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Executive summary: Workshop on Preeclampsia, January 25–26, 2021, cosponsored by the Society for Maternal-Fetal Medicine and the Preeclampsia Foundation
Preeclampsia is a substantial cause of maternal and perinatal morbidity and mortality. The prevalence of this condition has increased over the past several decades.
Additional opportunities are needed to foster interdisciplinary collaborations and improve patient care in the setting of preeclampsia. In recognition of the Preeclampsia Foundation’s 20th anniversary and its work to advance preeclampsia research and clinical agendas, a 2-day workshop on preeclampsia was cosponsored by the Society for Maternal-Fetal Medicine and the Preeclampsia Foundation and held in conjunction with the 41st Annual Pregnancy Meeting. Leaders with expertise in preeclampsia research, obstetrical care, primary care medicine, cardiology, endocrinology, and patient advocacy gathered to discuss preeclampsia prediction, prevention, management, and long-term impacts. The goals of the workshop were to review existing knowledge and create consensus concerning research and clinical priorities:
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To present innovative opportunities for research on predicting, preventing, and managing preeclampsia
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To review benefits and challenges associated with various strategies for prediction, prevention, and management of preeclampsia
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To identify research gaps for the prediction, prevention, and management of preeclampsia
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To discuss needs and opportunities for research, increasing awareness, and risk mitigation of the long-term impacts of preeclampsia
This executive summary briefly reviews the main outcomes of the workshop. A research paper that presents detailed clinical guidance and proposes future research directions will be published at a later date.
Background
Evidence presented at the workshop demonstrates that preeclampsia continues to be associated with substantial health risks during and after pregnancy, and there are ample opportunities to improve prediction and prevention of preeclampsia and management of patients with this disorder:
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Preeclampsia is prevalent, occurring in 5% to 7% of pregnancies, representing approximately 10,000,000 pregnancies per year worldwide.
The incidence of preeclampsia increased by 25% between 1987 and 2004, potentially related to population-level increases in known risk factors for preeclampsia, such as prepregnancy overweight and obesity, diabetes mellitus, multiple births, and increased maternal age.
In low- and middle-income countries, a history of chronic hypertension is associated with an approximately 8-fold increased risk of preeclampsia-related maternal death.
Improving outcomes related to preeclampsia globally will require ensuring access to quality care, addressing systemic and community factors impacting health outcomes, investing in innovative care delivery models, and adapting guidelines to be context-appropriate.
Specific interventions include access to and training in the appropriate utilization of magnesium sulfate, antihypertensive drugs, urine dipstick tests, and functional blood pressure machines.
Black women in the United States are at an increased risk of hypertensive disorders of pregnancy, and hypertension and cardiovascular diseases are more frequently associated with morbidity and mortality among Black women than White women.
Exposure to systemic racism and discrimination resulting in chronic stress and implicit and explicit biases within the healthcare system leading to inequitable treatment have been posited as contributors to these inequities in health outcomes.
Several risk factors for preeclampsia have recently been validated, such as mental health disorders and sleep-disordered breathing:
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In the Heart Health 4 Moms study of women with a recent pregnancy complicated by preeclampsia, 15% of participants had probable depression, and 23% endorsed ≥4 posttraumatic stress disorder (PTSD) symptoms specific to their pregnancy.
Stuart JJ. The impact of preeclampsia on long-term mental health. Oral presentation at: Preeclampsia Workshop; 41st Annual Pregnancy Meeting; January 25, 2021; Virtual.
In early and midpregnancy, there is an increased risk of preeclampsia when sleep-disordered breathing is present (adjusted odds ratio [aOR] for early pregnancy, 1.94; 95% CI, 1.07–3.51; aOR for midpregnancy, 1.95; 95% CI, 1.18–3.23).
Studies have reported a potential association with in utero exposure to preeclampsia and increased blood pressure, body mass index, and neurodevelopmental disorders in offspring.
Workshop participants were invited to 1 of 3 breakout groups to discuss the following key issues in greater depth: (1) innovative research strategies for preeclampsia prediction, priority areas for clinical and translational research, and gaps in knowledge of mechanism; (2) novel interventions for the management of preeclampsia and improving guidelines and bundles; and (3) investigating long-term impacts of preeclampsia and engaging healthcare practitioners in long-term care. The following sections summarize the findings and recommendations reported by each breakout group.
