Low Pregnancy-Associated Plasma Protein A (PAPP-A) and Pregnancy Outcome

Saturday, September 01, 2007

Kenneth F. Trofatter, Jr., MD, PhD

On August 27, 2007, K left the following comment on my previous post entitled
"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

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397 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
At Fri Mar 28, 05:56:00 AM 2008, Anonymous said…

Dr.T,
Thank you for your response. We're meeting with my OB-GYN this coming Tuesday to discuss further testing. I'll keep you posted. Thanks Again.

KH
At Fri Mar 28, 11:08:00 AM 2008, Anonymous said…

Dr. T: Thank you for your response. My name is Mary - I'm the one with low PAPP-A and high HCG and a bicornuate uterus.

I wanted to update - all of the tests came back fine from the amnio so now our only concern is the uterus. I had two miscarriages which is when they discovered it but got pregnant this time naturally and the baby is implanted in a good spot. I went for an u/s yesterday (18 weeks) and all looked good. I am going back on 4/25.

Do you think I should go more often than once a month? Are my chances of survival significantly lower with low PAPP-A and the b/c uterus? They have indicated I may have to go on bedrest if things go south - the baby was looking a bit more cramped than what they are used to.
At Fri Mar 28, 03:55:00 PM 2008, Anonymous said…

Dr. T,

I just turned 38 years old and got pregnant through IVF. I know that I may just be grasping for answers here but I would like to throw a question to you.

Today, I am 13 weeks 4 days which is right on target. The free bhcg was 2.2 and the PAPP-A was 0.57. The NT was 1.7 mm.

It seems as though the only abnormal test is the free bhcg. But when I first tested positive for pregnancy, my hcg was also relatively high (according to some internet charts) and there was a thought that I might have twins, which I don't. Do you think the initial high hcg has anything to do with a high free hcg result from today?

Thanks in advance.
At Sat Mar 29, 07:08:00 PM 2008, Meri said…

Hello Again,

This is Meri posting to Dr. T and everyone else.

My last post was on March 13th. I had the High HcG and low Pappa-A.

I had my level 2 ultrasound on Friday and the baby looked good(I am at 20 weeks). There were no markers for Trisomy 21 and the heart looked really good.

I am not going to be naive and think that I won't have a Down Syndrome baby because of this, but I am at least comforted to know that it looks healthy for now. It also happens to be a little girl. I have two little girls already, so what do ya know!

I did have a scare with my second daughter when she was in utero as well. My AFP did not come back as a positive for Down's, but it did come back a little odd. I think my odds were 1/300(I was 29 at the time). They had also found echogenic focus on the heart. My daughter does not have Down Syndrome, but does have Chiari 1 malformation. You would never think that there was anything wrong with her by looking at her.

What do you guys think?

Thanks for your time and patience.
At Sun Mar 30, 08:05:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To KH Mar 28: Good luck to you and thanks for letting us know.
Dr T
At Sun Mar 30, 08:12:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Mary Mar 28: So far , so good. My greatest concern for you at this point in the pregnancy is cervical incompetence. You are at very high risk for this because of the bicornuate uterus and the fact that "the baby appears cramped." Ask you doctors if they would consider serial tranvaginal ultrasounds to evalutae the cervical length and integrity of the internal cervical os. I will frequently do this weekly at this point in the pregnancy so that a cerclage can be placed on an emergecy basis if necessary before the cervix opens up too much. Good luck and let us know how things turn out.
Dr T
At Sun Mar 30, 03:04:00 PM 2008, Elisa said…

Hi Dr. T~

Thank you for providing such important and easily accessible information. I've learned more about low PAPP-A from reading this thread than from my genetics counselor or doctors. I've been paralyzed with fear since last Monday (March 24th) when my genetics counselor called to tell me the results of my 11th week genentic screening. I'm 36 yrs old & here are my numbers:
PAPP-A MoM .16
hCG: MoM 1.22
NT: MoM 1.13
My risk of Downs is 1/22 & my risk for Trisomy 18 is 1/41.

I had one miscarriage (embryo demise--which I was told was not a chromosomal defect) & one chemical pregnancy.

I had the CVS performed on Thursday. It was a horrific experience because I have some fibroids (which grew during the pregnancy) blocking the catheters (the doc tried both plastic and metal). As such, he had to abstract the placeta cells via a needle through my abdomen. Ouch!
The nightmare continued when the hospital called to say that the doc didn't take a big enough sample for the FISH results. Therefore, I have to wait 7-10 days for the cells to grow before I can find out what is happening.

In the meantime, I feel as if my life and especially my pregnancy are on pause. Its such an awful feeling. We thought we were out of the woods when we had our u/s and found out our nuchal was good.

Is there any correlation between fibroids and low PAPP-A??

How about a correlation between second hand smoke and/or social smokers and low PAPP-A?

