Low Pregnancy-Associated Plasma Protein A (PAPP-A) and Pregnancy Outcome
Saturday, September 01, 2007
Kenneth F. Trofatter, Jr., MD, PhD
"Abnormal First Trimester Screening Results" published earlier this year:
I had a 1st trimester screen and while most of the results came back normal, my PAPP-A level was 0.25 MoM (which the counselor told us was very low). My hCG was .78 MoM. She said that there is an increased risk for low birth weight but nothing else. I have done some online research though and seen that a low PAPP-A can also mean an increased risk for stillborn and delayed fetal development. Is that true? Can you shed any light on the PAPP-A result on its own. (Like I said, all other test results were within a normal range). Thanks, K
As we have pointed out before, first trimester screening for aneuploidy can have some benefits for detecting potential complications of pregnancy other than certain chromosomal abnormalities. For example, a widened nuchal translucency (NT) has also been correlated with risk for having a baby with a cardiovascular malformation, even when that fetus is confirmed to be chromosomally normal. In a similar vein (no pun intended), an abnormal Doppler waveform in the first trimester, showing reverse end-diastolic velocity in the fetal ductus venosus, presumably secondary to tricuspid regurgitation, has also been correlated with both cardiovascular malformations and aneuploidy.
Our reader was counseled regarding another observation that has been made of first trimester screening - the association between ‘abnormal’ levels of the maternal serum markers, PAPP-A and hCG, used in the screening assessment, and pregnancy outcome. She reports that her ‘composite’ first trimester screening result was reassuring with regard to risk for a chromosomally abnormal baby, but one of the maternal serum markers, PAPP-A (pregnancy-associated plasma protein-A), was “low” at 0.25 MoM (multiples of the median). The first thing I want to remind her about is that first trimester screening does not help to detect ALL chromosomal abnormalities – it is most reliable for trisomies 21 (Down syndrome), 18, and 13. Secondly, whether the baby is chromosomally normal or not, a ‘reassuring’ screen does not rule out the possibility of other fetal abnormalities – physical or developmental or abnormalities of placentation. In other words, a ‘normal’ screen does not ensure a normal baby or pregnancy outcome, although it does increase the probability of both!
PAPP-A is produced by the placental trophoblasts, especially, by the extravillous cytotrophoblasts (Handschuh, et al., Placenta 2006;27 suppl A:S127-34). It is a ‘protease’ for insulin-like growth factor (IGF) binding proteins 4 and 5 (Boldt and Conover. Growth Horm IGF Res. 207;17:10-18). This means it has the ability to help release IGF from these binding proteins so that it is free to interact with its cell receptor (Laursen, et al., Mol Endocrinol 2007;21:1246-57). IGF is thought to play an important role in trophoblast invasion and hence the early development and vascularization of the placenta and the placental bed. As we have mentioned in previous posts, these early events in formation of the placenta are critical to pregnancy outcome and, when abnormal, are associated with miscarriage, intrauterine growth restriction (IUGR) of the baby, pregnancy-induced hypertensive disorders, fetal death in utero, premature delivery, and even cesarean section for indications of fetal or maternal compromise. It has been postulated that low levels of PAPP-A, resulting in less release of IGF, could be a pathway by which placentation abnormalities occur that culminate in these poor pregnancy outcomes.
Recent studies would support this association between low PAPP-A levels in first trimester and risk for poor pregnancy outcome. Spencer and colleagues (Ultrasound Obstet Gynecol 2006;28:637-43) evaluated first trimester markers in 54,722 chromosomally normal singleton pregnancies. At the 5th percentile of PAPP-A (0.415 MoM), the odds ratios for fetal loss before 24 weeks, at or above 24 weeks, and at any gestational age were 3.3, 1.9, and 2.8. In other words, there was about a three-fold risk of losing a baby with low PAPP-A levels. Cowans and Spencer (Prenat Diagn 2007;27:264-71) recently confirmed the association between low PAPP-A and low for gestational age birth weight babies as well. Indeed, they found a linear relationship between the severity of growth restriction and the decrease in PAPP-A levels – in other words, the lower the PAPP-A, the smaller the babies at any gestational age.
Several other studies confirm the association of the other ‘pregnancy complications’ noted above with low levels of PAPP-A. For example, as a spin-off of the results in the First and Second Trimester Evaluation of Risk (FASTER) trial, it was found that women with PAPP-A at or below the 5th percentile “were significantly more likely to experience fetal loss at less than or equal to 24 weeks, low birth weight, preeclampsia, gestational hypertension, preterm birth (P < .001) and stillbirth, preterm premature rupture of membranes, and placental abruption (P < .02).” (Dugoff, et al., Am J Obstet Gynecol 2004; 191:1446-61).
Anyway, not to belabor the point, but to make a long story short, the simple answer to our reader’s question is that low PAPP-A levels are not only associated with certain fetal chromosomal abnormalities, but also with an increased risk for a poor pregnancy outcome. BUT, despite this association, the positive predictive value of a low PAPP-A for one of these outcomes is still relatively low. That means the chance of one of these events is higher with a low PAPP-A, but you shouldn’t panic at the outset that something bad is going to happen.
Several things our reader's providers could do that might help elucidate her actual risk for problems throughout her pregnancy include the following: 1) A screen for MSAFP at 16 weeks (ask your doctor to explain this); 2) a ‘targeted’ ultrasound to carefully evaluate the baby’s anatomy and growth; 3) Doppler flow velocimetry of the uterine arteries at the time of the ‘targeted’ ultrasound to look for increased resistance to maternal-placental perfusion (indicative of an abnormality of placentation); 4) Serial assessment of fetal growth, and; 5) Doppler flow studies on the fetal umbilical cord and middle cerebral arteries to look for evidence of increased resistance to fetal-placental perfusion (again, indicative of abnormal placental vascularization) and fetal blood flow redistribution (suggestive of preservation of the brain at the expense of perfusion of less ‘essential’ organs), respectively. None of these will accurately predict outcome, but if they are abnormal, can justify more intensive antepartum fetal surveillance so that chances of delivering a healthy baby, regardless of the gestational age, are improved.
