Fetal lower urinary tract obstruction: international Delphi consensus on management and core outcomes set.

OBJECTIVE: To reach a Delphi-generated international expert consensus on the diagnosis, prognostic, management, and core outcome set (COS) of fetal Lower Urinary Tract Obstruction (LUTO). METHODS: A three-round Delphi procedure was conducted among an international panel of LUTO experts. The panel was provided with a list of literature review-generated parameters for the diagnosis, prognostic, management, and outcomes. A parallel procedure was conducted along with patient groups during the development of COS. RESULTS: A total of 160 experts were approached, of whom 99 completed the first round and 80 (80/99, 80.8%) completed all three rounds. In the first trimester, an objective measurement of longitudinal bladder diameter (with ≥7 mm being abnormal) should be used to suspect LUTO. In the second trimester, imaging parameters of LUTO could include: a) an enlarged bladder, b) a keyhole sign, c) bladder wall thickening, d) bilateral hydro (uretero) nephrosis, and e) male sex. There was a lack of consensus on the current prognostic scoring literature. However, experts agreed on the value of amniotic fluid volume (< 24 weeks) to predict survival and that the value of fetal intervention is to improve neonatal survival. While experts endorsed the role of sonographic parameters of renal dysplasia, at least one vesicocentesis, and urine biochemistry for prognosis and counseling, these items did not reach a consensus for determining fetal intervention candidacy. On the other hand, imaging parameters suggestive of LUTO, absence of life-limiting structural or genetic anomalies, gestational age of ≥16 weeks, and oligohydramnios defined as deepest vertical pocket (DVP) <2 cm should be used as candidacy criteria for fetal intervention based on experts' consensus. If a bladder refill was evaluated, it should be assessed subjectively. Vesicoamniotic shunt should be the first line of fetal intervention. In the presence of suspected fetal renal failure, serial amnioinfusion should only be offered as an experimental procedure under research protocols. The core outcome set for future studies was agreed upon. CONCLUSION: International consensus on the diagnosis, prognosis, and management of fetal LUTO, as well as the Core Outcome Set, should inform clinical care and research to optimize perinatal outcomes. This article is protected by copyright. All rights reserved.

Epidural analgesia and emergency delivery for presumed fetal compromise: post-hoc analysis of RAVEL multicenter randomized controlled trial.

OBJECTIVE: To investigate the association between epidural analgesia (EDA) vs patient-controlled remifentanil analgesia (PCRA) and emergency delivery for presumed fetal compromise, in relation to birth-weight quintile. METHODS: This was a post-hoc per-protocol analysis of the RAVEL multicenter equivalence randomized controlled trial. Non-anomalous singleton pregnancies between 36 + 0 and 42 + 6 weeks' gestation were randomized at the time of requesting pain relief to receive EDA or PCRA. The primary outcome was emergency delivery for presumed fetal compromise. Secondary outcomes included mode of delivery and neonatal outcomes. Analysis was performed according to birth-weight quintile and was corrected for relevant confounding variables. RESULTS: Of 619 pregnant women, 336 received PCRA and 283 received EDA. Among women receiving EDA, 14.8% had an emergency delivery for presumed fetal compromise, compared with 8.3% of women who received PCRA. After adjusting for parity, women receiving EDA had higher odds of presumed fetal compromise compared to those receiving PCRA (odds ratio, 1.69 (95% CI, 1.01-2.83)). A statistically significant linear-by-linear association was observed between presumed fetal compromise and birth-weight quintile (P = 0.003). The incidence of emergency delivery for presumed fetal compromise was highest in women receiving EDA and delivering a neonate with a birth weight in the lowest quintile. CONCLUSIONS: Intrapartum EDA is associated with a higher rate of emergency delivery for presumed fetal compromise compared to treatment with PCRA. Birth-weight quintile is a strong predictor of this outcome, independent of pain management method. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Effect of intrapartum epidural analgesia on rate of emergency delivery for presumed fetal compromise: nationwide registry-based cohort study.