Preeclampsia prediction and prevention
Preeclampsia remains a challenging diagnosis owing in part to the complexity of the disorder and a lack of universal, objective diagnostic criteria, including a lack of a global consensus definition.
A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators.
Commonly, preeclampsia is defined as a disorder of pregnancy associated with new-onset hypertension, often accompanied by new-onset proteinuria. The presence of other severe features is also used for diagnosis.
Despite this basic definition, disease heterogeneity is clinically apparent (eg, early vs late, with vs without severe features, symptomatic vs asymptomatic, progressive vs stable). Evidence suggests that preeclampsia is a clinical syndrome resulting from multiple different biological pathways. However, the mechanisms underlying preeclampsia are not fully understood. Although pathophysiological subtypes of preeclampsia exist, they are not clearly defined or used routinely in clinical practice or research. Proposed mechanisms include placental ischemia, abnormal immune system activation (eg, autoimmune activation of the renin-angiotensin system, complement activation), angiogenic imbalance (elevated soluble fms-like tyrosine kinase 1 [sFlt-1], reduced placental growth factor [PlGF], and vascular endothelial growth factor), and metabolic dysfunction (not mutually exclusive).
However, the link between the underlying biologic mechanism and clinical manifestation of the disease is complex and poorly understood. This imprecision presents challenges for accurately predicting preeclampsia risk, tailoring management, and comparing and generalizing results across different studies. Increased funding and research support are necessary prerequisites for future work. One opportunity for future research is elucidating the pathways that lead to various subtypes of preeclampsia. With these mechanisms understood, prevention and treatment strategies can be targeted to preeclampsia subtype. In addition, the inclusion of diverse patient populations is essential for understanding the variations in normal and complicated pregnancies, because recent work has shown that a one-size-fits-all approach is wholly inadequate.
Various research strategies are being employed to better predict who is most at risk of developing preeclampsia and stratifying risk once a diagnosis has been established.
Several biomarkers have been investigated for their ability to predict early- and late-onset preeclampsia, including uterine artery pulsatility index, mean arterial pressure, pregnancy-associated plasma protein A, PlGF, and sFlt-1.
The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: a pragmatic guide for first-trimester screening and prevention.
Machine learning is a relatively new field of research being used for early detection of preeclampsia and identifying subtypes of the disorder and molecular targets for intervention. Multiomics, including genomics, transcriptomics, proteomics, and metabolomics, have uncovered insights into disease pathophysiology and further highlight the heterogeneity of preeclampsia. For example, genome-wide association studies have identified variations in the maternal and fetal genome associated with an increased risk of preeclampsia.
These global and comprehensive approaches are needed to identify novel mechanisms and targets for intervention.
Interventions are needed to prevent and treat preeclampsia and its associated sequelae. Different approaches have been studied with varying success and levels of evidence supporting their use. Currently, the best-studied preventive strategy is low-dose aspirin, which is recommended for pregnant people at high risk of preeclampsia,
U.S. Preventive Services Task Force Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: U.S. Preventive Services Task Force recommendation statement.
Other therapies designed to treat early-onset preeclampsia have been examined in small, proof-of-concept case series. Two exploratory pilot studies supported the hypothesis that short-term dextran sulfate apheresis in patients with early preterm preeclampsia may have the potential to reduce circulating sFlt-1 and proteinuria without major adverse consequences to the pregnant person or fetus. These results should be interpreted cautiously, because this strategy has not been evaluated through larger trials.
A recent study suggests that metformin for those with preeclampsia extends gestation by 1 week and may mediate several molecular pathways implicated in the pathogenesis of preeclampsia and fetal growth restriction.
An important caveat is that many interventions that seem promising on the basis of preclinical data or small pilot clinical studies have proved to be ineffective in the randomized controlled setting.
Prospective, randomized, double-blind, placebo-controlled evaluation of the pharmacokinetics, safety and efficacy of recombinant antithrombin versus placebo in preterm preeclampsia.
