Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage.

BACKGROUND: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28). CONCLUSIONS: Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).

Repeat placental growth factor-based testing in women with suspected preterm pre-eclampsia (PARROT-2): a multicentre, parallel-group, superiority, randomised controlled trial.

BACKGROUND: Placental growth factor (PlGF)-based testing has high diagnostic accuracy for predicting pre-eclampsia needing delivery, significantly reducing time to diagnosis and severe maternal adverse outcomes. The clinical benefit of repeat PlGF-based testing is unclear. We aimed to determine whether repeat PlGF-based testing (using a clinical management algorithm and nationally recommended thresholds) reduces adverse perinatal outcomes in pregnant individuals with suspected preterm pre-eclampsia. METHODS: In this multicentre, parallel-group, superiority, randomised controlled trial, done in 22 maternity units across England, Scotland, and Wales, we recruited women aged 18 years or older with suspected pre-eclampsia between 22 weeks and 0 days of gestation and 35 weeks and 6 days of gestation. Women were randomly assigned (1:1) to revealed repeat PlGF-based testing or concealed repeat testing with usual care. The intervention was not masked to women or partners, or clinicians or data collectors, due to the nature of the trial. The trial statistician was masked to intervention allocation. The primary outcome was a perinatal composite of stillbirth, early neonatal death, or neonatal unit admission. The primary analysis was by the intention-to-treat principle, with a per-protocol analysis restricted to women managed according to their allocation group. The trial was prospectively registered with the ISRCTN registry, ISRCTN 85912420. FINDINGS: Between Dec 17, 2019, and Sept 30, 2022, 1253 pregnant women were recruited and randomly assigned treatment; one patient was excluded due to randomisation error. 625 women were allocated to revealed repeat PlGF-based testing and 627 women were allocated to usual care with concealed repeat PlGF-based testing (mean age 32·3 [SD 5·7] years; 879 [70%] white). One woman in the concealed repeat PlGF-based testing group was lost to follow-up. There was no significant difference in the primary perinatal composite outcome between the revealed repeat PlGF-based testing group (195 [31·2%]) of 625 women) compared with the concealed repeat PlGF-based testing group (174 [27·8%] of 626 women; relative risk 1·21 [95% CI 0·95-1·33]; p=0·18). The results from the per-protocol analysis were similar. There were four serious adverse events in the revealed repeat PlGF-based testing group and six in the concealed repeat PlGF-based testing group; all serious adverse events were deemed unrelated to the intervention by the site principal investigators and chief investigator. INTERPRETATION: Repeat PlGF-based testing in pregnant women with suspected pre-eclampsia was not associated with improved perinatal outcomes. In a high-income setting with a low prevalence of adverse outcomes, universal, routine repeat PlGF-based testing of all individuals with suspected pre-eclampsia is not recommended. FUNDING: Tommy's Charity, Jon Moulton Charitable Trust, and National Institute for Health and Care Research Guy's and St Thomas' Biomedical Research Centre.

Planned delivery or expectant management for late preterm pre-eclampsia in low-income and middle-income countries (CRADLE-4): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality. Evidence regarding interventions in a low-income or middle-income setting is scarce. We aimed to evaluate whether planned delivery between 34+ 0 and 36+ 6 weeks' gestation can reduce maternal mortality and morbidity without increasing perinatal complications in India and Zambia. METHODS: In this parallel-group, multicentre, open-label, randomised controlled trial, we compared planned delivery versus expectant management in women with pre-eclampsia from 34+ 0 to 36+ 6 weeks' gestation. Participants were recruited from nine hospitals and referral facilities in India and Zambia and randomly assigned to planned delivery or expectant management in a 1:1 ratio by a secure web-based randomisation facility hosted by MedSciNet. Randomisation was stratified by centre and minimised by parity, single-fetus pregnancy or multi-fetal pregnancy, and gestational age. The primary maternal outcome was a composite of maternal mortality or morbidity with a superiority hypothesis. The primary perinatal outcome was a composite of one or more of: stillbirth, neonatal death, or neonatal unit admission of more than 48 h with a non-inferiority hypothesis (margin of 10% difference). Analyses were by intention to treat, with an additional per-protocol analysis for the perinatal outcome. The trial was prospectively registered with ISRCTN, 10672137. The trial is closed to recruitment and all follow-up has been completed. FINDINGS: Between Dec 19, 2019, and March 31, 2022, 565 women were enrolled. 284 women (282 women and 301 babies analysed) were allocated to planned delivery and 281 women (280 women and 300 babies analysed) were allocated to expectant management. The incidence of the primary maternal outcome was not significantly different in the planned delivery group (154 [55%]) compared with the expectant management group (168 [60%]; adjusted risk ratio [RR] 0·91, 95% CI 0·79 to 1·05). The incidence of the primary perinatal outcome by intention to treat was non-inferior in the planned delivery group (58 [19%]) compared with the expectant management group (67 [22%]; adjusted risk difference -3·39%, 90% CI -8·67 to 1·90; non-inferiority p<0·0001). The results from the per-protocol analysis were similar. There was a significant reduction in severe maternal hypertension (adjusted RR 0·83, 95% CI 0·70 to 0·99) and stillbirth (0·25, 0·07 to 0·87) associated with planned delivery. There were 12 serious adverse events in the planned delivery group and 21 in the expectant management group. INTERPRETATION: Clinicians can safely offer planned delivery to women with late preterm pre-eclampsia, in a low-income or middle-income country. Planned delivery reduces stillbirth, with no increase in neonatal unit admissions or neonatal morbidity and reduces the risk of severe maternal hypertension. Planned delivery from 34 weeks' gestation should therefore be considered as an intervention to reduce pre-eclampsia associated mortality and morbidity in these settings. FUNDING: UK Medical Research Council and Indian Department of Biotechnology.

Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis.

BACKGROUND: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored. OBJECTIVES: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP. SEARCH STRATEGY: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023. SELECTION CRITERIA: We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications. DATA COLLECTION AND ANALYSIS: We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology. MAIN RESULTS: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I2 = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I2 = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I2 = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I2 = 0%; low-certainty evidence). CONCLUSIONS: Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.

Functional assessment of brain development in fetuses that subsequently deliver very preterm: An MRI pilot study.

OBJECTIVES: To evaluate changes occurring in the fetal brain prior to very preterm delivery using MRI T2* relaxometry, an indirect assessment of tissue perfusion. METHOD: Fetuses that subsequently delivered spontaneously <32 weeks gestation and a control cohort were identified from pre-existing datasets. Participants had undergone a 3T MRI assessment including T2* relaxometry of the fetal brain using a 2D multi-slice gradient echo single shot echo planar imaging sequence. T2* maps were generated, supratentorial brain tissue was manually segmented and mean T2* values were generated. Groups were compared using quadratic regression. RESULTS: Twenty five fetuses that subsequently delivered <32 weeks and 67 that delivered at term were included. Mean gestation at MRI was 24.5 weeks (SD 3.3) and 25.4 weeks (SD 3.1) and gestation at delivery 25.5 weeks (SD 3.4) and 39.7 weeks (SD 1.2) in the preterm and term cohorts respectively. Brain mean T2* values were significantly lower in fetuses that subsequently delivered before 32 weeks gestation (p < 0.001). CONCLUSION: Alterations in brain maturation appear to occur prior to preterm delivery. Further work is required to explore these associations, but these findings suggest a potential window for therapeutic neuroprotective agents in fetuses at high risk of preterm delivery in the future.

Midwife continuity of care models versus other models of care for childbearing women.

