Research

Principal Investigator Nihar R. Nayak, DVM, PhD, Stanford University, recently reported successful progress in his efforts to better understand the role of certain placental proteins in the development of preeclampsia. His 2011 Vision Grant research project aimed to see how proteins act in the placenta during preeclampsia. In Nayak's multi-stage investigation, he first needed to develop a new method using a mouse model system to study the roles of specific proteins in placental function and disease, as well as testing novel therapeutic approaches to preeclampsia. In his model, protein expressions can be seen in all stages of pregnancy.

Nayak's team has also developed a way to study how genes act in the placentas of mice. Genes play an important part in the development of the placenta during pregnancy. Better ways to see how abnormal genes act will help us learn more about what causes the amount of certain proteins to be higher than normal. Additionally, the abnormality of the genes is thought to occur in the early stages of development of the placenta. Therefore, this new model allows them to see how the genes act in the early stages of development.

A protein called sFlt-1 is found in the blood of pregnant women at a higher level when they have preeclampsia. Understanding this protein and why it accumulates will have a direct impact on the design of clinical therapies for preeclampsia. With their new method, they have been able to see how sFlt-1 acts in mice by using a virus' genes to tell the placenta to stop making sFlt-1. This will help explain how the gene and proteins act together and what causes the abnormally high amount of sFlt-1 in preeclampsia.

The Stanford group is also trying to see how another protein, VEGF, acts during pregnancy. This protein is also higher in preeclampsia pregnancies than in normal pregnancies and they are currently using the same method to study it, believing that higher levels of VEGF in the placenta also has an important role in causing preeclampsia.

Nayak and his team will conclude this research toward the end of the year at which time they will seek to publish and report their results.

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Every two years, the International Society for the Study of Hypertension in Pregnancy (ISSHP) World Congress brings together the top researchers and clinicians in the field of hypertension in pregnancy to share innovations and encourage collaborations in research and clinical practice. As in year's past, the Preeclampsia Foundation participated in the 2012 meeting held July 9-12 in Geneva, Switzerland.

Like the current Olympics which inspire us to "Citius, Altius, Fortius" (Latin for "faster, higher, stronger"), the World Congress inspires participants to demonstrate new found knowledge and skills, and to push each other forward. In the enthusiasm of science-swapping and networking at a meeting like ISSHP, sometimes the larger purpose of our endeavors - saving lives and improving health outcomes of mothers and babies worldwide - may be forgotten by those racing from one intriguing lecture to the next.

That's where the Preeclampsia Foundation comes in. It is a testament to the extraordinary outreach of our mission that not only are we widely recognized as a key patient resource by individual health care providers, but are sought out by industry leaders as THE voice to provide a reminder of the patient perspective amongst the plethora of science and research. Our impact can be summarized in that one word: "voice." By joining our members' collective experiences along with the experience of wonderful new friends from European patient advocacy groups, we have become a powerful entity for change. A voice that is not only heard, but valued.

The Foundation's efforts to improve health care practices and catalyze research were also felt at ISSHP. Two investigators presented research findings developed through our collaboration in the Brain Study- and for many of our readers - it was your participation in this study that provided such meaningful data. In one oral presentation, findings suggested an association between history of preeclampsia and post-traumatic stress disorder. In the other, findings suggested an increase in neurocognitive disorders among women with history of preeclampsia. Both studies are being developed for publication and will be promoted via this newsletter when they're published. Both studies were exceedingly well received, with other researchers encouraging us to conduct further studies on long-term patient impact to improve clinical care.

We also presented two research travel grants, which helped promising young investigators attend this important meeting, interact with seasoned researchers, and become committed members of the hypertension in pregnancy community.

Every day, our website and social media platforms receive thousands of visitors from more than 200 countries around the world, so it was particularly wonderful to meet global health care providers who interact with those patients and who themselves use our website regularly. Unfortunately, we are sometimes the only source for additional patient support and education. So though no one received any laurel wreaths or gold medals during the Foundation's international journey, the patients are the real victors through the furthering of global preeclampsia research.