Hope that helped K. Best regards, thanks for reading, and best of luck to you!
Dr T
Labels: fetal growth restriction, PAPP-A, preeclampsia; low birth weight, preterm delivery
157 Comments:
At Thu Sep 20, 01:08:00 PM 2007,
Anonymous said…
I had exactly the same and it was due to high blood pressure. They never put me on medication and I lost the baby at 19 weeks. Remember blood pressure is much lower in pregnancy so put your foot down if your diastolic gets anywhere near 90!
At Thu Sep 20, 01:19:00 PM 2007,
radz said…
I had the same thing and it was because of my blood pressure. Make sure they put you on medication if your diastolic is anywhere near 90 - that is high for a pregnant woman. If not, ask for more tests. Make sure you put your foot down with them!
At Tue Oct 23, 03:46:00 AM 2007,
Anonymous said…
Thank you! Thank you! Thank you! I like K had the very same questions (Info has been extrememly difficult to come by). My PAPP-A result was 0.41MoM , free beta-HCG was 1.91 MoM and NT measurement 1.9mm and nasal bones identified. You were able to shed light on "other" pregnancy complications that may be associated with low PAPP-A results alone - this really put things into perspective for me while I have to wait 2.5 weeks for my amniocentesis appt. I now have a better attitude towards a possible broader outcome rather than only focusing on the view to having a DS diagnosis. Currently, I am waiting on test results for Thalassemia - does this condition affect PAPP-A levels? I have had two previous successsful pregnancies.
Regards, Aussie G, 30yrs old, 13.5 weeks pregnant.
At Fri Oct 26, 03:48:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Aussie G: And thank you for your comment! I have not heard of an association between thalassemia and PAPP-A levels, but if I find something out, I will let you know. Best of luck to you and your baby! Dr T
At Mon Oct 29, 04:02:00 PM 2007,
Anonymous said…
Thanks to everyone who has contributed to this Q & A.
I am 32 year old Australian
14 weeks pregnant
PAPP-A: 0.3MoM
free beta hCG: 1.7MoM
NT: 1.5
Nasal bone: seen
I have been waiting for my Amnio for 2 weeks. 1 week to go!! I am also FVL heterzygous. This is by far the best explanation I have come across.
Thanks once again, Lana.
At Tue Oct 30, 03:42:00 PM 2007,
Anonymous said…
Dr T - do you have any further explanations for my results (biochems were performed at 10 weeks). thanks, Lana
At Thu Nov 01, 12:29:00 PM 2007,
Anonymous said…
Lana,
Did you ever get your results back? I have similar results and just got an early amnio today. I'm curious if I have any hope for a good outcome.
I hope you have good news!
Kelly
At Mon Nov 05, 11:37:00 AM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Kelly and Lana: Thanks to both of you for your comments. We wish you the best. Remember, the odds are in your favor that all will be well. Let us know how things turn out and thanks for reading. Dr T
At Mon Nov 05, 03:33:00 PM 2007,
Anonymous said…
Hi Kelly
Still waiting... I had my amnio yesterday... good luck! cheers, Lana
At Wed Nov 07, 12:39:00 PM 2007,
Anonymous said…
Hi Everyone good news - my results came back all clear for the chromosome screening (initial results, full screen to follow in 2 weeks). Hope that gives some reassurance to others. So all there is to watch out for now is how the placenta feeds the baby and how the baby grows over the coming months. All the best and thanks again. Lana
At Wed Nov 07, 06:39:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
Lana: Congratulations! W are all pulling for you. Dr T
At Mon Nov 12, 05:34:00 PM 2007,
Anonymous said…
Lana~ Congrats! I'm so happy for your early results. That's wonderful. Thanks for your reply! Enjoy your pregnancy :)))
I got great news today. My amnio results showed completely normal baby BOY!
Thank you, Dr. T, for your support and well wishes.
Kelly
L
At Fri Nov 16, 10:47:00 AM 2007,
Thyago said…
This post has been removed by the author.
At Fri Nov 16, 03:11:00 PM 2007,
brazil said…
What a wonderful source of information!
I just received test results today, Friday Nov 16th and my doctor recommends an amnio this coming Monday. Imagine the stress!
All posts relate to low free-beta HCG and PAPP-A, but mine were high for bloodwork drawn wk 13 (PAPP: 8840 mU/L and HCG 47,6 ng/mL).
Here are my other stats:
Age: 41, entering 16th wk
4th natural pregnancy: (2 miscarriages, 1 very healthy, non-stop 16 month old)
Medications: heparin and baby aspirin for thrombophilia
Two Ultrasounds done wk 12. 1st showed an abnormal Doppler waveform with a reverse end-diastolic velocity in the fetal ductus venosus. 2nd US Doppler showed no problem.
Nuchal translucency (NT): and all other indicators normal in both US.
Family histories with heart disease (my father had mitral valve replaced; spouse's father, heart attack at age 50)
Last pregnancy received monthy immunoglobulin injections and heparin. This pregnancy I did paternal lympocite immunization treatments and am not receiving immunoglobulin monthly.
Dr. T can you shed some light? Do you recommend an amnio or is the miscarriage risk too high? What is there to gain?
Many thanks in advance!
