Low PAPP-A advice needed

[aka007]

I recently went for my 1st trimester screening. I was told that NT test and all other parameters were normal and I was not at risk for Chromosomal abnormalities. But my OB said that my PAPP-A protein level was low. I had a value of 0.45 MOM. I am not sure how low this value is. Is this considered very low or borderline low?

My OB said that I was at risk for Pre-e or IUGR. This is my 2nd pregnancy and I did not have any problems with my first pregnancy and delivered a baby at full term normally. So my OB said that it is a positive factor. He said that he is going to watch out for any symptoms and monitor me closely. I have my 20 week ultrasound at a hospital. Can they find any placental abnormalities in the normal 20 week scan or can it be done only by an advanced ultrasound or doppler?. Also both my pregnancies were through IVF - ICSI. Could this be causing my low PAPP-A value though I did not have any problems with my first pregnancy?

Will the QUAD screen provide any increased evidence for Pre-e? I am receiving conflicting informations on that.

Now my question is, can I do something to diagnose and possibly take any preventive actions?

* I read somewhere that a doppler scan of placenta can help identity any notching and could show more evidence for increased Pre-e risk
* Should I try to visit a Maternal Fetal Medicine specialist? Most MFMs are quite far away and most them require a referral from my OB. I don't think my OB is ready to send me to a MFM yet. So should I be visiting an MFM?

[lemons]

I'm sorry that you had to find us, but glad that you did. Hopefully, I can help with some of your questions. Multiples of the median (MoM) is a statistical term that (in theory) makes it easy to compare test results between different facilities. In practice, this is not always the case. I wonder if you could find out from your OB what percentile your MoM of 0.45 puts you in. When I was told that my PAPP-A was low, I was given a report that had three values- an absolute value, an MoM, and a percentile.

In your case, an MoM of 0.45 probably puts you right above the 5th percentile. That means that you have a lower PAPP-A level than about 95 out of 100 pregnant women. As your OB told you, a PAPP-A level less than the 10th percentile is considered low and has been associated with an increased risk of pregnancy complications (loss before 24 weeks, gestational hypertension, preeclampsia, IUGR, preterm birth). As PAPP-A levels fall the risk for complications increases, but only slightly at about the 5th percentile (it is women below the 1st percentile like me, that have the most risk). However, the good news for you is that most women with low PAPP-A do not have ANY complications. For instance in one study (American Journal of Obstetrics and Gynecology (2004) v191, p1446-51), less than 4% of women with PAPP-A levels below the 5th percentile ended up with PE. Another way to think about the numbers is asking how likely you are to get PE compared to a woman with a "normal" level of PAPP-A? The answer is that at the 5th percentile you have about a 1.5 fold chance of getting PE compared to a normal pregnancy- that means less than 2 times as likely. So, odds are in your favor

Your OB is correct, since you had a successful first pregnancy, you are less likely to develop PE than if you had not been pregnant before. But there are women who get PE for the first time in a second pregnancy. Usually, PE in subsequent pregnancies is less extreme and later than in first pregnancies.

Since your having your 20 week scan at a hospital, I would assume that you will be having a very detailed scan that would include Doppler imaging of the umbilical vessels. But you might want to confirm that with your OB since you are worried about it. I don't think that any ultrasound findings actually predict or can be used to diagnose PE. However, PE can affect blood flow to the placenta and therefore the baby. That is why once PE is diagnosed, many women get periodic ultrasounds to check blood flow and baby's growth. In addition, since low PAPP-A is associated with IUGR, your baby's growth should be followed closely- this is also best done by ultrasound.

I am not very familiar with the QUAD screen but I don't think that it will tell you any more than you already know- that you are at slightly higher risks for several pregnancy complications. The QUAD screen can only confirm this and not disprove it.