 

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At the Society for Gynecologic Investigation (SGI) Annual Scientific Meeting in San Diego, Calif., in March, the Preeclampsia Foundation, in collaboration with lead authors Dr. Ineke Postma, Dr. Gerda Zeeman, Dr H. Groen of the University Medical Center Groningen, the Netherlands, and Dr. Thomas Easterling of the University of Washington, presented a poster on cognition, quality of life and social functioning after a hypertensive pregnancy. Many formerly preeclamptic women report difficulties with memory or word choice postpartum, but so do many women with normal pregnancy courses. The unanswered question: what is the likelihood that preeclampsia causes brain changes independent of pregnancy itself? If there are preeclampsia-specific changes, can those be separated from the trauma of a medical crisis?

Enrolling more than 1,000 participants in this study, the Preeclampsia Foundation's survey queried women with (cases) and without (controls) a history of hypertension in pregnancy. Participants anonymously completed an online survey assessing their cognitive functions, their quality of life, and their social functioning. The study found that the population of women with a history of preeclampsia scored statistically significantly lower on all three assessments. Although there was significant overlap between the populations, the average score for the populations as a whole was shifted - which suggests that there is actually real change triggered by preeclampsia - and that shift persisted after the populations were adjusted for things that could potentially affect the scores, like current use of blood pressure medication. Seizure was particularly strongly correlated with long-term cognitive difficulty. The study will also be presented in July at the International Society for the Study of Hypertension in Pregnancy (ISSHP) World Congress in Geneva, Switzerland.

"More and more information is emerging suggesting that preeclampsia is a condition with long term implications," explained the lead author on the study, Dr. Ineke Postma. "Preeclampsia can be a very emotional and sometimes traumatizing experience with some women complaining about ongoing memory or attention-deficit problems. In order to provide adequate long term support to preeclampsia survivors, we need to identify the actual scope of the problem. This study is an important step in that direction."

Although this study used subjective neurocognitive testing (that is, the questions and test were not administered by a separate researcher, but self-reported), the study has some potential weaknesses, but it is an important step to investigating this question: does preeclampsia result in some level of permanent damage to your brain?

These kinds of research collaborations are but one way we catalyze research. See our research section for more information about our research initiatives.

 

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Is there a nutritional connection to preeclampsia? That idea seems plausible at first, as when the blood samples of women have been analyzed, some researchers have found altered levels of various vitamins and minerals. Furthermore, preeclamptic women have altered patterns of weight gain during pregnancy; and obese women are more likely to develop preeclampsia.

 

Such considerations may lead one to speculate that certain diets may prevent or reverse the disease, in which case the appropriate diet becomes a therapeutic intervention. However the best research to date suggests this just isn't so.

 

Reviews of all the trials we could locate show that the major and well-designed trials mainly show no benefit. The very large trials show either no benefit to the generalized population (i.e. Calcium supplementation), or even potential harm (i.e. Vitamins C and E). Likewise, attempts to alter rate of maternal weight gain during pregnancy towards normal levels does not alter preeclampsia rates either.


In some instances, preeclampsia itself might be causing the alterations in nutritional status. The placenta, because it is shallowly implanted, needs to use other strategies to improve its ability to ferry nutrients to the fetus, strategies that include altering the maternal metabolism. In addition, obese women may be more likely to carry genes that both make them more likely to develop obesity in a modern environment and to develop preeclampsia in pregnancy.


The example of Vitamin D shows how one such supplementation research line has developed and been disproved. Sure, vitamin D levels are lower in early-onset preeclamptic women, but this happens once the symptoms of the disease have already appeared. And if we check women at the end of the first trimester, the women who will go on to develop preeclampsia cannot be picked out of the rest of the population. Some reviewers wonder if the researchers analyzed the correct form or metabolyte of Vitamin D when deciding if the woman is "deficient." Supplementing vitamin D doesn't seem to do much beyond raising vitamin D levels in blood work

 

That said, there is an important role for nutrition in pregnancy and it behooves everyone to check with a qualified health care provider to assess the appropriateness of their diet as soon as they learn they are pregnant.

