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OBJECTIVE: We aimed to determine foetal losses for DCDA and MCDA twins following transabdominal CVS or amniocentesis performed

Background Building a dataset of individual participant data (IPD) for meta-analysis represents considerable research investment as well as collaboration across multiple institutions and researchers. Making arrangements to curate and share the dataset beyond the IPD meta-analysis project for which it was established, for reuse in future research projects, would maximise the value of this investment. Methods Our aim was to establish the Cochrane repository for individual patient data from clinical trials in pregnancy and childbirth (CRIB) as an example of how an IPD repository could become part of Cochrane infrastructure. We believed that establishing CRIB under Cochrane auspices would engender trust and encourage trial investigators to share data, and at the same time position Cochrane to take steps towards expanding the number of reviews with IPD synthesis. Results CRIB was designed as a web-based platform to receive, host and facilitate onward sharing of de-identified data. Development was not straightforward and we did not fully achieve our aim as intended. We describe the challenges encountered and suggest ways that future repositories might overcome these. In particular, securing the legal agreements required to facilitate data sharing proved to be the main barrier, being time-consuming and more complex than anticipated. Conclusions We would recommend that researchers conducting IPD meta-analysis should consider discussing the option to transfer the curated IPD datasets to a repository at the end of the initial meta-analysis and this should be recognised within the data sharing agreements made with the original data contributors.

ObjectivesTo compare the efficacy of bed rest, cervical cerclage (McDonald, Shirodkar, or unspecified type of cerclage), cervical pessary, fish oils or omega fatty acids, nutritional supplements (zinc), progesterone (intramuscular, oral, or vaginal), prophylactic antibiotics, prophylactic tocolytics, combinations of interventions, placebo or no treatment (control) to prevent spontaneous preterm birth in women with a singleton pregnancy and a history of spontaneous preterm birth or short cervical length.DesignSystematic review with bayesian network meta-analysis.Data sourcesThe Cochrane Pregnancy and Childbirth Group’s Database of Trials, the Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials.Eligibility criteria for selecting studiesRandomised controlled trials of pregnant women who are at high risk of spontaneous preterm birth because of a history of spontaneous preterm birth or short cervical length. No language or date restrictions were applied.OutcomesSeven maternal outcomes and 11 fetal outcomes were analysed in line with published core outcomes for preterm birth research. Relative treatment effects (odds ratios and 95% credible intervals) and certainty of evidence are presented for outcomes of preterm birth ResultsSixty one trials (17 273 pregnant women) contributed data for the analysis of at least one outcome. For preterm birth ConclusionVaginal progesterone should be considered the preventative treatment of choice for women with singleton pregnancy identified to be at risk of spontaneous preterm birth because of a history of spontaneous preterm birth or short cervical length. Future randomised controlled trials should use vaginal progesterone as a comparator to identify better treatments or combination treatments.Systematic review registrationPROSPERO CRD42020169006

BACKGROUND: Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.METHODS: We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.FINDINGS: Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture INTERPRETATION: Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.FUNDING: Patient-Centered Outcomes Research Institute.

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.

Preterm birth prevention is multifaceted and produces many nuanced questions. This review addresses six important clinical questions about preterm birth prevention as voted for by members of the UK Preterm Clinical Network. The questions cover the following areas: preterm birth prevention in 'low-risk' populations; screening for asymptomatic genital tract infection in women at high risk of preterm birth; cervical length screening with cerclage or vaginal pessary in situ; cervical shortening whilst using progesterone; use of vaginal progesterone in combination with cervical cerclage; and optimal advice about intercourse for women at high risk of preterm birth.