I'm not a smoker, but I grew up in a house with a smoking parent. In college I was a "social" smoker. Does this matter?

Your insight is greatly appreciated.

Elisa
At Tue Apr 01, 06:18:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Meri Mar 29" Great!!! I think you have a very good chance of everything turning out just fine. Best wishes and please let us know! Dr T
At Wed Apr 02, 07:17:00 AM 2008, Lana said…

Hi Dr T and all... well I am oging in for a c-section at 36 weeks and 5 days due to suspected poor placental function and a low AFI... AND the baby is breech. Please send lots of healthy baby thoughts and I hope to share good news with you soon. Best regards, Lana
At Wed Apr 02, 04:12:00 PM 2008, Anonymous said…

Hello Dr. T,

I'm not sure if you may have missed my previous post.

I am 38 years old and got pregnant through IVF.

On the day of my screening ultrasound, I was right on target by dates, 13 weeks 4 days. My free bhcg was 2.2MoM and the PAPP-A was 0.57MoM. The NT was 1.7 mm.

I was told that the only abnormality is my free hcg. When I first tested positive for pregnancy, my hcg was also relatively high (according to an internet chart). Do you think the initial high hcg has anything to do with a high free hcg result?

Anxiously trying to figure out what to do...
At Thu Apr 03, 04:05:00 PM 2008, Anonymous said…

Dear Dr. T,
I am 39 (will be 40 at delivery); I have one child, perfectly healthy, now 4 1/2, who was full term (39 weeks) low birth-weight (6lbs 4 oz). No cause was ever identified but the drs at the time said that I had low fluid and that the placenta didn't look very good.
I am now pregnant again after 3 miscarriages (2 missed, both around 7 weeks, one was a trisomy, I believe 22; and one chemical pregnancy at 5 weeks).
I have my first trimester screen and here are my results:
CRL 56.7 mm = 12 weeks (exactly correct given by LMP of Jan 4/08)
NT=1.2 mm
free hcg (performed at 11wks, 3 days) = .29 MoM
PAPP-A (at same time): .41 MoM
FHB 151
nasal bone detected; all else appears normal
I'm normal weight; non-smoker

age-related risk
trisomy 21: 1/87
trisomy 13+18: 1/153

adjusted risk:
trisomy 21: 1/1729
trisomy 13 + 18: 1/246

both are above the cut-off of 1/300 for trisomy 21 and 1/100 for trisomies 13 + 18 for the center I attended.

I have a few questions about these results:

1/ Do you think I need to be concerned about the risk for trisomy 13+18? the actual number (1/247) is not reassuring but isn't it the case that the test is more sensitive for these trisomies than for trisomy 21, with much fewer false negatives? How reassured should I be about being "over the cut-off" of 1/100 (I know it is not a diagnostic test; but again the results seem more clear-cut with this test, ie. if you have a negative result you have less to worry about). I am trying to avoid an amnio given my miscarriage history.

2/ the genetic counsellor suggested having a detailed ultrasound at 16 weeks to screen for trisomies 13 + 18, and said that if that looked fine we could be very reassured. In Canada, where I live, they don't do these until later, so I would have to go to the US. Do you agree that a detailed ultrasound at 16 weeks would give me sufficient information about my risk for these trisomies? (Our thinking is that if there was a problem, I could have the amnio then without it being too late).

3/ Given my history, I am probably even more worried that the low PAPP and hcg signal a placental rather than a chromosomal problem. Do these numbers strike you as very low? How relevant is the low hcg (does that provide evidence of more risk in addition to the low PAPP)? Is there any way of knowing at this point (now 13 weeks) whether this is a problem that might resolve like my son (ie. low birth weight) or result in a more serious outcome (miscarriage/stillbirth)? Do women with these numbers still manage go on to have healthy babies?

4/ I have always had low blood pressure. Not so far as I know clinically low, but low enough that most nurses are surprised at the result retake the test to be sure. Could this explain anything?

Sorry for the barrage of questions!! I really hope you can help. I have found the website very helfpul.

Michelle
At Thu Apr 03, 04:34:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Lana Apr 2: We love you darlin'! Good luck with the delivery and I expect to hear GOOD NEWS very soon! Dr T
At Thu Apr 03, 05:55:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Michelle:
1) You are correct, there are fewer false negatives for trisomies 18 and 13

2) The risk assessment for your age is very reassuring. Most babies (not all) with trisomies 18 or 13 have multiple abnormalities that might be detectable by 16 weeks. That is also a good time to have an amnio if something abnormal is seen. Often with the results you have, I recommend to wwomen that they simply wait until 18-20 weeks. It is the rare trisomy 18 baby that will be missed by ultrasound abnormalities at that point.

