Concerns about data integrity across 263 papers by one author.

OBJECTIVE: Comprehensive investigation of published work by authors suspected of academic misconduct can reveal further concerns. We aimed to test for data integrity concerns in papers published by an author with eight retracted articles. STUDY DESIGN: We investigated the integrity of all papers reporting on prospective clinical studies by this author. We assessed the feasibility of study methods, baseline characteristics, and outcomes. We plotted the author's clinical research activity over time. We conducted pairwise comparisons of text, tables, and figures to identify duplicate publications, and checked for consistency between conference abstracts, interim analyses, trial registrations, and final papers. Where indicated, we recalculated p-values from the reported summary statistics. RESULTS: We identified 263 papers claiming to have enrolled 74,667 participants between January 2009 and July 2022, 190 (72%) of which reported on studies that recruited from the Assiut Women's Health Hospital in Assiut, Egypt. The number of active studies per month was greatest between 2016 and 2019, with 88 ongoing studies in May 2017. We found evidence of data integrity concerns in 130 (49%) papers, 43 (33%) of which contained concerns sufficient to suggest that they could not be based on data reliably collected from human participants. CONCLUSION: Our investigation finds evidence of widespread integrity concerns in the collected work of one author. We recommend that the involved journals collaborate in a formal investigation.

Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

The carbon footprint of different modes of birth in the UK and the Netherlands: An exploratory study using life cycle assessment.

OBJECTIVE: To compare the carbon footprint of caesarean and vaginal birth. DESIGN: Life cycle assessment (LCA). SETTING: Tertiary maternity units and home births in the UK and the Netherlands. POPULATION: Birthing women. METHODS: A cradle-to-grave LCA using openLCA software to model the carbon footprint of different modes of delivery in the UK and the Netherlands. MAIN OUTCOME MEASURES: 'Carbon footprint' (in kgCO2 equivalents [kgCO2 e]). RESULTS: Excluding analgesia, the carbon footprint of a caesarean birth in the UK was 31.21 kgCO2 e, compared with 12.47 kgCO2 e for vaginal birth in hospital and 7.63 kgCO2 e at home. In the Netherlands the carbon footprint of a caesarean was higher (32.96 kgCO2 e), but lower for vaginal birth in hospital and home (10.74 and 6.27 kgCO2 e, respectively). Emissions associated with analgesia for vaginal birth ranged from 0.08 kgCO2 e (with opioid analgesia) to 237.33 kgCO2 e (nitrous oxide with oxygen). Differences in analgesia use resulted in a lower average carbon footprint for vaginal birth in the Netherlands than the UK (11.64 versus 193.26 kgCO2 e). CONCLUSION: The carbon footprint of a caesarean is higher than for a vaginal birth if analgesia is excluded, but this is very sensitive to the analgesia used; use of nitrous oxide with oxygen multiplies the carbon footprint of vaginal birth 25-fold. Alternative methods of pain relief or nitrous oxide destruction systems would lead to a substantial improvement in carbon footprint. Although clinical need and maternal choice are paramount, protocols should consider the environmental impact of different choices.

Checklist to assess Trustworthiness in RAndomised Controlled Trials (TRACT checklist): concept proposal and pilot.

OBJECTIVES: To propose a checklist that can be used to assess trustworthiness of randomized controlled trials (RCTs). DESIGN: A screening tool was developed using the four-stage approach proposed by Moher et al. This included defining the scope, reviewing the evidence base, suggesting a list of items from piloting, and holding a consensus meeting. The initial checklist was set-up by a core group who had been involved in the assessment of problematic RCTs for several years. We piloted this in a consensus panel of several stakeholders, including health professionals, reviewers, journal editors, policymakers, researchers, and evidence-synthesis specialists. Each member was asked to score three articles with the checklist and the results were then discussed in consensus meetings. OUTCOME: The Trustworthiness in RAndomised Clinical Trials (TRACT) checklist includes 19 items organised into seven domains that are applicable to every RCT: 1) Governance, 2) Author Group, 3) Plausibility of Intervention Usage, 4) Timeframe, 5) Drop-out Rates, 6) Baseline Characteristics, and 7) Outcomes. Each item can be answered as either no concerns, some concerns/no information, or major concerns. If a study is assessed and found to have a majority of items rated at a major concern level, then editors, reviewers or evidence synthesizers should consider a more thorough investigation, including assessment of original individual participant data. CONCLUSIONS: The TRACT checklist is the first checklist developed specifically to detect trustworthiness issues in RCTs. It might help editors, publishers and researchers to screen for such issues in submitted or published RCTs in a transparent and replicable manner.

