Modified Delphi study of ultrasound signs associated with placenta accreta spectrum.

OBJECTIVE: To determine, by expert consensus through a modified Delphi process, the role of standardized and new ultrasound signs in the prenatal evaluation of patients at high risk of placenta accreta spectrum (PAS). METHODS: A systematic review of articles providing information on ultrasound imaging signs or markers associated with PAS was performed before the development of questionnaires for the first round of the Delphi process. Only peer-reviewed original research studies in the English language describing one or more new ultrasound sign(s) for the prenatal evaluation of PAS were included. A three-round consensus-building Delphi method was then conducted under the guidance of a steering group, which included nine experts who invited an international panel of experts in obstetric ultrasound imaging in the evaluation of patients at high risk for PAS. Consensus was defined as agreement of ≥ 70% between participants. RESULTS: The systematic review identified 15 articles describing eight new ultrasound signs for the prenatal evaluation of PAS. A total of 35 external experts were approached, of whom 31 agreed and participated in the first round. Thirty external experts (97%) and seven experts from the steering group completed all three Delphi rounds. A consensus was reached that a prior history of at least one Cesarean delivery, myomectomy or PAS should be an indication for detailed PAS ultrasound assessment. The panelists also reached a consensus that seven of the 11 conventional signs of PAS should be included in the examination of high-risk patients and the routine mid-gestation scan report: (1) loss of the 'clear zone', (2) myometrial thinning, (3) bladder-wall interruption, (4) placental bulge, (5) uterovesical hypervascularity, (6) placental lacunae and (7) bridging vessels. A consensus was not reached for any of the eight new signs identified by the systematic review. With respect to other ultrasound features that are not specific to PAS but increase the probability of PAS at birth, the panelists reached a consensus for the finding of anterior placenta previa or placenta previa with cervical involvement. The experts were also asked to determine which PAS signs should be quantified and consensus was reached only for the quantification of placental lacunae using an existing score. For predicting surgical outcome in patients with a high probability of PAS at delivery, a consensus was obtained for loss of the clear zone, bladder-wall interruption, presence of placental lacunae and presence of placenta previa involving the cervix. CONCLUSIONS: We have confirmed the continued importance of seven established standardized ultrasound signs of PAS, highlighted the role of transvaginal ultrasound in evaluating the placental position and anatomy of the cervix, and identified new ultrasound signs that may become useful in the future prenatal evaluation and management of patients at high risk for PAS at birth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal exome sequencing and impact on perinatal outcome: cohort study.

OBJECTIVES: First, to determine the uptake of prenatal exome sequencing (pES) and the diagnostic yield of pathogenic (causative) variants in a UK tertiary fetal medicine unit following the introduction of the NHS England Rapid Exome Sequencing Service for fetal anomalies testing (R21 pathway). Second, to identify how the decision to proceed with pES and identification of a causative variant affect perinatal outcomes, specifically late termination of pregnancy (TOP) at or beyond 22 weeks' gestation. METHODS: This was a retrospective cohort study of anomalous fetuses referred to the Liverpool Women's Hospital Fetal Medicine Unit between 1 March 2021 and 28 February 2022. pES was performed as part of the R21 pathway. Trio exome sequencing was performed using an Illumina next-generation sequencing platform assessing coding and splice regions of a panel of 974 prenatally relevant genes and 231 expert reviewed genes. Data on demographics, phenotype, pES result and perinatal outcome were extracted and compared. Descriptive statistics and the χ-square or Fisher's exact test were performed using IBM SPSS version 28.0.1.0. RESULTS: In total, 72 cases were identified and two-thirds of eligible women (n = 48) consented to trio pES. pES was not feasible in one case owing to a low DNA yield and, therefore, was performed in 47 cases. In one-third of cases (n = 24), pES was not proposed or agreed. In 58.3% (14/24) of these cases, this was because invasive testing was declined and, in 41.7% (10/24) of cases, women opted for testing and underwent chromosomal microarray analysis only. The diagnostic yield of pES was 23.4% (11/47). There was no overall difference in the proportion of women who decided to have late TOP in the group in which pES was agreed compared with the group in which pES was not proposed or agreed (25.0% (12/48) vs 25.0% (6/24); P = 1.0). However, the decision to have late TOP was significantly more frequent when a causative variant was detected compared with when pES was uninformative (63.6% (7/11) vs 13.9% (5/36); P < 0.0009). The median turnaround time for results was longer in cases in which a causative variant was identified than in those in which pES was uninformative (22 days (interquartile range (IQR), 19-34) days vs 14 days (IQR, 10-15 days); P < 0.0001). CONCLUSIONS: This study demonstrates the potential impact of identification of a causative variant by pES on decision to have late TOP. As the R21 pathway continues to evolve, we urge clinicians and policymakers to consider introducing earlier screening for anomalies, developing robust guidance for late TOP and ensuring optimized support for couples. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Vaginal bacterial load in the second trimester is associated with early preterm birth recurrence: a nested case-control study.