OBJECTIVES: To determine the rate of emergency delivery for presumed fetal compromise after epidural analgesia (EDA) compared with that after alternative analgesia or no analgesia, and to assess whether this rate is increased in pregnancies with reduced placental reserve. METHODS: This was a nationwide registry-based cohort study of 629 951 singleton pregnancies delivered at 36 + 0 to 42 + 0 weeks of gestation that were recorded in the Dutch national birth registry between 2014 and 2018, including 120 426 cases that received EDA, 86 957 that received alternative analgesia and 422 568 that received no analgesia during labor. Pregnancies with congenital anomaly, chromosomal abnormality, fetal demise, planned Cesarean delivery, non-cephalic presentation at delivery and use of multiple forms of analgesia were excluded. The primary outcome was emergency delivery for presumed fetal compromise. Secondary outcomes included delivery characteristics and neonatal outcome. Negative binomial regression analysis was stratified by parity and results are presented according to birth-weight centile, after adjusting for confounding. RESULTS: Among women who received EDA, 13.2% underwent emergency delivery for presumed fetal compromise, compared with 4.1% of women who had no analgesia (relative risk (RR), 3.23 (95% CI, 3.16-3.31)) and 7.0% of women who received alternative analgesia (RR, 1.72 (95% CI, 1.67-1.77)). Independent of birth weight, the RR of presumed fetal compromise after EDA vs no analgesia was higher in parous women (adjusted RR (aRR), 2.15 (95% CI, 2.04-2.27)) compared with nulliparous women (RR, 1.88 (95% CI, 1.84-1.94)). Stratified for parity, the effect of EDA was modified significantly by birth-weight centile (interaction P-value, < 0.001 for nulliparous and 0.004 for parous women). The emergency delivery rate following EDA was highest in those with a birth weight < 5th centile (25.2% of nulliparous and 16.6% of parous women), falling with each increasing birth-weight centile category up to the 91st -95th centile (11.8% of nulliparous and 7.2% of parous women). CONCLUSIONS: Intrapartum EDA is associated with a higher risk of emergency delivery for presumed fetal compromise compared with no analgesia and alternative analgesia, after adjusting for relevant confounding. The highest rate of emergency delivery for presumed fetal compromise was observed at the lowest birth-weight centiles. RRs of emergency delivery for presumed fetal compromise after EDA were modestly but consistently modified by birth-weight centile, supporting the hypothesis that the adverse effects of EDA are exacerbated by reduced placental function. While EDA provides effective pain relief during labor, alternative strategies for pain management may be preferable in pregnancies with a high background risk of fetal compromise. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of fetal and neonatal outcomes after preterm manifestations of placental insufficiency: systematic review of prediction models.

OBJECTIVES: To identify all prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency (gestational hypertension, pre-eclampsia, HELLP syndrome or fetal growth restriction with its onset before 37 weeks' gestation) and to assess the quality of the models and their performance on external validation. METHODS: A systematic literature search was performed in PubMed, Web of Science and EMBASE. Studies describing prediction models for fetal/neonatal mortality or significant neonatal morbidity in patients with preterm placental insufficiency disorders were included. Data extraction was performed using the CHARMS checklist. Risk of bias was assessed using PROBAST. Literature selection and data extraction were performed by two researchers independently. RESULTS: Our literature search yielded 22 491 unique publications. Fourteen were included after full-text screening of 218 articles that remained after initial exclusions. The studies derived a total of 41 prediction models, including four models in the setting of pre-eclampsia or HELLP, two models in the setting of fetal growth restriction and/or pre-eclampsia and 35 models in the setting of fetal growth restriction. None of the models was validated externally, and internal validation was performed in only two studies. The final models contained mainly ultrasound (Doppler) markers as predictors of fetal/neonatal mortality and neonatal morbidity. Discriminative properties were reported for 27/41 models (c-statistic between 0.6 and 0.9). Only two studies presented a calibration plot. The risk of bias was assessed as unclear in one model and high for all other models, mainly owing to the use of inappropriate statistical methods. CONCLUSIONS: We identified 41 prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency. All models were considered to be of low methodological quality, apart from one that had unclear methodological quality. Higher-quality models and external validation studies are needed to inform clinical decision-making based on prediction models. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Predictive value of fetal growth trajectory from 20 weeks of gestation onwards for severe adverse perinatal outcome in low-risk population: secondary analysis of IRIS study.

