New Yorker: The Preeclampsia Puzzle

[shelley]

I would probably consider taking up somoking, should I get pregnant again; but my tolerance for smoke is rediculusly low. I would,however, seriousely try (not second hand, as it probably does have extra toxins). Anyway, I do believe several years ago there was information out about the possible use of hyperbarric chamber(s) to aide in the reduction of occurence of P.E. Does this seem like it might be a similar mechanism that is occuring with a healthier means of reducing the chemical process? (I hope this is not cague) If I can find an article on the sebject (which is long gone since around 1997...to about 2000) I will try and post it.

Another subject I noticed in that article is that in it the statement is made that humans are the only species that present with P.E.(I appoligize if I have missquoted). There are articles thst insicate sheep/ewes experiense a similar or the same symptoms ae humans. That was also found in articles written around the same time the information found on hyperbaric chambers.

All in all I Lovvve this article.(it brought tears and other emotion, as well as gratitude that this researcher(s) did not allow this information to be burried. somebody needs now to possibly annalyze the male sperm to see if it has any influence as the male species has been shown to possibly influence P.E. as well). I will be putting more articles under my o.b.'s doors.

Thank You

Ennever

[caryn]

I think we have a couple of biopsies in gorillas, and one in a bonobo female, that indicate true PE can occur in all great apes, though possibly somewhat less frequently than it occurs in humans. There's even some speculation that PE was what actually killed off the Neanderthals -- they couldn't keep their women alive because they hadn't invented modern medical care.

If I'm not mistaken, the variant in sheep doesn't produce the distinctive kidney lesion (glomerular endotheliosis) that we see in higher primates... so it isn't considered to be the same disease.

Researchers are still investigating what the protective mechanism from smoking might be -- is it nicotine? is it carbon monoxide? -- and in the meantime they're still adamant that smoking could likely cause even more problems than it could fix, since there are a boatload of bad side effects to go along with the one useful side effect -- so they don't recommend that we take up smoking just yet, KWIM?

[jacobdaniel]

If FLT levels can be assesed during pregnancy, then why don't they check this level in pregnant women? And if it is elevated and VECG reverses the the vessel damage in rats; then why don't they try it on a woman with severe pre-eclampsia at an early gestation when survival for the baby is so unlikely anyway. I, for one, would have been willing to try this!! Are there any perinatologists who have used this technique? And if so, do you have his/her phone number? How frustrating that they don't try this in such a desparate situation!!

[catherine]

One thing that we need to appreciate when thinking about possible interventions is that an effective treatment does exist, i.e. delivery. Thus, it will be very difficult to find an ethical way to test possible treatments, even on a "compassionate" basis. No matter how much we would be willing to risk in an effort to enable our babies to be carried to term, it's unlikely that any doctor would be willing to put our lives and/or future health in jeopardy, knowing that by proceeding to delivery we would be out of danger.

I'm very excited that so many advances are being made towards advancing our understanding of the factors that cause preeclampsia. However, that knowledge will not be easily translated into either diagnostic tests, nor treatments. Indeed, if I were offered a diagnostic test that might tell me my risk of severe preeclampsia early in pregnancy, I think I might be reluctant to do it when there are so few effective interventions that can help.

I'm hoping that some day, all of this research may lead to insights such as those regarding the need for adequate folic acid supplementation in early pregnancy as a way to minimise the risk of neural tube defects in a developing fetus. That way, every woman planning to become pregnant will be able to head off her risk of preeclampsia in advance of conception. I'm not certain that there will ever be a time when medicine can step in and avert early and severe hypertensive disease.

[caryn]

Supplemental VEGF wouldn't fix the underlying problem of having a shallowly implanted and underperfused placenta... because the remodelling of the spiral arteries at the maternal-fetal interface happens much earlier than the symptoms appear. So the baby would still be undersupplied with blood. Nor would supplemental VEGF necessarily shut down the rest of the "cascade" of released proteins that drive some of the increase in maternal blood pressure, etc. Inflammatory responses are necessary even in normal pregnancies, and we don't have any idea what'll really happen if we try to effectively shut them down. (And right now we don't even know how to shut inflammation down effectively.)