And now for your real question- and unfortunately, I am not going to give you the answer you seek- there is currently no way to accurately predict who is going to get preeclampsia. And there has not been any intervention that can prevent or delay the onset of preeclampsia. Over the years, people have tried many different diets, supplements, exercise and nothing has proven useful (with the exceptions of treating underlying conditions like immune disorders or clotting disorders and losing weight in obese women). Some women take low-dose aspirin on their doctor's advice, but rigorous studies have proven that it is not effective for most women with PE. Some women with underlying blood clotting disorders take heparin or low-molecular weight heparin, but again there is no evidence that in women without clotting disorders that this is effective. Since the only cure for PE is to deliver the placenta (and therefore the baby), OBs can only carefully watch for signs that PE is starting and then make care decisions based on how mild/severe the PE is and how far along the pregnancy is.

As for seeing an MFM- In your shoes, I would talk to your OB about how comfortable he/she is in dealing with a higher risk pregnancy. Since the low PAPP-A level does not guarantee that you are going to experience any complications, you may be fine to continue to see your OB. I would ask your OB how many cases of PE has he/she dealt with in the past? I would ask your OB what signs and symptoms would be concerning enough that you would be referred to an MFM? I would want to know who that MFM is. And where they are located. And I would want to know exactly what extra monitoring you will be doing and when. Please have your OB describe to you the signs and symptoms of preeclampsia and HELLP syndrome. And then I would also ask your OB what signs and symptoms does he/she want reported right away, no matter the time of day. And what is concerning enough that you should head straight to Labor and Delivery. If your OB is not able to answer these questions and have a conversation with you about your concerns, than you might want to think about seeing another OB or an MFM. Remember you are the best advocate for both you and your baby.

Good luck and I hope that the rest of your pregnancy is free from complication! Let me know if you have any other questions.

[aka007]

Thank you for taking time to explain everything in detail. I'll try to get all those questions answered by my OB. Its really helpful to get support from experienced people like you.
thanks again.

[lemons]

Please feel free to keep posting questions as you think of them. I know from experience that it is difficult to get unexpected news so early in a pregnancy. I was worried and frustrated that there was nothing I could do to influence what was going to happen. My PAPP-A levels were much lower than yours- I was in the 0.5th percentile, meaning that I had less PAPP-A than 995 out of 1,000 women. So, don't be too discouraged by the fact that I ended up with PE and a preemie, you have much better odds than I did! Good luck with speaking to your OB and remember that my list of questions is really a starting point for you. The most important thing is for you to feel comfortable with your OB and his plan for your care. Hang in there.

[aka007]

I had my regular OB appointment today. I asked him how frequently will I be monitored due to my low papp-a in my first trimester. He said I'll have an ultra sound every 4 weeks from 24 weeks since we'll know the effect of low papp-a only in the later weeks of pregnancy. He said if the growth is proper there must not be any placental problems. Does a problem in placenta cause preeclampsia? I like to know if we have to just wait and watch for any problems in growth or should we ask him to order a Doppler test to check the placental blood flow? Will a high risk OB have a different approach or is this what he'll recommend too?
I have another question which is not related to this board. At what week is the AFP test done normally? I keep reading mixed views. Some say it has to be done between 15-18 weeks and some say it can be done up to 20 weeks? I'm 19 +1 week and I just had my blood drawn today for the AFP test. I'm concerned if they missed to do this test at the right time. Your views are highly appreciated.

[angieb]

I am one who had bad results with the quad screen in my first pregnancy (high AFP levels, they ruled out spina bifida with ultrasound), by 22 weeks it was clear our daughter had severe IUGR, and by 23 weeks I had severe preeclampsia/HELLP syndrome and had to deliver. The quad screen is just a red flag like the papp-a test can be. (I have never had an NT scan or bloodwork so not sure if that would have been off in my first pregnancy or not.)

My second pregnancy I had a normal quad screen and normal pregnancy.

The American Pregnancy Association says the quad screen should be done by the 18th week, so I'm not sure how much I would trust those results. I had it at 17 weeks in my first pregnancy, and 16 weeks the next one.

IVF is a risk factor for preeclampsia. I don't think that there is much an MFM could really do for you at this point if everything else is normal. It wouldn't be a bad idea to start keeping an eye on your blood pressure at home.

