What happens biologically during Pre-E

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Re : What happens biologically during Pre-E

Postby jillmushet » Wed May 24, 2006 11:48 am

Great post. I also had my husband read it.

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Re : What happens biologically during Pre-E

Postby patricks mommy » Mon May 22, 2006 11:17 am

This has been a great thread! Thanks for all of the information. I just had my husband read it.


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Re : What happens biologically during Pre-E

Postby auntshelly » Sun May 21, 2006 11:01 pm

Wow this a great question. I have learned so much from your answers. This is the kind of information that is so hard to weed out when trying to do your own research!
Thank you

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Re : What happens biologically during Pre-E

Postby kimana » Sun May 21, 2006 05:45 pm

Abbie--thanks for asking these questions...I knew I wanted to know more, but didn't know how to phrase without sounding foolish...thanks for putting the words out there!

Thanks to everyone that has provided insight. I always feel better the more I know and enjoy learning new things. I better get DH on here to read this!!!

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Re : What happens biologically during Pre-E

Postby caryn » Sun May 21, 2006 01:40 am

Yes, there is definitely a correlation with things going wrong in early pregnancy -- we now know that a history of miscarriage raises your risk of PE, presumably because it means that your immune system isn't responding correctly to the arrival of the placenta.

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Re : What happens biologically during Pre-E

Postby missgamecock » Sat May 20, 2006 11:13 pm

Good thread guys!

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Re : What happens biologically during Pre-E

Postby catherine » Sat May 20, 2006 10:57 pm

Caryn and Laura have done an awesome job so I'll just do a little mop up here on "things" that might predispose to poor placentation.

1) Act of the Devine/Nature/Random Fate/Unpredictable Genetics. A newly fertilized egg is a completely unique pattern for a human being, and the placenta that supports it is too. Nothing is perfect so every once in a while things just might not string together as well as they could. People who experience this might just have one episode of preeclampsia during their entire reproductive career, not necessarily your first baby.

2) Women with hypertension, or with a tendency to develop this. It is simple to imagine that a newly forming placenta may struggle to establish the optimal maternal fetal connection in a system where the pressure in the circulation is high. So, if this happens to be your particular issue, it's simple to see that the best approach to trying to establish and maintain a healthy pregnancy is to have better control of your disease. This is why BP meds help some people, they ramp back the pressure which is high or tending high due to maternal factors unrelated to pregnancy. Some perinatologists also consider high cardiac output to be somewhat akin, and will treat women with this even when their BP falls within what would be normal levels.

3) Folks with thrombophilias otherwise known as blood clotting disorders. Some are well recognized with what is termed "poor pregnancy outcomes". Blood is a carefully balanced mixture of factors that promote clotting and factors that oppose it. Pregnancy kicks that balance over in order to accomodate all the new blood vessel formation, increase in blood volume etc. The formation of tiny blood clots may impair the formation of the spiral vessels etc. and lead to a less than perfect implantation event, and maybe preeclampsia down the line. For people who have recognized issues, there are therapies that can be considered, eg. blood thinners and using them during pregnancy may prevent those problems and thus reduce the risk of preeclampsia.

4) Folks with auto-immune diseases. These are diseases where the mothers immune system is, "testy". Diseases may "flare" under any situation of physical stress... hello pregnancy! On top of this.. the immune system is supposed to "turn itself down" during pregnancy so that the baby isn't considered a dangerous "non-self" signal. This process may not be optimally regulated in people with auto-immune disease. The depressing thing is that sometimes, a bout of preeclampsia may be your first warning sign that you may be developing such a condition.

5) Diabetes, PCOS, metabolic syndrome. There appears to be some association with increased risk of preeclampsia and these diseases or problems.

6) Multiples. Simple... count placentas [:p]. Realistically, 2 or more times the risk of something just not being as good as it could be.

The reason that I add this aspect of things to the discussion, is to highlight how current understanding of the disease may help with managing your risk of developing it again. It is totally worth doing what you can to rule out the predictable risk factors... It is equally worthwhile to do whatever you can to manage your hypertension, it can't hurt to follow the sensible recommendations of ACOG regarding diet and excercise in pregnancy. Once the BFP shows up.. well for now the majority of prior pre-eclampsia sufferers step onto the rollercoaster and hope for the best outcome possible. Future basic research (the whole SFlt-1 story comes from research groups interested in studying angiogenesis.. blood vessel formation.. I think one story goes that some men in a trial were taking an angiogenesis inhibitor to try and suppress tumor growth and developed symptoms that would be called preeclampsia if they'd been female, and pregnant past 20 weeks gestation[:)]) will help, translational research will bring this material out of laboratories and into OBs offices as early predictor tests, or better still, very specfic therapies that would help support the pregnancy but not hurt the fetus. Just think about how tricky it will be to come up with a good and safe approach!