At Mon Nov 19, 04:40:00 PM 2007,
Anonymous said…
hi,
I am 32 weeks and will have a growth ultrasound this week. I (my baby) will also have to have heart stress tests every two weeks. I feel quite positive about my upcoming tests, however ,what is troubling me most is my Dr.s advising that I be induced on or before my due date. I would really not like to be induced. Can you tell me how neccessary it is to be induced? What exactly are the chances of stillbirth? Thanks CML
At Tue Nov 20, 04:09:00 AM 2007,
Anonymous said…
Dear Brazil
I thought you might be interested in this support group/website who also cover thrombophilia during pregnancy:
http://www.fvleiden.org/
All the best, Lana
At Wed Nov 21, 04:04:00 PM 2007,
Anonymous said…
I also had a low PAPP-A result. All other levels were normal and NT scan was normal.
We had an Amnio that came back fine.
I did have hypertension (prior to preg) and was induced at 37 weeks due to very high bloodpressure (even on Medication)
My adorable perfect baby girl is now 5 months old.
Good Luck!!
At Fri Nov 23, 06:45:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Brazil Nov 16: I suggest that you go with the amniocentesis. The risk of that procedure in experienced hands is generally less than 1 in 1000. It will give you the answers you need and, hopefully, put your mind at ease for the rest of the pregnancy. Bet everything will turn out just fine. Good luck and let us know the results! Thanks for reading. Dr T
At Mon Nov 26, 06:29:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Nov 19: Sorry for the delay in answering you question, but for some reason I just got the comment in my mailbox today. Before I can answer any of your questions, you need to tell me what medical problems or complications you have had with this or other pregnancies so that I can understand why you are having antepartum testing and your doctor wants to induce you early! Get back to me with those answers and I will see what I can do to help! Thanks for reading. Dr T
At Mon Dec 03, 08:09:00 PM 2007,
Pip said…
Hi Dr T
I have an amnio booked for Friday this week.
Age: 27
second pregnancy. First was completely normal with low risk results for 1st trimester screen.
Results from this 1st trimester screen:
BhCG = 0.33 MOM
PAPP-A = 0.27 MOM
NT = 2.5mm
High risk result for Trisomy 13 and 18. Low risk for Trisomy 21.
I am concerned as not only me PAPP-A result is low but also my BhCG result. I can't help but think something must be wrong if my hormone levels are this low, and I did not have this problem in the 1st pregnancy.
Could you please comment on the ramifications of a combined low result of PAPP-A and BhCG?
At Fri Dec 14, 12:47:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Dec 3: As you have been told, the immediate concern when both the hCG and PAPP-A are low is that you could have a baby with a chromosomal abnormality such as trisomy 18 or 13. If the baby turns out to be normal chromosomally, you are still at greater risk later in the pregnancy for problems related to 'placental insufficiency' - small or growth-restricted baby, preeclampsia, early delivery, need for cesarean delivery, etc. But, this is NOT invariably the case. You may just have a pregnancy with serum markers that are on the low end of the bell-shaped curve! I certainly hope this is the cae. Good luck with the amnio and let us know how things turn out! Dr T
At Mon Feb 18, 09:20:00 AM 2008,
Anonymous said…
I had low PAPP-A levels in my first trimester but normal bHCG levels, so I had an ultrasound (which was normal) and an amnio, which came back normal. I am now 32 weeks pregnant with a seemingly healthy little boy who is spot on when it comes to crown-rump length. My doctors have no explanation for the PAPP-A levels. I was negative for gestational diabetes and my blood pressure is around 116/70-something, so no hypertension (at least not yet). Baby kicks all the time! Docs also say my placenta looks just fine and so does my level of amniotic fluid.
Erin, 27 years old, 32 weeks pregnant
At Thu Feb 28, 11:30:00 AM 2008,
Anonymous said…
I just received my test results for my first trimester screening and they are not good. My chances are 1:75. I also have high HCG and low PAPP-A. I have a number of issues: 38 years old, bicornuate uterus and a multiple pregnancy (one twin did not develop). I am concerned that the bicornuate uterus with the low PAPP-A is too much to overcome. Is there still a chance?
At Thu Feb 28, 01:43:00 PM 2008,
AndieF said…
I am 41 years old and pregnant with my 7th pregnancy (3 living children). I've had high blood pressure throughout this pregnancy. I had spotting from week 10-12 and was diagnosed with low-lying placenta and small subchorionic hemorrhage at 12 weeks. I had my NT test done at 11 weeks. I got a positive result at 12 weeks from my bloodwork and couldn't get in to see a specialist until 13 weeks. Here are my results.
Nuchal fold: 1.3
hCG: .53
PAPP-A: .21
Risk of Trisomy 21: 1 in 150
Risk of Trisomy 18: 1 in 10
I had an ultrasound with the specialist at 13 weeks and all looked normal, but he said that markers for T18 (the biggest concern) aren't visible at 13 weeks. I'm scheduled for an amnio in 3 weeks. I haven't seen any stories with good outcomes yet with someone with low numbers like mine, particularly the PAPP-A.
At Fri Feb 29, 05:52:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Erin Feb 18: Sounds good to me. Check back and tell us how the delivery turns out! Thanks for reading. Your comment will reassure other women in the same situation. Dr T
At Tue Mar 04, 05:42:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Feb 28: Oh, I don't know! Your risk is about equivalent to your "age alone" risk in first trimester and it depends on how you look at the cup - half full or half empty - you have a 74 out of 75 chance the baby does NOT have Down syndrome! I am worried about your bicornuate uterus. Have you had any children before or was this an 'infertility' find and assisted pregnancy of some sort. Women with Mullerian defects (congenital uterine anomalies) are at increased risk for cervical incompetence, so serial cervical evaluation should be a part of your follow-up. Incidentally, there are many women with similar first trimester findings that have had good outcomes, so don't give up hope right now. Let us know what happens as the pregnancy progresses. Best of luck. Dr T
At Tue Mar 04, 05:48:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Andief Feb 28: At your age and with those results, you are at increased risk for trisomy 18, however, there is a possibility the 'subchorionic hemorrhage' gave you an artificially low serum marker result. Of course, there is also the possibility that the hemorrhage was also the result of a chromsomally abnormal baby that was trying to miscarry (as so many will do in first trimester), so we will see. Your doctors have given you good information. At this point, identifying a baby with trisomy 18 can be difficult, but if that is the case, certain abnormalities may be visible at the time of your amniocentesis. Best of luck to you and let us know how things turn out. Dr T
At Sun Mar 09, 03:53:00 PM 2008,
Anonymous said…
I really needed this information!