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Currently there's no way to know for certain whether preeclampsia will develop during any given pregnancy. This leaves pregnant women and their care providers with little choice but to wait for symptoms to appear... dangerous symptoms that mean the disease has progressed to the point where mother and baby are critically ill and will need intensive monitoring and carefully timed delivery to protect their health and lives. The only screening method to date is to measure those symptoms when they appear.

Early detection wouldn't be a treatment. But what if a screening test could let us know, weeks or even months in advance, that we'd probably be getting ill? Knowing might change the way we seek care - possibly choosing specialist care providers with the education and experience to manage medically complicated pregnancies. Women in parts of the world (like Wyoming in the winter) where such care is in short supply might be moved to bigger cities where NICUs and maternal-fetal medicine (MFM) specialists are more accessible. Neonatal specialists could be brought into the consulting team, and steroid shots to accelerate fetal lung development could be planned. All of these interventions together have the potential to lower the rates of fetal and maternal death and severe complications dramatically. (By the way, you may agree or disagree with this assessment; either way, we'd really like to hear your perspective in this important survey we recently launched.)

 

Since many experts consider such a test preferable to our current screening methods, recent research has tried to find a workable test with high levels of both specificity and sensitivity. An ideal test would be one that picked up *all* cases of preeclampsia - it would be sensitive - and *only* cases of preeclampsia, with no false positives - it would be specific. In practice this is all but impossible to achieve, but it's quite possible to find tests with very high levels of sensitivity and specificity, with one measure performing slightly better than the other.

 

So for researchers this creates a choice between creating tests that would produce false positives, and tests that would miss some cases. The worst-case scenario of a false positive is likely to be unnecessary close monitoring; it would not be an indication for immediate delivery. It would provide a reason to follow the pregnancy more closely for symptoms that do indicate that the acute phase of the illness has developed. Since the worst-case scenario of a false negative is a missed case of preeclampsia leading to death of mother and/or baby, public health researchers would prefer to develop tests that will overdetect cases of preeclampsia, but with a low rate of false positives.

 

At a meeting of the American Society of Nephrology (ASN) in November, Dr. Vesna Garovic (Mayo Clinic) reported on a study into the use of urinary podocytes as a screening test for preeclampsia, a test that may turn out to have both high sensitivity and specificity for preeclampsia. Podocytes are cells which line the blood vessels in the kidneys and act as filters which keep protein in the bloodstream. Their loss allows protein to spill into the urine, one of the primary signs of preeclampsia.

 

Garovic's research team used a population of 267 women and collected their urine between 25-28 weeks gestation. The samples were examined for podocytes. The 15 women who went on to develop preeclampsia all had podocytes in their urine at that gestational age. The 15 women who developed gestational hypertension did not. The control group of women who had normal pregnancies also did not.

 

Previous research from the same group has indicated that podocytes are present in the urine when preeclampsia symptoms first appear. When they shed into the urine, they cause disruptions in the filtration barrier in the kidney, resulting in proteinuria. The "classic lesion" of preeclampsia - glomerular endotheliosis - may include the loss of these podocytes from the glomeruli in the kidneys.

 

To confirm that this test works well, it will need to be repeated in multiple centers serving broader populations of pregnant women, and to make it available for general use, it will need to be turned into a commercially available testing product. That said, these are very hopeful results - unlike the soluble factors researchers are also pursuing, podocytes appear to only be elevated in women who go on to develop preeclampsia. The soluble factors are elevated in all pregnant women, and just unusually elevated in preeclamptics, which makes it very difficult to develop a screening test with high sensitivity and specificity.