OBJECTIVE: To assess the association between vaginal microbiome (VMB) composition and recurrent early spontaneous preterm birth (sPTB)/preterm prelabour rupture of membranes (PPROM). DESIGN: Nested case-control study. SETTING: UK tertiary referral hospital. SAMPLE: High-risk women with previous sPTB/PPROM <34+0 weeks' gestation who had a recurrence (n = 22) or delivered at ≥37+0 weeks without PPROM (n = 87). METHODS: Vaginal swabs collected between 15 and 22 weeks' gestation were analysed by 16S rRNA gene sequencing and 16S quantitative PCR. MAIN OUTCOME MEASURE: Recurrent early sPTB/PPROM. RESULTS: Of the 109 high-risk women, 28 had anaerobic vaginal dysbiosis, with the remainder dominated by lactobacilli (Lactobacillus iners 36/109, Lactobacillus crispatus 23/109, or other 22/109). VMB type and diversity were not associated with recurrence. Women with a recurrence, compared to those without, had a higher median vaginal bacterial load (8.64 versus 7.89 log10 cells/mcl, adjusted odds ratio [aOR] 1.90, 95% CI 1.01-3.56, P = 0.047) and estimated Lactobacillus concentration (8.59 versus 7.48 log10 cells/mcl, aOR 2.35, (95% CI 1.20-4.61, P = 0.013). A higher recurrence risk was associated with higher median bacterial loads for each VMB type after stratification, although statistical significance was reached only for L. iners domination (aOR 3.44, 95% CI 1.06-11.15, P = 0.040). Women with anaerobic dysbiosis or L. iners domination had a higher median vaginal bacterial load than women with a VMB dominated by L. crispatus or other lactobacilli (8.54, 7.96, 7.63, and 7.53 log10 cells/mcl, respectively). CONCLUSIONS: Vaginal bacterial load is associated with early sPTB/PPROM recurrence. Domination by lactobacilli other than L. iners may protect women from developing high bacterial loads. Future PTB studies should quantify vaginal bacteria and yeasts. TWEETABLE ABSTRACT: Increased vaginal bacterial load in the second trimester may be associated with recurrent early spontaneous preterm birth.

Cervical cerclage, pessary, or vaginal progesterone in high-risk pregnant women with short cervix: a randomized feasibility study.

Objective: To assess feasibility for a definitive randomized controlled trial (RCT) comparing three treatments for short cervix in a population at high risk for spontaneous preterm birth (sPTB) over a 1-year period.Design: Three arm, open label feasibility randomized clinical study.Methods: Women with singleton pregnancy with risk factors for sPTB (history of sPTB or prelabor premature rupture of membranes (PPROM) <34 weeks or significant cervical surgery), and short cervix on transvaginal ultrasound scan detected between 16+0 and 24+6 weeks gestation were randomized to receive either cervical cerclage, vaginal pessary, or vaginal progesterone 200 mg nocte. Pregnancy outcomes and treatment costs were collected from hospital records, NHS Reference costs, and British National Formulary costs.Main outcome measures: Feasibility targets were defined as (i) at least 55% of eligible women randomized; (ii) maximum 5% failure to adhere to the protocol per arm; (iii) maximum 5% loss to short-term follow-up.Results: Of 417 women screened between October 2015 and 2016, 25 (6%) were eligible for trial inclusion, of whom 18 (72%) agreed to participate at the rate 0.75 participants/site/month. Adherence to protocol was 100% in pessary and cerclage arms and 80% in vaginal progesterone arm (95% CI 24-100%). No participants were lost to follow up. Cost of interventions accounted for 6% (95% CI 2-10%) of overall health care expenditure.Conclusions: A definitive clinical trial comparing treatments for prevention of sPTB in high-risk women with short cervix is feasible but will be challenging due to small numbers of eligible participants.