Introduction: Midtrimester prelabor rupture of membranes (PROM) between 16 and 24 weeks of gestational age is a major obstetric complication with high rates of perinatal morbidity and mortality. Amnioinfusion has been proposed in women with midtrimester PROM to target oligohydramnios and subsequently enhance pulmonary development and perinatal outcomes. Material and Methods: The purpose of this study was to perform a systematic review and meta-analysis including all randomized clinical trials investigating amnioinfusion versus no intervention in women with PROM between 16+0 and 24+0 weeks of gestational age. Databases Central, Embase, Medline, ClinicalTrials.gov and references of identified articles were searched from inception of database to December 2021. The primary outcome was perinatal mortality. Secondary outcomes included neonatal, maternal, and long-term developmental outcomes as defined in the core outcome set for preterm birth studies. Summary measures were reported as pooled relative risk (RR) or mean difference with corresponding 95% confidence interval (CI). Results: Two studies (112 patients, 56 in the amnioinfusion group and 56 in the no intervention group) were included in this review. Pooled perinatal mortality was 66.1% (37/56) in the amnioinfusion group compared with 71.4% (40/56) in no intervention group (RR 0.92, 95% CI: 0.72–1.19). Other neonatal and maternal core outcomes were similar in both groups, although due to the relatively small number of events and wide CIs, there is a possibility that amnioinfusion can be associated with clinically important benefits and harms. Long-term healthy survival was seen in 35.7% (10/28) of children assessed for follow-up and treated with amnioinfusion versus 28.6% (8/28) after no intervention (RR 1.30, 95% CI: 0.47–3.60, “best case scenario”). Conclusions: Based on these findings, the benefits of amnioinfusion for midtrimester PROM

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Objective: To establish if low maternal selenium (Se) was associated with sPTB in women with recurrent sPTB and identify genetic link with maternal Se levels. Design: Nested case-control study. Setting: Tertiary Maternity Hospital. Population: Plasma and whole blood from pregnant women with history of early sPTB/PPROM < 34 +0 and European ancestry were obtained at 20 weeks (range 15–24 weeks). ‘Cases’ were recurrent PTB/PPROM < 34 +0 weeks and term (≥37 +0) deliveries were classified as ‘high-risk controls.’ Women with previous term births and index birth ≥ 39 weeks were ‘low-risk controls’. Methods: Maternal plasma Se measured by ICP-MS was used as a continuous phenotype in a GWAS analysis. Se was added to a logistic regression model using PTB predictor variables. Main outcome measures: Maternal Se concentration, recurrent early sPTB/PPROM. Results: 53/177 high-risk women had a recurrent sPTB/PPROM < 34 +0weeks and were 2.7 times more likely to have a Se level < 83.3 ppm at 20weeks of pregnancy compared with low-risk term controls (n = 179), (RR 2.7, 95%CI 1.5–4.8; p =.001). One SNP from a non-coding region (FOXN3 intron variant, rs55793422) reached genome-wide significance level (p = 3.73E −08). Targeted analysis of Se gene variant did not show difference between preterm and term births. (χ 2 test, OR = 0.95; 95%CI = 0.59–1.56; p = 0.82). When Se levels were added to a clinical prediction model, only an additional 5% of cases (n = 3) and 0.6% (n = 1) of controls were correctly identified. Conclusions: Low plasma Se is associated with sPTB risk but is not sufficiently predictive at individual patient level. We did not find a genetic association between maternal Se levels and Se-related genes.

Objectives Induction of labour (IOL), or starting labour artificially, can be a lifesaving intervention for pregnant women and their babies, and rates are rising significantly globally. As rates increase, it becomes increasingly important to fully evaluate all available data, especially that from low income settings where the potential benefits and harms are greater. The goal of this paper is to describe the datasets collected as part of the Induction with Foley OR Misoprostol (INFORM) Study, a randomised trial comparing two of the recommended methods of cervical ripening for labour induction, oral misoprostol and Foley catheter, in women being induced for hypertension in pregnancy, at two sites in India during 2013–15. Data description This dataset includes comprehensive data on 602 women who underwent IOL for hypertensive disorders in pregnancy. Women were randomly assigned to cervical ripening with oral misoprostol or a transcervical Foley catheter in two government hospitals in India. The main dataset has 367 variables including monitoring during the induction of labour, medications administered, timing and mode of delivery, measures of neonatal morbidity and mortality, maternal mortality and morbidity, maternal satisfaction and health economic data. The dataset is anonymised and available on ReShare.