Effectiveness of laparoscopic removal of isolated superficial peritoneal endometriosis for the management of chronic pelvic pain in women (ESPriT2): protocol for a multi-centre randomised controlled trial.

BACKGROUND: Endometriosis affects 190 million women and those assigned female at birth worldwide. For some, it is associated with debilitating chronic pelvic pain. Diagnosis of endometriosis is often achieved through diagnostic laparoscopy. However, when isolated superficial peritoneal endometriosis (SPE), the most common endometriosis subtype, is identified during laparoscopy, limited evidence exists to support the common decision to surgically remove it via excision or ablation. Improved understanding of the impact of surgical removal of isolated SPE for the management of chronic pelvic pain in women is required. Here, we describe our protocol for a multi-centre trial to determine the effectiveness of surgical removal of isolated SPE for the management of endometriosis-associated pain. METHODS: We plan to undertake a multi-centre participant-blind parallel-group randomised controlled clinical and cost-effectiveness trial with internal pilot. We plan to randomise 400 participants from up to 70 National Health Service Hospitals in the UK. Participants with chronic pelvic pain awaiting diagnostic laparoscopy for suspected endometriosis will be consented by the clinical research team. If isolated SPE is identified at laparoscopy, and deep or ovarian endometriosis is not seen, participants will be randomised intraoperatively (1:1) to surgical removal (by excision or ablation or both, according to surgeons' preference) versus diagnostic laparoscopy alone. Randomisation with block-stratification will be used. Participants will be given a diagnosis but will not be informed of the procedure they received until 12 months post-randomisation, unless required. Post-operative medical treatment will be according to participants' preference. Participants will be asked to complete validated pain and quality of life questionnaires at 3, 6 and 12 months after randomisation. Our primary outcome is the pain domain of the Endometriosis Health Profile-30 (EHP-30), via a between randomised group comparison of adjusted means at 12 months. Assuming a standard deviation of 22 points around the pain score, 90% power, 5% significance and 20% missing data, 400 participants are required to be randomised to detect an 8-point pain score difference. DISCUSSION: This trial aims to provide high quality evidence of the clinical and cost-effectiveness of surgical removal of isolated SPE. TRIAL REGISTRATION: ISRCTN registry ISRCTN27244948. Registered 6 April 2021.

WILL (When to induce labour to limit risk in pregnancy hypertension): Protocol for a multicentre randomised trial.

OBJECTIVES: To address optimal timing of birth for women with chronic or gestational hypertension who reach term and remain well. STUDY DESIGN: Pragmatic, non-masked randomised trial. INCLUSION: maternal age ≥16 years, chronic or gestational hypertension, singleton pregnancy, live fetus, 36+0-37+6 weeks' gestation, and able to give documented informed consent. EXCLUSION: contraindication to either trial arm (e.g., pre-eclampsia or another indication for birth at term), blood pressure (BP) ≥ 160/110 mmHg until controlled, major fetal anomaly anticipated to require neonatal care unit admission, or participation in another timing of birth trial. Randomisation (1:1 ratio, minimised for key prognostic variables: site, hypertension type, and prior Caesarean) to 'planned early term birth at 38+0-3 weeks' or 'usual care at term' (revised from 'expectant care until at least 40+0 weeks', Aug 2022). OUTCOMES: Maternal co-primary: composite of 'poor maternal outcome' (severe hypertension, maternal death, or maternal morbidity). Neonatal co-primary: neonatal care unit admission for ≥4 h. Each co-primary is measured until primary hospital discharge or 28 days post-birth (whichever is earlier). Key secondary: Caesarean birth. ANALYSIS: Sample of 1080 participants (540/arm) will detect an 8% reduction in the maternal co-primary (90% power, superiority hypothesis), and give 94% power for a between-group non-inferiority margin of difference of 9% in the neonatal co-primary. Analysis will be by intention-to-treat. Ethics approval has been obtained (NHS Health Research Authority London Fulham Research Ethics Committee, 18/LO/2033). CONCLUSIONS: The study will provide data for women to make informed choices about their care and allow health systems to plan services.

