What Causes Preeclampsia?

Jovian Wat, PhD

Preeclampsia is one of the most common disorders of pregnancy, affecting up to 7% of all pregnancies. Even Beyonce had preeclampsia with the twins (referred to as toxemia in the article)!

In the past, preeclampsia was thought to be caused by improper development of the placenta. However, recent research suggests that the cause of preeclampsia is more complicated. Let’s dive deeper into the latest research to discuss what is the cause of preeclampsia.

What is preeclampsia?

Preeclampsia is a hypertensive disorder of pregnancy, meaning that pregnant women develop high blood pressure (or hypertension). Pregnant women are diagnosed with preeclampsia if they develop high blood pressure after 20 weeks of pregnancy and show signs of organ damage. The most common type of organ damage in women with preeclampsia is kidney damage.

Symptoms of preeclampsia include severe headache, blurry vision, nausea, dizziness, chest pain, shortness of breath, abdominal pain and/or swelling of the legs.

The only way to fully treat preeclampsia in pregnant women is to deliver the baby and the placenta. Most women see their high blood pressure and other symptoms of preeclampsia normalize within a few days of delivery. This led to the thought that preeclampsia is caused by the placenta.

Read here for a more detailed clinical article about preeclampsia.

A short history of preeclampsia - the 'disease of theories'

Preeclampsia is often called 'the disease of theories' because there have been so many different theories attempting to explain what causes this disorder.

Preeclampsia was first described as early as 400 BC by Hippocrates. Women with preeclampsia commonly developed seizures or convulsions, known as eclampsia. He believed that a 'wandering uterus' was soaking up moisture from the mother's body, causing an imbalance in the bodily fluids or 'humors'. He recommended treatments such as changes to the mother's diet and bloodletting.

The anatomy of the female reproductive tract was better examined and understood in the Renaissance period in the 1400-1600s. In 1668, Dr. Francois Mauriceau noted that the seizures of pregnant women could be due to uterus problems or death of the fetus, resulting in the accumulation of unwanted fluids. Not surprisingly, bloodletting was still the recommended treatment for pregnancy complications.

In the 18th and 19th centuries. Dr. Bossier de Sauvages observed that the seizures preeclamptic women suffered from were different from the seizures of patients with epilepsy, since the convulsions stopped after delivery. He named this pregnancy-related condition 'eclampsia', a Greek word meaning 'lightning', referring to flashes of light that women sometimes describe during their seizures. Doctors also noticed that women with preeclampsia had excessive swelling and high levels of protein in the urine.

In 1843, Dr. Robert Johns documented the symptoms leading up to seizures in women with preeclampsia, including headaches, visual disturbances, swelling, and severe abdominal pain. With the invention of the mercury blood pressure monitor in 1896, doctors could see that pregnant women with preeclampsia had high blood pressure before they developed seizures.

The condition preeclampsia (pre-, the condition before eclampsia or seizures) became a medical term in 1903.

Where do scientists currently stand?

Modern science has made significant progress to the understanding what causes preeclampsia in pregnant women. Although scientists and doctors do not fully understand the cause of preeclampsia, it is understood that preeclampsia is a complex disease that involves many organs of the mother's body.

Overall, it is hypothesized that preeclampsia involves the mother's placenta, cardiovascular system and immune system.

Does the placenta cause preeclampsia?

Women with preeclampsia typically see their symptoms of hypertension and other organ damage disappear when the baby and placenta are delivered. Scientists have discovered that the majority of placentas from women with preeclampsia look and act differently, when compared to placentas of pregnant women who have healthy pregnancies. In more scientific terms, the anatomy and physiology of the placenta is typically abnormal in women with preeclampsia.

In the first trimester of normal pregnancy, the blood vessels that supply the placenta with blood become wider and more relaxed. The relaxation of these arteries lets large amounts of maternal blood to reach the placenta at low blood pressures.

This process is disrupted in women who develop preeclampsia. The arteries that supply the placenta with blood tend to be smaller and less relaxed in women with preeclampsia, causing blood to reach the placenta at higher blood pressures. In the same way, a constricted hose causes water to exit at a higher pressure than a loose hose. These blood vessel and blood flow abnormalities in women with preeclampsia can damage the placenta and impact its growth.