[caryn]

Yes, preeclampsia is a placental development issue - for what appear to be primarily genetic reasons the placenta does not implant normally and/or is not tolerated by our immune systems as the fetus grows, probably because there's something wacky about the ability of this particular placenta to turn down your immune response to the foreign DNA of the placenta.

[sam10]

When I asked my MFM about low levels of Papp-a, I was told that it does not necessarily mean that one develops PE. We have not discussed it any further though.

[lemons]

Low PAPP-A is associated with a placenta that is not able to due its job, which is to supply baby with oxygen and “food” and take away waste. Before 20 weeks, baby spends most of its time developing the different organ systems: heart, lungs, brain, legs, arms, and the placenta. So, before 20 weeks, the placenta is forming and is not being used heavily. After 20 weeks, baby shifts from working mainly to “building” him/herself to maturing and putting on weight. And baby starts growing much more rapidly. This means that the placenta has to start working harder. It is at this point that problems from an improperly implanted placenta or a small placenta can start to be seen. As Caryn has said, problems with the placenta can lead to the development of preeclampsia. Problems with the placenta can also lead to problems with baby’s growth (intrauterine growth restriction or IUGR). And problems with the placenta can lead to IUGR because of preeclampsia. So, you can have just preeclampsia, just IUGR or both together.

Your physician is following the recommended screening protocol for a woman with a low PAPP-A value- monthly ultrasounds to measure baby’s growth starting at the time when really rapid growth is seen (~24 weeks). Until baby really starts growing fast, you and your physician can not tell if there is definitely a problem with baby’s growth. Since I saw both my regular OB and an MFM during my pregnancy, I don’t think an MFM would do anything different- mine didin’t. She recommended starting the extra ultrasounds at 24 weeks (remember that you already have an ultrasound scheduled for 20 weeks, so really you are getting a monthly ultrasound from when baby starts his/her growth spurt).

As for using Doppler to check placental blood flow- my understanding (from my experience) is that the Doppler is not a separate test. It is part of a high resolution ultrasound. Since your 20 week ultrasound is a high resoulution one, the placental blood flow should be checked as a standard part of the ultrasound. The ultrasound will also determine if the umbilical cord has the right number of viens and arteries which carry the blood to and from the baby. In addition, the extra ultrasounds starting at 24 weeks should also be high resolution and should aslo contain Doppler imaging as standard. I know from your previous posts that you seem really concerned with getting the Doppler study- I think you should clarify with you physician what the high resolution ultrasounds witll be checking.

As for the AFP test-
There are actually three different second trimester tests that can be done and they seem to have different timing requirements:

(1) MSAFP- maternal serum AFP testing. This test only looks at AFP. And according to the American Pregnancy Association: “MSAFP may be performed between the 14th and 22nd weeks of pregnancy, however it seems to be most accurate during the 16th to 18th week.” (http://www.americanpregnancy.org/prenat ... g/afp.html)

(2) Triple Screen- This test checks AFP, hCG, and estriol. And according to the American Pregnancy Association: “The triple screen test is performed between the 15th and 20th week of pregnancy although results obtained in the 16th -18th week are said to be the most accurate.” (http://www.americanpregnancy.org/prenat ... etest.html)

(3) Quad Screen- This test checks AFP, hCG, estriol, and Inhibin-A. And according to the American Pregnancy Association: “The quad screen test is performed between the 16th and 18th week of pregnancy.” (http://www.americanpregnancy.org/prenat ... creen.html)

The American College of Obstetricians and Gynecologists (ACOG) states that “These tests usually are done around 15-20 weeks of pregnancy.” (http://www.americanpregnancy.org/prenat ... creen.html)

Since you were 19+1 when your blood was taken, I would think that your results will be reliable. Remember “18 weeks” means 18+6 weeks. And since you know exactly how far along you are (given the IVF), your results are probably more reliable than a woman who dates her pregnancy from her last period.

Hope this info helps. Good luck!

[lemons]

Just wondering how you are doing? Hope you had good news at your ultrasound.