Feasibility of a RCT of techniques for managing an impacted fetal head during emergency caesarean section: the MIDAS scoping study.

Background: Second-stage caesarean sections, of which there are around 34,000 per year in the UK, have greater maternal and perinatal morbidity than those in the first stage. The fetal head is often deeply impacted in the maternal pelvis, and extraction can be difficult. Numerous techniques are reported, but the superiority of one over another is contentious and there is no national guidance. Objective: To determine the feasibility of a randomised trial of different techniques for managing an impacted fetal head during emergency caesarean. Design: A scoping study with five work packages: (1) national surveys to determine current practice and acceptability of research in this area, and a qualitative study to determine acceptability to women who have experienced a second-stage caesarean; (2) a national prospective observational study to determine incidence and rate of complications; (3) a Delphi survey and consensus meeting on choice of techniques and outcomes for a trial; (4) the design of a trial; and (5) a national survey and qualitative study to determine acceptability of the proposed trial. Setting: Secondary care. Participants: Health-care professionals, pregnant women, women who have had a second-stage caesarean, and parents. Results: Most (244/279, 87%) health-care professionals believe that a trial in this area would help guide their practice, and 90% (252/279) would be willing to participate in such a trial. Thirty-eight per cent (98/259) of parents reported that they would take part. Women varied in which technique they thought was most acceptable. Our observational study found that impacted head is common (occurring in 16% of second-stage caesareans) and leads to both maternal (41%) and neonatal (3.5%) complications. It is most often treated by an assistant pushing the head up vaginally. We designed a randomised clinical trial comparing the fetal pillow with the vaginal push technique. The vast majority of health-care professionals, 83% of midwives and 88% of obstetricians, would be willing to participate in the trial proposed, and 37% of parents reported that they would take part. Our qualitative study found that most participants thought the trial would be feasible and acceptable. Limitations: Our survey is subject to the limitation that, although responses refer to contemporaneous real cases, they are self-reported by the surgeon and collected after the event. Willingness to participate in a hypothetical trial may not translate into recruitment to a real trial. Conclusions: We proposed a trial to compare a new device, the fetal pillow, with a long-established procedure, the vaginal push technique. Such a trial would be widely supported by health-care professionals. We recommend that it be powered to test an effect on important short term maternal and baby outcomes which would require 754 participants per group. Despite the well-known difference between intent and action, this would be feasible within the UK. Future work: We recommend a randomised controlled trial of two techniques for managing an impacted fetal head with an in-built internal pilot phase and alongside economic and qualitative substudies. Study registration: This study is registered as Research Registry 4942. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 6. See the NIHR Journals Library website for further project information.