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Re : What happens biologically during Pre-E

Postby scrapang » Sat May 20, 2006 10:26 pm

Wow, what an extremely informative thread! Not sure I can re-explain it if someone asks me, but it makes a lot of things make sense in my own head at least! I wonder if there is any correlation with problems in early pregnancy, maybe the beginning of things not quite setting up right. Seems like I always had trouble "getting started" with a bit of bleeding, low hcg numbers, etc. Kind of makes me go hmmm... Also makes me go hmmm... that my dr. has said he doesn't think I am actually heading towards PE and is leaning more towards an autoimmune something not related to pg. Sounds like they really are more related than I thought.

Thank you for the great information. I've never seen it explained so well!

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Re : What happens biologically during Pre-E

Postby abbie » Sat May 20, 2006 09:42 pm

Thank you all so very much!!! These are exactly the answers I was looking for. If anyone else has further insight - please feel free to chime in. I think I'm actually starting to understand the biological process... which actually makes me less fearful - now that I kind of know what is going on.

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Re : What happens biologically during Pre-E

Postby caryn » Sat May 20, 2006 09:32 pm

I'm only one of the resident science chicks, so this will probably get expanded further, but here's a little more expansion on Laura...

It is looking very much these days like the problem with the initial implantation of the placenta is caused by a response to the foreign proteins of the placenta, which the immune system either a) recognizes as an invader, and attempts to reject, or b) fails to reject strongly enough (!) . All sorts of things can predispose you to this problem: an autoimmune disease, a family history of hypertension, multiples, any of the various forms of insulin resistance like diabetes or PCOS or GD, and so forth. Perhaps the reason "first baby" is a risk factor is that the immune system has to practice recognizing and responding to fetal DNA in order to handle it properly; we really don't know.

At any rate, the placenta's spiral arteries just don't get in there deeply enough, and the placenta ends up shallowly implanted and sometimes abnormally small because its normal growth has been compromised by the immune system as well. Scientists are pretty sure about this part; almost every study I've seen lately starts off with a first sentence along the lines of "Preeclampsia is characterized by poorly implanted placentae that..."

The theory goes: right around mid-pregnancy, the fetus begins to pack on weight and demand more blood across the placenta, but the placenta can't ferry it. The fetus begins to be shortchanged with respect to oxygen and nutrients (so IUGR is often associated with PE.) Our best guess at this point is that when the placenta becomes hypoxic, a protein called sFlt-1 gets expressed in its cells. (SFlt-1 stands for soluble fms-like tyrosine kinase, which is a mouthful.)

Ordinarily our bodies produce a lot of something called VEGF, for vascular endothelial growth factor. VEGF's "job" is to rattle around the blood vessels looking for leaks, and plug them -- it shepherds repair molecules into the holes blood vessels develop as they age. SFlt-1 is a VEGF antagonist, which means it binds to VEGF and makes it unable to do its job.

This loss of VEGF means the vessels become leaky (so swelling, sometimes oliguria, and cerebral edema, which explains the headache, visual disturbances, and hyperreflexia) and the kidneys aren't repaired so they can't filter properly (so you start to spill protein) and the liver starts to become toxic (so all the bad bloodwork showing liver damage -- sFlt-1 is hepatotoxic.) Edema can increase pressure on the blood vessels from the surrounding tissue. As if this weren't enough, all sorts of vasoconstrictors start to be expressed as well, tightening down the blood vessel walls and further raising pressures. That constellation of responses is pretty much the clinical definition of "multiple organ failure."

Oddly enough, sFlt-1 is present in *all* pregnancies -- it's just present early, and in phenomenally large quantities, in hypertensive pregnancies. The hypothesis here is that ordinarily placentae are only significantly hypoxic during labor contractions, and that production of sFlt-1 would help to detach the placenta from the uterine wall. So this explains the high rates of placental abruption in the population of hypertensive pregnancies.

And some people have existing hypertension, kidney or liver damage, etc -- which means their bodies are just that much more sensitive to the beginning of this cascade. When things start to go wrong, they touch off a feedback loop, and things often get much worse very quickly as one cause drives an increase in the effect of another. The average time from diagnosis to delivery is right around two weeks, and we've had the whole gamut from mild PE posters who go for months on bedrest, to women who crash into HELLP syndrome between their 2 pm OB appointment and the start of SNL.

So it's *REALLY* important to monitor your own symptoms, push for further testing, and generally keep your eyes peeled for further problems if you've gotten a positive diagnosis and you aren't already in the delivery room. Better safe than sorry.

Hope this helps some, and I don't mean to scare you. Unfortunately it's a scary disease. :-/

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