40 years old in a couple of months
hcg = 0.91
PAPPA = 0.28
NT = 0.55
Pregnancy history includes a child with a chromosomal abnormality. No BP problems at all. Since the scores are conflicting, I've been searching for more information. Although the thought of a placental problem is quite disturbing, I am reassured that the PAPPA score might mean something OTHER than a trisomy. Amnio scheduled in a week and a half. Thank you for giving me something positive to distract my mind from all the negative thoughts! kc
At Tue Mar 11, 07:16:00 AM 2008,
Meri said…
Hello,
I am very concerned but am hesitant to get an amnio because of the risk involved(any risk is too much). Here are my stats, tell me what you think please:
NT: .79MoM
PAPP-A: .28MoM
AFP: .73MoM
HCG: 2.02 MoM
UE3: .53 MoM
Inhibin: 1.61 MoM
These are the results of an NT screening and an intergrated blood screen. The perinatologist has advised me to get the Amnio done due to my increased risk of Trisomy 21 (1/14 chance).
I will deal with a Downs baby, but I am just really concerned about the baby dying in-utero.
Can someone please give me their opinion.
Thank you
Meri
At Tue Mar 11, 06:30:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To kc: Thanks for the kind comments and good luck with the amniocentesis. Let us know what you find out. Dr T
At Tue Mar 11, 06:33:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Meri: The high hCG and the low PAPP-A put you at high risk for Down syndrome. If the baby has Down syndrome, it is much more likely to die in utero as a result of the chromosomal abnormality than it is as the result of a complication from an amniocentesis. But, in the end, the choice is yours. No one can make you have a procedure you don't want to have done! Best of luck and let us know how things turn out. Dr T
At Wed Mar 12, 03:39:00 AM 2008,
Anonymous said…
Hi, any views in my results? I am 39 years old had an NT at 12w3days and came back as 2.8 which I was told high risk of Down's syndrome (1 in 17) they did a blood test and the results came back as follow:
PAPP-A 0.19 MoM
free-beta hCG 0.76 MoM
AFP 1.24
uE3 1/31
I was told that there was a nasal bone and that the CRL of 59.7 mm was perfect for the 12w 3days the baby was dated at.
But with the blood test results the chance of a Down syndrome was 1 in 10.
I'm having an amnio next Monday to check for down or any other syndrome.
I've been told that the free-beta is normal but the PAPP-A is very low, what else, other that down could this be due to?
At Wed Mar 12, 01:19:00 PM 2008,
Anonymous said…
HI this is the most relevant discussion/advice site I have found - hallelujah!
I am 16 wks pg with my first baby following IVF and am aged 33.At 12 weeks had a scan and screening tests. Results were as follows:
NT - 1.6mm
Beta HCG - 0.99 MoM
Papp a - 0.28 MoM
Combined risk result for Downs was 1:292
I just had a 16 wk anomoly scan due to the low Pappa result. Baby looked fine, nasal bone, heart, lungs, spine, leg bone length etc and they also checked my placenta, which although there was evidence of some small tears the blood flow on the doppler I'm told was fine.
The consultant said that the other indications of this low Pappa result could be risk of late miscarriage.
Please could you offer me any views? I'm very concerned.
Thanks! VH
At Wed Mar 12, 06:23:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Mar 12: The combination of your age, the NT measurement, and the very low PAPP-A drove your high risk for Down syndrome. Since the placental cells (trophoblasts) produce both hCG and the PAPP-A, sometimes folks will have a low value because the placenta is either behind in development or not forming properly. This can happen whether or not the baby has a chromosomal abnormality for a variety of reasons. The latter is why women who have abnormal maternal serum screening are at increased risk for pregnancies that result in growth-restricted babies and pregnancy-induced hyperetnesive disorders later in pregnancy. But, as several of our readers, who have been in your situation and ended up with normal outcomes have pointed out, ty to keep your chin up until you have some real answers. Best of luck with the amnio and let us know how things turn out. Dr T
At Thu Mar 13, 07:51:00 AM 2008,
Meri said…
Hello Doctor T.
I left out some info when I sent a post to you last time.(Meri with the bad blood results)
Not that it will make much of a difference, but I just turned 35 in December, and I do not have a history of chromosomal abnormalities and neither does my husband.
I was told by my perinatologist that my NT scan was great and that he did not see any abnormalities in my 12 week old fetus.
How much weight is given to these results? If the blood test comes back showing markers for Down Syndrome, is the NT result tossed aside? I do not understand how I could have a "great" NT scan result and a horrible blood screen result. How does this work exactly?
Thanks for your help
meri
At Thu Mar 13, 07:51:00 AM 2008,
Meri said…
Hello Doctor T.
I left out some info when I sent a post to you last time.(Meri with the bad blood results)
Not that it will make much of a difference, but I just turned 35 in December, and I do not have a history of chromosomal abnormalities and neither does my husband.
I was told by my perinatologist that my NT scan was great and that he did not see any abnormalities in my 12 week old fetus.
How much weight is given to these results? If the blood test comes back showing markers for Down Syndrome, is the NT result tossed aside? I do not understand how I could have a "great" NT scan result and a horrible blood screen result. How does this work exactly?
Thanks for your help
meri
At Sat Mar 15, 08:55:00 AM 2008,
Anonymous said…
Hi, everyone. I came back to add yet another detail that might explain why some women's Papp-A levels come back low. I can't say definitively, but my peri said it's always possible.