 

Interestingly, it's likely that the podocytes are damaged because of the increased level of sFlt-1, which binds VEGF, which impairs repair of the podocytes and increases the rate at which they die off. It seems likely, given this new research, that it will be easier to detect the damage to the podocytes themselves than it will be to detect an increase of the soluble factors above the point where damage is likely.

 

If it's possible to develop a test similar to a standard pregnancy test, this might be a very effective method which wouldn't require laboratory work, and would make screening much easier and more rapid. Pregnant women who will likely go on to develop preeclampsia could be moved to the care teams that manage complications before they are critically ill, allowing both them and their babies to receive appropriate medical care that would probably reduce poor outcomes substantially.

 

 

A special thanks to Dr. Vesna Garovic at Mayo Clinic, for her expertise and technical input.

 

 

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Filtering the Factors
A new therapy may be developed for very preterm preeclampsia patients, if the results of a small pilot study are confirmed in a larger trial. Researchers have been looking for a safe way to prolong pregnancy by at least the 48 hours needed to allow steroid shots to mature fetal lungs. (Each safe extra day in utero eliminates two or three days in NICU, and means higher survival rates for many of the babies affected by preeclampsia.)

In 2003 a paper published by Dr. Ananth Karumanchi in the Journal of Clinical Investigation presented evidence that a protein named soluble fms-like tyrosine kinase (sFlt-1) caused many of the symptoms in preeclampsia. Karumanchi studied the placentas from preeclamptic pregnancies and found that they were producing far more sFlt-1 than the placentas from normal pregnancies. The protein binds to another protein and compromises the repair of blood vessels, leading to many of the symptoms such as hypertension and proteinuria as damage to the maternal bloodstream accumulates. Since then, dozens of studies have confirmed the role of sFlt-1 in preeclampsia, although as with all scientific research there are likely to be further interesting developments.

A recent paper published in Circulation reports on a small pilot study by Drs Karumanchi and Ravi Thadhani that seeks to filter out excess sFlt-1, thus prolonging the pregnancy. Initially the treatment was only offered once, so that researchers could confirm that it did not worsen matters. After confirming that it did drop sFlt-1 blood levels without any obvious complications, the trial looked at the effect of multiple treatments. In the three women with very preterm preeclampsia where this therapy was attempted more than once, delivery was delayed by two or three weeks before delivery became necessary.

However, since this therapy won't help the placenta implant any better in the first phase of pregnancy, this approach won't eliminate the disease. And since sFlt-1 is only one of the proteins implicated in the development of the disease, women and babies will still suffer some preeclampsia symptoms even if this protein is removed from maternal circulation. However, this targets some of the symptoms that make delivery most urgent. This approach appears to be supported by the basic research and current understanding of this condition and is promising, although very preliminary. A much larger trial will need to be conducted to confirm these results and to confirm the safety of this strategy.

Asthma Increases Risk for Preeclampsia
This month the British Journal of Obstetrics and Gynaecology published a meta-analysis of many smaller studies which reported a correlation between poorly-controlled asthma and preeclampsia. Women with poorly-controlled asthma were at 1.5 times the normal ~5% risk of developing preeclampsia. This means that many women with bad asthma symptoms had normal pregnancies, and that many women with no asthma developed preeclampsia, but more women with poorly-controlled asthma developed preeclampsia than would have been expected.

In a normal pregnancy, the placenta is able to establish what's known as "maternal tolerance" - the mother's immune system tolerates the foreign placenta and doesn't try to reject it. When this tolerance is established, it often affects other immune conditions (like asthma) as well, and the symptoms of those conditions will improve during pregnancy. So when symptoms actually worsen instead of improving, it can be a warning that maternal tolerance hasn't been properly established, which can alert the pregnant woman and her care providers that she is more likely to develop preeclampsia.

If your asthma symptoms worsen in pregnancy, please do mention this study and the worsened symptoms immediately to your care providers and follow up as they recommend.

