placental growth factor (PlGF) Research

[hfwarner3]

I have been reading about all the research done with urinary placental growth factor (PlGF) in the past year and how low levels at mid pregnancy seems to be a indicator (95% accurate according to the study in the New England Journal of Med) of pre-e.

Are doctors able to test for this now using a urine sample? It would seem to me that the peri's would be all over this. Has there been any correlation between the levels of PlGF versus levels of severity of pre-e?

Thanks!

[anathor21]

That sounds like a very good question - I have not seen anything on it. How many other published studies have you come across on it? (sorry, I have not researched this one at all myself).

[hfwarner3]

Here is the link to the article I was reading:

[url]http://jama.ama-assn.org/cgi/content/abstract/293/1/77[/url]

and when I googled its title I found that it was being referenced by dozens of articles that have come out in the past 6 months.

[anathor21]

Sounds to me like you hit on one of the key questions already - would the test result relate in any way to the severity of the PE. The other question that I (and I'm sure all the rest of us) would like to know is the timing of onset - or timing of critical events to come. I somehow doubt that this one test could give that, but it may well be pointing us towards that battery of indicators that may eventually provide enough data to help point to the answers.

Just knowing that PE is "95%" likely to happen - without a sense of severity or timing may not actually change anything for the treatment algorithm for the best peri's out there. As a "high risk" patient, what exactly would be done differently anyway? And even if tested and didn't get into that category, it doesn't appear that you would be in the clear (i.e. there doesn't seem to be anything her to indicate that the question of an "all clear" signal was even asked, much less answered).

Thus, the funding for followup on this study may just not be there to ask these questions - the 'more interesting' questions may be in why does this particular growth factor level change at different points in pregnancy for PE and non PE pregnancies. Those may get the funding rather than the "does this indicate severity" as the answers may point to more actionable followup questions or answers.

What I would have given during our last pregnancy for some test that would have told us when the PE we were watching was going to go critical on us and how it was going to 'attack' (i.e. mom or boby).

I'd also love to see a test that could give the "all clear" for folks - i.e. something that could say early in the pregancy "you are all set, you won't develop PE during this pregnacny - go worry about the colors in the nursery instead." oh well, back to the reality of today...

[caryn]

As I understand things they'll likely be starting to draw blood tests soon at early gestation, combining the ratio of a couple of proteins (sFlt-1 and PlGF) and a direct measure of another (sEng) to get both an idea of PE severity and of whether or not it will be term or preterm. IIRC the full-text of this study says that if administered after 33 weeks this test has an infinite odds ratio, so there's your nursery test, Erik:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16957146&query_hl=18&itool=pubmed_docsum

or

http://tinyurl.com/v7x2s

But all tests take some time to develop, and I don't believe this one is broadly available yet. Since it's a blood test, though, I do expect development to move fast. One thing they'll have to work out is how often to administer it -- twice during gestation for low-riskers? three times? -- and since it *also* predicts to some extent IUGR and preterm labor (also both somewhat driven by these same proteins) I expect it to shortly become a staple of prenatal exams for the usual public health reasons.

[annegarrett]

I know that the sFlt studies are launching nationally and internationally fairly soon and one site doing the study is here in Washington State. I also know that our Medical Board is extremely strict about saying for certain that "this is it". There are definitely members of our medical board who are very excited about this but others remind me that this marker has been noted for sometime and that there are other markers in early pregnancy that are promising. At this point--there is no test to diagnose preeclampsia. The good news is that this work is getting so much support in part because of research politics--the original samples used for the retrospective (looking back) study were from the CLASP trial out of the NIH and so the author of that work is now able to get his name on this work--which makes the NIH interested in the research. I know when Dr. Karumanchi went to the NIH for funding initially he was turned down and had to use money from his own institution to do the research. Now we have big pharmas sniffing around for the first time in six years. It was really ONLY last year that big pharmas started researching this issue and even those studies have been precariously funded at best. Thank god for Dr. Karumanchi's work and for Ben Sachs New Yorker article. Whether or not the research is right--it shone a light on the issue and so now this research is being fast-tracked through funding from the WHO, the NIH, and a whole network that wants to be part of something that is potentially very big.

SO what does that mean for the woman who is pregnant right now? It means that she might be able to be a part of this national trial. This trial is the first "prospective" research (looking forward) so in my mind--the most important. The sad thing is that even when we get a test--we don't have a cure--and even when we get a test--we know that most women in this country have bad outcomes because of poor care, because even now a doctor doesn't know the difference between PIH and preeclampsia, take BPs lying down, have Physician's Assistants' Assistants on the front line of first-time prenatal care. This test, while very promising, will take a long time and a lot of public awareness to filter down into the women who tend to be high risk--the very young, the very poor, the African American community, and those without access to health care. I wish I could be as optimistic as Caryn (and I am hoping she is right) but I am a bit more jaded about the prospect of the test being a staple at prenatal exams anytime soon--especially when insurance companies are reducing protienuria tests in pregnancy because it is "unnecessary". I really hope the wave of enthusiasm brings this test forward quickly but I am also mindful of the time when they decided calcium was the cause and TUMS actually started advertising it and then the CLASP trial (where Karumanchi got his genetic material) determined it to be unexciting. But the good news is that we have momentum--we have big pharma interest--and we have movement--which is more than I can say for two years ago when big pharma laughed at the NOTION of studying pregnancy and preeclampsia.

[hfwarner3]

I guess my frustration is the whole "pick your diagnosis" game. There are many OBs in our area who will tell you to your face that there is no definitive test for pre-e but that it is something a doctor must determine from the whole picture of the mother and baby situation. I find that unacceptable.