My fb-hcg was high (forget the number) and my papp-a was only .26
I had an amnio done which came back normal! All ultrasounds showed normal findings except the cord insertion site was *lateral*. I'm being monitered via ultrasound and NST to make sure growth is OK, which it has been. Baby is actually in the 95th percentile, measuring large for gestational age. No gestational DM on my part, as my 1 hr. glucose came back fine.
Also, the genetic counselor told me that she has seen many instances of low papp-a levels and nothing was wrong at all. So, please don't take this blood result number too hard, as there are many good outcomes despite it.
At Sun Mar 16, 01:32:00 PM 2008,
Anonymous said…
Dear Dr T... its Lana in Australia back again...
I am now 34 weeks and have a breech baby... I am wondering if the low PAPP-A result and breech position are pointing to some kind of abnormality... lots of literature talks about links between breech babies and Cerebral Palsy...
i just cant find anything reassuring...
Our baby girl is within normal growth range, but has been in breech position for as long as I can remember and her feet seem to be permanently by her head, with her bottom down... is it possible that some congenital problem is not allowing her to move much?
The placenta is right, anterior.
Looking forward to any insights.
Thanks, Lana
At Sun Mar 16, 05:56:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To VH Mar 12: See my response to the other 'anonymous' from Mar 12. I am glad things are going well with your pregnancy to this point. In your case, simply followuing the growth of the baby and, perhaps, having Doppler studies performed (to see if the baby is having any trouble pushing blood through the placenta) in late-mid or early third trimester will help determine if you are increased risk for complications related to 'placental insufficiency' later in the pregnancy. It sounds like you are in good hands, so relax and enjoy your pregnancy! Let us know how things turn out. Dr T
At Sun Mar 16, 06:04:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Meri Mar 13: Some babies with Down syndrome have perfectly normal NT measurements. It is the COMBINATION of test results, as well as your age, that determines your 'risk'. Down syndrome can have a broad spectrum of presentations - some of the babies have very few abnormalities and are not suspected of having trisomy 21 until they are born; others have very characteristic abnormalities such as A-V canal heart defects, duodenal atresia, thick nuchal skin-fold, hypoplastic nasal bone, etc. Anyone can have a baby with Down syndrome, reagrdless of their age, but the risk does increase with age and a 'negative' family history has nothing to do with that 'age alone' risk. You still have to make a decision as to how badly you need to know one way or the other before the baby is born. If you find out that your baby does not have Down syndrome, you will be able to relax for the rest of the pregnancy, and if it does, you will be able to prepare for the baby's special needs before it is born. Best of luck with all your decisions and, please stay in touch! Dr T
At Wed Mar 19, 09:32:00 PM 2008,
Anonymous said…
Hi everyone. I am Jean, 33 years old, a Singaporean Chinese, now 15-week pregnant. I am a non-smoker.
I had my 1st trimester screening at 11 week 6 days. The screening test has however misclassified me as a smoker. I wonder how this would have affected the risk estimation outcome.
The test results are as follows :-
NT scan : 1mm
Hcg : 0.62 MoM
Papp-a : 0.58 MoM
Risk for Trisomy 21 is 1/8000
Risk for Trisomy 13+18 is 1/14000
The Risk is low despite the lower than normal Papp-a & Hcg. Also, would wrongly be classified as a smoker reduce my papp-a & hcg MoM ratio ?
Anyone has any ideas ? I intend to bring this up to my Obs at the 16th week appointment too.
Regards,
Jean
At Thu Mar 20, 09:06:00 AM 2008,
jlwgator said…
I am scared to death. I found out yesterday that my integrated screening put me at high risk for Trisomy 18. First test was done at 12 weeks, second was done at 16 weeks. I am now 17 weeks and having am amnio tomorrow.
PAPP-A = 0.93
hcG= 0.40
E-3 = 0.39
Inhibin = 0.53
AFP = 1.32
NT= 1.3 and nasal bone was present at 1st trimester ultrasound.
The risk they gave me is 1:31. I know that translates to 3% risk, with a 97% chance the baby is fine.
However, I am scared to death. I have the amnio on Friday and then have to wait until next week to get FISH results.
They have told me that although they were not able to get all the baby's measurements on ultrasound, that what they did get has been perfectly normal. They did see the brain (no cysts), heart, hands, liver, stomach, but not the kidneys, lungs or legs yet. The baby was too wiggly and wouldn't cooperate and then curled up into a ball.
PLEASE give me something I can hold onto b/c right now I am simply terrified my baby has T-18. THANK YOU
At Thu Mar 20, 09:07:00 AM 2008,
jlwgator said…
PS I forgot to tell you I am 36 yrs old. Thanks.
At Thu Mar 20, 06:43:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Jean Mar 19: Your question is excellent and when I get around to it, I will write a complete post on the topic! But, to answer briefly here, smoking reduces BOTH PAPP-A and hCG in first trimester screening. Most laboratories do perform a 'correction' factor for smokers but I do not know what that factor actually is. In your case that means, you are probably at greater risk than indicated by your final results, but even if that risk was doubled (and I cannot believe the correction factor is that much), you would still be at very low risk for trisomy 21 and trisomies 18/13. For peace of mind, you could ask your doctors to call the lab and get a corrected result based on the fact you are not a smoker. Thanks again for the great question and let us know how your pregnancy turns out! Dr T
At Thu Mar 20, 06:50:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To jlwgator: What you can hold on to is that the PAPP-A was 'normal' (and is often low in trisomy 18), the baby has grown normally and has no gross abnormalities to this point (most babies with trisomy 18 lag in growth and have many physical abnormalities), and you do have a 97% chance the baby does not have trisomy 18! You should have the FISH results back within 72 hours after you have the amnio. We will ALL be pulling for you. Good luck and please let us know how things turn out. Thanks for writing! Dr T
At Thu Mar 20, 07:31:00 PM 2008,
jlwgator said…
THANK YOU for your reassuring comment. Do you have any idea why the other #s are so low? Are they THAT low? The genetic counselor told me they are not "really" low, but I'm still a nervous wreck. Thanks in advance.