BACKGROUND: Midwives are primary providers of care for childbearing women globally and there is a need to establish whether there are differences in effectiveness between midwife continuity of care models and other models of care. This is an update of a review published in 2016. OBJECTIVES: To compare the effects of midwife continuity of care models with other models of care for childbearing women and their infants. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Trials Register, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) (17 August 2022), as well as the reference lists of retrieved studies. SELECTION CRITERIA: All published and unpublished trials in which pregnant women are randomly allocated to midwife continuity of care models or other models of care during pregnancy and birth. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion criteria, scientific integrity, and risk of bias, and carried out data extraction and entry. Primary outcomes were spontaneous vaginal birth, caesarean section, regional anaesthesia, intact perineum, fetal loss after 24 weeks gestation, preterm birth, and neonatal death. We used GRADE to rate the certainty of evidence. MAIN RESULTS: We included 17 studies involving 18,533 randomised women. We assessed all studies as being at low risk of scientific integrity/trustworthiness concerns. Studies were conducted in Australia, Canada, China, Ireland, and the United Kingdom. The majority of the included studies did not include women at high risk of complications. There are three ongoing studies targeting disadvantaged women. Primary outcomes Based on control group risks observed in the studies, midwife continuity of care models, as compared to other models of care, likely increase spontaneous vaginal birth from 66% to 70% (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.03 to 1.07; 15 studies, 17,864 participants; moderate-certainty evidence), likelyreduce caesarean sections from 16% to 15% (RR 0.91, 95% CI 0.84 to 0.99; 16 studies, 18,037 participants; moderate-certainty evidence), and likely result in little to no difference in intact perineum (29% in other care models and 31% in midwife continuity of care models, average RR 1.05, 95% CI 0.98 to 1.12; 12 studies, 14,268 participants; moderate-certainty evidence). There may belittle or no difference in preterm birth (< 37 weeks) (6% under both care models, average RR 0.95, 95% CI 0.78 to 1.16; 10 studies, 13,850 participants; low-certainty evidence). We arevery uncertain about the effect of midwife continuity of care models on regional analgesia (average RR 0.85, 95% CI 0.79 to 0.92; 15 studies, 17,754 participants, very low-certainty evidence), fetal loss at or after 24 weeks gestation (average RR 1.24, 95% CI 0.73 to 2.13; 12 studies, 16,122 participants; very low-certainty evidence), and neonatal death (average RR 0.85, 95% CI 0.43 to 1.71; 10 studies, 14,718 participants; very low-certainty evidence). Secondary outcomes When compared to other models of care, midwife continuity of care models likely reduce instrumental vaginal birth (forceps/vacuum) from 14% to 13% (average RR 0.89, 95% CI 0.83 to 0.96; 14 studies, 17,769 participants; moderate-certainty evidence), and may reduceepisiotomy 23% to 19% (average RR 0.83, 95% CI 0.77 to 0.91; 15 studies, 17,839 participants; low-certainty evidence). When compared to other models of care, midwife continuity of care models likelyresult in little to no difference inpostpartum haemorrhage (average RR 0.92, 95% CI 0.82 to 1.03; 11 studies, 14,407 participants; moderate-certainty evidence) and admission to special care nursery/neonatal intensive care unit (average RR 0.89, 95% CI 0.77 to 1.03; 13 studies, 16,260 participants; moderate-certainty evidence). There may be little or no difference in induction of labour (average RR 0.92, 95% CI 0.85 to 1.00; 14 studies, 17,666 participants; low-certainty evidence), breastfeeding initiation (average RR 1.06, 95% CI 1.00 to 1.12; 8 studies, 8575 participants; low-certainty evidence), and birth weight less than 2500 g (average RR 0.92, 95% CI 0.79 to 1.08; 9 studies, 12,420 participants; low-certainty evidence). We are very uncertain about the effect of midwife continuity of care models compared to other models of care onthird or fourth-degree tear (average RR 1.10, 95% CI 0.81 to 1.49; 7 studies, 9437 participants; very low-certainty evidence), maternal readmission within 28 days (average RR 1.52, 95% CI 0.78 to 2.96; 1 study, 1195 participants; very low-certainty evidence), attendance at birth by a known midwife (average RR 9.13, 95% CI 5.87 to 14.21; 11 studies, 9273 participants; very low-certainty evidence), Apgar score less than or equal to seven at five minutes (average RR 0.95, 95% CI 0.72 to 1.24; 13 studies, 12,806 participants; very low-certainty evidence) andfetal loss before 24 weeks gestation (average RR 0.82, 95% CI 0.67 to 1.01; 12 studies, 15,913 participants; very low-certainty evidence). No maternal deaths were reported across three studies. Although the observed risk of adverse events was similar between midwifery continuity of care models and other models, our confidence in the findings was limited. Our confidence in the findings was lowered by possible risks of bias, inconsistency, and imprecision of some estimates. There were no available data for the outcomes: maternal health status, neonatal readmission within 28 days, infant health status, and birth weight of 4000 g or more. Maternal experiences and cost implications are described narratively. Women receiving care from midwife continuity of care models, as opposed to other care models, generally reported more positive experiences during pregnancy, labour, and postpartum. Cost savings were noted in the antenatal and intrapartum periods in midwife continuity of care models. AUTHORS' CONCLUSIONS: Women receiving midwife continuity of care models were less likely to experience a caesarean section and instrumental birth, and may be less likely to experience episiotomy. They were more likely to experience spontaneous vaginal birth and report a positive experience. The certainty of some findings varies due to possible risks of bias, inconsistencies, and imprecision of some estimates. Future research should focus on the impact on women with social risk factors, and those at higher risk of complications, and implementation and scaling up of midwife continuity of care models, with emphasis on low- and middle-income countries.

Adrenal volumes in fetuses delivering prior to 32 weeks' gestation: An MRI pilot study.