Therefore, randomized controlled trials with larger populations optimally characterized by preeclampsia subtype are needed to confirm these findings.
Although many prediction and prevention strategies were presented during this workshop in the context of the United States healthcare system, workshop participants emphasized the importance of designing strategies that meet the needs of low- and middle-income countries where the burden of disease is highest.
Eliminating inequitable systemic and community-level factors that limit access to innovative and high-quality care domestically and internationally is critical for the early identification and prevention of preeclampsia and other hypertensive disorders of pregnancy worldwide.
Preeclampsia management
Optimal management of preeclampsia involves addressing medical and nonmedical factors that contribute to disease progression. The health impact pyramid
(Figure) was proposed during the workshop as one framework for designing and implementing interventions. Workshop participants emphasized that although counseling, education, and clinical interventions are commonly employed by healthcare professionals, interventions that target socioeconomic factors and the environmental context in which patients live have the greatest potential to improve health outcomes and reduce disparities.
Underlying every management strategy presented during the workshop was the need to prioritize health equity. Participants discussed the current evidence and improvement opportunities for implementing bundles within healthcare systems,
such as investigating implementation outcomes across race and ethnicity and educating and engaging interdisciplinary and diverse healthcare teams in bundle implementation. One consideration for bundle sustainability was the integration of bundles into healthcare systems during public health emergencies or at times of competing priorities. Remote blood pressure monitoring,
and social media were highlighted as tools to educate and empower patients and deliver healthcare. Workshop participants also recognized that access to the internet and mobile devices is not equitably distributed within the United States or globally. Opportunities exist for clinicians to improve the accuracy and accessibility of health information online, such as developing resources for different literacy levels or in multiple languages. It was noted during the workshop that although screening for social determinants of health is becoming more common, healthcare practitioners need tools and education on how to manage these nonmedical factors depending on a patient’s screening results. For patients in high-need or low-resource settings, leveraging community partners was identified as a key mechanism to ensure access to high-quality care.
Further research on preeclampsia management is needed, particularly large, randomized controlled trials that include patient and interdisciplinary input at all stages of the research process. Research that identifies which patients are at the highest risk of immediate adverse outcomes is an important first step to better triaging and transitioning follow-up care in the early postpartum period. Clinical interventions presented during the workshop with the potential to improve preeclampsia outcomes include the use of diuretics, complement inhibition,
and postpartum angiotensin-converting enzyme inhibitors. Investigating such novel management strategies will require both funding and support for conducting research in pregnant and lactating people.
Long-term impacts of preeclampsia
Evidence presented during the workshop demonstrated that preeclampsia can impact the pregnant person and their offspring throughout the life course. The risk of adverse cardiovascular and mental health outcomes is increased for people who have experienced preeclampsia compared with those who have not.
However, patients and clinicians are often unaware of these risks, and there is a dearth of risk-reduction programs specifically developed to accommodate the unique challenges faced by new parents with recently diagnosed preeclampsia and their families.
Collaborative care models, such as the medical home model and postpartum transition clinics, have demonstrated success in connecting patients to care, early screening for cardiovascular disease, and initiating prevention measures for patients at increased risk of later disease.
An online intervention designed for postpartum women with recent preeclampsia has led to significantly greater knowledge about the link between preeclampsia and future cardiovascular disease (corrected P=.01), increased self-efficacy for healthy eating (P=.03), and decreased physical inactivity after 9 months (P=.0006) among intervention participants compared with postpartum women who received only internet links to risk reduction information.
Workshop participants emphasized the important role nurses and physicians in the emergency department can have in risk assessment and care coordination during this time.
Emergency Nurses Association, Association of Women’s Health, Obstetric and Neonatal Nurses Emergency care for patients during pregnancy and the postpartum period: Emergency Nurses Association and Association of Women’s Health, Obstetric and Neonatal Nurses consensus statement.
Participants also emphasized the opportunity to increase awareness and engagement of primary care and gynecologic providers in identifying patients with a history of pregnancy-induced hypertensive disorders as part of their standard medical history. Identifying these patients is an important step to help ensure that they receive appropriate cardiovascular health assessments and education about lowering their risks (eg, maintaining a healthy weight, optimizing blood pressure control).
