Development of a core outcome set for immunomodulation in pregnancy (COSIMPREG): a protocol for a systematic review and Delphi study

Abstract

IntroductionTo establish pregnancy, the maternal immune system must adapt to tolerate the semiallogenic fetus. Less than optimal adaptation of the maternal immune system during (early) pregnancy is implicated in several complications of pregnancy. The development of effective immune modulation interventions as preventive or therapeutic strategies for pregnancy complications holds promise. Several studies sought to evaluate the safety and effectiveness of various approaches. However, a limitation is the high variability in clinical and immune outcomes that are reported. We, therefore, aim to develop a core outcome set for application to studies of immune modulation in pregnancy (COSIMPREG).Methods and analysisWe will use a stepwise approach to develop a COSIMPREG. First, we will perform a systematic review to identify reported outcomes. For this review, Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. Second, we will use the Delphi method to develop a preliminary COSIMPREG. In three rounds, the outcomes of the systematic review will be scored. A panel comprising experts from relevant disciplines and diverse geographical locations will be assembled until a sufficient quality of the panel is reached. We will use predefined decision rules for outcomes. After each round outcomes, including scores, will be returned to the panel for further refinement. The outcomes not excluded after the third round will be taken to a consensus meeting. In this meeting, experts from all relevant disciplines will discuss and finalise the COSIMPREG.Ethics and disseminationFor this study ethical approval is not required. The systematic review will be published in an appropriate open access reproductive immunology journal. Once the COSIMPREG is finalised, it will be published in an open access reproductive immunology journal, and disseminated at appropriate international meetings, as well as through relevant research and scientific societies. Experts involved in the Delphi study will be asked to give informed consent.

The Role of Regulatory T Cells and Their Therapeutic Potential in Hypertensive Disease of Pregnancy; A Literature Review

“…There are broadly two schools of thought in the existing literature: using ex-vivo expanded Treg populations directly as therapy or using other medicines to increase Treg numbers/function. These other therapies include preconception strategies and pharmacological intervention [48,63,[79][80][81]. Strategies to increase or maintain endogenous Tregs preconception are mainly theoretical, with little literature available.…”

“…A wide range of markers is used to predict HDP in research, reflected in clinical practice [63]. Progressing in this area of research will require a consensus on which Treg markers to measure and their minimum levels; tools such as those developed by Prins et al [79] will be central to standardising the clinical and immune outcomes measured and compared. Extensive cytometry marker panels that consider standard Treg and emerging markers will likely need to be developed.…”

The Role of Regulatory T Cells and Their Therapeutic Potential in Hypertensive Disease of Pregnancy: A Literature Review

“…There is a shortage of literature exploring the therapeutic potential of Tregs in HDP [67,69,70]. There are, broadly, two schools of thought in the existing literature: using ex vivo expanded Treg populations directly as therapy or using other medicines to increase Treg numbers/function.…”

“…A wide range of markers is used to predict HDP in research, reflected in clinical practice [58]. Progressing in this area of research will require a consensus on which Treg markers to measure and their minimum levels; tools such as those developed by Prins et al [70] will be central to standardising the clinical and immune outcomes measured and compared. Extensive cytometry marker panels that consider standard Treg and emerging markers will likely need to be developed.…”

Therapeutic Potential of Regulatory T Cells in Preeclampsia—Opportunities and Challenges

“…A recent meta-analysis of Treg cell parameters quantified in preeclampsia highlights the considerable variability in markers that different groups have measured to date (67). A useful step will be to develop a consensus definition of minimum essential Treg markers to facilitate harmonization across future studies, and to determine the best stage in preconception cycles or early pregnancy for analysis (164). Given the significance of tTreg cells vs. pTreg cells, and of naïve vs. memory cells in preeclampsia (68, 69), extensive marker panels to discriminate these subsets in flow cytometry-based tests will be most informative.…”