OBJECTIVES: The placental dysfunction underlying fetal growth restriction (FGR) may result in severe adverse perinatal outcome (SAPO) related to fetal hypoxia. Traditionally, the diagnostic criteria for FGR have been based on fetal size, an approach that is inherently flawed because it often results in either over- or underdiagnosis. The anomaly ultrasound scan at 20 weeks' gestation may be an appropriate time at which to set a benchmark for growth potential of the individual fetus. We hypothesized that the fetal growth trajectory from that point onwards may be informative regarding third-trimester placental dysfunction. The aim of this study was to investigate the predictive value for SAPO of a slow fetal growth trajectory between 18 + 0 to 23 + 6 weeks and 32 + 0 to 36 + 6 weeks' gestation in a large, low-risk population. METHODS: This was a post-hoc data analysis of the IUGR Risk Selection (IRIS) study, a Dutch nationwide cluster-randomized trial assessing the (cost-)effectiveness of routine third-trimester sonography in reducing SAPO. In the current analysis, for the first ultrasound examination we used ultrasound data from the routine anomaly scan at 18 + 0 to 23 + 6 weeks' gestation, and for the second we used data from an ultrasound examination performed between 32 + 0 and 36 + 6 weeks' gestation. Using multilevel logistic regression, we analyzed whether SAPO was predicted by a slow fetal growth trajectory, which was defined as a decline in abdominal circumference (AC) and/or estimated fetal weight (EFW) of more than 20 percentiles or more than 50 percentiles or as an AC growth velocity (ACGV) < 10th percentile (p10). In addition, we analyzed the combination of these indicators of slow fetal growth with small-for-gestational age (SGA) (AC or EFW < p10) and severe SGA (AC/EFW < 3rd percentile) at 32 + 0 to 36 + 6 weeks' gestation. RESULTS: Our sample included the data of 6296 low-risk singleton pregnancies, among which 82 (1.3%) newborns experienced at least one SAPO. Standalone declines in AC or EFW of > 20 or > 50 percentiles or ACGV < p10 were not associated with increased odds of SAPO. EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation combined with a decline in EFW of > 20 percentiles was associated with an increased rate of SAPO. The combination of AC or EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation with ACGV < p10 was also associated with increased odds of SAPO. The odds ratios of these associations were higher if the neonate was SGA at birth. CONCLUSIONS: In a low-risk population, a slow fetal growth trajectory as a standalone criterion does not distinguish adequately between fetuses with FGR and those that are constitutionally small. This absence of association may be a result of diagnostic inaccuracies and/or post-diagnostic (e.g. intervention and selection) biases. We conclude that new approaches to detect placental insufficiency should integrate information from diagnostic tools such as maternal serum biomarkers and Doppler ultrasound measurements. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Birth-weight centile at term and school performance at 12 years of age: linked cohort study.