3) You should not look at any one test and worry. It is the COMBINED assessment that provides you with the result you need to focus upon. Your sn was small, but well within the range of 'normal', however, as I have said many times before, history tends to repeat itself in obstetrics even if we are not smart enough to know why. My suggestion is that if everything looks good in midtrimester, your doctors might consider andother sonogram with Doppler flow studies somewhere in the range of 28-32 weeks. they can explain my reasoning and the value of those studies at that time.

4) I don't think your low blood pressure has anything to do with the maternal serum marker results. Have you ever been checked for hypothyroidism?

Good luck with the rest of the pregnancy and let us know how things turn out! Dr T
At Thu Apr 03, 06:08:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Anonymous Apr 2: Sorry I missed your initial query. I don't actually screen the comments, and sometimes I get them on an unpredictable schedule! Anyway, you gave me the results of the individual tests but NOT the results of the combined risk assesssment itself! What was that? Were you at increased risk for trisomy 21 (Down syndrome)? Yes, high hCG frequently correlates with high free beta-hCG. However, if your risk was increased for trisomy 21 it is probably being driven by the relatively high hCG compared to the PAPP-A. Let me know your results and then perhaps I can offer some other advice. Dr T
At Thu Apr 03, 11:12:00 PM 2008, Anonymous said…

This is anonymous from Apr 2. Thank you so much for your time, Dr. T.

Let me present my results in greater detail:
Free Beta hCG: 2.20 MoM(90th %ile)
PAPP-A: 0.57 MoM (20th %ile)

Down Syndrome before screening 1 in 156, after screening 1 in 86
Trisomy 18/13 before screening 1 in 296, after screening 1 in 5901

Again, I was an IVF patient and I was told my hcg was relatively high when I tested positive, 183 (4 week LMP) and 500 (4 week 2 day LMP). Thank you so much in advance for any advice you can offer.
At Fri Apr 04, 05:50:00 AM 2008, Elisa said…

Hi Dr. T~

You skipped my comment? Just wondering why? We are still waiting for the results of our CVS. The doctor who performed the test didn't take a big enough sample and now the culture has to grown ANOTHER week and a half. This is the worst experience in our lives.

Please, can you provide any insight on the probability that my low Papp A is caused by something other than a genetic defect?? Here's my question again. I am 36 years old and in good health. I've never had a health problem & I'm not over-weight (not sure if that even matters):

Hi Dr. T~

Thank you for providing such important and easily accessible information. I've learned more about low PAPP-A from reading this thread than from my genetics counselor or doctors. I've been paralyzed with fear since last Monday (March 24th) when my genetics counselor called to tell me the results of my 11th week genentic screening. I'm 36 yrs old & here are my numbers:
PAPP-A MoM .16
hCG: MoM 1.22
NT: MoM 1.13
My risk of Downs is 1/22 & my risk for Trisomy 18 is 1/41.
THIS IS VERY SCARY!!!!!! Especially when our family history is totally clear of any kind of genetic problems.

I had one miscarriage (embryo demise--which I was told was not a chromosomal defect) & one chemical pregnancy.

I had the CVS performed on Thursday. It was a horrific experience because I have some fibroids (which grew during the pregnancy) blocking the catheters (the doc tried both plastic and metal). As such, he had to abstract the placeta cells via a needle through my abdomen. Ouch!
The nightmare continued when the hospital called to say that the doc didn't take a big enough sample for the FISH results. Therefore, I have to wait 7-10 days for the cells to grow before I can find out what is happening.

In the meantime, I feel as if my life and especially my pregnancy are on pause. Its such an awful feeling. We thought we were out of the woods when we had our u/s and found out our nuchal was good.

Is there any correlation between fibroids and low PAPP-A??

How about a correlation between second hand smoke and/or social smokers and low PAPP-A?

I'm not a smoker, but I grew up in a house with a smoking parent. In college I was a "social" smoker. Does this matter?

Your insight is greatly appreciated.

Elisa
At Fri Apr 04, 06:47:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Elisa Mar 30: Past history of smoking or exposure to smokers should not have an effect on the current pregnancy maternal serum markers. However, your fibroids might, particularly, if you have submucosal fibroids just beneath the endometrium - the inner lining of the uterus - and they caused the endometrium to be thinner and less favorable for implantation and early growth of the placenta. If that is the case, and the baby is chromosomally normal, you might still be at risk for intrauterine growth restriction later in the pregnancy. Please let us know what your CVS results show. Best of luck to you and thanks for reading. Dr T
At Fri Apr 04, 07:42:00 AM 2008, Lana said…

well Imani was born on the 3rd April (36 wks 5 days gestation) and weighed only 2.2kg (44cm long). My obs was right... She is being fed via tube through her nose and isnt strong enough yet to breast feed... she is breathing well and looks so beautiful... just so tiny... I am scared for her but she is being brave... any reasurance that things will be ok will be most welcome!!
At Fri Apr 04, 12:38:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous Apr 2 and 3: Unfortunately, regardless of the hCG levels earlier in pregnancy, ther results are what they are. You have to decide YOURSELF how comfortable you are with the result and whether or not you undergo invasive diagnostic testing or simply another ultrasound later in midtrimester (18-20 weeks). There are risks and benefits of all approaches! Good luck, let us know what you decide and what you find out.
At Fri Apr 04, 01:52:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Lana: Congratulations!!!! She will grow my friend, just be patient. No other problems, right? Have fun with her. Dr T
At Fri Apr 04, 03:57:00 PM 2008, Anonymous said…