INTRODUCTION: Spontaneous preterm birth prior to 32 weeks' gestation accounts for 1% of all deliveries and is associated with high rates of morbidity and mortality. A total of 70% are associated with chorioamnionitis which increases the incidence of morbidity, but for which there is no noninvasive antenatal test. Fetal adrenal glands produce cortisol and dehydroepiandosterone-sulphate which upregulate prior to spontaneous preterm birth. Ultrasound suggests that adrenal volumes may increase prior to preterm birth, but studies are limited. This study aimed to: (i) demonstrate reproducibility of magnetic resonance imaging (MRI) derived adrenal volumetry; (ii) derive normal ranges of total adrenal volumes, and adrenal: body volume for normal; (iii) compare with those who have spontaneous very preterm birth; and (iv) correlate with histopathological chorioamnionitis. MATERIAL AND METHODS: Patients at high risk of preterm birth prior to 32 weeks were prospectively recruited, and included if they did deliver prior to 32 weeks; a control group who delivered an uncomplicated pregnancy at term was also recruited. T2 weighted images of the entire uterus were obtained, and a deformable slice-to-volume method was used to reconstruct the fetal abdomen. Adrenal and body volumes were obtained via manual segmentation, and adrenal: body volume ratios generated. Normal ranges were created using control data. Differences between groups were investigated accounting for the effect of gestation by use of regression analysis. Placental histopathology was reviewed for pregnancies delivering preterm. RESULTS: A total of 56 controls and 26 cases were included in the analysis. Volumetry was consistent between observers. Adrenal volumes were not higher in the case group (p = 0.2); adrenal: body volume ratios were higher (p = 0.011), persisting in the presence of chorioamnionitis (p = 0.017). A cluster of three pairs of adrenal glands below the fifth centile were noted among the cases all of whom had a protracted period at risk of preterm birth prior to MRI. CONCLUSIONS: Adrenal: body volume ratios are significantly larger in fetuses who go on to deliver preterm than those delivering at term. Adrenal volumes were not significantly larger, we hypothesize that this could be due to an adrenal atrophy in fetuses with fulminating chorioamnionitis. A straightforward relationship of adrenal size being increased prior to preterm birth should not be assumed.

The Fetal Spleen in Low-Risk Pregnancies and prior to Preterm Birth: Observational Study of the Role of Anatomical and Functional Magnetic Resonance Imaging.

INTRODUCTION: Spontaneous preterm birth complicates ∼7% of pregnancies and causes morbidity and mortality. Although infection is a common etiology, our understanding of the fetal immune system in vivo is limited. This study aimed to utilize T2-weighted imaging and T2* relaxometry (which is a proxy of tissue oxygenation) of the fetal spleen in uncomplicated pregnancies and in fetuses that were subsequently delivered spontaneously prior to 32 weeks. METHODS: Women underwent imaging including T2-weighted fetal body images and multi-eco gradient echo single-shot echo planar sequences on a Phillips Achieva 3T system. Previously described postprocessing techniques were applied to obtain T2- and T2*-weighted imaging of the fetal spleen and T2-weighted fetal body volumes. RESULTS: Among 55 women with uncomplicated pregnancies, an increase in fetal splenic volume, splenic:body volume, and a decrease in splenic T2* signal intensity was demonstrated across gestation. Compared to controls, fetuses who were subsequently delivered prior to 32 weeks' gestation (n = 19) had a larger spleen when controlled for the overall size of the fetus (p = 0.027), but T2* was consistent (p = 0.76). CONCLUSION: These findings provide evidence of a replicable method of studying the fetal immune system and give novel results on the impact of impending preterm birth on the spleen. While T2* decreases prior to preterm birth in other organs, preservation demonstrated here suggests preferential sparing of the spleen.

Preterm premature rupture of the membranes (PPROM): a study of patient experiences and support needs.

BACKGROUND: Preterm prelabour rupture of membranes (PPROM) is a common obstetric condition but outcomes can vary depending on gestation. Significant maternal and foetal complications occur including preterm birth, infection, abruption, cord prolapse, pulmonary hypoplasia and even death. Although the need for psychological support is recognised it is unclear how much is actually offered to women and their families. This study aimed to survey the views of women and their families who have undergone PPROM in order to understand the care and psychological burden these families face. METHODS: An online survey was conducted, recruiting women via social media with collaboration from the patient advocacy support group Little Heartbeats. Responses were collated where fields were binary or mean and standard deviations calculated. Framework analysis was used to identify and analyse themes in free text responses. RESULTS: 180PPROM pregnancies were described from 177 respondents. Although carewas variable and respondents were from across the world there werecommon themes. Five themes were highlighted which were: a lack ofbalanced information regarding the condition, support in decisionmaking and support with the process, specific psychological supportand ongoing psychological consequences of PPROM. CONCLUSION: This survey highlights areas in which care needs to be improved for women with PPROM. Previous studies have shown that providing good care during the antenatal period reduces long-term psychological morbidity for the whole family. The need for support, with regard both to information provided to women and their families and their psychological support needs to be addressed urgently.

Monofilament suture versus braided suture thread to improve pregnancy outcomes after vaginal cervical cerclage (C-STICH): a pragmatic randomised, controlled, phase 3, superiority trial.