Yesterday, we have a nurse freak out because my wife has a BP that is in the high zone. They do a dip stick in the urine that comes back no protein. The sono-tech finds low amniotic fluid level. This is not sounding good. The peri comes in, looks at the situation and says it looks fine and just requires more monitoring. So the nurse is freaked out and the peri is cool with things. The only thing that makes sense to me is that the peri is looking at that urine sample and saying "no protein, so we are okay for today" when we know that you really need a 24 hour urine sample to get a good snapshot of the situation. Furthermore, if there is protein, that means there is already damage going on. I find all this unacceptable.

It is asinine to me that there is not a test, even if it is only 95% accurate, being used where the peri says, "Yes, we are calling it pre-e and treating it as such until convinced otherwise since you came up positive".

Look at it this way -- they will do a alpha protein on you knowing its inaccuracy knowing that a sizable percentage of false positives will lead to the abortion of a healthy child. Do you see the illogic here?

[anathor21]

I feel your frustration - believe me. I didn't actually put you and Kelly W together until today for some reason.. funny how that happens sometimes.. guess I should pay more attention.

Anyway, on the question of the 24hr protein collection. I too would be pushing very hard to get that done. Based on what has been posted on the other threads I would not be surprised to see some protein in her 24hr. My wife only showed a trace once I think - and that was when her 24hr came back over 1100 as I recall. She tends to drink a lot and as such has very dilute urine. Last pregnacny we had PE criteria from 29 weeks on to end, yet never had a dip stick show anything... scary if you think about it. IF your doctors are waiting for protein to show up to make a change in course of treatment, then I think pushing hard for the 24hr may be in order.

The low fluid would definitly concern me - and I'd take the paranoid approach there too. What I mean by this is that if ANY concern about movement comes up, I'd be right there in L&D for evaluation. With Isabel (#2) it was ultimately her distress that caused us to have to deliver early - she too had low fluid (although not as low as you are reporting)...

I'm thinking of your family - very concerned. Hope you keep posting with updates and let us know how things work out. Feel free to shoot me a direct email if you wish.

[annegarrett]

I know what you mean--I think it is particularly tough for Dads to be "powerless" in these situations. As some perspective, my ex-husband was with me during my emergency surgery and while I "nearly died" and then when they took me to ICU from surgery they told him there wasn't enough room in the ICU room so he would need to wait outside. He was incensed. This guy was a Senior Director at Microsoft in charge of managing translations for the company and not used to being told "no". He got quite loud (something he rarely did in public) and said, "I've just watched them eviscerate my wife--I think I can handle watching her get her BP taken" and marched past the nurse. (It was the first time I had thought of my surgery in that way--but it was telling...)

There is a diagnosis--the NIH Working Group has a guideline in place but like we say--not making it to the bar of diagnosis doesn't mean you're not sick. I agree with you about the alpha fetal protein test and the sFlt test. I am very hopeful that in a few years we will have that sflt test but a bit jaded about a) how long that will take to filter in and b) how seriously it will be done. Consider--the occurrence rate for preeclampsia is just about 5%--and there is "no cure" so will doctors and insurance companies be able to justify using a test on 100% of the women when it may identify <5%? just from a cost-benefit ratio--identifying it likely means more testing (more costs), more observation (more costs) and still most doctors will tell you (even our experts) that there is nothing to be done until that woman hits the wall of 140/90 (2x) and 300 grams of proteinuria--which is already being tested for at every single prenatal appointment. Some will say using antihypertensives is an option--most won't--(my doctor would have). This is an area of healthcare that is appalling. That we, non-medical (mostly) volunteers are actually one of the best sources of information for the average woman is appalling. We could use your very appropriate indignation in our volunteer corps. As long as people find this standard of care acceptable--then we will continue to fight this.

[catherine]

Test or no test, new or old, the treatment of a woman with a hypertensive disorder during pregnancy does come down to the prior experience and expertise of the particular doctor that treats her. While there are distinct guidelines, eg. woman @36 weeks gestation and a "bad" blood test is a "no-brainer" for immediate delivery, in many cases where the pregnancy is not so advanced, disease is milder or not progressing very rapidly then spotting the moment to deliver becomes less obvious, particularly for the woman who is experiencing it. Even if there was a test that said, "no matter how sick you/your wife appears, she's not getting preeclampsia", would you believe it? Especially if you were experiencing signs or symptoms that had raised your level of concern? I certainly wouldn't and I think that you've done the only thing that anyone in your situation can do which is to find OBs with the best level of experience and expertise that you can. I have to point out too that even a 24 hour quantitative analysis may not be relevent in the context of your wife's current condition. They are monitoring her and your baby by multiple methods. I suspect, and lord knows I'm no doctor, that perhaps they plan to deliver at the first sign of fetal distress, or if your wife shows defintive signs of a rapidly worsening problem, like an insanely high BP that doesn't come down, or a bad blood test but absent that, they want her to get as close to the finish line as possible, limping or or perhaps even crawling. Identifying the "sweet spot" where you can deliver a baby who will not need NICU time, to a mom in good enough shape is what high risk obstetrics is all about. Babies that are born early are at risk for complications and that is a concern that is always paramount with OBs, even if our parental instincts are to "cut and run" to use a horribly over-worked phrase. In saying this, I hope that you don't think that I'm indifferent to poor care, I'm not; I just want to emphasise that no matter how frustrated you feel, you have a safety net, all the monitoring and access that you've already had means that a signifcant change for the worse will be recognized and responded to.