectively. In the A (vs E) stratum, 71.95% (vs 33.52%) of births were medically indicated. Compared with women in stratum E, women in higher risk strata were more likely to deliver, and to deliver following spontaneous labor, before their due date. For example, of the women in stratum A (vs E), 14.2% (vs 1.1%; risk ratio, 12.5 [95% confidence interval, 9.45-15.35]), 48.5% (vs 5.1%; risk ratio, 8.47 [7.48-9.35]), 69.6% (vs 15.5%; risk ratio, 3.86 [3.59-4.08]), and 90.1% (vs 44.8%; risk ratio, 6.72 [4.53-9.95]) gave birth before 37 0/7, 38 0/7, 39 0/7, and 40 0/7 weeks, respectively. For women in stratum A (vs E), when censored for medically indicated births, spontaneous labor occurred more commonly before 37 0/7 (risk ratio, 4.31 [1.99-6.57]), 38 0/7 (risk ratio, 3.71 [2.48-4.88]), 39 0/7 (risk ratio, 2.87 [2.22-3.46]), and 40 0/7 (risk ratio, 1.42 [1.14-1.77]) weeks. CONCLUSION: Women in higher-risk strata gave birth earlier, and more frequently following medically indicated delivery, compared with those in lower-risk strata. Importantly, the proportion of women who gave birth following spontaneous onset of labor before their due date was also greater in higher-risk than in lower-risk women. The Fetal Medicine Foundation 36-week competing-risk model incorporates biomarkers of placental aging, including angiogenic imbalance; these results imply that a fetoplacental response to placental aging may be an important trigger for the onset of labor at term.

Effect of race on the measurement of angiogenic factors for prediction and diagnosis of pre-eclampsia.

OBJECTIVE: To examine the effect of self-declared race on serum placental growth factor (PlGF) and sFlt-1/PlGF ratio and the impact on pre-eclampsia (PE) prediction. DESIGN: Prospective observational study. SETTING: Two UK maternity hospitals. POPULATION: 29 035 women with singleton pregnancies attending a routine 35+0 to 36+6 weeks' gestation hospital visit, including 654 (2.3%) who subsequently developed PE. METHODS: The predictive performance of PlGF and sFlt-1/PlGF for PE in minority racial groups (versus white) was examined. MAIN OUTCOME MEASURE: Delivery with PE. RESULTS: Compared with white women, mean PlGF was higher and sFlt-1/PlGF ratio lower in black, South Asian, East Asian and mixed race women. In white women at a PlGF concentration cut-off corresponding to a screen-positive rate (SPR) of 10%, detection rates (DRs) were 49.1% for PE at any time and 72.3% for PE within 2 weeks after screening. In black women, at the same PlGF concentration cut-off for white women, the SPR was 5.5%, and DRs 33.6% and 55.0%, respectively; the number of PE cases was too small to evaluate screening performance in other racial groups. Using a fixed cut-off in sFlt-1/PlGF ratio to identify women at risk of developing PE, similarly diagnostically disadvantaged black women. Bias was overcome by adjusting metabolite concentrations for maternal characteristics and use of the competing risks model to estimate patient-specific risks. CONCLUSION: Screening for PE with fixed cut-offs in PlGF or sFlt-1/PlGF diagnostically disadvantages black women. It is essential that measured levels of PlGF be adjusted for race as well as other maternal characteristics.

Thrombophilia screening in women with recurrent first trimester miscarriage: is it time to stop testing? - a cohort study and systematic review of the literature.

OBJECTIVE: There are numerous studies reporting a disproportionally high prevalence of thrombophilia in women with a history of recurrent miscarriage (RM), which has led to overdiagnosis and treatment without an improvement in clinical outcomes. The objective of our study was to assess the prevalence of inherited and acquired thrombophilia in a large cohort of women with a history of early RM using internationally agreed diagnostic criteria and inclusion parameters and compare it to the meta-analysis results of existing literature. METHODS: DESIGN: Retrospective cohort study and systematic review of literature. SETTING: This is a retrospective cohort study set-up in two dedicated tertiary centres for women with RM in Southwest London and Surrey. We reviewed all the available literature related to causes of RMs. We ascertained the prevalence of thrombophilia in the study population and compared it with historical and published prevalence in the general population. PARTICIPANTS: 1155 women between 2012 and 2017. All patients had three or more first trimester miscarriages and a full thrombophilia screen. RESULTS: The overall prevalence of thrombophilia in our study population is 9.2% (106/1155) with 8.1% (94/1155) of cases positive for inherited thrombophilia, which is similar to the general population; Factor V Leiden (4.9%; 57/1155) and prothrombin gene mutation (2.9%; 34/1155) were the most common inherited thrombophilias, while only 1% (12/1155) tested positive for acquired thrombophilia. Persistent positive lupus anticoagulant (LA) was found in 0.5% (6/1155) and persistent positive anticardiolipin (ACL) antibodies with a value ≥40 U/mL was found in 0.5% (6/1155) of patients. Tests for LA/ACL were performed a minimum of 12 weeks apart thus meeting the revised Sapporo criteria for a diagnosis of antiphospholipid syndrome. CONCLUSION: The findings of our study demonstrate that the prevalence of inherited thrombophilia is similar in women with RM to that in the general population. Similarly, the prevalence of acquired thrombophilia, using the revised Sapporo criteria, in the cohort of RMs is similar to that in the general population. Therefore, we do not recommend investigation or treatment of inherited or acquired thrombophilia in women with RM. PROSPERO REGISTRATION NUMBER: CRD42020223554.

Maternal Race and Stillbirth: Cohort Study and Systematic Review with Meta-Analysis.

Accurate identification of independent predictors of stillbirth is needed to define preventive strategies. We aim to examine the independent contribution of maternal race in the risk of stillbirth after adjusting for maternal characteristics and medical history. There are two components to the study: first, prospective screening in 168,966 women with singleton pregnancies coordinated by the Fetal Medicine Foundation (FMF) and second, a systematic review and meta-analysis of studies reporting on race and stillbirth. In the FMF study, logistic regression analysis found that in black women, the risk of stillbirth, after adjustment for confounders, was higher than in white women (odds ratio 1.78, 95% confidence interval 1.50 to 2.11). The risk for other racial groups was not significantly different. The literature search identified 20 studies that provided data on over 6,500,000 pregnancies, but only 10 studies provided risks adjusted for some maternal characteristics; consequently, the majority of these studies did not provide accurate contribution of different racial groups to the prediction of stillbirth. It is concluded that in women of black origin, the risk of stillbirth, after adjustment for confounders, is about twofold higher than in white women. Consequently, closer surveillance should be granted for these women.