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

INTRODUCTION: To 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 ANALYSIS: We 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 DISSEMINATION: For 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.