Systemic lupus erythematosus, regulatory T cells and pregnancy

Systemic lupus erythematosus (SLE) is the most common autoimmune disease affecting women of reproductive age and is associated with poor maternal and fetal outcomes. CD4 +CD25 + Treg cells are a subset of T lymphocytes with potent immunosuppressive activity that play crucial roles in controlling immunological self tolerance. Evidence suggests that they are augmented in pregnancy, especially in the first trimester, suggesting an important role in early placental development. The literature describing Treg cells in SLE is conflicting, but SLE is associated with reduced numbers and functionally defective Treg cells, which may predispose pregnant women with the disease to pregnancy complications. This article discusses the role of Treg cells in SLE and pregnancy, and how these cells may contribute to poor pregnancy outcome in SLE-affected women. © 2011 Expert Reviews Ltd

Routine testing for group B streptococcus in pregnancy: protocol for a UK cluster randomised trial (GBS3)

Introduction It is unclear whether routine testing of women for group B streptococcus (GBS) colonisation either in late pregnancy or during labour reduces early-onset neonatal sepsis, compared with a risk factor-based strategy.Methods and analysis Cluster randomised trial.Sites and participants 320 000 women from up to 80 hospital maternity units.Strategies Sites will be randomised 1:1 to a routine testing strategy or the risk factor-based strategy, using a web-based minimisation algorithm. A second-level randomisation allocates routine testing sites to either antenatal enriched culture medium testing or intrapartum rapid testing. Intrapartum antibiotic prophylaxis will be offered if a test is positive for GBS, or if a maternal risk factor for early-onset GBS infection in her baby is identified before or during labour. Economic and acceptability evaluations will be embedded within the trial design.Outcomes The primary outcome is all-cause early (<7 days of birth) neonatal sepsis, defined as either a positive blood/cerebrospinal fluid culture, early neonatal death from infection or a negative/unknown culture status with ≥3 agreed clinical signs or symptoms, who receive intravenous antibiotics ≥5 days. All women giving birth ≥24 weeks’ gestation, regardless of mode of birth, and all her babies will be included in the dataset. Cost-effectiveness will be expressed in terms of incremental cost per case of early neonatal sepsis avoided and incremental cost per quality-adjusted life-year associated with each strategy.Ethics and dissemination The trial received a favourable opinion from Derby Research Ethics Committee on 16 September 2019 (19/EM/0253). The allocated testing strategy will be adopted as standard clinical practice by the site. Women in the routine testing sites will give verbal consent for the test. The trial will use routinely collected data retrieved from National Health Service databases, supplemented with limited participant-level collection of process outcomes. Individual written consent will not be sought. The trial results, and parallel economic, qualitative, implementation and methodological results, will be published in the journal Health Technology Assessment.Trial registration number ISRCTN49639731

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

© 2022 The Authors, published by BMC. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1186/s13063-022-06834-4Background: 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.NIHR Health Technology Assessment (HTA) programme is funding the WILL trial. HTA Project: 16/167/123 — WILL (When to Induce Labour to Limit risk in pregnancy hypertension) — a multicentre, randomised controlled trial.Published versio