Risk Stratification for Preeclampsia Would Save Lives, Reduce Burden of Cost to Health Care System

Rebecca Khan, MD (Courtesy of Thermo Fisher Scientific)

Globally, 76 000 women and 500 000 babies die each year from complications of preeclampsia,1 and many more mothers are at risk of medically necessary preterm delivery, intrauterine growth restriction, and other complications. Preeclampsia, a serious medical condition that can occur 20 weeks into a pregnancy, is characterized by high blood pressure, protein in the urine, swelling, headaches, and blurred vision.2 When it progresses to severe features, both mother and baby are at serious risk.

Although standard approaches exist for clinical diagnosis of preeclampsia, such as blood pressure and proteinuria evaluation, they have been shown to be inadequate predictors of severe adverse maternal and perinatal outcomes—and in many cases, abnormal results do not appear until maternal and fetal organ damage has already occurred.3,4 This makes it difficult for clinicians to identify patients at greatest risk for developing preeclampsia with severe features and tailor treatment plans for them. As outlined below, this difficulty increases costs significantly.

Costly, potentially avoidable

The high costs of preeclampsia management are well documented, particularly within severe preeclampsia. A recent study of 1 918 482 women in California showed that median hospitalization costs and length-of-stays were significantly higher in patients with severe preeclampsia or eclampsia (a serious form of the disease which causes seizures in the mother).5 In that study, the costs of severe preeclampsia and eclampsia were notably higher for both women and infants, with a nearly $10 000 difference in the cost of treatment for women without hypertension vs women with eclampsia or severe preeclampsia.

In another recent meta-analysis of the most common maternal morbidity conditions, $7.5 billion of the $18.7 billion in total medical costs was attributed to hypertensive disorders during pregnancy. This was, by far, the costliest condition, making it a significant public health concern from both health economic and patient outcomes perspectives. The study authors concluded that, collectively, these most common morbidities—led by hypertensive disorders—add an average of $8624 in additional costs to society for each maternal–child pair across the 3.7 million births in the United States annually.6

The high economic burden and poor patient outcomes of preeclampsia have forced a reckoning in recent years, with data showing a doubling in the incidence of new‐onset hypertensive disorders of pregnancy in women from 2007 to 2019 in both rural and urban areas, with accelerating rates since 2014.7 Diagnostic ambiguity has led to clinician and health system frustration, increasing calls for lab-based tests that can help improve preeclampsia assessment and patient management so that costs and outcomes are better aligned.

Biomarkers and improved risk assessment

Increased incidence, coupled with higher costs and poorer outcomes systemwide, have sparked extensive research and development into objective biomarker tests to aid in preeclampsia assessment and patient management. In one recent review of biomarker use in clinical settings, authors concluded that “the greatest clinical value is likely to be realized with new screening tests to identify women at high risk of developing—or of already having—established disease, enabling risk stratification for ongoing care. In preeclampsia, such tests could identify women who may benefit from increased clinical surveillance and carefully timed birth. Conversely, they may identify low-risk patients who could safely reduce their antenatal visits.”8

The authors of the review mentioned above discuss the viability of using complementary assays for soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), both validated biomarkers for preeclampsia. If, the authors conclude, a laboratory test showing the sFlt-1:PlGF ratio could be clinically validated, it “could dramatically reconfigure antenatal clinical care. The number of visits could be safely reduced for those who screen negative, saving pregnant women valuable time and vastly reducing medical costs.”

Other clinical studies confirm the potential economic benefits of testing using a sFlt-1:PlGF ratio. One study, launched to estimate the value to the US health care system of adopting such a test into clinical practice, concluded that the use of the sFlt-1/PlGF ratio reduced hospital admissions for study participants suspected of preeclampsia by 34% to 49%.9 The study’s authors estimated that testing would yield cost savings from reducing hospital admissions of approximately $1050 per patient.

In May 2023, the FDA cleared the first biomarker-based assays to assist with preeclampsia assessment, specifically the risk of developing preeclampsia with severe features in the ensuing 2 weeks. The newly cleared test, clinically validated by the multicenter PRAECIS (Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification) study, showed that a sFlt-1:PlGF ratio of 40 or higher “predicted the development of severe preeclampsia, adverse outcomes, and delivery within 2 weeks of testing.”10 The new test is now widely available to clinicians across the United States.

Managing resources, improving care

As discussed, cases of preeclampsia that advance to severe features put mothers and babies at risk and put a high, but potentially preventable economic burden on society. Clinicians can now use a routine, low-cost test to risk-stratify women who may or may not develop preeclampsia with severe features in the ensuing 2 weeks. This new prognostic tool, in conjunction with other laboratory and clinical findings, can help better and more equitably allocate finite health care resources by ensuring that the costliest interventions are reserved for the patients in greatest need.

New assays for preeclampsia risk assessment and patient management are an important first step toward better maternal health overall. The exhaustive clinical research and peer focus behind the new test sets the stage for validation and use of more biomarkers in clinical settings to assess patient risk, inform care decision-making, and improve maternal and fetal outcomes globally.

References

1. Poon LC, Shennan A, Hyett JA, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia. Int J Gynaecol Obstet. 2019;145(suppl 1):1-33. doi:10.1002/ijgo.12802
2. High blood pressure during pregnancy. CDC. Updated June 19, 2023. Accessed November 27, 2023. https://www.cdc.gov/bloodpressure/pregnancy.htm
3. Zhang J, Klebanoff MA, Roberts JM. Prediction of adverse outcomes by common definitions of hypertension in pregnancy. Obstet Gynecol. 2001;97(2):261-267. doi:10.1016/s0029-7844(00)01125-x
4. Rana S, Powe CE, Salahuddin S, et al. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation. 2012;125(7):911-919. doi:10.1161/CIRCULATIONAHA.111.054361
5. Hersh AR, Mischkot BF, Greiner KS, Garg B, Caughey AB. Maternal and infant hospitalization costs associated with hypertensive disorders of pregnancy in a California cohort. J Matern Fetal Neonatal Med. 2022;35(21):4208-4220. doi:10.1080/14767058.2020.1849096
6. O’Neil SS, Platt I, Vohra D, et al. Societal cost of nine selected maternal morbidities in the United States. PLoS One. 2022;17(10):e0275656. doi:10.1371/journal.pone.0275656
7. Cameron NA, Everitt I, Seegmiller LE, Yee LM, Grobman WA, Khan SS. Trends in the incidence of new‐onset hypertensive disorders of pregnancy among rural and urban areas in the United States, 2007 to 2019. J Am Heart Assoc. 202218;11(2):e023791. doi:10.1161/JAHA.121.023791
8. MacDonald TM, Walker SP, Hannan NJ, Tong S, Kaitu'u-Lino TJ. Clinical tools and biomarkers to predict preeclampsia. EBioMedicine. 2022;75:103780. doi:10.1016/j.ebiom.2021.103780
9. Khosla K, Espinoza J, Perlaza L, et al. Cost effectiveness of the sFlt1/PlGF ratio test as an adjunct to the current practice of evaluating suspected preeclampsia in the United States. Pregnancy Hypertens. 2021;26:121-126. doi:10.1016/j.preghy.2021.10.009
10. Ravi Thadhani et al, circulating angiogenic factor levels in hypertensive disorders of pregnancy. NEJM Evidence. 2022;1(12). doi:10.1056/EVIDoa2200161