Tracing the molecular causes of preeclampsia

September 10, 2012, Helmholtz Association of German Research Centres

Preeclampsia is one of the most dangerous conditions for the expectant mother and the unborn child and is characterized by elevated blood pressure and protein in the urine in the last trimester of pregnancy. The cause for this life-threatening disease has long remained elusive. Recently however, Dr. Ananth Karumanchi (Associate Professor of Medicine, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, Massachusetts, USA) has identified a new molecular pathway that leads to preeclampsia in humans and thus creating new avenues for the development of a therapy, he reported at the 1st ECRC "Franz-Volhard" Symposium on September 8, 2012 at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch.

" is among the three diseases that cause death amongst mothers, their unborn and newly born babies, accounting for nearly 70,000 maternal deaths a year worldwide," Dr. Karumanchi pointed out in Berlin. The other two are severe bleeding and infection. Researchers suspect that the number of deaths caused by preeclampsia is underreported and is actually much higher. "Preeclampsia is especially lethal in the underdeveloped world where medical care and facilities for emergencies and for caring for premature babies are lacking," Dr. Karumanchi said. Therefore, the death rate among those newborns is clearly higher than in countries with better medical care.

However, preeclampsia is a serious problem in industrialized countries, too. In Germany, for example, every year more than 20,000 babies are born prematurely due to preeclampsia. "In fact preeclampsia is among the leading causes of prematurely born babies," Dr. Karumanchi stressed. As each additional week in the uterus of the mother lowers fetal morbidity and mortality, physicians strive to prolong pregnancy without compromising the safety of the mother.

If the condition becomes too dangerous for the pregnant woman, they intervene and induce labor. As soon as the child is born, the mother's symptoms disappear. But later in life the mothers can develop heart disease, hypertension and thyroid disorders due to preeclampsia. And premature babies run the risk, if they survive, of life-long disability.

Findings on molecular causes open up avenues for early diagnosis as well as therapy

Dr. Karumanchi was able to show that the placenta, the organ in the uterus which nourishes the embryo and the fetus, plays an important role in the onset of preeclampsia. It releases two different proteins. One of the proteins, the PlGF (placental growth factor) makes blood vessels grow towards the placenta. It is an angiogenisis factor which is part of the VEGF family, a large group of proteins that induces blood vessel growth. The antagonist to PlGF is sFlt-1 (soluble fms-like tyrosine kinase-1). It binds to PlGF and inhibits blood vessel growth. The levels of these two proteins in the blood of the pregnant women must be in balance for mother and unborn baby to stay healthy.

Dr. Karumanchi's team discovered that pregnant women with preeclampsia have too much sFlt-1 circulating in their blood, and too little PlGF. As a result the placenta is no longer well supplied with blood, and the fetus does not get enough nutrients. Also, lack of PlGF constricts the blood vessels, and the expectant mother's blood pressure becomes elevated – the main symptom of preeclampsia. As the kidneys are affected, too, the patient develops proteinuria, characterized by too much protein in the urine.

Whereas formerly preeclampsia in pregnant women could only be diagnosed by these symptoms – hypertension and proteinuria – the findings of Dr. Karumanchi now make it possible to detect preeclampsia at a very early stage, even before the first symptoms appear. Researchers and clinicians measure sFlt-1 and PlGF levels and they can determine if sFLT-1 levels are too high. They can then monitor the expectant mothers at a very early stage and help prevent the disease from progressing in order to avoid seizures and liver failure.

Dr. Karumanchi's research has already led to the first step to treat the disease through extracorporeal removal of excessive sFLT-1 from the blood. In a pilot study, Professor Ravi Thadhani (a colleague of his at Harvard Medical School) working with nephrologists and obstetricians in Germany (Cologne and Leipzig), showed last year that a single treatment of five with preeclampsia lowered elevated levels of sFLt-1 in the . Repeated treatment of three additional patients with preeclampsia in the early onset of pregnancy (28, 27, 30 weeks of pregnancy) could reduce not only sFlt-1 but also proteinuria and stabilize without apparent adverse events to either mother or fetus. In addition, the obstetricians were able to prolong pregnancy duration thus allowing the delivery of healthier babies. Dr. Karumanchi stressed that further studies are necessary to determine whether this intervention safely and effectively prolongs pregnancy and improves the condition of mother and child.

Explore further: New findings may help explain high blood pressure in pregnancy

Related Stories

New findings may help explain high blood pressure in pregnancy

October 31, 2011
Virginia Commonwealth University School of Medicine researchers have discovered that the infiltration of white blood cells into an expectant mother's blood vessels may explain high blood pressure in pregnancy.

Pilot study suggests new approach to treat preeclampsia

August 2, 2011
A novel therapy that reduces elevated blood levels of a potentially toxic protein in women with preeclampsia, a dangerous complication of pregnancy, may someday address the therapeutic dilemma posed by the condition – ...

Recommended for you

New study offers insights on genetic indicators of COPD risk

January 16, 2018
Researchers have discovered that genetic variations in the anatomy of the lungs could serve as indicators to help identify people who have low, but stable, lung function early in life, and those who are particularly at risk ...

Previous influenza virus exposures enhance susceptibility in another influenza pandemic

January 16, 2018
While past exposure to influenza A viruses often builds immunity to similar, and sometimes different, strains of the virus, Canadian researchers are calling for more attention to exceptions to that rule.

Don't hold your nose and close your mouth when you sneeze, doctors warn

January 15, 2018
Pinching your nose while clamping your mouth shut to contain a forceful sneeze isn't a good idea, warn doctors in the journal BMJ Case Reports.

New antifungal provides hope in fight against superbugs

January 12, 2018
Microscopic yeast have been wreaking havoc in hospitals around the world—creeping into catheters, ventilator tubes, and IV lines—and causing deadly invasive infection. One culprit species, Candida auris, is resistant ...

Dengue takes low and slow approach to replication

January 11, 2018
A new study reveals how dengue virus manages to reproduce itself in an infected person without triggering the body's normal defenses. Duke researchers report that dengue pulls off this hoax by co-opting a specialized structure ...

Different strains of same bacteria trigger widely varying immune responses

January 11, 2018
Genetic differences between different strains of the same pathogenic bacterial species appear to result in widely varying immune system responses, according to new research published in PLOS Pathogens.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.