Improving long-term health outcomes for people who have experienced preeclampsia and their children will require additional research and practice improvements. It is unknown which patients are at the highest risk of long-term adverse outcomes (eg, stroke, PTSD) and would benefit the most from tailored interventions in the postpartum period. Investigating the link between chronic health conditions, including mental health conditions, and social determinants of health with preeclampsia and later cardiovascular risk was reiterated throughout the workshop as another important area of research. Workshop participants highlighted that long-term risks follow other adverse pregnancy outcomes, such as gestational hypertension, fetal growth restriction, and preterm birth, and proposed investigating these outcomes as different manifestations of similar pathophysiology. Although substantial epidemiologic evidence links in utero exposure to preeclampsia with cardiovascular and neurodevelopmental pathology, more evidence is needed to understand the effect of modifiers and the mechanism underlying the pathophysiology and mitigating factors to improve outcomes in offspring. Structural changes to the healthcare system are also needed, including building equitable infrastructure to enable patients to access long-term care and educating patients and clinicians about the important role of follow-up care.
Conclusion and Research Gaps
Although workshop participants proposed many recommendations for preeclampsia prediction, prevention, and management and identified several opportunities to improve postpartum and long-term follow-up care, substantial research and practice improvement opportunities remain. Issues proposed for further research include the following:
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Identification of mechanisms underlying various subtypes of preeclampsia
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Development of screening, prevention, and management strategies tailored to disease subtype
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Interdisciplinary, patient-centered research investigating long-term maternal and child health outcomes and interventions after preeclamptic pregnancies
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Inclusion of diverse patient populations to better understand and differentiate normal biologic variation from abnormal pathophysiology
It is hoped that this workshop serves as a catalyst for developing clinical guidelines and patient education, generates new research questions, and strengthens relationships among researchers and clinicians to increase collaboration and support for patients with preeclampsia.
References
Wallis A.B.
Saftlas A.F.
Hsia J.
Atrash H.K.
Secular trends in the rates of preeclampsia, eclampsia, and gestational hypertension, United States, 1987–2004.
Stuart JJ. The impact of preeclampsia on long-term mental health. Oral presentation at: Preeclampsia Workshop; 41st Annual Pregnancy Meeting; January 25, 2021; Virtual.
A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators.
The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: a pragmatic guide for first-trimester screening and prevention.
Prospective, randomized, double-blind, placebo-controlled evaluation of the pharmacokinetics, safety and efficacy of recombinant antithrombin versus placebo in preterm preeclampsia.
Emergency Nurses Association, Association of Women’s Health, Obstetric and Neonatal Nurses
Emergency care for patients during pregnancy and the postpartum period: Emergency Nurses Association and Association of Women’s Health, Obstetric and Neonatal Nurses consensus statement.
All authors and committee members have filed a disclosure of interests delineating personal, professional, business, or other relevant financial or nonfinancial interests in relation to this publication. Any substantial conflicts of interest have been addressed through a process approved by the Society for Maternal-Fetal Medicine (SMFM) Board of Directors. SMFM has neither solicited nor accepted any commercial involvement in the specific content development of this publication.
This document has undergone an internal peer review through a multilevel committee process within SMFM. This review involves critique and feedback from the SMFM Publications and Document Review Committees and final approval by the SMFM Executive Committee. SMFM accepts sole responsibility for the document content. SMFM publications do not undergo editorial and peer review by the American Journal of Obstetrics & Gynecology. The SMFM Publications Committee reviews publications every 18 to 24 months and issues updates as needed. Further details regarding SMFM publications can be found at www.smfm.org/publications.
SMFM recognizes that obstetrical patients have diverse gender identities and is striving to use gender-inclusive language in all of its publications. SMFM will be using terms such as “pregnant person/persons” or “pregnant individual/individuals” instead of “pregnant woman/women” and will use the singular pronoun “they.” When describing study populations used in research, SMFM will use the gender terminology reported by the study investigators.
All questions or comments regarding the document should be referred to the SMFM Publications Committee at [email protected]
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