Stroke on the Rise
The CDC reported that their hospital data show a substantial rise in the number of pregnancy-related strokes between 1994-1995 and 2006-2007. This rise correlates almost exactly to the rise in rates of hypertension and obesity in the population of pregnant women over that timeframe. The increase translates to an increase from 15 to 22 strokes per 100,000 pregnant women. Preeclampsia is the most likely explanation for this dramatic rate increase of 47%. Women with a history of hypertension or obesity can improve their chance of a safe pregnancy outcome by working closely with their care providers to watch for preeclampsia symptoms and treating the condition in a timely fashion if it does arise.

 

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When preeclampsia studies are reported in the news, there’s rarely enough background to evaluate, from the news article alone, how important the research is, or how strong the findings are, or how likely they are to lead to some sort of improvement in care or treatment of preeclampsia. That’s just a consequence of the way news reporting happens these days; preeclampsia is hard to explain, column inches are scarce, and science reporting divisions have largely been cut from media staff.

Really, when a new bit of research is published in the media, it’s an announcement that some new research was published and then put into an attention-getting wrapper. And that’s all. The way science is handled in the media has become so predictable that it’s been the subject of parody lately.

So it’s best to be a bit leery of media coverage of this condition, if you’re trying to learn true things about preeclampsia. Take, as an example, the widespread coverage in October 2010 of an interesting paper published in the journal Nature.

The Guardian , a UK newspaper, reported it as the discovery of “the root cause” of preeclampsia.

A medical news aggregator, MedPage Today, picked up the story, and got more specific and more cautious.

We had a lively discussion at the Preeclampsia Foundation Forums.

The British National Health Service responded with a thorough discussion.

And I asked the PF’s Medical Board to weigh in (anonymously).

It’s almost stunning to realize that all of these conversations and reports are about the same scientific paper.

The advantage to the coverage from the NHS or the PF lies largely in their ability to tap experts - actual authorities in preeclampsia - and to use background information about the disease to illustrate the current state of the research and how this new information fits into the greater context of what is already known about hypertensive pregnancy disease. They’re also both willing to say that *they don’t know things* - which, since there are a lot of unknown things about these conditions, is very likely to be the best possible answer to some questions.

This research blog is going to attempt to illustrate the current state of the research, put it into context, explain the statistics, and bring in principal investigators and PF volunteers with professional skills in this area to comment on their research and interests in the disease. And I’ll be shooting my mouth off as I usually do (for those of you who know me from the forums.)

This process works best if you, the reader, ask us a bunch of questions, partly because that way we can figure out what we forgot to explain well, and partly because many of our posters are very well-informed and will know the answer to your question before a blogger can respond. Having an in-depth discussion with other people over how good an explanation is, and finding the weak spots, gives you the best reason to trust the research of all - you know, then, the extent of the explanatory power of the claims made by the researchers. The crucial point is that the research is only trustable if peer review agrees that the study and argument are sound and that it provides a novel explanation of the phenomena it studies - and even then, it might be wrong. Newton had a great explanation of how gravity worked that covered a bunch of phenomena better than anyone else had before him, and then Einstein came along. Some stuff we believe now about preeclampsia is also bound to be wrong.

It isn’t unusual for our posters here at the PF to ask the same questions that researchers are asking. Please don’t hesitate to jump in and get involved; anyone hit by this disease deserves the best explanations and we’ll be trying to find the right people to provide them.

If you run across an article and want to evaluate it, here's a handy tool. If you’re looking for more research blogging, here is a good site for more discussion of individual research articles. And if there’s something you’d like to see discussed here, please don’t hesitate to email me at caryn.rogers@preeclampsia.org.

 

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Several major disorders that occur during pregnancy result from failure of the placenta to implant correctly into the uterus or womb. During early pregnancy cells from the placenta, known as trophoblast cells, invade into the uterus and tap into the mother’s blood supply to sustain the growing baby. Failure of this process can lead to insufficient supply of blood to the placenta resulting in preeclampsia, as well as low birth weight babies, stillbirth or recurrent miscarriage.