OBJECTIVE: Birth weight, fetal growth and placental function influence cognitive development. The gradient of these associations is understudied, especially among those with a birth weight considered appropriate-for-gestational age. The aim of this study was to evaluate the associations between birth-weight centile and intellectual development in term/near-term infants across the entire birth-weight spectrum, in order to provide a basis for better understanding of the long-term implications of fetal growth restriction and reduced placental function. METHODS: This was a population-based cohort study of 266 440 liveborn singletons from uncomplicated pregnancies, delivered between 36 and 42 weeks of gestation. Perinatal data were obtained from the Dutch Perinatal Registry over the period 2003-2008 and educational data for children aged approximately 12 years were obtained from Statistics Netherlands over the period 2016-2019. Regression analyses were conducted to assess the association of birth-weight centile with school performance. The primary outcomes were mean school performance score, on a scale of 501-550, and proportion of children who reached higher secondary school level. RESULTS: Mean school performance score increased gradually with increasing birth-weight centile, from 533.6 in the 1st -5th birth-weight-centile group to 536.8 in the 81st -85th birth-weight-centile group. Likewise, the proportion of children at higher secondary school level increased with birth-weight centile, from 43% to 57%. Compared with the 81st -85th birth-weight-centile group, mean school performance score and proportion of children at higher secondary school level were significantly lower in all birth-weight-centile groups below the 80th centile, after adjusting for confounding factors. CONCLUSIONS: Birth-weight centile is associated positively with school performance at 12 years of age across the entire birth-weight spectrum, well beyond the conventional and arbitrary cut-offs for suspected fetal growth restriction. This underlines the importance of developing better tools to diagnose fetal growth restriction and reduced placental function, and to identify those at risk for associated short- and long-term consequences. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction.

PURPOSE: To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). MATERIALS AND METHODS: A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0-36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. RESULTS: 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. CONCLUSION: An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.

Study protocol for a randomized trial on timely delivery versus expectant management in late preterm small for gestational age pregnancies with an abnormal umbilicocerebral ratio (UCR): the DRIGITAT study.

BACKGROUND: The clinical inability to correctly identify late fetal growth restriction (FGR) within a group of fetuses who are identified as small for gestational age (SGA) is an everyday problem for all obstetrician-gynecologists. This leads to substantial overtreatment of healthy small fetuses but also inadequate detection of the growth-restricted fetuses that may benefit from timely delivery. Redistribution of the fetal circulation, signaled by an abnormal ratio of the Doppler velocity flow profiles of the umbilical artery and the middle cerebral artery, more specifically an increased umbilicocerebral ratio (UCR) (or its inverse: a decreased cerebroplacental ratio (CPR)), is an adaptation to chronic hypoxemia and nutritional scarcity with long-term consequences in survivors. The relevance of an abnormal UCR has been signaled extensively, and there is a general consensus that it is a signal of FGR, independent of size, with a strong association with poor outcomes. Yet, in the current literature, no comparisons of a monitoring-delivery strategy based on unfavorable UCR have been published. The objective of the Doppler Ratio In fetal Growth restriction Intervention Trial At (near) Term (DRIGITAT) is to evaluate if the timing of the delivery based on an abnormal UCR in late preterm fetuses identified as SGA improves neurodevelopmental outcomes at 2 years of age. METHODS: The DRIGITAT study is a national multicenter cohort study of women with singleton pregnancies between 32 and 37 weeks of gestation identified as SGA, with a nested randomized controlled trial (RCT) in case of an abnormal UCR (> 0.8). Recruiting centers are in The Netherlands. In the nested RCT, women are randomized to either immediate induction of labor or expectant management from 34 weeks in case of severely abnormal size (EFW or FAC < p3) and from 36 weeks in case of mildly abnormal size (EFW or FAC p3-p10). The primary outcome measure is the 7-point average difference in the composite cognitive score (CCS) and composite motor score (CMS) on the Bayley-3 at 2 years. Secondary outcome measures include a composite outcome of neonatal morbidity, perinatal mortality, mode of delivery, maternal quality of life, costs, and predictive value of serum biomarkers. Analyses will be by intention to treat. The required sample size is determined for the nested RCT as 185 patients. DISCUSSION: This study will provide insight into the diagnostic efficacy of UCR measurement in the evaluation of SGA fetuses in order to differentiate the healthy SGA fetus from the growth-restricted fetus and to determine if a fetus with abnormal UCR benefits from early delivery. TRIAL REGISTRATION: Healthcare Evaluation Netherlands NTR6663 . Registered on 14 August 2017.