Hi Dr. T,
I just wanted to give you an update on my situation. I had the low PAPP-A with a 1:12 risk of T21 and suspected IUGR with my first son in 2004. Well, we went for the amnio today and the news was terrible. I had almost no amniotic fluid so they could no do the amnio. The U/S showed brightening with the intestines and the fetus measured much smaller than normal.I'm 15.5 weeks and the fetus is still very low in my pelvis. My Dr. believes the fetus does have a chromosol defect and with the fluid levels so low he does not expect us to hear a heart beat in the next 2-3 weeks. We're devestated, but know that things must happen for a reason. Thank you very much for your earlier advise. This is a great website for women with low PAPP-A.

Thanks again KH
At Fri Apr 04, 04:39:00 PM 2008, Lana said…

no other problems... she scored 9 on APGAR after 1 minute then 10 after 5 minutes... my husband and I are so in love with her...she is just the most gorgeous thing!!! thanks for your support, expertise and encouragement!!! I am the happiest woman in the world!!!
At Fri Apr 04, 05:21:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To KH: I am so sorry. Although it is most likely the baby does have a chromsosomal abnormality, another possibility is a congenital viral infection (the most common being cytomegalovirus) or that you do have some underlying medical condition (an autoimmune disease or an inherited or acquired thrombophilia) that increased your risk for a poor placenta. My heart goes out to you. Thank you so much for letting us know. We will be here if you have anymore questions. Dr T
At Sun Apr 06, 08:45:00 AM 2008, Elisa said…

Thanks Dr. T~

Thank you for this information. I'm seeing my OB tomorrow morning & I am going to ask her exactly where these fibroids are located & if they present any kind of risk to my pregnancy.
At Mon Apr 07, 09:38:00 AM 2008, Anonymous said…

Can someone please help and explain these results to me. All I could gather was that the PAPP_A reading is too high and that this could signify Downs Syndrome.

HCGb 1.20
NT 0.69
PAPP-A 2.76

The doc said I can have more tests dome at 16 weeks or I can opt for amniosemthesis straight away.

I am really confused and not sure what to do. Thanks
At Mon Apr 07, 01:55:00 PM 2008, AndieF said…

I don't know if you want to publish this comment or not. I will leave it to your discretion. I posted a couple of times about my low PAPP-A levels. I had an amnio on March 18th, and got my results on March 24th that my son was chromosomally normal. Three days later, I had a sonogram done, and his heart had stopped beating. I delivered him at 17 weeks and 4 days. It is unknown what the cause was of his death, but I believe that certainly could have been related to the low PAPP-A.

Andie
At Mon Apr 07, 02:10:00 PM 2008, Anonymous said…

Just got scan result today and was told PAPP-A level is low. The scan reads:
PAPP-A 0.3499 MoM,
HCG 2.0459 MoM and
NT 1.8.

What does this mean? In my last pregnancy I developed placenta praevia and had to have CS at 37 weeks. I also have an underactive thyroid and take Thyroxine daily. Is there a link between an underactive thyroid and low PAPPA-A or could a low PAPP-A lead to a Placenta problem in pregnancy. Please advise.
At Mon Apr 07, 02:25:00 PM 2008, Anonymous said…

Just got scan result today and was told PAPP-A level is low. The scan reads:
PAPP-A 0.3499 MoM,
HCG 2.0459 MoM and
NT 1.8.