Text: One-quarter of UK pregnant women have a caesarean section. Most of these procedures are straightforward, but in a small number of cases unexpected complications can make the birth difficult. One complication, an impacted fetal head, may happen when caesarean sections are done in the second 'pushing' stage of labour. If the baby's head is low and wedged in the woman's pelvis, lifting it can be difficult, which can result in damage to the mother's womb and vagina, and to her baby. Occasionally, babies die. There are different techniques doctors and midwives can use to make these births easier, but there is uncertainty around which is best. To plan a trial to test these techniques, we needed to know how often impacted head happens, what techniques are used to manage it and whether or not research is acceptable to parents and health-care professionals. We surveyed doctors and midwives to find out which techniques they use and what training they need. We surveyed parents and pregnant women and interviewed women who had experienced a second-stage caesarean. We collected information from UK hospitals to find out how common this is and the impact on women and babies. We found out the following. List: • Around 7% of caesareans take place in second stage, and impacted fetal head occurs in 16% of these births. List: • One-third of women would consent to take part in a trial, if the complication happened to them. List: • Nearly all midwives and doctors thought that this research was important and would be willing to take part. Text: Using all of the information we collected, we designed a clinical trial. We wanted to compare two techniques for managing an impacted fetal head. The first is the vaginal push technique, where the doctor or midwife puts their hand into the mother's vagina to push her baby's head up, and the second is the fetal pillow, a device inserted into the mother's vagina before the operation starts to dislodge the baby's head upwards.

Induction of labour at or near term for suspected fetal macrosomia.

BACKGROUND: Women with a suspected large-for-dates fetus or a fetus with suspected macrosomia (birthweight greater than 4000 g) are at risk of operative birth or caesarean section. The baby is also at increased risk of shoulder dystocia and trauma, in particular fractures and brachial plexus injury. Induction of labour may reduce these risks by decreasing the birthweight, but may also lead to longer labours and an increased risk of caesarean section. OBJECTIVES: To assess the effects of a policy of labour induction at or shortly before term (37 to 40 weeks) for suspected fetal macrosomia on the way of giving birth and maternal or perinatal morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2016), contacted trial authors and searched reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials of induction of labour for suspected fetal macrosomia. DATA COLLECTION AND ANALYSIS: Review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We contacted study authors for additional information. For key outcomes the quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: We included four trials, involving 1190 women. It was not possible to blind women and staff to the intervention, but for other 'Risk of bias' domains these studies were assessed as being at low or unclear risk of bias. Compared to expectant management, there was no clear effect of induction of labour for suspected macrosomia on the risk of caesarean section (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.76 to 1.09; 1190 women; four trials, moderate-quality evidence) or instrumental delivery (RR 0.86, 95% CI 0.65 to 1.13; 1190 women; four trials, low-quality evidence). Shoulder dystocia (RR 0.60, 95% CI 0.37 to 0.98; 1190 women; four trials, moderate-quality evidence), and fracture (any) (RR 0.20, 95% CI 0.05 to 0.79; 1190 women; four studies, high-quality evidence) were reduced in the induction of labour group. There were no clear differences between groups for brachial plexus injury (two events were reported in the control group in one trial, low-quality evidence). There was no strong evidence of any difference between groups for measures of neonatal asphyxia; low five-minute infant Apgar scores (less than seven) or low arterial cord blood pH (RR 1.51, 95% CI 0.25 to 9.02; 858 infants; two trials, low-quality evidence; and, RR 1.01, 95% CI 0.46 to 2.22; 818 infants; one trial, moderate-quality evidence, respectively). Mean birthweight was lower in the induction group, but there was considerable heterogeneity between studies for this outcome (mean difference (MD) -178.03 g, 95% CI -315.26 to -40.81; 1190 infants; four studies; I2 = 89%).  For outcomes assessed using GRADE, we based our downgrading decisions on high risk of bias from lack of blinding and imprecision of effect estimates. AUTHORS' CONCLUSIONS: Induction of labour for suspected fetal macrosomia has not been shown to alter the risk of brachial plexus injury, but the power of the included studies to show a difference for such a rare event is limited. Also antenatal estimates of fetal weight are often inaccurate so many women may be worried unnecessarily, and many inductions may not be needed. Nevertheless, induction of labour for suspected fetal macrosomia results in a lower mean birthweight, and fewer birth fractures and shoulder dystocia. The observation of increased use of phototherapy in the largest trial, should also be kept in mind. Findings from trials included in the review suggest that to prevent one fracture it would be necessary to induce labour in 60 women. Since induction of labour does not appear to alter the rate of caesarean delivery or instrumental delivery, it is likely to be popular with many women. In settings where obstetricians can be reasonably confident about their scan assessment of fetal weight, the advantages and disadvantages of induction at or near term for fetuses suspected of being macrosomic should be discussed with parents. Although some parents and doctors may feel the evidence already justifies induction, others may justifiably disagree. Further trials of induction shortly before term for suspected fetal macrosomia are needed. Such trials should concentrate on refining the optimum gestation of induction, and improving the accuracy of the diagnosis of macrosomia.