Foley catheter vs oral misoprostol for induction of labor: individual participant data meta-analysis.

OBJECTIVE: To compare the effectiveness and safety of Foley catheter and oral misoprostol for induction of labor (IOL). METHODS: The Cochrane Review on Mechanical Methods for Induction of Labour and Ovid MEDLINE, EMBASE via Ovid, Ovid Emcare, CINAHL Plus, ClinicalTrials.gov and Scopus, from inception to April 2019, were searched for randomized controlled trials (RCTs) comparing Foley catheter to oral misoprostol for IOL in viable singleton gestations. Eligible trials for which raw data were obtained were included and individual participant data meta-analysis was performed. Primary outcomes were vaginal birth, a composite of adverse perinatal outcome (including stillbirth, neonatal death, neonatal seizures, admission to the neonatal intensive care unit, severe respiratory compromise or meconium aspiration syndrome) and a composite of adverse maternal outcome (including admission to the intensive care unit, maternal infection, severe postpartum hemorrhage, maternal death or uterine rupture). The quality of the included RCTs was assessed using the Cochrane Risk of Bias 2 tool and the certainty of evidence was evaluated using the GRADE approach. A two-stage random-effects model was used for meta-analysis according to the intention-to-treat principle and interactions between treatment and baseline characteristics were assessed. RESULTS: Of seven eligible trials, four provided individual participant data for a total of 2815 participants undergoing IOL, of whom 1399 were assigned to Foley catheter and 1416 to oral misoprostol. All four trials provided data for each of the primary outcomes in all 2815 women. Compared with those receiving oral misoprostol, Foley catheter recipients had a slightly decreased chance of vaginal birth (risk ratio (RR), 0.95 (95% CI, 0.91-0.99); I2 , 2.0%; moderate-certainty evidence). A trend towards a lower rate of composite adverse perinatal outcome was found in women undergoing IOL using a Foley catheter compared with oral misoprostol (RR, 0.71 (95% CI, 0.48-1.05); I2 , 14.9%; low-certainty evidence). Composite adverse maternal outcome did not differ between the groups (RR, 1.00 (95% CI, 0.97-1.03); I2 , 0%; moderate-certainty evidence). Meta-analyses of effect modifications did not show significant interactions between intervention and parity or gestational age for any of the primary outcomes. CONCLUSIONS: For women undergoing IOL, Foley catheter is less effective than oral misoprostol, as it was associated with fewer vaginal births. However, while we found no significant difference in maternal safety, Foley catheter induction may reduce adverse perinatal outcomes. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction: planned subgroup analysis from a multicenter randomized placebo-controlled double-blind trial.

OBJECTIVES: Fetal growth restriction (FGR) is associated with maternal cardiovascular changes. Sildenafil, a phosphodiesterase type-5 inhibitor, potentiates the actions of nitric oxide, and it has been suggested that it alters maternal hemodynamics, potentially improving placental perfusion. Recently, the Dutch STRIDER trial was stopped prematurely owing to excess neonatal mortality secondary to pulmonary hypertension. The main aim of this study was to investigate the effect of sildenafil on maternal hemodynamics in pregnancies with severe early-onset FGR. METHODS: This was a cardiovascular substudy within a UK multicenter, placebo-controlled trial, in which 135 women with a singleton pregnancy and severe early-onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10th centile and absent/reversed end-diastolic flow in the umbilical artery on Doppler velocimetry, diagnosed between 22 + 0 and 29 + 6 weeks' gestation) were assigned randomly to receive either 25 mg sildenafil three times daily or placebo until 32 + 0 weeks' gestation or delivery. Maternal blood pressure (BP), heart rate (HR), augmentation index, pulse wave velocity (PWV), cardiac output, stroke volume (SV) and total peripheral resistance were recorded before randomization, 1-2 h and 48-72 h post-randomization, and 24-48 h postnatally. For continuous data, analysis was performed using repeated measures ANOVA methods including terms for timepoint, treatment allocation and their interaction. RESULTS: Included were 134 women assigned randomly to sildenafil (n = 69) or placebo (n = 65) who had maternal BP and HR recorded at baseline. At 1-2 h post-randomization, compared with baseline values, sildenafil increased maternal HR by 4 bpm more than did placebo (mean difference, 5.00 bpm (95% CI, 1.00-12.00 bpm) vs 1.25 bpm (95% CI, -5.38 to 7.88 bpm); P = 0.004) and reduced systolic BP by 1 mmHg more (mean difference, -4.13 mmHg (95% CI, -9.94 to 1.44 mmHg) vs -2.75 mmHg (95% CI, -7.50 to 5.25 mmHg); P = 0.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60 m/s more than did placebo (mean difference, -0.90 m/s (95% CI, -1.31 to -0.51 m/s) vs -0.26 m/s (95% CI, -0.75 to 0.59 m/s); P = 0.001). Sildenafil was associated with a non-significantly greater decrease in SV index after 1-2 h post-randomization than was placebo (mean difference, -5.50 mL/m2 (95% CI, -11.00 to -0.50 mL/m2 ) vs 0.00 mL/m2 (95% CI, -5.00 to 4.00 mL/m2 ); P = 0.056). CONCLUSIONS: Sildenafil in a dose of 25 mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early-onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short- or long-term clinical impact on the mother. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Reducing the impact of preterm birth: Preterm birth commissioning in the United Kingdom.