At Fri Mar 21, 01:55:00 AM 2008,
Anonymous said…
Hi Jlwgator,
Based on the results you posted ie.
PAPP-A = 0.93
hcG= 0.40
E-3 = 0.39
Inhibin = 0.53
AFP = 1.32
NT= 1.3 and nasal bone was present at 1st trimester ultrasound.
May I verify if your results for PAPP-A, Hcg & NT are those obtained during the 1st trimester screening and not 2nd trimester. If these 3 results are from 1st trimester screening, they don't appeared to me as carrying high risk for Trisomy 18. Both NT & PAPP-A are in normal range while HCG is only slightly below average. How did they work out the risk as 1:31 for trisomy 18 ???
I suppose the risk could well be from your second trimester screening results of E-3, Inhibin & AFP that I have no knowledge about thus far.
Regards,
Jean
At Fri Mar 21, 06:04:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To jlwgator Mar 20: As Jean points out (above), based on the numbers, the trisomy 21 risk seems a little high. One of the things that can lead to lower hCG and PAPP-A results is smoking. Are you a smoker? (IF SO QUIT!). You will soon get your test results, so count to 10 every time you start to get anxious and let us know what you find out! Dr T
At Fri Mar 21, 06:53:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Lana Mar 16: Most breech babies come out just fine in EVERY way. Sure , there are certain fetal abnormalities that increase the risk for breech, but your baby has grown well and none of those abnormalities have been seen. There are also placental abnormalities (such as a short umbilical cord) that keep the baby in a breech lie, as well as maternal uterine abnormalities, such as a uterine septum (even a very small one). This is NOT the time to panic. Some breech babies are in that position for very good reasons and are happier that way and some turn around all by themselves at the last minute! Best wishes and please let us know how things turn out. Dr T
At Sat Mar 22, 06:27:00 AM 2008,
jlwgator said…
They did not tell me which results were from either the 1st or 2nd trimester blood. That's a question I didn't know to ask.
They told me my Down's risk was 1 in 10,000, and that T-18 was 1 in 31. I am NOT a smoker. Never have been.
Yesterday I had the amnio and the perinatologist said his theory on my blood work is that it's probably more reflective of what MY body is doing than the baby's body. He said that if my kidneys are working very efficiently, as they should during pregnancy, they are probably flushing out a lot of the stuff the baby is putting into my bloodstream. Although they still could not finish taking all the baby's measurements (kidneys, heart, lungs, diaphragm) yesterday, the dr. said so far it all looks fine, and that he has NEVER seen a T-18 baby look normal on an ultrasound. He told me he thinks my risk is basically zero. I am praying he's right.
What do you think of that?
Thank you for being so helpful and reassuring. I really appreciate your quick responses. It has helped me to calm down.
At Sun Mar 23, 02:20:00 PM 2008,
Anonymous said…
First of all I want to thank you for this wonderful website. This is the best papp-a site on the internet, and believe me I have seen all of them.
These are my first trimester results:
Nuchal scan was normal
Free beta hcg: 0.7677 MoM
papp-a: 0.1358 MoM
This papp-a put me in high risk of genetic abnormality. I did CVS and results were normal.
Now I am worried about non-genetic issues like placenta dysfunction and restricted fetal growth.
I have a number of questions:
1) For the blood test they dated my pregnancy based on the scan as 13w. I am sure that I was 12w3d or 12w4d only. I read that papp-a doubles each 3 or 4 days during first trimester. I wonder if the result would not be so low if they would have dated my pregnancy as 12w3d or 12w4d. Would it be 0.2716 MoM instead of 0.1358 MoM?
2) The fact that hcg is also low, does it mean anything?
3) What is the risk of placenta dysfunction with papp-a levels as low as mine?
4) I am a non-smoker but I am a passive smoker, could this influence the papp-a levels?
5) In the nuchal scan the baby size was normal or even big for the age. Is this a good sign or it is irrelevant?
6) I have been advised to have a scan at 28-30w to assess fetal growth. Could I start monitoring earlier?
If there is placenta dysfunction, does it only start in 3rd trimester or could it start earlier? If the latter, wouldn't it be better to start monitoring earlier? You recommend serial assessment of fetal growth, what is the frequency and when to start? Same question for the doppler.
7) Is it worth buying my own blood pressure monitor to control the preeclampsia risk? My doctor will only test me every 3 weeks.
8)Is the low papp-a level and placenta dysfunction related to the age (I am 36) and do I have more chance of having the same issue in a future pregnancy?
9) Is there a link between restricted fetal growth and cerebral palsy?
Regards,
mj
At Mon Mar 24, 07:02:00 AM 2008,
Anonymous said…
Hi Kenneth, this is Jean here from Singapore. I have earlier posted my Oscar results done at 11wk 6days on the forum as below :-
The test results were as follows :-
NT scan : 1mm
Hcg : 0.62 MoM ( 25.7 IU/I )
Papp-a : 0.58 MoM ( 1.254 IU/I )
The MoM is corrected for maternal weight ( 74kg ), Ethnicity : Oriental, Smoking status etc.
Risk for Trisomy 21 is 1/8000
Risk for Trisomy 13+18 is 1/14000
I will update the new Risk factor once I got from the lab after they correct my smoking status to non-smoker.
I have one more question to check with you, Kenneth. I have noted in the scan report the followings :-
Skull/brain : appears normal
Spine : appears normal
Abdomen : appears normal
Stomach : not visible
Bladder : not visible
Hands : both visible
feet : both visible
Is it common for bladder & stomach to be not visible at the high resolution scan at 11 week 6 days or CRL 53mm ? I have read from some internet source that bladder is almost always visible by 12 weeks. Is there a concern here in your opinion ?