Preterm birth (PTB) is a leading global cause of infant mortality. Risk factors include genetics, lifestyle choices and infection. Understanding the mechanism of PTB could aid the development of novel approaches to prevent PTB. This study aimed to investigate the metabolic biomarkers of PTB in early pregnancy and the association of significant metabolites with participant genotypes. Maternal sera collected at 16 and 20 weeks of gestation, from women who previously experienced PTB (high-risk) and women who did not (low-risk controls), were analysed using 1H nuclear magnetic resonance (NMR) metabolomics and genome-wide screening microarray. ANOVA and probabilistic neural network (PNN) modelling were performed on the spectral bins. Metabolomics genome-wide association (MGWAS) of the spectral bins and genotype data from the same participants was applied to determine potential metabolite-gene pathways. Phenylalanine, acetate and lactate metabolite differences between PTB cases and controls were obtained by ANOVA and PNN showed strong prediction at week 20 (AUC = 0.89). MGWAS identified several metabolite bins with strong genetic associations. Cis-eQTL analysis highlighted TRAF1 (involved in the inflammatory pathway) local to a non-coding SNP associated with lactate at week 20 of gestation. MGWAS of a well-defined cohort of participants highlighted a lactate-TRAF1 relationship that could potentially contribute to PTB.

Introduction A 2018 Cochrane review found that omega-3 supplementation in pregnancy was associated with a risk reduction of early preterm birth of 0.58; prompting calls for universal supplementation. Recent analysis suggests the benefit may be confined to women with a low baseline omega-3 fatty acid status. However, the contemporary omega-3 fatty acid status of pregnant women in the UK is largely unknown. This is particularly pertinent for women with a previous preterm birth, in whom a small relative risk reduction would have a larger reduction of absolute risk. This study aimed to assess the omega-3 fatty acid status of a UK pregnant population and determine the association between the long-chain omega-3 fatty acids and recurrent spontaneous early preterm birth. Material and methods A total of 283 high-risk women with previous early preterm birth were recruited to the prospective observational study in Liverpool, UK. Additionally, 96 pregnant women with previous term births and birth ≥39+0 weeks in the index pregnancy provided a low-risk population sample. Within the high-risk group we assessed the odds ratio of recurrent early preterm birth compared with birth at ≥37+0 weeks of gestation according to plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) at 15-22 weeks of gestation. Results Our participants had low EPA+DHA; 62% (143/229) of women with previous preterm birth and 69% (68/96) of the population sample had levels within the lowest two quintiles of a previously published pregnancy cohort. We found no association between long-chain omega-3 status and recurrent early preterm birth (n = 51). The crude odds ratio of a recurrent event was 0.91 (95% CI 0.38-2.15, p = 0.83) for women in the lowest, compared with the highest three quintiles of EPA+DHA. Conclusions In the majority of our participants, levels of long-chain omega-3 were low; within the range that may benefit from supplementation. However, levels showed no association with risk of recurrent early spontaneous preterm birth. This could be because our population levels were too low to show benefit in being omega-3 "replete"; or else omega-3 levels may be of lesser importance in recurrent early preterm birth.

Background Every year approximately 30,000 women die from hypertensive disease in pregnancy. Magnesium sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. Low dose oral misoprostol, a prostaglandin E1 analogue, is a highly effective method for labour induction. Usually, once active labour has commenced, the misoprostol is replaced with an intravenous oxytocin infusion if ongoing stimulation is required. However, some studies have shown that oral misoprostol can be continued into active labour, a simpler and potentially more acceptable protocol for women. To date, these two protocols have never been directly compared. Methods This pragmatic, open-label, randomised trial will compare a misoprostol alone labour induction protocol with the standard misoprostol plus oxytocin protocol in three Indian hospitals. The study will recruit 520 pregnant women being induced for hypertensive disease in pregnancy and requiring augmentation after membrane rupture. Participants will be randomised to receive either further oral misoprostol 25mcg every 2 h, or titrated intravenous oxytocin. The primary outcome will be caesarean birth. Secondary outcomes will assess the efficacy of the induction process, maternal and fetal/neonatal complications and patient acceptability. This protocol (version 1.04) adheres to the SPIRIT checklist. A cost-effectiveness analysis, situational analysis and formal qualitative assessment of women’s experience are also planned. Discussion Avoiding oxytocin and continuing low dose misoprostol into active labour may have a number of benefits for both women and the health care system. Misoprostol is heat stable, oral medication and thus easy to store, transport and administer; qualities particularly desirable in low resource settings. An oral medication protocol requires less equipment (e.g. electronic infusion pumps) and may free up health care providers to assist with other aspects of the woman’s care. The simplicity of the protocol may also help to reduce human errors associated with the delivery of intravenous infusions. Finally, women may prefer to be mobile during labour and not restricted by an intravenous infusion. There is a need, therefore, to assess whether augmentation using oral misoprostol is superior clinically and economically to the standard protocol of intravenous oxytocin. Trial registration Clinical Trials.gov, NCT03749902, registered on 21st Nov 2018.