Pregnancy outcomes in women with Budd-Chiari syndrome or portal vein thrombosis - a multicentre retrospective cohort study.

OBJECTIVE: To evaluate current practice and outcomes of pregnancy in women previously diagnosed with Budd-Chiari syndrome and/or portal vein thrombosis, with and without concomitant portal hypertension. DESIGN AND SETTING: Multicentre retrospective cohort study between 2008 and 2021. POPULATION: Women who conceived in the predefined period after the diagnosis of Budd-Chiari syndrome and/or portal vein thrombosis. METHODS AND MAIN OUTCOME MEASURES: We collected data on diagnosis and clinical features. The primary outcomes were maternal mortality and live birth rate. Secondary outcomes included maternal, neonatal and obstetric complications. RESULTS: Forty-five women (12 Budd-Chiari syndrome, 33 portal vein thrombosis; 76 pregnancies) were included. Underlying prothrombotic disorders were present in 23 of the 45 women (51%). Thirty-eight women (84%) received low-molecular-weight heparin during pregnancy. Of 45 first pregnancies, 11 (24%) ended in pregnancy loss and 34 (76%) resulted in live birth of which 27 were at term (79% of live births and 60% of pregnancies). No maternal deaths were observed; one woman developed pulmonary embolism during pregnancy and two women (4%) had variceal bleeding requiring intervention. CONCLUSIONS: The high number of term live births (79%) and lower than expected risk of pregnancy-related maternal and neonatal morbidity in our cohort suggest that Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contraindication for pregnancy. Individualised, nuanced counselling and a multidisciplinary pregnancy surveillance approach are essential in this patient population. TWEETABLE ABSTRACT: Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contraindication for pregnancy.

The windsor definition for hyperemesis gravidarum: A multistakeholder international consensus definition.

OBJECTIVE: To develop an international definition for hyperemesis gravidarum to assist in clinical diagnosis and harmonize hyperemesis gravidarum definition for study populations. STUDY DESIGN: A mixed-methods approach was used to identify potential hyperemesis gravidarum definition criteria (i.e. systematic review, semi-structured interviews and closed group sessions with patients and Project Steering Committee input). To reach consensus on the definition we used a web-based Delphi survey with two rounds, followed by a face-to-face consensus development meeting, held in Windsor UK, and a web-based consultation round, in which the provisional hyperemesis gravidarum definition was fed back to the stakeholders. Four stakeholder groups were identified 1) researchers; 2) women with lived experience of hyperemesis gravidarum and their families; 3) obstetric health professionals (obstetricians, gynecologists, midwives); and 4) other health professionals involved in care for women with hyperemesis gravidarum (general practitioners, dieticians, nurses). To reflect the opinions of the international community, stakeholders from countries in all global regions were invited to participate. RESULTS: Twenty-one identified potential criteria entered the Delphi survey. Of the 277 stakeholders invited, 178 completed round one, and 125 (70%) also completed round two. Twenty stakeholders attended the consensus development meeting, representing all stakeholder groups. The consultation round was completed by 96 (54%) stakeholders, of which 92% agreed with the definition as presented. The consensus definition for hyperemesis gravidarum consisted of: start of symptoms in early pregnancy (before 16 weeks gestational age); nausea and vomiting, at least one of which severe; inability to eat and/or drink normally; strongly limits daily living activities. Signs of dehydration were deemed contributory for the definition for hyperemesis gravidarum. CONCLUSIONS: The proposed definition for hyperemesis gravidarum will help clinical studies to achieve more uniformity, and ultimately increasing the value of evidence to inform patient care.

Cerebroplacental ratio in predicting adverse perinatal outcome: a meta-analysis of individual participant data.