What does this mean? In my last pregnancy I developed placenta praevia and had to have CS at 37 weeks. I also have an underactive thyroid and take Thyroxine daily. Is there a link between an underactive thyroid and low PAPPA-A or could a low PAPP-A lead to a Placenta problem in pregnancy. Please advise.
At Mon Apr 07, 04:58:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous Apr 7 at 0938: Please check with your doctor. I think you probably have the numbers mixed up. If you are at increased risk for Down syndrome, then the hCG level is probably 2.76 MoM, the PAPP-A level is probably 0.69 MoM and the NT (nuchal translucency) is 1.2 mm. What is your age and what was the risk result you were given? Dr T
At Mon Apr 07, 05:02:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Andie Apr 7: I am so sorry. Even though the baby was chromosomally normal, perhaps he/she had a genetic problem or a congenital infection (the most common being cytomegalovirus, or CMV) that affected the baby and the growth of the placenta. We will be thinking of you and if you do find anythiing else out, please let us know. Best regards, Dr T
At Mon Apr 07, 05:09:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Anonymous Apr 7 02:10 PM: Based on those screen results, you are probably at increased risk for having a baby with Down syndrome. What is your age and the actual risk result you were given? I do not know of an association between hypothyroidism and abnormal placentation if you are taking adequate replacement for your thyroid disease. Hypothyroidism that is not adequately treated is associated with early pregnancy loss. And, if you have an autoimmune condition causing your thyroid disease, you could have other 'autoimmune' antibodies that might deleteriously affect placentation. Regardless, a low PAPP-A does not CAUSE a poor placenta, but it may RESULT from one for any number of reasons, including fetal chromosomal abnormalities. Thanks for reading and let us know what you find out. Dr T
At Mon Apr 07, 06:07:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Lana Apr 4; I can FEEL the love. That baby is so lucky to have you for a MOM! Send us a picture! Dr T
At Mon Apr 07, 07:21:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Elisa Apr 6: You are welcome and please let us know how things turn out. Dr T
At Tue Apr 08, 06:57:00 AM 2008, Elisa said…

Dr. T,

Here's the latest update on my situation. My OB said that my fibroids are NOT located in the lining of my uterus & are harmless. As such, they can't be contributing to the low papp-a. They are located in the bottom part of my uterus & the placenta is at the top. She said I have 2 of them (one is 2cm & the other 4cm). She said some women have them as big as 20cm and they're still totally fine. I also asked her some quesitons about my low papp-a level & other growth problems, but she didn't seem too concerned about it. She said the information/research on the correlation b/t low papp-a and pregnancy problems is so minimal that it isn't even a red flag to her. She also said that she will be very surprised if my CVS results show a chromosomal problem b/c usually with Downs the HCG level and nuchal scans are abnormal (high numbers) & mine were normal. I was sort of surprised that she wasn't very concerned with my low papp-a level. Now I'm wondering if I'm being paranoid?
At Tue Apr 08, 12:15:00 PM 2008, senlik said…

Please can someone help me with these results. Unlike most of the results on here I have had a problem with a high PAPP-A result. I am 34 years of age and had the double test done at 12 weeks and 3 days.

HCGb 50.70/ mom 1.12
NT 0.93mm / mom 0.69
PAPP-A 5858 mUL / mom 2.80

My downs risk came back as 1:13000 which seems pretty good to me, however the doctor is concerned about the high PAPP-A result and suggests more tests at 16 weeks. Has anyone heard about or had high PAPP-A levels?

Thanks
At Tue Apr 08, 05:09:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Elisa: You are not being "paranoid." You are worried about your baby and there is a big difference! The low PAPP-A may or may not signify a chromosomal abnormality or some other problem associated with an abnormality of placentation (unrelated to the fibroids). Let us know what the results are when you get the CVS back and I can give you some other thoughts then. Still wishing you the best! Dr T
At Tue Apr 08, 07:01:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To senlik Apr 8: Multiple gestations and perhaps partial molar pregnancies may be associated with elevated PAPP-A levels. Interestingly, in nonpregnant women (and men) elevated levels of PAPP-A are found under conditions associated with intravascular 'inflammation' such as hypercholesterolemia and type 2 diabetes and are frequently found in individuals with coronary artery disease during episodes of chest pain. I will have to do some more literature research on this myself and think about the potential implications of this for pregnancy. If I find something that makes sense, I will write some more on the topic. Thanks for a great question. Dr T
At Tue Apr 08, 09:01:00 PM 2008, Anonymous said…

Dear Dr. T,

Thanks so much for answering my post (it is Michelle)! It is wonderful that you give your time to answer our questions.

I had a few other questions, too! I had the low PAPP and very low hcg and normal NT. I realized I misstated the birth weight of my son -- he was 4 lbs, 11 oz. Not sure that changes anything??

The plan at present is to have the detailed ultrasound at 18 weeks, and decide then if an amnio is needed. The dr also ordered the blood flow test; and said I would have monthly ultrasounds thereafter to monitor for fetal growth.

I am reassured that a detailed ultrasound will catch a trisomy 18 (which I was at higher risk for, at 1/247, though still above the cutoff), but am still worried about my adjusted downs risk of about 1/1700.

--what do you think about the quad screen as a follow-up from the first trimester screen? My dr. is discouraging because of the false positives, but I feel that I want to use all of the non-invasive tests at my disposal. Also, isn't the risk of a false positive lower with the quad test? I've read that the test can catch most of the cases that were missed on the first trimester screen.

--how much can a detailed ultrasound reduce one's adjusted risk for downs? My adjusted risk is about 1/1700. What is the best it could get down to?