BACKGROUND: Miscarriage in the second trimester and preterm birth are significant global problems. Vaginal cervical cerclage is performed to prevent pregnancy loss and preterm birth. We aimed to determine the effectiveness of a monofilament suture thread compared with braided suture thread on pregnancy loss rates in women undergoing a cervical cerclage. METHODS: C-STICH was a pragmatic, randomised, controlled, superiority trial done at 75 obstetric units in the UK. Women with a singleton pregnancy who received a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were centrally randomised (1:1) using minimisation to receive a monofilament suture or braided suture thread for their cervical cerclage. Women and outcome assessors were masked to allocation as far as possible. The primary outcome was pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life, analysed in the intention-to-treat population (ie, all women who were randomly assigned). Safety was also assessed in the intention-to-treat population. The trial was registered with ISRCTN, ISRCTN15373349. FINDINGS: Between Aug 21, 2015, and Jan 28, 2021, 2049 women were randomly assigned to receive a monofilament suture (n=1025) or braided suture (n=1024). The primary outcome was ascertained in 1003 women in the monofilament suture group and 993 women in the braided suture group. Pregnancy loss occurred in 80 (8·0%) of 1003 women in the monofilament suture group and 75 (7·6%) of 993 women in the braided suture group (adjusted risk ratio 1·05 [95% CI 0·79 to 1·40]; adjusted risk difference 0·002 [95% CI -0·02 to 0·03]). INTERPRETATION: Monofilament suture did not reduce rate of pregnancy loss when compared with a braided suture. Clinicians should use the results of this trial to facilitate discussions around the choice of suture thread to optimise outcomes. FUNDING: National Institute of Health Research Health Technology Assessment Programme.

Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis.

BACKGROUND: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. OBJECTIVES: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. DATA SOURCES: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). STUDY SELECTION AND DATA EXTRACTION: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. RESULTS: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2  = 62%, and 0.59 (95% CI 0.42, 0.82), I2  = 0 before; and 0.95 (95% CI 0.81, 1.11), I2  = 59%, and 0.90 (95% CI: 0.72, 1.12), I2  = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. CONCLUSIONS: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.

Googling preterm prelabour rupture of the membranes: A systematic review of patient information available on the internet.

BACKGROUND: Preterm prelabour rupture of the membranes (PPROM) complicates 3% of pregnancies and is associated with an increased risk of maternal and perinatal morbidity and mortality. In an attempt to better understand this diagnosis, patients routinely resort to the internet for medical information. The lack of governance online leaves patients at risk of relying on low-quality websites. OBJECTIVES: To assess systematically the accuracy, quality, readability and credibility of World Wide Web pages on PPROM. SEARCH STRATEGY: Five search engines (Google, AOL, Yahoo, Ask and Bing) were searched with location services and browser history disabled. Websites from the first page of all searches were included. SELECTION CRITERIA: Websites were included if they provided at least 300 words of health information aimed at patients relating to PPROM. DATA COLLECTION AND ANALYSIS: Validated assessments of health information readability, credibility and quality were undertaken, as was an accuracy assessment. Pertinent facts for accuracy assessment were based on feedback from healthcare professionals and patients through a survey. Characteristics were tabulated. MAIN RESULTS: In all, 39 websites were included, with 31 different texts. No pages were written with a reading age of 11 years or less, none were considered credible, and only three were high quality. An accuracy score of 50% or more was obtained by 45% of websites. Information that patients considered pertinent was not consistently reported. CONCLUSIONS: Search engines produce information on PPROM that is low quality, low accuracy and not credible. It is also difficult to read. This risks disempowerment. Healthcare professionals and researchers must consider how to ensure patients have access to information that they can recognise as high quality.

Antenatal detection of large-for-gestational-age fetuses following implementation of the Growth Assessment Protocol: secondary analysis of a randomised control trial.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP) affects the antenatal detection of large for gestational age (LGA) or maternal and perinatal outcomes amongst LGA babies. DESIGN: Secondary analysis of a pragmatic open randomised cluster control trial comparing the GAP with standard care. SETTING: Eleven UK maternity units. POPULATION: Pregnant women and their LGA babies born at ≥36+0  weeks of gestation. METHODS: Clusters were randomly allocated to GAP implementation or standard care. Data were collected from electronic patient records. Trial arms were compared using summary statistics, with unadjusted and adjusted (two-stage cluster summary approach) differences. MAIN OUTCOME MEASURES: Rate of detection of LGA (estimated fetal weight on ultrasound scan above the 90th centile after 34+0  weeks of gestation, defined by either population or customised growth charts), maternal and perinatal outcomes (e.g. mode of birth, postpartum haemorrhage, severe perineal tears, birthweight and gestational age, neonatal unit admission, perinatal mortality, and neonatal morbidity and mortality). RESULTS: A total of 506 LGA babies were exposed to GAP and 618 babies received standard care. There were no significant differences in the rate of LGA detection (GAP 38.0% vs standard care 48.0%; adjusted effect size -4.9%; 95% CI -20.5, 10.7; p = 0.54), nor in any of the maternal or perinatal outcomes. CONCLUSIONS: The use of GAP did not change the rate of antenatal ultrasound detection of LGA when compared with standard care.