Although VEGF and sFlt-1 are really interesting keys that will help us unlock the rest of the problem, we're just not at a theraputic stage yet with any of this.

As Catherine suggested, there are ethical oversight boards which would quickly put a stop to the practice of any physician who experimented on women with this disease in a way that would cause them to run more risk... we need animal trials, and Stage I and II human trials, before any of this will get into practice.

[jacobdaniel]

What if they found elevated fLT very early in preganancy. Could VECG then possibly reverse the process? What would be the risks of trying this? They are both proteins, right? Thank you for your input in helping me understand how this works. Delivery may be the cure, but it doesn't help save the baby at 24 weeks. If it could be caught very early, maybe they would have a better chance. I guess I jumped the gun on this, but it just sounds so promising. What adverse reactions could occur administering VECG early on, before symptoms appear if fLT is found to be very elevated? Just wanting to understand better. Thanks

[caryn]

As a broad generalization, most cases of PE are plays in (at least) two acts -- first the spiral arteries get remodelled and the placenta embeds and grows, and then there's a symptomatic phase where that placenta has become inadequate to support preganancy and begins to release these angiogenic factors. (This isn't true in all cases of PE, like the sudden severe late cases where a clot has lodged in an umbillical artery and suddenly compromised the placenta, but it's true for most.)

These studies Karumanchi has been doing are all about the second act. But the stage is set in the first.

SFlt-1 and sEng are possibly going to be useable to prevent some of the severe maternal consequences of PE -- for example, we could possibly combat the hypertension and liver damage with supplemental VEGF -- but doing so wouldn't be likely to embed the placenta any more deeply, because it isn't one of the proteins that controls embedment (at least, as I understand things.)

In fact, lowering maternal blood pressure might *compromise* the fetus, because it would mean less blood was being forced across the placenta. It's very likely that the fetus is responsible for at least some of the increase in the maternal blood pressure, with the "goal" of increasing its blood supply.

As for the inflammation -- the question you just asked ("What adverse reactions could occur") has no known answer as I understand things. They've only just begun to understand that inflammation underpins a whole bunch of chronic diseases, and is an essential component of our innate immune system. They're starting to ask questions like, "If we shut it down to treat arthritis, will we see a vastly increased rate of death from the common cold?"

[catherine]

One thing that we need to remember is that these growth factors have roles to play else where in our bodies. Although we are seeing a tissue-specific problem (growth factors regulating placental establishment and development), these same molecules do other jobs all over our bodies. They are pretty fundemental jobs too. It's very hard to do research on these proteins because scientists can't make viable "knockout" mice to study them [specifically inactivating the gene(s) that encode the protein]; they die as embryos because the loss of the protein has very profound effects on development.

Growth factors work as different key-like elements that engage with specific "locks" on cells that are going to be part of the vascular system. One code isn't sufficient to get the door open as it were, you need the ID card, the retinal scan, the thumbprint as well before the cell will agree to carry out the process that you are asking for. Each of the growth factors acts as one of those components. If you were to come and "fool" with the system, you might suddenly find that you were flicking open locks all over the place, not just where you want it to happen. Does that make sense?

[caryn]

And on that note, Karumanchi just mentioned in passing that this therapy would first be tried in non-pregnant humans, to see what other systems are affected, to see if it's even tenable as a therapy for expectant management. If we can give it to non-pregnant people without serious compromise, then we can test it in pregnant people, and see if it actually does help the mother without harming the fetus, or if it helps the fetus too, or if it doesn't allow any further prolongation of pregnancy.

(Whee, this conference is fun!)

[laura]

One more thing- your friendly voice from tobacco control would like to remind everyone that regardless of how great it might ulitimately prove to the placenta, smoking while pregnant is *not* a good idea. Babies subjected to smoking moms have problems with the development of their lungs, SIDS, and it has even been associated with an estimated 1/3 of kids with ADD.

As someone subjected with prenatal exposure to smoking and SHS exposure as a child, I can say that the ADD I have and reactive airway disease/asthma isn't worth it.