Regards,
Jean
At Mon Mar 24, 01:23:00 PM 2008,
Anonymous said…
I posted a comment a few weeks ago (I had low bhcg AND very low PAPP-A) and I was given a 1 in 10 chance that the baby had Trisomy 18. I had to wait 3 weeks to get an amnio, and then 6 days to get my preliminary (FISH) results, but I'm thrilled to report that according to my FISH results, the baby DOES NOT have Trisomy 18 (or 13 or 21).
Dr., do you think I still need to have closer follow-up due to my very low PAPP-A? (it was .21) I had a low-lying placenta and a subchorionic hematoma earlier in my pregnancy, but both had resolved by my 16 week ultrasound.
Thank you,
Andie
At Tue Mar 25, 06:51:00 PM 2008,
jlwgator said…
Jean
Just so you know, they were unable to visualize some of my baby's organs, at 17 weeks...bladder, lungs, kidneys, whatever.
At Tue Mar 25, 06:52:00 PM 2008,
jlwgator said…
Dr. T
I am THRILLED to tell you that I got my FISH results today and the baby is healthy! There is no T-21, T-13, or the dreaded T-18 that I had come up for as high risk. I am incredibly relieved.
If you wouldn't mind, could you please refer to my earlier post where I listed my blood test #s? I would like to know if you think there is anything else I should be concerned about as my pregnancy progresses. I am 18 weeks now.
Thank you so very much for maintaining this website. It's the best one I found after hours & days of extensive research. You are a god-send.
At Wed Mar 26, 04:01:00 PM 2008,
Anonymous said…
My wife just received the results from her 1st trimester screening results and after reading your site and all of the questions felt this was the best site to get some answers as we havent met with genetic counciling yet and would like to get some preliminary answers from her results and they are are as follows:
nuchal trans:1.87 MoM
PAPP-A: .67 MoM
hCG: 2.64 MoM
she has just turned 33 in feb and according to the interpretation she has an increased risk of Down Syndrome. Can you please explain these results as what are the normal levels. We are stressed and would like some leads on what is next
Also she was told that the age of the baby now is 13 weeks as per the doctor she had this test a couple of weeks ago and they used a Gestation age of 12.3 weeks when screening (which should have been 11 weeks based upon doctors determination.) Does this have an affect on the results? Also can there be errors made as far a Nuchal translucency is concerned due to the fact that the baby was very active during the sonogram and she was having a hard time obtaining it. Your answers are very much appreciated.
At Wed Mar 26, 05:50:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To jlwgator Mar 25: Well, congratulations. Best wishes for the rest of the pregnancy and let us know how things turn out! Dr T
At Wed Mar 26, 05:57:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Mar 26: Your wife's risk results are being driven by the relatively high hCG in comparison to the PAPP-A. The NT is well within a reassuring range. Could the NT masurement be off? Sure, but that's why only certifed sonographers are allowed to do the test - to minimize that risk. I am more concerned by the possibility of uncertainty related to the gestational age at the time the test was performed. ALL of the test results require good estimates of the gestational age at the time the test is done for interpretation of the results (i.e., the results VARY by gestational age). If there is the possibility of a week or more error and that was recorded on the requisition sheet, then the test results need to be reinterpreted in terms of the best estimate of the gestational age. Please check with your doctors on this point. If there was an error, the lab can usually give you an 'amended result' in a simple phone call. Let us know what you find out and best of luck to you. Dr T
At Wed Mar 26, 07:11:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To mj Mar 23: OMG Girl, you are going to wear me out! Let me try to answer your questions the best I can in the order you asked:
1) 3-4 days should not make any difference in the interpretation of the test and the MoM does not chnage at the same rate as the PAPP-A
2) The hCG is NOT particularly low
3) The lower the PAPP-A, the greater the risk for intrauterine growth restriction and other complications (see my post from yesterday March 25)
4) Passive exposure to cigarette smoke could potentially reduce the PAPP-A levels (again, see yesterday's post that specifically addresses PAPP-A and smoking!)
5) I would rather see a larger baby than a smaller one at this point although it's probably irrelevant!
6) Placental dysfunction can lead to IUGR much earlier than 28-30 weeks. Although low PAPP-A levels are not invariably associated with IUGR, yours is low enough that I would consider assessment of growth at 24-26 weeks. If there is a significant abnormality of placental vascularization (not just a small placenta), Doppler flow studies can often detect those that early, even before the baby starts to fall off the growth curve.
7) Just go to a local pharmacy store. Most of those have blood pressure devices that you can use for free and they are more accurate than if you did it yourself (P.S., Remember to relax and uncross your legs while you are having your BP checked!).
8) It is conceiveable that your age is contributing to a suboptimal site for placentation if you have had, for example, other pregnancies, D&Cs, a uterine septum or adhesions, or if you have ueterine fibroids. Chance of recurrence is going to depend on why it happened this time! One of the old adages in obstetrics, however, is that "history tends to repeat itself" even if we aren't smart enough to figure out why!
9)There is a greater risk for CP and developmental problems in growth restricted babies for various reasons: congenital infections; chromosomal abnormalities; genetic problems or syndromes; poor oxygenation form the placenta; premature delivery; maternal preeclampsia are the most common.
Anyway, I hope this helps. Any more and I would have to send you a bill for my time! (JUST KIDDING). Great questions and good luck for the rest of the pregnancy. Let us know how things turn out.