--do different labs use different risk adjustments. Sometimes I see the risks that other women have received for their screens and think that my risk should have been higher, if that makes any sense?? Are all of these numbers standardized, and is there a danger that my adjusted risk could understate the real risk. I know that the dr doing the first trimester screen use the Fetal Medicine Foundation database.

And in answer to your question, yes, I have had my thyroid checked many times--it always comes back normal.

Thanks again for all of your help!

Michelle
At Tue Apr 08, 09:02:00 PM 2008, Anonymous said…

Dear Dr. T,

Thanks so much for answering my post (it is Michelle)! It is wonderful that you give your time to answer our questions.

I had a few other questions, too! I had the low PAPP and very low hcg and normal NT. I realized I misstated the birth weight of my son -- he was 4 lbs, 11 oz. Not sure that changes anything??

The plan at present is to have the detailed ultrasound at 18 weeks, and decide then if an amnio is needed. The dr also ordered the blood flow test; and said I would have monthly ultrasounds thereafter to monitor for fetal growth.

I am reassured that a detailed ultrasound will catch a trisomy 18 (which I was at higher risk for, at 1/247, though still above the cutoff), but am still worried about my adjusted downs risk of about 1/1700.

--what do you think about the quad screen as a follow-up from the first trimester screen? My dr. is discouraging because of the false positives, but I feel that I want to use all of the non-invasive tests at my disposal. Also, isn't the risk of a false positive lower with the quad test? I've read that the test can catch most of the cases that were missed on the first trimester screen.

--how much can a detailed ultrasound reduce one's adjusted risk for downs? My adjusted risk is about 1/1700. What is the best it could get down to?

--do different labs use different risk adjustments. Sometimes I see the risks that other women have received for their screens and think that my risk should have been higher, if that makes any sense?? Are all of these numbers standardized, and is there a danger that my adjusted risk could understate the real risk. I know that the dr doing the first trimester screen use the Fetal Medicine Foundation database.

And in answer to your question, yes, I have had my thyroid checked many times--it always comes back normal.

Thanks again for all of your help!

Michelle
At Wed Apr 09, 02:20:00 AM 2008, senlik said…

Dr T, Thankyou for your reply. Due to my increased PAPP-A level, the doctor has a concern about Down's Syndrome, but as far as I understand a low PAPP-A level can be an indicator of Down's. My HCGb result and NT result were normal. In your experience, is a raised PAPP-A level an indication of Down's syndrome and would you recommend amnio?

Once again thanks.
At Thu Apr 10, 05:39:00 AM 2008, Anonymous said…

I am 40 years old, 11 weeks pregnant (ICSI) and very worried.
Can you please help me to understand these results (MoM?) taken 10+3 week.

PAPP-A: 1169,58 mU/L
free beta hCG: 47,40 Mg/l
NT: 2.5

The risk for abnormalities was estimated to be 1:10 (serum, nt, age, pregnancy week)
Thank you!
At Thu Apr 10, 02:19:00 PM 2008, Anonymous said…

Hello Dr T,
I first want to thank you for the wonderful blog you write. It's very informative and I have consulted it many times during this and previous pregnancies.
I just received my results for my Modified Sequential test. The levels are as follow:
First Trimester:
Gestational age: 11w4
CRL 48.6mm
Maternal age: 37 (38 at term). Wight 152
PAPP-A: 0.95 MoM
hCG: 0.93 MoM
NT: 1.60mm - 1.52 MoM
Risk Assessment at first trimester:
DS: 1: 357
T18: 1: 4530

Second Trimester:
Gestational age: 16w2
Wight: 152
AFP: 0.65 MoM
uE3: 0.95 MoM
hCG: 0.72 MoM
Inh A: 1.23 MoM
Risk Assessment at mid-trimester:
DS: 1: 384
T18: 1: 58800
OSB: 1: 41500

My T18 risk decreased significantly while my DS risk only decreased slightly. In your opinion, what is keeping the DS risk so elevated relative to the first stage? And which level caused the T18 risk to decreased so much?
I understand my levels are negative, but given that the DS is so borderline it makes me uneasy to not do an amnio. I am schedule a growth scan for early next week (at 17w) and we will determine then if an amnio is necessary. Is it safer to have an amnio done at 16w compared to 18 or 19w? Why?
Also, I noticed that my risks weren't calculated including my Race (it shows it as "Other" while I'm "Caucasian"). Is Race a factor to be included?
Thank you in advance! Mamma-to-be
At Thu Apr 10, 04:01:00 PM 2008, Elisa said…