Preterm birth (PTB) occurs before 37 weeks of gestation. Risk factors include genetics and infection/inflammation. Different mechanisms have been reported for spontaneous preterm birth (SPTB) and preterm birth following preterm premature rupture of membranes (PPROM). This study aimed to identify early pregnancy biomarkers of SPTB and PPROM from the maternal genome and transcriptome. Pregnant women were recruited at the Liverpool Women’s Hospital. Pregnancy outcomes were categorised as SPTB, PPROM (≤ 34 weeks gestation, n = 53), high-risk term (HTERM, ≥ 37 weeks, n = 126) or low-risk (no history of SPTB/PPROM) term (LTERM, ≥ 39 weeks, n = 188). Blood samples were collected at 16 and 20 weeks gestation from which, genome (UK Biobank Axiom array) and transcriptome (Clariom D Human assay) data were acquired. PLINK and R were used to perform genetic association and differential expression analyses and expression quantitative trait loci (eQTL) mapping. Several significant molecular signatures were identified across the analyses in preterm cases. Genome-wide significant SNP rs14675645 (ASTN1) was associated with SPTB whereas microRNA-142 transcript and PPARG1-FOXP3 gene set were associated with PPROM at week 20 of gestation and is related to inflammation and immune response. This study has determined genomic and transcriptomic candidate biomarkers of SPTB and PPROM that require validation in diverse populations.

BackgroundSevere early-onset fetal growth restriction (FGR) predisposes to fetal death, neonatal death, neonatal morbidity and neurodisability. The use of placental biomarkers has been proposed for risk stratification in pre-eclampsia, but they could be equally useful in fetal growth restriction in aiding management.ObjectiveTo determine the efficacy of angiogenic biomarkers at predicting adverse pregnancy outcome in severe early-onset fetal growth restriction.Study designThis is a secondary analysis of the multicentre, placebo-controlled STRIDER UK randomised controlled trial of singleton pregnancies with severe early-onset fetal growth restriction.Women with FGR pregnancies between 22+0 and 29+6 weeks of gestation were randomly assigned to receive either sildenafil 25 mg three times daily or placebo until 32+0 weeks’ gestation or delivery. We developed prediction models based upon maternal demographics (age, parity, blood pressure, preeclampsia, gestational hypertension), fetal biometric (estimated fetal weight) and Doppler measurements (Middle Cerebral Artery (MCA), Umbilical Artery (UA)) and maternal angiogenic biomarkers [placental growth factor (PlGF), soluble endoglin (sEng), soluble fms-like tyrosine kinase 1 (sFlt-1) and sFlt-1:PlGF ratio) using both univariate and multivariate analysis.ResultsA complete data set was available for 105 of 135 randomised women. Multivariate regression analysis identified estimated fetal weight (EFW) and sFlt-1:PlGF as independent predictors of livebirth (EFW OR: 1.01 (1.008, 1.021); p ConclusionsIn severe early-onset FGR pregnancies livebirth and overall survival can be predicted using a model involving EFW and sFlt-1:PlGF ratio. This model require validation in a larger cohort but may allow informed decision making about pregnancy management, especially in previable cases.