"I had given up on being a mother": a survey of 183 women's experience of transabdominal cerclage (TAC).

BACKGROUND: Transabdominal cerclage (TAC) is a relatively uncommon intervention for preventing preterm birth. This study aimed to investigate the experience of women who had undergone this procedure. METHODS: The survey was designed in collaboration with a preterm birth studies public and patient involvement (PPI) group and ethical approval was granted by KCL BDM Research Ethics Panel (LRS-19/20-13205). Members of closed Facebook group, UK TAC Support, were invited to complete an online questionnaire about their experience of TAC, and pregnancies before and after having it placed. The survey was open between December 2019 and May 2020. Open and closed questions provided both qualitative and quantitative data for analysis, which was carried out using NVivo Pro 2020 v.1.4.1 qualitative data management software and SPSS Statistics 27 (IBM). RESULTS: One hundred eighty-three participants completed the survey, having had TAC procedures carried out in 36 hospitals. Altogether, participants had experienced 287 preterm births (PTB) and late miscarriages (LM), equating to an average of 1.6 each (range 0-5), including 18 stillbirths. TAC was indicated in 123 (67%) for previous PTB and/or LM, 29 (16%) for cervical surgery and 31 (17%) for both. 151 (83%) TAC procedures were open, 32 (17%) laparoscopic. 86% (n = 157) were placed outside pregnancy. Of those placed in pregnancy, gestation at TAC ranged from 7 to 16 weeks. When comparing earliest pre- and post-TAC pregnancy gestation (excluding first trimester losses), median gestational weeks gained following TAC was 15.5 weeks (SD 6.89). Qualitative themes included: the struggle to get treatment; lack of TAC knowledge amongst clinicians; gratitude, hope and feeling protected; possible detrimental effects of TAC. CONCLUSIONS: This very high-risk group found having a TAC gave great reassurance and hope, and were very grateful to have found the care they needed. However, they often struggled to get this support, frequently due to lack of clinician awareness. This may improve following roll-out of NHS England's Saving Babies Live Care Bundle and NHS commissioning guidelines for care of women at risk of PTB.

How are hospitals in England caring for women at risk of preterm birth in 2021? The influence of national guidance on preterm birth care in England: a national questionnaire.

BACKGROUND: National guidance (Saving Babies Lives Care Bundle Version 2 (SBLCBv2) Element 5) was published in 2019, with the aim to standardise preterm care in England. We plan to identify how many preterm birth surveillance clinics there are in England, and to define current national management in caring for women who are both asymptomatic and high-risk of preterm birth, and who arrive symptomatically in threatened preterm labour, to assist preterm management both nationally and internationally. METHODS: An online survey comprising of 27 questions was sent to all maternity units in England between February 2021 to July 2021. RESULTS: Data was obtained from 96 units. Quantitative analysis and free text analysis was then undertaken. We identified 78 preterm birth surveillance clinics in England, an increase from 30 preterm clinics in 2017. This is a staggering 160% increase in 4 years. SBLCBv2 has had a considerable impact in increasing preterm birth surveillance clinic services, with the majority (61%) of sites reporting that the NHS England publication influenced their unit in setting up their clinic. Variations exist at every step of the preterm pathway, such as deciding which risk factors warrant referral, distinguishing within particular risk factors, and offering screening tests and treatment options. CONCLUSIONS: While variations in care still do persist, hospitals have done well to increase preterm surveillance clinics, under the difficult circumstances of the COVID pandemic and many without specific additional funding.

Breech specialist midwives and clinics in the OptiBreech Trial feasibility study: An implementation process evaluation.