Full-term induction of labor vs expectant management and cesarean delivery in women with obesity: systematic review and meta-analysis.

OBJECTIVE: This study aimed to review the literature comparing full-term induction of labor with expectant management in women with obesity on the risk of cesarean delivery and other adverse outcomes. DATA SOURCES: A literature search was performed on PubMed, EMBASE, Scopus, ClinicalTrials.gov, and the Cochrane Library. This study had no time, language, or geographic restriction. STUDY ELIGIBILITY CRITERIA: Studies were eligible if (1) they were cohort or randomized controlled trials, (2) they compared induction of labor at early or late term with expectant management, and (3) they included women with a body mass index of ≥30 kg/m2. Studies restricted to women with multiple pregnancy, premature rupture of membranes, or noncephalic presentation were excluded. The primary outcome was cesarean delivery. The secondary outcomes included maternal and neonatal mortality and morbidities and were evaluated. METHODS: The risk of bias was assessed by 2 authors using the Risk of Bias In Non-Randomized Studies of Interventions tool. Only studies assessed with low or moderate risk of bias contributed to the meta-analysis. Data were combined to pooled relative risks and 95% confidence intervals using random effects models. The quality of evidence was assessed for selected outcomes. RESULTS: Of the 232 studies identified, 13 were aligned with the inclusion criteria, and 4 cohort studies, including 216,318 women with induction of labor and 1,122,769 women managed expectantly, were included in the meta-analysis for the primary outcome. In women with obesity, full-term induction of labor was associated with a lower risk of cesarean delivery than expectant management (19.7% vs 24.5%; relative risk, 0.71; 95% confidence interval, 0.63-0.81). Moreover, this study found the same direction of the association for other selected outcomes: severe perineal lacerations (relative risk, 0.65; 95% confidence interval, 0.48-0.89), maternal infection (relative risk, 0.42; 95% confidence interval, 0.21-0.84), perinatal mortality (relative risk, 0.41; 95% confidence interval, 0.18-0.90), low Apgar score (relative risk, 0.48; 95% confidence interval, 0.26-0.91), meconium aspiration syndrome (relative risk, 0.40; 95% confidence interval, 0.28-0.56), and macrosomia (relative risk, 0.57; 95% confidence interval, 0.43-0.75). Conversely, induction of labor was associated with an increased risk of instrumental vaginal delivery (relative risk, 1.12; 95% confidence interval, 1.02-1.22). The quality of evidence ranged from low to very low. CONCLUSION: Full-term induction of labor in women with obesity may reduce the risk of cesarean delivery compared with expectant management, but the quality of the evidence is low.

Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

BACKGROUND: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. METHODS: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. FINDINGS: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose. INTERPRETATION: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. FUNDING: None.

Concerns about Data Integrity of 22 Randomized Controlled Trials in Women's Health.