Hi Dr. T~

We just got the results back from the CVS & everything is normal. NO chromosome problems! We are very excited!!! Also, the best news yet--ITS A GIRL! I am so happy!!! I assumed it was a girl because my hcg level was slightly elevated. I read a few studies which concluded that women carrying girl babies have slightly higher hcg levels (and mine was slightly higher). The same exact thing happened to my cousin last year. She had the low papp-a and the slightly elevated hcg & her baby was fine & it was a girl. I think there's a pattern here. :-)
At Thu Apr 10, 04:02:00 PM 2008, Elisa said…

Hi Dr. T~

We just got the results back from the CVS & everything is normal. NO chromosome problems! We are very excited!!! Also, the best news yet--ITS A GIRL! I am so happy!!! I assumed it was a girl because my hcg level was slightly elevated. I read a few studies taht concluded that women carrying girl babies have slightly higher hcg levels. The same exact thing happened to my cousin last year. She had the low papp-a and the slightly elevated hcg & her baby was fine & it was a girl. I think there's a pattern here. :-)
At Sat Apr 12, 10:52:00 AM 2008, Anonymous said…

This site truly helped me get through the time between the screening results and the amnio results. Original post on 3/9/08. FISH results came back that this little girl is chromosomally OK! Dr.T - Thank you for the hours you dedicate to our comments. To everyone else - My heart is hoping for your happiness and healthy babies. kc
At Sat Apr 12, 02:52:00 PM 2008, Anonymous said…

Dr. T,
Reading your honest and caring comments is the only relief I've had from constant worry in the last three days. Information, positive or negative, is very helpful. This is the most wonderful resource I've found.

I'm 37 but will almost be 38 at delivery so the physician used 38 for my age-related risk.

After our NT scan my husband and I were prematurely thrilled that everything looked normal. My risk for Down syndrome went from 1:97 to 1:350.

Then we got the blood test results.

12 weeks/1 day
NT - .59
HCG - 1.80 (very high?)
PAPP - .52 (very low?)
Ds Screen risk - 1:96
Ds Age related risk 1:97
T18 Screen risk - 1:10,000

The nasal bone was present though I was told that was not included in the risk number.

Can you please tell me what "normal" ranges are for HCG and PAPP-A for this point in the pregnancy (12 weeks)? I know 1 is the magic number, but is there a range?

What I'm most concerned about is the association between the high HCG and the low PAPP-A since they are going in opposite bad directions and that seems like a big deal for risk of Down syndrome even though the NT was good. Is that a valid assessment? Oh, I think I'm going to be sick, good thing I'm posing this question online and not in person.

Thank you so much for your time Dr. T.
Sarah
At Mon Apr 14, 10:49:00 AM 2008, Anonymous said…

To clarify my earlier post regarding my due date. The physician took the calendar date I was due (October 16) and the ultrasound estimated due date (October 18) and came up with October 17, exactly my 38th birthday. I'm having a c-section so I really wanted him to use two weeks earlier -- he said nice try.
Didn't want you to think he's a hack!
Sarah
At Mon Apr 14, 01:28:00 PM 2008, Rev said…

Dr T:
This is the best site with good information on pregnancy. I am 15 weeks pregnant age 40 years and will turn 41 just before the due date. I had positive screen results for Down Syndrome at first trimester screen test. The data is as below
NT - 1.25 MoM (2 mm) Doc said it is normal.
PAPP-A - 0.80 MoM
HCG - 1.83 MoM.
Down syndrome risk - 1 in 35
Age related risk - 1 in 42
Trisomy 18 - 1 in 5208.

I am having the second trimester serum test tomorrow. I wanted to know your opinion as my doc wants me to do Amnio. I am scared of this test and wanted to get your opinion on the numbers.
Please advise.

Thanks,
Rev.
At Mon Apr 14, 02:47:00 PM 2008, Elisa said…

Dr. T~

I extend my condolences to you. I was very sorry to read about the passing of your brother-in-law. I hope you and your sister are doing ok.

Elisa
At Mon Apr 14, 04:54:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Michelle Apr 8: To put things in perspective, the 1 in 1700 risk is about what we quote a 17 year old as the risk for having a baby with Down syndrome. I would NOT recommend doing the quad screen at this point. A detailed (level 2, or 'targeted', or 'genetic')ultrasound can reduce your risk by at least 60-80% (if not as much as 90%). In other words, if completely unremarkable for major defects or soft markers for aneuploidy, your risk is less than 1 in 3000. But, if you cannot live without knowing for sure, then have the amnio. Just remember, if you do, babies can have other problems that will not be detected by an amniocentesis, but again the odds of toe are small.. Good luck Michelle! Dr T
At Mon Apr 14, 04:56:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Senlik Apr 9: As far as I know, I high PAPP-A is not a marker for Down syndrome and I would not use that alone to recommend an amniocentesis unless the baby appeared abnormal in some way. Dr T
At Mon Apr 14, 06:02:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous Apr 10: In your case, the increased risk for Down syndrome is probably being driven by at least your age and the relatively increased NT measurements. I cannot comment on the absolute values of the PAPP-A and hCG because I need the multiples of the median (MoM) for these to see how they might be contributing to the overall risk. Let me explain...