The invading placental trophoblast cells intermingle with maternal immune cells in the uterine lining. Trophoblast express not only maternal but also paternal genes and these will be different or “foreign” to the mother. Maternal immune cells can recognize these “foreign” fetal molecules and are thought to regulate the implantation process, allowing sufficient but not excessive invasion of the placenta. In the preeclamptic pregnancy this interactive process goes wrong and there is inadequate modification of the blood vessels which can lead to “starvation” of the placenta and subsequently triggering of the preeclamptic syndrome later in gestation in the mother.

The important molecules displayed by the trophoblast that are recognized by maternal immune cells are members of the HLA (Human Leucocyte Antigen) family known as HLA-C. The maternal receptors that recognize and interact with HLA-C are the KIR family (Killer Immunoglobulin-like Receptors). These two gene families (HLA and KIR) are very variable or polymorphic meaning that each mother will inherit a particular set of KIR genes and the fetus an HLA-C gene from both mother and father. This means maternal KIR will bind to fetal HLA-C can vary from one pregnancy to another. The interaction should lead to successful implantation but sometimes the combination of these genes from mother and baby results in inadequate invasion and leads to complications in the pregnancy.

Last month, in the Journal of Clinical Investigation, a team from the University of Cambridge reported new findings on the genetics underlying preeclampsia and other placental diseases. Women with a particular set of KIR genes – the KIR-AA genotype – who were carrying a fetus with a HLA-C2 gene were at higher risk of developing preeclampsia than those carrying other KIR/HLA-C gene combinations. This was especially so if the fetus had inherited the HLA-C2 gene from the father.

These genetic findings do not translate directly into therapeutic interventions in preeclampsia although it may be useful eventually in choosing a compatible sperm donor in IVF. The results tell us more about why placental implantation goes wrong sometimes. They might explain the old idea of the “dangerous male”, where pregnancy with particular men often results in preeclampsia. The report does emphasize the common underlying processes that would explain why a history of miscarriage or infertility is associated with a heightened risk of preeclampsia in subsequent pregnancies. Furthermore this risk cannot be affected by lifestyle, which helps those of us who “did everything right” to explain what went wrong.

Also this month, a team from the University of British Columbia, Vancouver, followed up on the connection between blood levels of vitamin D and preeclampsia in the British Journal of Obstetrics and Gynecology. It makes sense to think that the levels of vitamin D in the maternal bloodstream might have something to do with the later development of preeclampsia, because the vitamin is already known to affect some immune responses and because early small observational studies have shown an increased level of preeclampsia in the group of women with low vitamin D levels.

To check this, researchers measured serum levels of vitamin D in a population of women at high risk for preeclampsia, and then recorded their pregnancy outcomes. While the majority of the women had low levels (over three-quarters of the test population had lower levels than normal, and half were technically deficient), there was no connection between the severity of their pregnancy outcomes and the level of deficiency. In other words, some women with normal vitamin D levels still had severe preeclampsia, and some women who were deficient according to current guidelines did not go on to develop preeclampsia at all. This finding suggests that supplementing vitamin D may not have an effect on preeclampsia, although it is still interesting that women who develop the condition also tend to have low levels. There may be some connection between "having the sorts of genes or environment that lead you to develop low levels of vitamin D" and "having the sorts of genes or environment that lead you to develop preeclampsia."

 

A special thanks to Dr. Ashley Moffett, University of Cambridge, and Dr. Timothy Green, University of British Columbia for their expertise and technical input.

 

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Last month, a team from the University of Alberta reported in the journal Hypertension on a method to determine that a woman is at high risk of developing preeclampsia. While this method may or may not be developed into a screening test in the future, it confirmed that changes in the metabolism and the vasculature of women who go on to develop preeclampsia can be detected at 15 weeks gestation.

Two Preeclampsia Foundation members were involved in media coverage on the topic and we are very grateful to them for bringing a human face to the stories about preeclampsia. Because of the press conference and media efforts of the University, a lot of lay press picked up the story and we are fortunate that the Foundation was mentioned in several of those stories. The research findings while seemingly exciting to a lay public are far from commercial realization and would need more validation for most governmental oversight bodies (e.g., FDA). Our message of "cautious optimism" is a responsible middle ground at this early juncture. Read more here.