OBJECTIVE: During a review on postpartum hemorrhage, we identified randomized controlled trials (RCTs) of one author conducted at the same time and place for the same condition, with large differences in baseline characteristics. We assessed the data integrity of the RCTs of this author. STUDY DESIGN: We undertook a focused analysis of the data integrity of all RCTs published by Dr. Ahmed M. Maged. We examined the studies for clinical logic and made pairwise comparisons of baseline characteristics and outcomes between trials. We used mathematical methods to assess whether the distribution of baseline characteristics was compatible with chance. RESULTS: Between March 2015 and December 2019, Dr. Maged published 22 RCTs (n = 3,722). The median number of participants randomized per center per month was 32 (range = 1-89). Fifteen studies were either not or retrospectively registered, with one study registered 1 year after publication. One study was submitted for publication prior to the completion of the described study period. There were many unusual findings in the studies, including biologically implausible occurrences such as the absence of an association between gestational age and birthweight in seven studies and very different body mass index between three trials, which ran at the same time in the same hospital on the same topic as well as unlikely occurrences such as limited participant drop outs. One paper contained considerable text duplication and identical data to that in a paper published by a different author group from a different hospital, with both papers submitted at the same time. Mathematical analysis of the baseline characteristics of all 22 trials indicated that at least some of the reported baseline characteristics were unlikely to be the result of proper randomization. CONCLUSION: Our analyses of the 22 RCTs of Dr. Maged suggest potential data integrity issues in at least some of them. We suggest that journals investigate according to the Committee on Publication Ethics guidelines. The procedures demonstrated in this paper may help to assess data integrity in future attempts to verify the authenticity of published RCTs. KEY POINTS: · We identified a number of findings biologically implausible in RCTs by Maged.. · Monte Carlo simulation found pooled data of Maged RCTs were unlikely result of proper randomization.. · Textual overlap and almost identical data were found between a Maged paper and another paper.. · The methods we described may be useful for future efforts in validating scientific data integrity..

WILL (When to Induce Labour to Limit risk in pregnancy hypertension): a multicentre randomised controlled trial - adaptations to deliver a timing-of-birth trial during the COVID-19 international pandemic.

BACKGROUND: As a pragmatic randomised timing-of-birth trial, WILL adapted its trial procedures in response to the COVID-19 pandemic. These are reviewed here to inform post-pandemic trial methodology. METHODS: The trial (internal pilot) paused in March 2020, re-opened in July 2020, and is currently recruiting in 37 UK NHS consultant-led maternity units. We evaluated pandemic adaptations made to WILL processes and surveyed sites for their views of these changes (20 sites, videoconference). RESULTS: Despite 88% of sites favouring an electronic investigator site file (ISF), information technology requirements and clinical trial unit (CTU) operating procedures mandated the ongoing use of paper ISFs; site start-up delays resulted from restricted access to the CTU. Site initiation visits (SIVs) were conducted remotely; 50% of sites preferred remote SIVs and 44% felt that it was trial-dependent, while few preferred SIVs in-person as standard procedure. The Central team felt remote SIVs provided scheduling and attendance flexibility (for sites and trial staff), the option of recording discussions for missing or future staff, improved efficiency by having multiple sites attend, and time and cost savings; the negative impact on rapport-building and interaction was partially mitigated over time with more familiarity with technology and new ways-of-working. Two methods of remote consent were developed and used by 30/37 sites and for 54/156 recruits. Most (86%) sites using remote consenting felt it improved recruitment. For remote data monitoring (5 sites), advantages were primarily for the monitor (e.g. flexibility, no time constraints, reduced cost), and disadvantages primarily for the sites (e.g. document and access preparation, attendance at a follow-up meeting), but 81% of sites desired having the option of remote monitoring post-pandemic. CONCLUSIONS: COVID adaptations to WILL trial processes improved the flexibility of trial delivery, for Central and site staff, and participants. Flexibility to use these strategies should be retained post-pandemic. TRIAL REGISTRATION: ISRCTN77258279. Registered on 05 December 2018.

Recruitment of pregnant women to randomised trials of COVID 19 treatments, and pharmaceutical treatments received outside such trials: A research article.

