Preeclampsia originates in the placenta. More specifically, it begins with abnormal development of the blood vessels that connect the placenta to the uterine wall, triggering a chain reaction that eventually damages blood vessels throughout the mother’s body. About 4.4% of pregnancies worldwide are affected, though rates vary dramatically by region, from around 1.4% in Poland to over 14% in Tanzania.
The condition has no single cause. It emerges from a collision of factors: how the placenta implants, how the mother’s immune system responds to the pregnancy, and genetic contributions from both parents and the fetus itself.
It Starts With How the Placenta Connects
In a healthy pregnancy, specialized cells from the developing placenta invade the uterine wall in two waves. The first wave reaches the inner layer of the uterine arteries around 8 to 10 weeks of pregnancy. The second wave pushes deeper into the muscular layer of those arteries between 16 and 18 weeks. These cells essentially remodel the mother’s spiral arteries, stripping away their muscular walls and replacing them with softer material. The result is wide, relaxed blood vessels that can deliver large volumes of blood to the growing fetus with minimal resistance.
In preeclampsia, this remodeling fails. The placental cells don’t invade deeply enough, and the spiral arteries stay narrow and stiff. Fewer than 20% of the deeper arterial segments undergo the normal transformation. The placenta is left underfed, sitting in a low-oxygen environment that generates significant oxidative stress. This stressed placenta then releases harmful signals into the mother’s bloodstream.
How a Placenta Problem Becomes a Whole-Body Problem
The poorly developed placenta doesn’t just affect the fetus. It floods the mother’s circulation with inflammatory molecules, oxidative stressors, and proteins that damage the lining of blood vessels throughout her body. This widespread blood vessel damage is what produces the hallmark symptoms: high blood pressure, protein spilling into the urine, and in severe cases, liver and kidney dysfunction or a dangerous drop in blood platelet counts (known as HELLP syndrome).
One key part of this process involves proteins that the placenta releases to regulate blood vessel growth. In preeclampsia, the balance tips toward too much of a protein that blocks blood vessel maintenance and too little of a growth factor that supports it. Clinicians can now measure this imbalance with a blood test. A ratio below 38 between these two proteins reliably rules out preeclampsia for at least one week, while higher ratios point toward an active or imminent diagnosis. Extremely high ratios are closely linked with the need for delivery within 48 hours.
The Immune System’s Role
Pregnancy requires the mother’s immune system to tolerate a fetus that is genetically half foreign. This tolerance isn’t passive. It involves active suppression of immune responses that would otherwise attack fetal tissue the same way the body rejects a transplanted organ. When this tolerance breaks down, the result can be preeclampsia.
Several well-known risk factors point directly to immune mismatch as a driver. First pregnancies carry higher risk because the mother’s immune system has never been exposed to that particular father’s genetic material. Pregnancies conceived through certain fertility treatments that limit prior exposure to a partner’s cells also carry elevated risk. Women with autoimmune disorders, where the immune system is already prone to overreaction, face higher odds as well.
Part of the immune problem happens right at the placenta. The complement system, a branch of immunity that tags foreign cells for destruction, becomes overactive in preeclampsia. Researchers have found significantly higher levels of complement proteins deposited on the surface of placental cells in affected pregnancies, suggesting the mother’s immune system is actively damaging placental tissue.
Genetics From Both Parents Matter
Preeclampsia runs in some families, but the inheritance pattern is complex. Researchers have identified at least five distinct genetic regions associated with the condition, and the contributing genes appear to involve fluid balance, blood vessel function, and placental development. Many cases, however, occur in women with no family history at all.
What makes preeclampsia genetically unusual is that the father’s genes matter too. The placenta is a biparental organ, built from both maternal and paternal DNA. One large Swedish study estimated that the genetic risk for preeclampsia breaks down roughly as 35% attributable to the mother’s genes, 20% to the fetus’s genes, and 13% to the couple’s genetic interaction.
The paternal contribution shows up in striking ways. Changing partners between pregnancies shifts risk in both directions: a woman who had preeclampsia with one partner may not develop it with another, and a woman who never had it can develop it with a new partner. There is even a documented case of a man who fathered children with two different women, both of whom developed fatal preeclampsia, leading researchers to propose a “fatal father factor.” Men who were themselves born from a preeclamptic pregnancy also pass higher risk to their partners. Paternal obesity independently raises the odds as well.
At the molecular level, certain immune markers inherited from the father can increase the incompatibility between the mother’s immune system and fetal tissue, making the immune tolerance problem described above more likely.
Early Onset vs. Late Onset
Preeclampsia that develops before 34 weeks of pregnancy (early onset) and preeclampsia that appears at or after 34 weeks (late onset) likely have somewhat different origins. Early-onset preeclampsia is more strongly tied to the deep placental implantation failure described above. The placenta is severely compromised, and the condition tends to be more dangerous for both mother and baby.
Late-onset preeclampsia may have more to do with the mother’s underlying cardiovascular and metabolic health colliding with the increasing demands of a growing pregnancy. The placenta may have developed more normally but still can’t keep up, or the mother’s blood vessels may have been more vulnerable to the inflammatory stress of pregnancy from the start.
Prevention and Long-Term Consequences
For women identified as high risk, daily low-dose aspirin (81 mg) started after 12 weeks of pregnancy and continued until delivery is the primary preventive measure. The U.S. Preventive Services Task Force, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine all recommend this approach, ideally beginning before 16 weeks. Effective preventive doses range from 60 to 150 mg per day, but 81 mg is the standard tablet size available in the U.S.
The origins of preeclampsia don’t disappear after delivery. Women who have had the condition carry three to four times the normal risk of developing high blood pressure later in life and double the risk of heart disease and stroke. This makes sense given what causes the condition: the same blood vessel dysfunction that drives preeclampsia during pregnancy reflects a cardiovascular vulnerability that persists long after the placenta is gone.