Clinical Opinion
Mapping the theories of preeclampsia: The need for systematic reviews of mechanisms of the disease

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Preeclampsia, a major cause of morbidity in pregnancy, is still a disease of unknown cause, despite considerable research in recent times. We believe that progress in understanding the disorder would be enhanced if the systematic review methodology, similar to that used to assess data from clinical trials, is applied to studies that investigate the many theories advanced to explain its cause. This article discusses the need for and a frame work of such an endeavor. The systematic review approach helps to determine where research should be focused, to prioritize the use of resources, to understand, and then hopefully to conquer a disease that still kills mothers and infants each year, worldwide.

Section snippets

Conceptual framework: Systematic reviews to study mechanisms in preeclampsia

When faced with an extensive literature on disease mechanisms and their implications, assessment of causation is challenging.8 This is aggravated by the “citation bias” that exists in narrative reviews of investigators interested in supporting a given hypothesis. Often primary studies focus on a small part of a complex biologic chain of events. Some may provide information on the initial (etiologic) events; others evaluate the subsequent sequence of events (pathophysiology) that lead to

Generating hypotheses on the disease mechanisms in preeclampsia

In an exercise seeking evidence on the mechanisms proposed to explain the development of preeclampsia, we carried out an electronic search in MEDLINE (1980-2004) for the concept “preeclampsia” and “mechanisms of disease” combining appropriate MESH terms, text words, and word variants, without language restrictions. Citations on both primary research and reviews examining these mechanisms increased over recent years. Contrary to the case of systematic reviews of clinical trials, narrative

Implications for practice and research

A scientific strategy based on systematic literature review methodology can be developed to assess the hypothesized mechanisms in preeclampsia. They can help to understand current controversies and uncertainties and to identify gaps in the research evidence.4 However, with few exceptions,5, 13, 34, 35, 36 there is almost nothing published about how disease mechanisms could be assessed using systematic reviews. In Figure 3 we describe the main principles of reviews of mechanisms of disease. We

Acknowledgments

J.V., L.M., and K.S.K. conceptualized, developed, and applied systematic review methods to study mechanisms in preeclampsia. L.M. undertook the relevant reviews under supervision of K.S.K. and J.V.

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    Supported by a Research Training Grant from WHO/World Bank Special Programme of Research, Department of Reproductive health and Research, World Health Organization, Geneva, Switzerland (L.E.M).

    Reprints not available from the authors.

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