OBJECTIVES: To document how many pregnant women with COVID-19 reported in the literature had participated in randomised trials, what treatments they received outside such trials and compare the latter with evidence-based treatment recommendations. STUDY DESIGN: A systematic review of observational studies. METHODS: Two clinical trial registries were searched to identify COVID-19 trials open to pregnant women. Studies were then extracted from a regularly updated list of scientific case reports and case series of confirmed or suspected maternal COVID-19 in pregnancy to identify the number of women enrolled into a trial and the pharmaceutical treatments they received outside such trials. RESULTS: 156 studies (case reports, case series and registries) reporting 43,185 pregnant women with COVID-19, after de-duplication. Of these 2,671 (6.2%) were potentially eligible for a randomised trial but only seven women (0.26%) were reported to have enrolled. For 2,839 women the papers included information on treatment received, 1515/2829 (54%) women had received ≥ 1 treatment and in total a COVID-19 pharmaceutical treatment was administered 1,296 times outside of a trial. In 566 (44%) cases the treatments administered to the pregnant women were not recommended by the National Institutes of Health (NIH) at the time of administration. Of 179 case reports of women with COVID 19 in pregnancy, 109/179 women received ≥ 1 COVID-19 pharmaceutical treatment and in total COVID-19 experimental pharmaceutical treatments were administered 274 times. CONCLUSION: During the early phase of the COVID-19 pandemic, pregnant women excluded from randomised trials did not avoid unproven or ineffective treatments.

Induction of labour at 39 weeks versus expectant management in low-risk obese women: study protocol for a randomised controlled study.

INTRODUCTION: Obesity is associated with many pregnancy complications, including both fetal macrosomia and prolonged labour. As a result, there is often also an increased risk of caesarean section. In other settings, labour induction near to term reduces adverse outcomes such as stillbirth and birth injury, without causing more caesarean deliveries. It has been suggested that induction will reduce adverse events in this setting too, but there have been no trials and the effect on caesarean section is unknown. The objective of this study is to compare induction of labour in gestational week 39 with expectant management on the risk of caesarean section in women with body mass index ≥30 kg/m2. METHODS AND ANALYSIS: An open label randomised controlled multicentre trial are conducted at Danish delivery departments with an in-house neonatal intensive care unit. Recruitment started October 2020. A total of 1900 women with a prepregnancy body mass index ≥30 kg/m2 are randomised in a 1:1 ratio to either labour induction at 39 weeks and 0 to 3 days of gestation or to expectant management; that is, waiting for spontaneous labour onset or induction if medically indicated. The primary outcome is caesarean section. Data will be analysed according to intention-to-treat. ETHICS AND DISSEMINATION: The Central Denmark Region Committee on Biomedical Research Ethics approved the study. The study is conducted in accordance with the ethical principles outlined in the latest version of the 'Declaration of Helsinki' and the 'Guideline for Good Clinical Practice' related to experiments on humans. The trial findings will be disseminated to participants, clinicians, commissioning groups and via peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04603859.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

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.

Impacted fetal head during second stage Caesarean birth: A prospective observational study.

OBJECTIVE: To determine the incidence of, and complication rates from, impacted fetal head at full dilatation Caesarean birth in the UK, and record what techniques were used. DESIGN: Prospective observational study using the UK Obstetric Surveillance System (UKOSS). SETTING: 159 (82%) of the 194 UK hospitals with obstetric units. POPULATION: All women who underwent second stage Caesarean birth in the UK between 1st March and 31st August 2019. Further information was collected on cases where a dis-impaction technique was used, or the operating surgeon experienced 'difficulty' in delivering the head. METHODS: Prospective observational study. MAIN OUTCOME MEASURES: Technique(s) used, maternal and neonatal outcomes. RESULTS: 3,518 s stage Caesarean births reported. The surgeon used a dis-impaction technique or reported 'difficulty' in 564 (16%) of these. The most common dis-impaction techniques used were manual elevation of the head by an assistant through the vagina (n = 235) and a fetal "pillow" (n = 176). Thirteen babies (2%) died or sustained severe injury. Four babies died (two directly attributable to the impacted fetal head). CONCLUSIONS: Difficulty with delivery of the fetal head and the use of dis-impaction techniques during second stage Caesarean sections are common but there is no consensus as to the best method to achieve delivery and in what order.