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 small‐for‐gestational age (SGA), and large‐for‐gestational 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 appropriate‐for‐gestational 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 8–14 weeks, based on measurement of the fetal crown–rump 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 dating2–4. HC, with or without FL, can be used for estimation of gestational age from the mid‐trimester if a first‐trimester 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 diferentesISUOG实践指南:胎儿生物测量与生长的超声评估 引言: 本指南旨在描述胎儿生物测量的正确评估及胎儿生长障碍的诊断。这些疾病主要包括又称为宫内生长受限(IUGR)且往往与小于胎龄(SGA)有关的胎儿生长受限(FGR)，以及可能导致胎儿巨大的大于胎龄(LGA)。这两种疾病都与各种孕产期围产期不良结局有关。胎儿生长异常的筛查和适当处理是产前保健的重要组成部分，胎儿超声检测在这些疾病的评估中起着关键作用。最常测量的胎儿生物特征参数有双顶径(BPD)、头围(HC)、腹围(AC)和股骨骨干长度(FL)。可以根据这些生物特征测量值，运用各种不同的公式估算胎儿体重(EFW)。

Obstetric anal sphincter injury (OASI) is a significant complication of vaginal delivery. Water birth has become a popular preference for women giving birth in the UK, however, there is limited data on the risk of OASI following water birth. Our aim was to assess OASI risk in low-risk women giving birth in water without medical intervention compared with on land and to create a prognostic model for OASI prediction. This was a retrospective study of 15,734 low-risk women giving birth by spontaneous vaginal delivery between January 2008 and October 2014 in a midwifery-led unit (MLU). Patient factors and delivery data were analysed to identify differences between water and land births. Univariate analysis determined factors that statistically predicted OASI and was then used to create multivariate analysis. Significant multivariate factors were used to create a prognostic model to predict likelihood of OASI. OASI rates were 1.6% on land and 3.3% in water [odds ratio (OR) 2.10, 95% confidence interval (CI) 1.5–2.94). Multivariate analysis confirmed water birth, ethnicity and parity as independent risk factors for OASI (adjusted OR water birth: 1.77 (CI 1.25–2.51). Our prognostic model showed Black and Asian primigravidae following water birth had the highest risk of OASI and white multiparae on land the lowest. This study of comparable low-risk women shows an increased risk of OASI following water birth compared with land birth. Use of this prognostic model will help women determine their risk of OASI following birth in water or on land.

Background Antenatal detection of the small for gestational (SGA) fetus has become an important indicator of quality of antenatal care in the UK. This has been driven by a desire to reduce stillbirth in this at risk group. Methods We conducted a postal survey of 187 NHS consultant units within the UK to determine what the current practice for the detection and subsequent management of the suspected SGA fetus was following the guidance from the Royal College of Obstetricians and Gynaecologists (RCOG) in 2013. Results The survey was performed in 3 rounds between 2016 and 2017 with a response rate of 65%. 85% of units assessed risk factors for SGA at booking. 81% of units used a customized symphysis fundal height (SFH) chart to screen for SGA with 95% of them using a cut off of

ObjectiveTo assess the association between vaginal microbiome (VMB) composition and recurrent early spontaneous preterm birth (sPTB)/preterm prelabour rupture of membranes (PPROM).DesignNested case-control study.SettingUK tertiary referral hospital.SampleHigh-risk women with previous sPTB/PPROM +0 weeks gestation who had a recurrence (n=22) or delivered at ≥37+0 weeks without PPROM (n=87).MethodsVaginal swabs collected between 15-22 weeks gestation were analysed by 16S rRNA gene sequencing and 16S quantitative PCR.Main outcome measureRecurrent early sPTB/PPROM.Results28/109 high-risk women had anaerobic vaginal dysbiosis, with the remainder dominated by lactobacilli (L. iners 36/109, L. crispatus 23/109, or other 22/109). VMB type, diversity, and stability were not associated with recurrence. Women with a recurrence, compared to those without, had a higher median vaginal bacterial load (8.64 vs. 7.89 log10 cells/μl, adjusted odds ratio (aOR)=1.90, 95% confidence interval (CI)=1.01-3.56, p=0.047) and estimated Lactobacillus concentration (8.59 vs. 7.48 log10 cells/μl, aOR=2.35, 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, 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/μl, respectively).ConclusionsVaginal 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.FundingWellbeing of Women, London, UKTweetable abstractIncreased vaginal bacterial load in the second trimester may be associated with recurrent early spontaneous preterm birth.

BackgroundPostpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, further administration of uterotonic agents as 'first-line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first-line' treatment of PPH.ObjectivesTo identify the most effective uterotonic agent(s) with the least side-effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side-effect profile.Search methodsWe searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies.Selection criteriaAll randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion.Data collection and analysisTwo review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence.Main resultsSeven trials, involving 3738 women in 10 countries, were included in this review. All trials were conducted in hospital settings. Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion. Pairwise meta-analysis of two trials (1787 participants), suggests that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) compared with oxytocin. Low-certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57, 95% CI 1.00 to 6.64). The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, low-certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, 95% CI 0.57 to 2.94, low-certainty). The risk of side-effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, low-certainty). According to pairwise meta-analysis of four trials (1881 participants) generating high-certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, high-certainty) compared with misoprostol alone. Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty).Authors' conclusionsThe available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.

Background Stillbirth remains a major concern across the globe and in some high-resource countries, such as the UK; efforts to reduce the rate have achieved only modest reductions. One third of stillborn babies are small for gestational age (SGA), and these pregnancies are also at risk of neonatal adverse outcomes and lifelong health problems, especially when delivered preterm. Current UK clinical guidance advocates regular monitoring and early term delivery of the SGA fetus; however, the most appropriate regimen for surveillance of these babies remains unclear and often leads to increased intervention for a large number of these women. This pilot trial will determine the feasibility of a large-scale trial refining the risk of adverse pregnancy outcome in SGA pregnancies using biomarkers of placental function sFlt-1/PlGF, identifying and intervening in only those deemed at highest risk of stillbirth. Methods PLANES is a randomised controlled feasibility study of women with an SGA fetus that will be conducted at two tertiary care hospitals in the UK. Once identified on ultrasound, women will be randomised into two groups in a 3:1 ratio in favour of sFlt-1/PlGF ratio led management vs standard care. Women with an SGA fetus and a normal sFlt-1/PlGF ratio will have a repeat ultrasound and sFlt-1/PlGF ratio every 2 weeks with planned birth delayed until 40 weeks. In those women with an SGA fetus and an abnormal sFlt-1/PlGF ratio, we will offer birth from 37 weeks or sooner if there are other concerning features on ultrasound. Women assigned to standard care will have an sFlt-1/PlGF ratio taken, but the results will be concealed from the clinical team, and the woman’s pregnancy will be managed as per the local NHS hospital policy. This integrated mixed method study will also involve a health economic analysis and a perspective work package exploring trial feasibility through interviews and questionnaires with participants, their partners, and clinicians. Discussion Our aim is to determine feasibility through the assessment of our ability to recruit and retain participants to the study. Results from this pilot study will inform the design of a future large randomised controlled trial that will be adequately powered for adverse pregnancy outcome. Such a study would provide the evidence needed to guide future management of the SGA fetus. Trial registration ISRCTN58254381. Registered on 4 July 2019