Reducing preterm birth is a priority for Maternity and Children's services. In the recent UK Department of Health publication 'Safer Maternity Care' the Secretary of State for Health aimed to achieve the national maternity safety ambition by pledging to reduce the rate of preterm birth from 8% to 6%. It was proposed that specialist preterm birth services should be established in the UK in order to achieve this aim. In response the Preterm Clinical Network has written Commissioning Guidance aimed to establish best practice pathways and agreed models of care to reduce variation nationally. They have been developed by clinical experts in the field, from within the UK, to provide recommendations for commissioning groups and to recommend pathways to organisations with the aim of reducing the incidence of preterm birth. Three key areas of care provision are focused on: prediction, prevention and preparation of women at high risk of PTB. This Expert Opinion, will summarise the Commissioning Guidance.

Effect of QUiPP prediction algorithm on treatment decisions in women with a previous preterm birth: a prospective cohort study.

OBJECTIVE: The QUiPP algorithm combines cervical length, quantitative fetal fibronectin (qfFN) and medical history to quantify risk of preterm birth. We assessed the utility of QUiPP to inform preterm birth prevention treatment decisions. DESIGN: A prospective cohort study with a subsequent impact assessment using the QUiPP risk of birth before 34 weeks' gestation. SETTING: A UK tertiary referral hospital. SAMPLE: In all, 119 women with previous spontaneous preterm birth (sPTB) or preterm premature rupture of membranes (PPROM) before 34 weeks' gestation. METHODS: Cervical length and qfFN were measured at 19+0 to 23+0  weeks' gestation. Clinical management was based on history and cervical length. After birth, clinicians were unblinded to qfFN results and QUiPP analysis was undertaken. MAIN OUTCOME MEASURES: Predictive statistics of QUiPP algorithm using 10% risk of sPTB before 34+0  weeks as treatment threshold. RESULTS: Fifteen of 119 women (13%) had PPROM or sPTB before 34 weeks. Of these, 53% (8/15) had QUiPP risk of sPTB before 34+0  weeks above 10%. Applying this treatment threshold in practice would have doubled our treatment rate (20 versus 42%). QUIPP threshold of 10% had positive likelihood ratio (LR) of 1.3 (95% CI 0.76-2.18), and negative LR of 0.8 (95% CI 0.45-1.40) for predicting sPTB before 34+0  weeks. CONCLUSIONS: Use of the QUiPP algorithm in this population may lead to substantial increase in interventions without evidence that currently available treatment options are beneficial for this particular group. TWEETABLE ABSTRACT: Independent study finds that the QUiPP algorithm could lead to substantial increases in treatment without evidence of benefit.

ISUOG Practice Guidelines: ultrasound assessment of fetal biometry and growth.