OBJECTIVE: To investigate if cerebroplacental ratio (CPR) adds to the predictive value of umbilical artery pulsatility index (UA PI) alone - standard of practice - for adverse perinatal outcome in singleton pregnancies. DESIGN AND SETTING: Meta-analysis based on individual participant data (IPD). POPULATION OR SAMPLE: Ten centres provided 17 data sets for 21 661 participants, 18 731 of which could be included. Sample sizes per data set ranged from 207 to 9215 individuals. Patient populations varied from uncomplicated to complicated pregnancies. METHODS: In a collaborative, pooled analysis, we compared the prognostic value of combining CPR with UA PI, versus UA PI only and CPR only, with a one-stage IPD approach. After multiple imputation of missing values, we used multilevel multivariable logistic regression to develop prediction models. We evaluated the classification performance of all models with receiver operating characteristics analysis. We performed subgroup analyses according to gestational age, birthweight centile and estimated fetal weight centile. MAIN OUTCOME MEASURES: Composite adverse perinatal outcome, defined as perinatal death, caesarean section for fetal distress or neonatal unit admission. RESULTS: Adverse outcomes occurred in 3423 (18%) participants. The model with UA PI alone resulted in an area under the curve (AUC) of 0.775 (95% CI 0.709-0.828) and with CPR alone in an AUC of 0.778 (95% CI 0.715-0.831). Addition of CPR to the UA PI model resulted in an increase in the AUC of 0.003 points (0.778, 95% CI 0.714-0.831). These results were consistent across all subgroups. CONCLUSIONS: Cerebroplacental ratio added no predictive value for adverse perinatal outcome beyond UA PI, when assessing singleton pregnancies, irrespective of gestational age or fetal size. TWEETABLE ABSTRACT: Doppler measurement of cerebroplacental ratio in clinical practice has limited added predictive value to umbilical artery alone.

The impact of pre-eclampsia definitions on the identification of adverse outcome risk in hypertensive pregnancy - analyses from the CHIPS trial (Control of Hypertension in Pregnancy Study).

OBJECTIVE: To examine the association between pre-eclampsia definition and pregnancy outcome. DESIGN: Secondary analysis of Control of Hypertension in Pregnancy Study (CHIPS) trial data. SETTING: International multicentre randomised controlled trial (RCT). POPULATION: In all, 987 women with non-severe non-proteinuric pregnancy hypertension. METHODS: We evaluated the association between pre-eclampsia definitions and adverse pregnancy outcomes, stratified by hypertension type and blood pressure control. MAIN OUTCOME MEASURES: Main CHIPS trial outcomes: primary (perinatal loss or high-level neonatal care for >48 hours), secondary (serious maternal complications), birthweight <10th centile, severe maternal hypertension, delivery at <34 or <37 weeks, and maternal hospitalisation before birth. RESULTS: Of 979/987 women with informative data, 280 (28.6%) progressed to pre-eclampsia defined restrictively by new proteinuria, and 471 (48.1%) to pre-eclampsia defined broadly as proteinuria or one/more maternal symptoms, signs or abnormal laboratory tests. The broad (versus restrictive) definition had significantly higher sensitivities (range 62-79% versus 36-50%), lower specificities (range 53-65% versus 72-82%), and similar or higher diagnostic odds ratios and 'true-positive' to 'false-positive' ratios. Stratified analyses showed similar results. Addition of available fetoplacental manifestations (stillbirth or birthweight <10th centile) to the broad pre-eclampsia definition improved sensitivity (74-87%). CONCLUSIONS: A broad (versus restrictive) pre-eclampsia definition better identifies women who develop adverse pregnancy outcomes. These findings should be replicated in a prospective study within routine healthcare to ensure that the anticipated increase in surveillance and intervention in a larger number of women with pre-eclampsia is associated with improved outcomes, reasonable costs and congruence with women's values. TWEETABLE ABSTRACT: A broad (versus restrictive) pre-eclampsia definition better identifies the risk of adverse pregnancy outcomes.

Fetal cerebral Doppler changes and outcome in late preterm fetal growth restriction: prospective cohort study.

