Preeclampsia May Involve the Fetal Genes

Preeclampsia genes

Preeclampsia is a serious complication of pregnancy that has been recognized as far back as ancient Egypt, but its causes have eluded researchers even in modern times. The condition is characterized by elevated blood pressure (systolic >140 mm Hg and/or diastolic >90 mm Hg, detected on two separate readings at least 4 hours apart) occurring after 20 weeks gestation. Along with the elevated blood pressure, there is dysfunction of a maternal organ –usually the kidney, showing up as protein in the urine. Preeclampsia affects about 5 percent of expecting mothers and is an obstetric emergency that threatens the mother and especially the fetus. In extreme cases, it can be a prelude to other, worse conditions. One is called HELLP syndrome and the other is eclampsia. Both can lead quickly to maternal death.

Science has recognized family factors associated with preeclampsia risk for quite a while. If your mother or sister has had it, for instance, you have an elevated risk. Obstetricians and scientists also have known for some time that preeclampsia is more likely if the fetus is a boy, rather than a girl, in non-Asian populations. For Asians, the fetal gender doesn’t seem to matter, a fact that should be giving you the idea that underlying causes of preeclampsia are quite complex.

Nevertheless, a new international study, published in the prestigious journal Nature Genetics has provided some insight. The research involves thousands of babies and mothers and dozens of universities and hospitals in the United Kingdom, Norway, Finland, Iceland, Uzbekistan, and Kazakhstan has added a new dimension to the equation, while opening the door to finding a specific, underlying cause.

Prompted by research suggesting that fathers too can contribute to preeclampsia risk of a pregnancy, the new study shows that a specific genetic sequence in the fetal DNA can trigger preeclampsia. Specifically, it’s a variation in a gene called sFlt-1, and it’s very common; about 50 percent of the population carries the sequence. So clearly, fetal genetics alone cannot lead to preeclampsia. But it is a start at understanding preeclampsia at the genetic level, and it may turn out that the sFlt-1 sequence and the male fetal gender phenomenon work together, through a related mechanism. Whatever the details, it’s clear that something that’s generated in the fetus affects the mother’s physiology –certainly though factors that are heritable (transmissible from parent to child), possibly by affecting the expression of genes in the mother’s cells.

Another implication of the discovery is that, as far as risk goes, it’s not just having a mother or a sister with a history of preeclampsia that should go into the records. Cases of preeclampsia among your male partner’s female relatives –his mother, his sisters, his aunts, his grandmothers– also could be important to the family history.

So given that the genetic element from the fetus –including the presence of a Y chromosome if the fetus is male– merely makes preeclampsia possible, let’s discuss the other risk factors. This means the various situations that have been known for a while to be associated with preeclampsia that now appear to work in concert with the fetal genetics. One factor is age. Women older than 35 years carry an elevated preeclampsia risk. That’s just simple math. It’s not a reason to worry if you’re in your mid thirties or higher, since the chances of developing preeclampsia are still quite low. But it is something to keep in mind.

Another factor is body mass index (BMI). Women who are obese (very high BMI) or borderline obese have an elevated risk, just as they have an elevated risk for other complications, such as type 2 diabetes. First time mothers have an increased risk as well. So do women with co-existing health problems, such as type 1 diabetes, systemic lupus erythematosus (SLE, “lupus”), kidney disease, or if you have what’s called antiphospholipid antibody syndrome. Also, if you’ve had preeclampsia with a previous pregnancy, that puts you at risk for having it again.

A woman developing preeclampsia may experience any or all of the following symptoms: pain in the upper abdomen, a throbbing headache, fatigue, decreased urination, trouble with the eyes, chest pain, cough, and breathing difficulty, and swelling, especially in the face. Notice that some of these symptoms (abdominal pain or burning above the stomach, fatigue, headache, and vision problems) also correspond to a condition that you know very well, namely pregnancy. So don’t be alarmed if you experience any of them. If anything develops out of the ordinary for your pregnancy –if you have breathing problems, chest pain, or if you stop peeing as much as you have been peeing throughout pregnancy, call your doctor immediately.

In the event that preeclampsia is suspected, your blood pressure will be tested frequently and documented systematically. They’ll ask you for urine samples multiple times, plus the doctors will check your lungs for evidence of edema (swelling). They’ll do some blood tests to evaluate your red blood cells and platelets, and function of your liver and kidneys. They’ll check the oxygen saturation in your blood and they may do an echocardiogram, a kind of ultrasound that looks at your heart, plus they do ultrasonography to check your fetus, just as they do on a normal obstetric checkup.

For a patient who is diagnosed with preeclampsia, and if the preeclampsia is severe, the first goal is to prevent seizures –a development that would indicate transformation of preeclampsia into eclampsia. They may check your brain with an MRI scan and electroencephalography (EEG). They’ll giving magnesium sulfate to prevent seizures if they determine that the risk is high. In such cases, if the pregnancy is beyond 34 weeks, they’ll deliver the baby early. If it’s before 34 weeks, they’ll administer steroids to accelerate maturation of the fetal lungs in order to carry out delivery as soon as possible. Hormones are also an important treatment in cases when HELLP syndrome develops. As for the high blood pressure, the obstetrician will order medication to lower the pressure. A lot of effort also goes into management of the fluids administered to the women through an intravenous line.

As noted early, the causes of preeclampsia have not been worked out entirely, but we know fairly well who is at risk. For those who are at risk, the US Preventive Services Task Force and the American College of Obstetricians and Gynecologists both recommend low-dose aspirin as a preventive measure.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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