INTRODUCTION These Guidelines aim to describe appropriate assessment of fetal biometry and diagnosis of fetal growth disorders. These disorders consist mainly of fetal growth restriction (FGR), also referred to as intrauterine growth restriction (IUGR) and often associated with small­for­gestational age (SGA), and large­for­gestational age (LGA), which may lead to fetal macrosomia; both have been associated with a variety of adverse maternal and perinatal outcomes. Screening for, and adequate management of, fetal growth abnormalities are essential components of antenatal care, and fetal ultrasound plays a key role in assessment of these conditions. The fetal biometric parameters measured most commonly are biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur diaphysis length (FL). These biometric measurements can be used to estimate fetal weight (EFW) using various different formulae1. It is important to differentiate between the concept of fetal size at a given timepoint and fetal growth, the latter being a dynamic process, the assessment of which requires at least two ultrasound scans separated in time. Maternal history and symptoms, amniotic fluid assessment and Doppler velocimetry can provide additional information that may be used to identify fetuses at risk of adverse pregnancy outcome. Accurate estimation of gestational age is a prerequisite for determining whether fetal size is appropriate­for­gestational age (AGA). Except for pregnancies arising from assisted reproductive technology, the date of conception cannot be determined precisely. Clinically, most pregnancies are dated by the last menstrual period, though this may sometimes be uncertain or unreliable. Therefore, dating pregnancies by early ultrasound examination at 8­14 weeks, based on measurement of the fetal crown­rump length (CRL), appears to be the most reliable method to establish gestational age. Once the CRL exceeds 84 mm, HC should be used for pregnancy dating2­4. HC, with or without FL, can be used for estimation of gestational age from the mid­trimester if a first­trimester scan is not available and the menstrual history is unreliable. When the expected delivery date has been established by an accurate early scan, subsequent scans should not be used to recalculate the gestational age1. Serial scans can be used to determine if interval growth has been normal. In these Guidelines, we assume that the gestational age is known and has been determined as described above, the pregnancy is singleton and the fetal anatomy is normal. Details of the grades of recommendation used in these Guidelines are given in Appendix 1. Reporting of levels of evidence is not applicable to these Guidelines.

Pautas de ISUOG para la práctica: evaluación ecográfica de la biometría y el crecimiento fetal INTRODUCCIÓN: El objetivo de estas Pautas es describir la evaluación adecuada de la biometría fetal y el diagnóstico de los trastornos del crecimiento fetal. Estos trastornos consisten principalmente en la restricción del crecimiento fetal (RCF), también conocida como restricción del crecimiento intrauterino (RCIU), que a menudo está asociada con un tamaño pequeño para la edad gestacional (PEG) o grande para la edad gestacional (GEG), que pueden dar lugar a la macrosomía fetal; ambos se han asociado con una variedad de resultados maternos y perinatales adversos. La detección y el tratamiento adecuado de las anomalías del crecimiento fetal son componentes esenciales de la atención prenatal, y la ecografía fetal desempeña un papel fundamental en la evaluación de estas afecciones. Los parámetros biométricos fetales medidos con mayor frecuencia son (todas las siglas procedentes del inglés) el diámetro biparietal (BPD), el perímetro cefálico (HC), el perímetro abdominal (AC) y la longitud de la diáfisis del fémur (FL). Estas mediciones biométricas se pueden utilizar para estimar el peso del feto (PEF) mediante fórmulas diferentes1 . Es importante diferenciar entre el concepto de tamaño fetal en un momento dado y el crecimiento fetal en sí, siendo este último un proceso dinámico cuya evaluación requiere al menos dos ecografías separadas en el tiempo. La historia y los síntomas de la madre, la evaluación del líquido amniótico y la velocimetría Doppler pueden proporcionar información adicional que se puede utilizar para identificar los fetos bajo riesgo de resultados adversos del embarazo. La estimación precisa de la edad gestacional es un prerrequisito para determinar si el tamaño del feto es apropiado para la edad gestacional (AEG). Excepto en el caso de los embarazos procedentes de tecnologías de reproducción asistida, la fecha de concepción no se puede determinar con precisión. Clínicamente, la fecha de la mayoría de los embarazos se establece en función del último período menstrual, aunque a veces esto puede ser incierto o poco fiable. Por lo tanto, el fechado de los embarazos mediante ecografía temprana a las 8-14 semanas, mediante la medición de la longitud céfalo-caudal (LCC) fetal, parece ser el método más fiable para establecer la edad gestacional. Una vez que la LCC excede los 84 mm, se debe usar el HC2-4 para establecer la fecha del embarazo. El HC, con o sin FL, se puede utilizar para estimar la edad gestacional a partir de la mitad del primer trimestre si no se dispone de una ecografía del primer trimestre y el historial menstrual no es fiable. Cuando se ha establecido la fecha prevista del parto mediante una exploración temprana precisa, no se deben utilizar exploraciones posteriores para recalcular la edad gestacional1 . Las exploraciones en serie se pueden utilizar para determinar si el intervalo del crecimiento ha sido normal. En estas Pautas se asume que la edad gestacional es conocida y ha sido determinada según lo anterior, que el embarazo es de feto único y que la anatomía fetal es normal. En el Apéndice 1 se detallan los grados de recomendación utilizados en estas Pautas. El informe sobre los niveles de evidencia no es aplicable a estas Pautas.