Also, a new study into changes in maternal weight between pregnancies was published in the journal Obstetrics and Gynecology by a team from the University of St. Louis Medical Center. It confirmed that women who lose weight after a preeclamptic pregnancy have a lower risk of preeclampsia in later pregnancies than women who maintain their weight or who gain weight. Losing weight may change the uterine environment and help encourage normal placental development. A link to the abstract and discussion among forum participants may be found here.

The National Institutes of Health announced that research shows taking vitamin C and E supplements early in pregnancy does not reduce the risk for hypertensive disorders and other complications during pregnancy.

An Irish study to be published in an upcoming issue of Hypertension shows that metabolites found in women's blood early in pregnancy may be able to serve as accurate predictors of preeclampsia. This is a significant breakthrough, as biomarkers for preeclampsia have not previously been very precise. Further studies on the topic are planned.

 

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Research into preeclampsia and its relationship to the long-term health of mother and baby reveals both good news and bad news for preeclampsia survivors.

Evidence is unequivocal now that women who have experienced preeclampsia, particularly severe or early onset preeclampsia, are at a significantly increased risk for cardiovascular problems later in life compared to women with a history of healthy pregnancies. The "take home lesson" for preeclampsia survivors is to establish a healthy lifestyle (weight loss, exercise, no smoking) and to discuss cardiovascular assessment and follow up with your health care provider.

"There are very few identified risk factors for later life heart disease in women; preeclampsia is one of the few warning signs we'll get and we should take advantage of it," explained Executive Director Eleni Tsigas.

One study demonstrated that women who have a history of preeclampsia experienced an increased risk of cardio-vascular health hazard equivalent to that of someone who has smoked for much of her life. That is the bad news.

As Dr. James Roberts reported at the Preeclampsia Foundation Patient Symposium, October 2009, "There is also some good news!" Although not all studies agree, most have shown a reduced risk of breast cancer in women who have had preeclampsia, as much as 15-20% lower risk, with the largest reductions in pregnancies with boy babies.

Dr. Anne Gingery of the Department of Physiology and Pharmacology at the University of Minnesota Medical School in Duluth has investigated how specific factors released from the placenta of women with preeclampsia inhibit the growth of breast cancer cells. Her research focuses on two factors released during preeclampsia: sFlt-1, a soluble version of a protein called VEGF (vascular endothelial growth factor), that regulates the growth of beta cells, and soluble endoglin, a co-receptor for transforming growth factor (TGF) beta cells. Gingery's research, looking at rat models, found placental factors released into the blood stream that may possess anti-cancer properties. She proposes that soluble endoglin inhibits cell growth by reducing the signaling of the TGF pathway, an important factor in breast cancer development and progression.

Other studies have found that breast cancer risk following preeclampsia varies by the gender of the baby delivered. A team in Norway that studied more than 700,000 women through the Cancer Registry of Norway determined that the risk of breast cancer was reduced even more if the woman delivered a son, rather than a daughter (relative risks of 0.79 vs. 0.94). If the preeclamptic pregnancy resulted in a premature birth, the risk reduction from the birth of a son or daughter grows more dramatically - by about four times. These results suggest that the effect of preeclampsia may be attributed to factors associated with the particular pregnancy rather than an underlying biological trait of the mother.

However, cautions the Foundation's medical board, a "reduced risk" does not let a woman off the hook for monthly breast self-exams and regular mammograms. "The risk is reduced, but not enough to avoid the need for awareness and diligent health care," said Roberts.

 

 

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The Preeclampsia Registry

    The Preeclampsia Registry is a "Living Database" bringing together those affected, their family members, and researchers to advance knowledge and discover preventions and treatments for preeclampsia, HELLP syndrome, and related hypertensive disorders of pregnancy.

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