In normal pregnancy, the placenta releases different proteins and molecules into the mother's circulation as a method of communicating with the mother's body. In most women with preeclampsia, the damaged placenta releases abnormal levels of these proteins. These abnormal protein levels can damage the lining of the mother's blood vessels, causing hypertension and other symptoms of preeclampsia.

However, not all women who develop preeclampsia have abnormal or damaged placentas, and not all women with damaged placentas develop preeclampsia. Let's discuss how the mother's cardiovascular system can lead to the development of preeclampsia.

Does the cardiovascular system cause preeclampsia?

Pregnancy is a huge stress on the mother's cardiovascular system. As discussed in this article, the mother's heart and blood vessels have to adapt to support healthy pregnancy. The cardiovascular has to circulate blood throughout the mother’s body as usual, and supply the placenta with blood to support fetal growth. Normal pregnancy is characterized by high blood volumes with high levels of blood vessel relaxation.

In women who do not have normal cardiovascular adaptation to pregnancy, disorders that involve the mother's heart and blood vessels can develop. Women who develop preeclampsia have abnormal cardiovascular function that is characterized by low blood volumes with low levels of blood vessel relaxation. Pregnant women who develop severe preeclampsia have much lower cardiac output in the second trimester of pregnancy, when compared to healthy pregnant women (4.5 L/min in preeclamptic women vs. 6.6 L/min in healthy women).

The involvement of the mother's cardiovascular system in the development of preeclampsia explains why some risk factors for preeclampsia involve the cardiovascular system. For example, women with high body mass index, pre-pregnancy cardiovascular disease and diabetes are at higher risk of developing preeclampsia. If there is dysfunction or abnormality of the mother's cardiovascular system prior to pregnancy, these women are at higher risk of developing cardiovascular dysfunction during pregnancy.

Exercising before and during pregnancy lowers the risk of preeclampsia, most likely by improving the strength and function of the mother's cardiovascular system. Read here for more information.

However, abnormal function of the mother's cardiovascular system alone or pre-pregnancy cardiovascular disease does not guarantee preeclampsia development during pregnancy. Let's discuss how the mother's immune system can impact the development of preeclampsia.

Does the immune system cause preeclampsia?

Pregnancy is one of the few situations where the immune system is okay with having a foreign living being co-habitate in the body. Under normal conditions, the immune system will quickly try to remove anything that doesn't belong to your body that your immune system doesn't recognize. If you suffer from allergies of any sort, you know what your body usually does when it thinks there is a foreign invader inside you.

But isn't the baby part of the mother's body, containing her genes? It's not exactly a foreign invader.

This is only half-correct - remember that the baby is the result of an egg and a sperm coming together, and the baby’s DNA is roughly a 50/50 mix of both mom and dad. In healthy pregnancy, the mother's immune system must not react and reject the baby. The placenta acts as a barrier between the baby and the mother's immune system. In normal pregnancy, the mother's immune system is also suppressed to reduce the chances of an immune reaction to the baby.

Abnormal function of the mother's immune system may also contribute to the development of preeclampsia. Women with pre-pregnancy chronic inflammatory diseases are at higher risk of developing preeclampsia.

How does the father impact the mother's immune response to pregnancy? There is evidence that prior exposure of the mother's immune system to paternal proteins before pregnancy can decrease the risk of preeclampsia. Long periods of unprotected vaginal and even oral sex with exposure to semen has been shown to increase the mother's immune tolerance to the fetus. First pregnancies, having a different partner after the first pregnancy, and assisted fertilization techniques are all risk factors for preeclampsia.

Summary

There is no one single cause of preeclampsia. Preeclampsia is a complex syndrome that scientists hypothesize involves the mother's placenta, cardiovascular system and immune system.

Disclaimer

Every woman and every pregnancy is unique. Pregnant women should speak to their healthcare provider to ensure maternal and fetal safety. This article is meant to provide readers with current information and opinions. All medical and treatment decisions should be discussed with your healthcare provider.

This article was written by Dr. Jovian Wat and edited by Dr. Kelsey McLaughlin and Dr. Melanie Audette.

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What Causes Preeclampsia?

Jovian Wat, PhD