Dr T
At Wed Mar 26, 07:24:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Jean Mar 24: I wouldn't worry much that the bladder and stomach were "not visible" at that early gestational age. Most folks don't take the time to even look and they are just being honest in the report. Dr T
At Wed Mar 26, 07:32:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Andie Mar 24: So far, so good! Your baby will still need follow-up of growth and should probably also have Doppler flow studies done at 24-28 weeks to look for abnormalities of placental vascularization. Anyway, good luck and let us know how things turm=n out! Dr T
At Thu Mar 27, 01:04:00 AM 2008,
Lana said…
Dear Dr T, I have just come back from my seeing my obstetrician (I am 35weeks 5days). Aparently I have a low volume of amniotic fluid (AF) and my obstetrician wants to see me again next week. She puts my chances of a c-section at more that 50% for next week. She has suggested that the low AF levels may be linked to poor placental function. My BP, baby heartrate etc are all fine. CTG is all fine. I would like some more information about normal ranges of AF and the link between placental funtion. If you have anything to suggest, I would be very grateful.
Best regards, Lana
At Thu Mar 27, 07:51:00 AM 2008,
Anonymous said…
Hello Dr.T,
What a great website. I too have had a "postive" result come back after the ERA screen. I'm 38 years old, non-smoker, non-drug user, 14 weeks pregnant. My results were as follows.
NT - 1.7mm
nasal bone present
Hcg - 1.32 MoM
PAAP-A - 0.18 MoM
Our genetic counselor told us all my results were fine except the PAPP-A was very low. This put me at risk for Down's at 1:12. Can one low level really drop it down that low? My question is how common is IUGR in other pregnancies? I have a 3.5 year old son. At the time I was pregnant with him the ERA wasn't available.I had the AFP test and came back positive again for Down's (1:141) I was very small throughout my pregnancy. Each time I mentioned my concern to my Dr. she didn't seem bothered at all by it. I looked about 6 months pregnant at full term. I delivered him by c-section ( fetal distress) at 39 weeks and he weighed only 5 pounds 11 ounces (4%). He is a normal, healthy child, but was born small with a larger head which I read is common in the IUGR babies. I'm wondering if I had the same or similar PAPP-A results when I was pregnant with him and didn't know it. I'm having a level 2 ultra sound next week and if anything looks suspicious I'll have the amnio afterwards.
Thanks for your help,
KH
At Thu Mar 27, 09:04:00 AM 2008,
Anonymous said…
Hi Kenneth, this is Jean here again. I have got a new risk estimation from the lab after they corrected my smoking status. Listed below for everyone is info.
When classified as smoker, the readings were :-
NT scan : 1mm
Hcg : 0.62 MoM ( 25.7 IU/I )
Papp-a : 0.58 MoM ( 1.254 IU/I )
Risk for Trisomy 21 is 1/8000
Risk for Trisomy 13+18 is 1/14000
But when corrected to non-smoker, the readings become :-
NT scan : 1mm
Hcg : 0.602 MoM ( 25.7 IU/I )
Papp-a : 0.49 MoM ( 1.254 IU/I )
Risk for Trisomy 21 is 1/8000
Risk for Trisomy 13+18 is 1/9000
Also regarding ultrasound scanning, I had been told that the bladder would detected on the ultrasound only when it is full and would not if it is emptied.
At Thu Mar 27, 11:16:00 AM 2008,
Lana said…
Dear Dr T,
I should also add, baby is still in the frank breech position and settled well into my pelvis. AFI was 11cm 3 weeks ago and now 7.6cm (5th percentile I was told). Growth is within normal range (approx 2.5kg). I am so worried that the combined low PAPP-A, breech presentation, low AFI and FVL hetero are all pointing to a possible abnormality in my baby...or if it is just chance... I hope that makes a clearer picture... BOY OH BOY... after 2 years of trying to fall pregnant I didnt expect all of this!!
Kind regards and a big thanks for this wonderful resource!! Lana
At Thu Mar 27, 06:06:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Lana Mar 27: Lana, what am I going to do with you, Girl! You MUST relax. You are in good hands with your doctors. I still sincerely doubt that your baby has any abnormality. It does sound like you are cruising for a c/section though. Are your doctors doing any regular fetal heart rate testing (NSTs) at this point? With your 'risk factors' and the decreasing fluid, they might want to do that as much for your peace of mind as anything at this point! Hang in there! Dr T
At Thu Mar 27, 06:21:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Lana (again) Mar 27: Sorry, I missed your first post from earlier today. Amniotic fluid generally does begin to fall in later pregnancy even under normal circumstances. The reason that it falls more with placental insufficiency is because if the baby is not entirely happy inside, the redirect blood to their brains to preserve that VERY important organ. When that happens, they send less blood to their kidneys and as a result make less urine (which is what most of the amniotic fluid is at this point in the pregnancy). That does NOT hurt the baby's kidneys. There is little you can do at this time, if that is what is happening, except to rest and drink plenty of fluids and even that may not help if the baby has 'outgrown' its placenta. Still sounds like your doctors are on top of things, so continue to count to 10 whenever you fell anxious! Dr T
At Thu Mar 27, 06:43:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To KH Mar 27: Well "history does tend to repeat itself" in obstetrics, so perhaps you did have a low PAPP-A with that previous pregnancy and perhaps you have some underlying (not clinically evient) medical condition that predisposes you to having a small or poorly vascularized placenta. Still, the first thing you need to decide is if you are going to have any invasive diagnostic testing for the current pregnancy. That is a high risk for Down syndrome and the risk is being driven by your age and the very low PAPP-A compared to the hCG. Even if the ultrasound is absolutely perfect, the best they can do is reduce your a priori risk (based on the screen result of 1 in 10, NOT your age alone risk) by 80-90%. That will still be a calculated risk of about 1 in 40-50 which is still high. Good luck and let us know what you find out! Dr T
At Thu Mar 27, 06:45:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Jean Mar 27: So, it looks like we were right! Being a nonsmoker did increase your risk for trisomy 18, but that risk is still wonderfully LOW! Thanks for letting us know. Dr T