Background\ud The setting in which induction of labour takes place (home or inpatient) is likely to have implications for safety, women's experiences and costs.\ud \ud Home induction may be started at home with the subsequent active phase of labour happening either at home or in a healthcare facility (hospital, birth centre, midwifery‐led unit). More commonly, home induction starts in a healthcare facility, then the woman goes home to await the start of labour. Inpatient induction takes place in a healthcare facility where the woman stays while awaiting the start of labour.\ud \ud Objectives\ud To assess the effects on neonatal and maternal outcomes of third trimester home induction of labour compared with inpatient induction using the same method of induction.\ud \ud Search methods\ud For this update, we searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (31 January 2020)), and reference lists of retrieved studies.\ud \ud Selection criteria\ud Published and unpublished randomised controlled trials (RCTs) in which home and inpatient settings for induction have been compared. We included conference abstracts but excluded quasi‐randomised trials and cross‐over studies.\ud \ud Data collection and analysis\ud Two review authors independently assessed study reports for inclusion. Two review authors carried out data extraction and assessment of risk of bias independently. GRADE assessments were checked by a third review author.\ud \ud Main results\ud We included seven RCTs, six of which provided data on 1610 women and their babies. Studies were undertaken between 1998 and 2015, and all were in high‐ or upper‐middle income countries. Most women were induced for post dates. Three studies reported government funding, one reported no funding and three did not report on their funding source. Most GRADE assessments gave very low‐certainty evidence, downgrading mostly for high risk of bias and serious imprecision.\ud \ud 1. Home compared to inpatient induction with vaginal prostaglandin E (PGE) (two RCTs, 1028 women and babies; 1022 providing data).\ud \ud Although women's satisfaction may be slightly better in home settings, the evidence is very uncertain (mean difference (MD) 0.16, 95% confidence interval (CI) ‐0.02 to 0.34, 1 study, 399 women), very low‐certainty evidence.\ud \ud There may be little or no difference between home and inpatient induction for other primary outcomes, with all evidence being very low certainty:\ud \ud ‐ spontaneous vaginal birth (average risk ratio (RR) [aRR] 0.91, 95% CI 0.69 to 1.21, 2 studies, 1022 women, random‐effects method);\ud \ud ‐ uterine hyperstimulation (RR 1.19, 95% CI 0.40 to 3.50, 1 study, 821 women);\ud \ud ‐ caesarean birth (RR 1.01, 95% CI 0.81 to 1.28, 2 studies, 1022 women);\ud \ud ‐ neonatal infection (RR 1.29, 95% CI 0.59 to 2.82, 1 study, 821 babies);\ud \ud ‐ admission to neonatal intensive care unit (NICU) (RR 1.20, 95% CI 0.50 to 2.90, 2 studies, 1022 babies).\ud \ud Studies did not report serious neonatal morbidity or mortality.\ud \ud 2. Home compared to inpatient induction with controlled release PGE (one RCT, 299 women and babies providing data).\ud \ud There was no information on whether the questionnaire on women's satisfaction with care used a validated instrument, but the findings presented showed no overall difference in scores.\ud \ud We found little or no difference between the groups for other primary outcomes, all also being very low‐certainty evidence:\ud \ud ‐ spontaneous vaginal birth (RR 0.94, 95% CI 0.77 to 1.14, 1 study, 299 women);\ud \ud ‐ uterine hyperstimulation (RR 1.01, 95% CI 0.51 to 1.98, 1 study, 299 women);\ud \ud ‐ caesarean births (RR 0.95, 95% CI 0.64 to 1.42, 1 study, 299 women);\ud \ud ‐ admission to NICU (RR 1.38, 0.57 to 3.34, 1 study, 299 babies).\ud \ud The study did not report on neonatal infection nor serious neonatal morbidity or mortality.\ud \ud 3. Home compared to inpatient induction with balloon or Foley catheter (four RCTs; three studies, 289 women and babies providing data).\ud \ud It was again unclear whether questionnaires reporting women's experiences/satisfaction with care were validated instruments, with one study (48 women, 69% response rate) finding women were similarly satisfied.\ud \ud Home inductions may reduce the number of caesarean births, but the data are also compatible with a slight increase and are of very low‐certainty (RR 0.64, 95% CI 0.41 to 1.01, 2 studies, 159 women).\ud \ud There was little or no difference between the groups for other primary outcomes with all being very low‐certainty evidence:\ud \ud ‐ spontaneous vaginal birth (RR 1.04, 95% CI 0.54 to 1.98, 1 study, 48 women):\ud \ud ‐ uterine hyperstimulation (RR 0.45, 95% CI 0.03 to 6.79, 1 study, 48 women);\ud \ud ‐ admission to NICU (RR 0.37, 95% CI 0.07 to 1.86, 2 studies, 159 babies).\ud \ud There were no serious neonatal infections nor serious neonatal morbidity or mortality in the one study (involving 48 babies) assessing these outcomes.\ud \ud Authors' conclusions\ud Data on the effectiveness, safety and women's experiences of home versus inpatient induction of labour are limited and of very low‐certainty. Given that serious adverse events are likely to be extremely rare, the safety data are more likely to come from very large observational cohort studies rather than relatively small RCTs.