Preeclampsia develops because the placenta fails to establish a healthy blood supply early in pregnancy, triggering a chain reaction that damages blood vessels throughout the mother’s body. It affects 3 to 8% of pregnancies worldwide, and while researchers have identified the key mechanisms driving it, the condition involves a complex interplay of placental development, immune function, and genetics that makes it difficult to prevent entirely.
It Starts With the Placenta
In a normal pregnancy, the placenta sends specialized cells deep into the wall of the uterus to tap into the mother’s blood supply. These cells invade the spiral arteries, which are small blood vessels that feed the uterine lining, and widen them dramatically. The artery walls lose their muscular lining and expand to 5 to 10 times their original diameter. This remodeling ensures the placenta receives enough blood to support a growing fetus.
In preeclampsia, this process goes wrong. The placental cells don’t invade deeply enough, and the spiral arteries stay narrow and muscular. The result is a placenta that’s chronically starved of oxygen and nutrients. This is particularly linked to early-onset preeclampsia (before 34 weeks), which tends to be more severe. The same faulty artery remodeling is also connected to other pregnancy complications like restricted fetal growth and placental abruption, where the placenta detaches from the uterine wall.
The poorly remodeled arteries can also develop a type of damage similar to what happens in atherosclerosis. Foam cells, which are fat-laden immune cells, build up in the artery walls downstream of the narrowed segments. Abnormal blood flow through these tight vessels appears to trigger inflammation that feeds the problem.
How a Struggling Placenta Makes the Mother Sick
A poorly supplied placenta doesn’t just affect the fetus. It releases substances into the mother’s bloodstream that poison her blood vessel lining. The key player is an anti-angiogenic protein produced by the placenta. In preeclampsia, the placenta floods the mother’s blood with this protein, which blocks the growth factors her blood vessels need to stay healthy and relaxed. Normally during pregnancy, the placenta produces growth factors that help blood vessels dilate and function well. In preeclampsia, those protective factors drop while the damaging protein surges.
This imbalance is what produces the hallmark symptoms: high blood pressure (because blood vessels can no longer relax properly) and protein in the urine (because the tiny blood vessels in the kidneys become leaky). The same vascular damage can affect the liver, brain, and other organs, which is why severe preeclampsia can lead to seizures, organ failure, and stroke if untreated.
The Immune System Plays a Central Role
Pregnancy requires the mother’s immune system to tolerate a fetus that is genetically half-foreign. In a healthy pregnancy, the immune system shifts toward a tolerant state, dampening inflammation at the site where the placenta meets the uterus. In preeclampsia, this tolerance breaks down.
Women with preeclampsia show excessive activation of immune cells called neutrophils and monocytes, which pump out inflammatory signals. Their immune profile tips toward a pro-inflammatory state, with certain T-cell populations (Th1 and Th17 cells) dominating over the regulatory T cells that normally keep immune responses in check. Natural killer cells at the placental site also behave differently: instead of secreting factors that help placental cells invade the uterine wall, they produce fewer of these invasion-promoting signals. This immune dysfunction may be one reason the spiral arteries don’t remodel properly in the first place.
Genetics Account for More Than Half the Risk
Preeclampsia runs in families, and its overall heritability is estimated at roughly 55%. If your mother or sister had preeclampsia, your risk is significantly higher. But the genetics are unusual: the risk comes partly from the fetus, not just the mother.
A large genetic study comparing over 2,600 offspring born to women with preeclampsia against more than 300,000 controls found that genetic variants near a specific gene on chromosome 13 were strongly associated with the condition. This gene encodes the very protein that, when overproduced by the placenta, damages the mother’s blood vessels. The finding suggests that dysregulation in the fetal (and therefore placental) genome is a fundamental molecular driver of preeclampsia. In other words, the baby’s genes can influence whether the placenta malfunctions, which then makes the mother sick.
Who Is Most at Risk
Beyond genetics, several factors increase the likelihood of developing preeclampsia. First pregnancies carry a higher risk than subsequent ones, likely because the mother’s immune system hasn’t previously adapted to a placenta. Other well-established risk factors include chronic high blood pressure, diabetes, kidney disease, obesity, being over 35 or under 20, and carrying multiples (twins or more). A previous pregnancy with preeclampsia raises the risk substantially for future pregnancies.
Pregnancies conceived through IVF also carry higher rates of preeclampsia. The interval between pregnancies matters too: a very long gap between pregnancies (10 years or more) can increase risk, possibly because the immune system’s “memory” of tolerating a placenta fades over time.
A Blood Test Can Now Predict It
Because the imbalance between protective and damaging proteins in the blood is so central to preeclampsia, it’s now possible to measure it. The FDA has approved a blood test that measures the ratio of the harmful anti-angiogenic protein to the protective growth factor in women hospitalized with high blood pressure during pregnancy. In clinical trials, this test predicted with 96% accuracy which women would not develop severe preeclampsia within the next two weeks, helping doctors decide who can safely be monitored less intensively and who needs urgent intervention.
Low-Dose Aspirin for Prevention
For women at high risk, there is one proven preventive measure. The U.S. Preventive Services Task Force recommends a daily low-dose aspirin (81 mg) starting after 12 weeks of pregnancy, ideally before 20 weeks. Aspirin works by reducing inflammation and improving blood flow through the placenta during the critical window when spiral artery remodeling is happening. It doesn’t eliminate the risk entirely, but it meaningfully reduces it. This recommendation applies specifically to women with identified risk factors, not to all pregnant women.
Long-Term Heart Health After Preeclampsia
Preeclampsia isn’t just a pregnancy problem. Women who have had it face a significantly elevated risk of cardiovascular disease for the rest of their lives. A major meta-analysis found that preeclampsia is independently associated with a fourfold increase in future heart failure, a 2.5-fold increase in coronary heart disease, roughly double the risk of stroke, and more than double the risk of dying from cardiovascular disease. These elevated risks held up even after accounting for age, body mass index, and diabetes, meaning preeclampsia itself appears to be an independent cardiovascular risk factor.
The reasons aren’t entirely clear. The vascular damage during preeclampsia may leave lasting changes, or the same underlying predisposition to blood vessel dysfunction that enabled preeclampsia may continue to cause problems decades later. Either way, a history of preeclampsia is a signal to monitor blood pressure, cholesterol, and heart health more closely in the years that follow.