OBJECTIVES: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. METHODS: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. RESULTS: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. CONCLUSION: In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

A core outcome set for hyperemesis gravidarum research: an international consensus study.

OBJECTIVE: To develop a core outcome set for trials on the treatment of hyperemesis gravidarum (HG). DESIGN: Identification of outcomes is followed by a modified Delphi survey combined with a consensus development meeting and a consultation round. SETTING: An international web-based survey combined with a consensus development meeting. POPULATION: Stakeholders including researchers; women with lived experience of HG and their families; obstetric health professionals; and other health professionals. METHODS: We used systematic review, semi-structured patient interviews, closed group sessions and Steering Committee input to identify potential core outcomes. We conducted two web-based survey rounds, followed by a face-to-face consensus development meeting and a web-based consultation round. MAIN OUTCOME MEASURES: A core outcome set for research on HG. RESULTS: Fifty-six potential outcomes were identified. The modified Delphi process was completed by 125 stakeholders, the consensus development meeting by 20 stakeholders and the consultation round by 96 stakeholders. Consensus was reached in ten domains on 24 outcomes: nausea; vomiting; inability to tolerate oral fluids or food; dehydration; weight difference; electrolyte imbalance; intravenous fluid treatment; use of medication for hyperemesis gravidarum; hospital treatment; treatment compliance; patient satisfaction; daily functioning; maternal physical or mental or emotional wellbeing; short- and long-term adverse effects of treatment; maternal death; pregnancy complications; considering or actually terminating a wanted pregnancy; preterm birth; small for gestational age; congenital anomalies; neonatal morbidity and offspring death). CONCLUSIONS: This core outcome set will help standardise outcome reporting in HG trials. TWEETABLE ABSTRACT: A core outcome set for treatment of hyperemesis gravidarum in order to create high-quality evidence.

Consensus diagnostic criteria and monitoring of twin anemia-polycythemia sequence: Delphi procedure.

OBJECTIVES: Twin anemia-polycythemia sequence (TAPS) is associated with increased perinatal morbidity and mortality. Inconsistencies in the diagnostic criteria for TAPS exist, which hinder the ability to establish robust evidence-based management or monitoring protocols. The main aim of this study was to determine, by expert consensus using a Delphi procedure, the key diagnostic features and optimal monitoring approach for TAPS. METHODS: A Delphi process was conducted among an international panel of experts on TAPS. Panel members were provided with a list of literature-based parameters for diagnosing and monitoring TAPS. They were asked to rate the importance of the parameters on a five-point Likert scale. Consensus was sought to determine the cut-off values for accepted parameters, as well as parameters used in the monitoring of and assessment of outcome in twin pregnancy complicated by TAPS. RESULTS: A total of 132 experts were approached. Fifty experts joined the first round, of whom 33 (66%) completed all three rounds. There was agreement that the monitoring interval for the development of TAPS should be every 2 weeks and that the severity should be assessed antenatally using a classification system based on middle cerebral artery (MCA) peak systolic velocity (PSV), but there was no agreement on the gestational age at which to start monitoring. Once the diagnosis of TAPS is made, monitoring should be scheduled weekly. For the antenatal diagnosis of TAPS, the combination of MCA-PSV ≥ 1.5 MoM in the anemic twin and ≤ 0.8 MoM in the polycythemic twin was agreed. Alternatively, MCA-PSV discordance ≥ 1 MoM can be used to diagnose TAPS. Postnatally, hemoglobin difference ≥ 8 g/dL and intertwin reticulocyte ratio ≥ 1.7 were agreed criteria for diagnosis of TAPS. There was no agreement on the cut-off of MCA-PSV or its discordance for prenatal intervention. The panel agreed on prioritizing perinatal and long-term survival outcomes in follow-up studies. CONCLUSIONS: Consensus-based diagnostic features of TAPS, as well as cut-off values for the parameters involved, were agreed upon by a panel of experts. Future studies are needed to validate these diagnostic features before they can be used in clinical trials of interventions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.