Misoprostol vaginal insert (Mysodelle) versus Dinoprostone intravaginal gel (Prostin) for induction of labour.

OBJECTIVE: The aim of this study is the compare the effectiveness and safety of Misoprostol Vaginal Insert (Mysodelle) versus Dinoprostone intravaginal gel (Prostin) for induction of labour. STUDY DESIGN: We performed a prospective cohort study of the use of misoprostol vaginal inserts (Mysodelle) in the induction of pregnancy and compared it to a historical cohort of women induced with the Dinoprostone intravaginal gel (Prostin) at the Liverpool Women's Hospital, a large UK teaching hospital. RESULTS: A total of 4102 women were induced between December 2016 and September 2018 of whom 2540 were induced with dinoprostone gel until September 2017. Since October 2017 1562 were induced using misoprostol vaginal inserts (MVI). The MVI demonstrated a significantly quicker median time to delivery compared with dinoprostone gel (18.2 h versus 21.8 h; p < 0.0001). There was a 32% reduced risk of Caesarean section with MVI (7.5% vs 10.9%; RR 0.62 95%CI 0.56-0.84) There was no significant difference in any of the key maternal or neonatal adverse outcomes. CONCLUSIONS: The results of this study suggest that misoprostol vaginal inserts, compared with dinoprostone intravaginal gel, achieve quicker delivery times, and a reduction in caesarean sections with no increased rate of adverse maternal or neonatal outcomes.

Should phenotype of previous preterm birth influence management of women with short cervix in subsequent pregnancy? Comparison of vaginal progesterone and Arabin pessary.

OBJECTIVE: To investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound. METHODS: This was a retrospective cohort study of asymptomatic high-risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log-rank test on Kaplan-Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL-IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery. RESULTS: Between 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL-IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL-IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth. CONCLUSIONS: Cervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Core outcome sets for prevention and treatment of postpartum haemorrhage: an international Delphi consensus study.

OBJECTIVE: To develop core outcome sets (COS) for studies evaluating interventions for (1) prevention and (2) treatment of postpartum haemorrhage (PPH), and recommendations on how to report the COS. DESIGN: A two-round Delphi survey and face-to-face meeting. POPULATION: Healthcare professionals and women's representatives. METHODS: Outcomes were identified from systematic reviews of PPH studies and stakeholder consultation. Participants scored each outcome in the Delphi on a Likert scale between 1 (not important) and 9 (critically important). Results were discussed at the face-to-face meeting to agree the final COS. Consensus at the meeting was defined as ≥ 70% of participants scoring the outcome as critically important (7-9). Lectures, discussion and voting were used to agree how to report COS outcomes. MAIN OUTCOME MEASURES: Outcomes from systematic reviews and consultations. RESULTS: Both Delphi rounds were completed by 152/205 (74%) participants for prevention and 143/197 (73%) for treatment. For prevention of PPH, nine core outcomes were selected: blood loss, shock, maternal death, use of additional uterotonics, blood transfusion, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, and adverse effects. For treatment of PPH, 12 core outcomes were selected: blood loss, shock, coagulopathy, hysterectomy, organ dysfunction, maternal death, blood transfusion, use of additional haemostatic intervention, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, and adverse effects. Recommendations were developed on how to report these outcomes where possible. CONCLUSIONS: These COS will help standardise outcome reporting in PPH trials. TWEETABLE ABSTRACT: Core outcome sets for PPH: nine core outcomes for PPH prevention and 12 core outcomes for PPH treatment.