BACKGROUND: Attendance of skilled and experienced professionals at breech births has been associated with a reduction in adverse perinatal outcomes. We aimed to determine whether United Kingdom National Health Service (NHS) sites could reliably provide attendants with OptiBreech training and/or advanced proficiency (intervention feasibility) and consistent care (fidelity) that meets women's needs (acceptability), with low neonatal admission rates (safety) and recruitment adequate to support a clinical trial (trial feasibility). METHODS: Mixed methods implementation evaluation was used. Settings were 13 services in England and Wales. Participants were 82 women requesting support for a vaginal breech birth (VBB) at term. Outcomes were descriptively analyzed. Twenty-one women were interviewed, and transcripts were analyzed using the Theoretical Framework of Acceptability. Iterative analysis informed subsequent interviews and the ongoing process of implementation across sites. RESULTS: Although we initially suggested multidisciplinary teams, actively recruiting Trusts yielded services where VBB care was provided through a dedicated clinic, organized and delivered primarily by a lead midwife who functioned as a specialist. This model achieved 87.5% fidelity with the intervention's goal of ensuring the attendance of OptiBreech-trained professionals. Neonatal outcomes remained stable, with an admission rate of 5.5%. Women reported care from specialist midwives as highly acceptable, but the model is vulnerable without a strategic effort to develop additional proficient team members. CONCLUSIONS: Dedicated clinics coordinated by specialist midwives appear to be an acceptable and feasible implementation strategy to test the safety and effectiveness of proficient team care for VBB in a clinical trial. Back-up arrangements should be maintained while additional members of the team develop proficiency.

Scale-up of a novel vital signs alert device to improve maternity care in Sierra Leone: a mixed methods evaluation of adoption.

BACKGROUND: The CRADLE (Community blood pressure monitoring in Rural Africa: Detection of underLying pre-Eclampsia) Vital Signs Alert device-designed specifically to improve maternity care in low resource settings-had varying impact when trialled in different countries. To better understand the contextual factors that may contribute to this variation, this study retrospectively evaluated the adoption of CRADLE, during scale-up in Sierra Leone. METHODS: This was a mixed methods study. A quantitative indicator of adoption (the proportion of facilities trained per district) was calculated from existing training records, then focus groups were held with 'CRADLE Champions' in each district (n = 32), to explore adoption qualitatively. Template Analysis was used to deductively interpret qualitative data, guided by the NASSS (non-adoption, abandonment, scale-up, spread, sustainability) Framework. FINDINGS: Substantial but non-significant variation was found in the proportion of facilities trained in each district (range 59-90%) [X2 (7, N = 8) = 10.419, p = 0.166]. Qualitative data identified complexity in two NASSS domains that may have contributed to this variation: 'the technology' (for example, charging issues, difficulty interpreting device output and concerns about ongoing procurement) and 'the organisation' (for example, logistical barriers to implementing training, infighting and high staff turnover). Key strategies mentioned to mitigate against these issues included: transparent communication at all levels; encouraging localised adaptations during implementation (including the involvement of community leaders); and selecting Champions with strong soft skills (particularly conflict resolution and problem solving). CONCLUSIONS: Complexity related to the technology and the organisational context were found to influence the adoption of CRADLE in Sierra Leone, with substantial inter-district variation. These findings emphasise the importance of gaining an in-depth understanding of the specific system and context in which a new healthcare technology is being implemented. This study has implications for the ongoing scale-up of CRADLE, and for those implementing or evaluating other health technologies in similar contexts.

Many women die during pregnancy and childbirth from causes that could be prevented, and the vast majority of these deaths occur in low-resource settings. The 'CRADLE Vital Signs Alert' is a medical device that helps identify problems during pregnancy­designed specifically for healthcare professionals in low-resource settings. However, for unknown reasons, the device appears to have varying impact according to the country or setting in which it is used. This study aimed to explore in depth whether, and why, healthcare professionals in Sierra Leone adopted the device and engaged in training (or not). Between March 2020 and January 2021, the CRADLE device and training package was disseminated across 8 districts in Sierra Leone. This relied on a few healthcare workers (nominated 'CRADLE Champions') to voluntarily distribute the devices and training in their local areas. Group discussions were held with CRADLE Champions in each district after the rollout to gather their feedback. In addition, the proportion of facilities trained in each district was recorded. The study found differences in how well the device and training was adopted in each district. Common challenges reported across districts related to technological difficulties (such as issues charging the devices) and organisational barriers (such as high levels of staff turnover at facilities). These findings will help to inform future rollout of the CRADLE device and training in Sierra Leone and highlight factors that may need to be considered by those implementing other health technologies in similar settings.

Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial.

BACKGROUND: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. METHODS AND FINDINGS: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes. CONCLUSIONS: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings. TRIAL REGISTRATION: This trial is registered with the ISRCTN registry, ISRCTN67698474.

The assessment of blood pressure in pregnant women: pitfalls and novel approaches.

