What Is Preeclampsia 2.0 and Why Does It Matter?

By Amit Saxena
December 9, 2025

Why Preeclampsia Demands a Rethink

Preeclampsia is no longer a rare complication that clinicians encounter only occasionally; it is a growing global threat that demands a complete rethink of how it is understood, predicted, and prevented. This pregnancy‑specific syndrome, defined by hypertension and multi‑organ involvement, is a leading driver of maternal and perinatal morbidity and mortality and leaves a lifelong imprint on the cardiovascular and metabolic health of both mother and child. In the United States, the rate of all types of preeclampsia has nearly doubled in just over a decade—from about 1 in 22.5 pregnancies in 2008 to 1 in 12 by 2021—while severe cases increased by 50% between 2005 and 2014. Globally, hypertensive disorders of pregnancy have risen by 15% since 1990, with a staggering 63% increase in countries with low sociodemographic index.

The fraction of severe preeclampsia cases is increasing, and in the USA the overall rate has almost doubled within little more than a decade—this is not a static disease, it is an escalating one

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Despite decades of research and multiple “two‑stage” and placental insufficiency models, no single hypothesis fully explains the spectrum of preeclampsia—from early‑onset disease with fetal growth restriction to late‑onset cases at term. Current biomarkers such as sFlt‑1 and PlGF work well once preeclampsia is clinically established but have limited predictive value for the full range of cases, and low‑dose aspirin benefits only about 15–20% of women, largely those with early‑onset disease. “Preeclampsia 2.0” calls for new thinking that looks earlier—before pregnancy and during the first trimester—at subtle alterations in the maternal cardiovascular system and villous trophoblast, using tools like single‑cell and spatial transcriptomics to build a more complete picture of this complex syndrome.

Key Highlights

A rapidly growing global burden

The proportion of pregnancies affected by preeclampsia in the USA has increased nearly two‑fold in 13 years, and hypertensive disorders in pregnancy globally have risen by 15% since 1990, with a 63% rise in low‑SDI countries.

The “syndrome of hypotheses” problem

Numerous models—impaired spiral artery remodeling, angiogenic imbalance, oxidative stress—describe parts of the disease, but none explains all phenotypes or why some women present early with severe disease and others at term with mild maternal‑only features.

Limitations of current biomarkers and therapies

Anti‑angiogenic markers sFlt‑1 and PlGF are excellent diagnostic adjuncts when disease is already present, yet their predictive accuracy remains confined to a minority of cases; aspirin prophylaxis significantly benefits only about 15–20% of women, mostly early‑onset.

First‑trimester data reveal villous trophoblast alterations long before clinical onset in all types of preeclampsia, suggesting that the foundations of the syndrome are laid early and that we must redirect research to this window

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Early villous trophoblast changes across preeclampsia types

Studies of first‑trimester placental tissue and chorionic villus samples from women who later develop preeclampsia show structural and molecular changes—including altered differentiation and signs of senescence—long before maternal symptoms appear, and across early, preterm, and term disease.

A call for integrated, multi‑scale research

The paper argues that combining pre‑pregnancy cardiovascular profiling, first‑trimester placental biology, and advanced spatial omics is essential to generate new, testable hypotheses that can finally unify maternal and placental contributions in “Preeclampsia 2.0.”

Future work must integrate pre‑pregnancy cardiovascular status, early placental cell biology, and spatial omics—only then can ‘Preeclampsia

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Key Takeaways

Preeclampsia rates and severity are rising worldwide, particularly in low‑resource settings, despite improved obstetric care.
Existing theories and biomarkers explain only fragments of the syndrome; they do not capture its clinical diversity or timing, especially late‑onset cases.
Emerging data show measurable changes in the villous trophoblast and maternal cardiovascular system before clinical onset, sometimes even before conception, underscoring the need to shift research upstream.