Accurate assessment of blood pressure is fundamental to the provision of safe obstetrical care. It is simple, cost effective, and life-saving. Treatments for preeclampsia, including antihypertensive drugs, magnesium sulfate, and delivery, are available in many settings. However, the instigation of appropriate treatment relies on prompt and accurate recognition of hypertension. There are a number of different techniques for blood pressure assessment, including the auscultatory method, automated oscillometric devices, home blood pressure monitoring, ambulatory monitoring, and invasive monitoring. The auscultatory method with a mercury sphygmomanometer and the use of Korotkoff sounds was previously recommended as the gold standard technique. Mercury sphygmomanometers have been withdrawn owing to safety concerns and replaced with aneroid devices, but these are particularly prone to calibration errors and regular calibration is imperative to ensure accuracy. Automated oscillometric devices are straightforward to use, but the physiological changes in healthy pregnancy and pathologic changes in preeclampsia may affect the accuracy of a device and monitors must be validated. Validation protocols classify pregnant women as a "special population," and protocols must include 15 women in each category of normotensive pregnancy, hypertensive pregnancy, and preeclampsia. In addition to a scarcity of devices validated for pregnancy and preeclampsia, other pitfalls that cause inaccuracy include the lack of training and poor technique. Blood pressure assessment can be affected by maternal position, inappropriate cuff size, conversation, caffeine, smoking, and irregular heart rate. For home blood pressure monitoring, appropriate instruction should be given on how to use the device. The classification of hypertension and hypertensive disorders of pregnancy has recently been revised. These are classified as preeclampsia, transient gestational hypertension, gestational hypertension, white-coat hypertension, masked hypertension, chronic hypertension, and chronic hypertension with superimposed preeclampsia. Blood pressure varies across gestation and by ethnicity, but gestation-specific thresholds have not been adopted. Hypertension is defined as a sustained systolic blood pressure of ≥140 mm Hg or a sustained diastolic blood pressure of ≥90 mm Hg. In some guidelines, the threshold of diagnosis depends on the setting in which blood pressure measurement is taken, with a threshold of 140/90 mm Hg in a healthcare setting, 135/85 mm Hg at home, or a 24-hour average blood pressure on ambulatory monitoring of >126/76 mm Hg. Some differences exist among organizations with respect to the criteria for the diagnosis of preeclampsia and the correct threshold for intervention and target blood pressure once treatment has been instigated. Home blood pressure monitoring is currently a focus for research. Novel technologies, including early warning devices (such as the CRADLE Vital Signs Alert device) and telemedicine, may provide strategies that prompt earlier recognition of abnormal blood pressure and therefore improve management. The purpose of this review is to provide an update on methods to assess blood pressure in pregnancy and appropriate technique to optimize accuracy. The importance of accurate blood pressure assessment is emphasized with a discussion of preeclampsia prediction and treatment of severe hypertension. Classification of hypertensive disorders and thresholds for treatment will be discussed, including novel developments in the field.

Planned delivery or expectant management in preeclampsia: an individual participant data meta-analysis.

OBJECTIVE: Pregnancy hypertension is a leading cause of maternal and perinatal mortality and morbidity. Between 34+0 and 36+6 weeks gestation, it is uncertain whether planned delivery could reduce maternal complications without serious neonatal consequences. In this individual participant data meta-analysis, we aimed to compare planned delivery to expectant management, focusing specifically on women with preeclampsia. DATA SOURCES: We performed an electronic database search using a prespecified search strategy, including trials published between January 1, 2000 and December 18, 2021. We sought individual participant-level data from all eligible trials. STUDY ELIGIBILITY CRITERIA: We included women with singleton or multifetal pregnancies with preeclampsia from 34 weeks gestation onward. METHODS: The primary maternal outcome was a composite of maternal mortality or morbidity. The primary perinatal outcome was a composite of perinatal mortality or morbidity. We analyzed all the available data for each prespecified outcome on an intention-to-treat basis. For primary individual patient data analyses, we used a 1-stage fixed effects model. RESULTS: We included 1790 participants from 6 trials in our analysis. Planned delivery from 34 weeks gestation onward significantly reduced the risk of maternal morbidity (2.6% vs 4.4%; adjusted risk ratio, 0.59; 95% confidence interval, 0.36-0.98) compared with expectant management. The primary composite perinatal outcome was increased by planned delivery (20.9% vs 17.1%; adjusted risk ratio, 1.22; 95% confidence interval, 1.01-1.47), driven by short-term neonatal respiratory morbidity. However, infants in the expectant management group were more likely to be born small for gestational age (7.8% vs 10.6%; risk ratio, 0.74; 95% confidence interval, 0.55-0.99). CONCLUSION: Planned early delivery in women with late preterm preeclampsia provides clear maternal benefits and may reduce the risk of the infant being born small for gestational age, with a possible increase in short-term neonatal respiratory morbidity. The potential benefits and risks of prolonging a pregnancy complicated by preeclampsia should be discussed with women as part of a shared decision-making process.