Maternal serum markers (in this case the free beta-hCG and the PAPP-A)steadily change as the pregnancy progresses (i.e., by weeks' gestation) and these changes are quite rapid during this early part of the pregnancy while the placental tissues are rapidly proliferating. Therefore, for accurate interpretation of the test results, a different reference range must be used for each week (sometimes days) of gestation, depending on when the test is drawn.

To avoid the multiple reference range problems and also to standardize test results between laboratories, whose reference ranges also vary, a MEDIAN value for test results in normal pregnancies is determined in each laboratory for each week of gestation. A patient's results are then expressed as a multiple of this median (MoM), rather than as a raw 'marker' concentration.

It has been found that maternal weight, maternal race, smoking, and maternal diabetes mellitus (insulin-dependent) variably affect maternal serum marker value. Most laboratories today correct the MoM for these conditions so that a given MoM value accurately reflects the risk of abnormality. Laboratories request that information related to these conditions be included, along with the gestational age, when the specimen is submitted. There is sufficient data available now that these 'corrections' improve the reliability of the screening tests. All this is done by computer analysis of very large data bases, so I am not able to push the numbers with my own little brain!

Thanks for a good question and I hope this helps you understand your test results better. Dr T
At Mon Apr 14, 06:12:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Mamma to be: Your risk estimate for Down syndrome is about half your 'age alone risk, so that isn't too bad. There really is not any difference between the first and midtrimester Down's risks so I imagine your age is the major contributing factor there. The T18 risk is low because the serum markers are all so normal that it is very unlikely your baby has this. Race usually is included in the calculation that gives you a risk estimate. I imagine the default is 'caucasian' if your doctor fails to include it. If you have an ultrasound done and it shows no major fetal abnormalities, nor 'soft markers' for Down syndrome, your risk is reduced by at least 60-80%. That would put you in the range of 1 in 800 or less. That ain't too bad! I don't know if there is any greater risk from an amnio at 16 weeks than at 18 weeks. It depends on the skill and experience of your doctor. Good luck to you and let us know what you find out!
Dr T
At Mon Apr 14, 06:13:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Elisa Apr 10! Congratulations! And, if it's a girl, I will understand when you don't name the baby after me. Let us know how things turn out in the end! Dr T
At Mon Apr 14, 06:15:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To kc Apr 12: Well, CONGRATULATIONS to you too! We are running a special on little girls at this site. Please let us know how things turn out. Dr T
At Mon Apr 14, 06:23:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Sarah Apr 12: Actually, your MoM on the hCG is just slightly up and that on the PAPP-A just a little low. Your baby had a wonderful NT measurement. There is NOT a 'normal' range and the test varies by gestational age - that's why we use the multiple of the median (MoM) approach to interpretation. I think other than your age, the 'risk assessment' is being driven by the differences between the MoMs for the hCG and the PAPP-A. So, you have about a 1 in 100 result. I am wagering right now that this baby is fine. The other way to look at it is that the baby has about a 99 out of 100 chance of NOT having Down syndrome. Best wishes and let us know what you decide to do and what you find out! Dr T
At Mon Apr 14, 06:26:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Rev Apr 14: The risk of an amniocentesis is only about one-tenth the risk (1 in 500) and in some habnds even better. See what results you get back from the next study, let us know what those are and perhaps I can give you some more thoughts. Remember, in the end the decision is entirely yours! Best wishes to you, thanks for reading and for the kind words. Dr T
At Mon Apr 14, 06:27:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Elisa: Thank you for your thoughts. My brothet-in law was a very special person! Dr T
At Tue Apr 15, 12:05:00 AM 2008, senlik said…

Dear Dr T,

I would just like to say thankyou so much for replies. I think you do a wonderful job giving up your free time to answer all our questions. You have definitely helped me and I am sure hundreds others in what can be a scary and stressful time.

Once again thanks
At Tue Apr 15, 01:40:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Senlik: And thank you for the kind words...Dr T
At Tue Apr 15, 02:36:00 PM 2008, Anonymous said…

Thank you so much for your reply. I know I'm not out of the woods yet, but I think I'll be able to sleep at night. We're having an amnio in three weeks and I'll let you know what happens. I saw Elisa's comment and I read your April newsletter. I think it's amazing that you take what little free time you probably have, to answer our questions, especially during this time of loss. My condolences. And again, thank you. Sarah
At Tue Apr 15, 06:22:00 PM 2008, Lana said…

Hi Dr T and everyone...

Just wanted to let you know that Imani is 2 weeks old now and thriving!!!

Thanks again to Dr T for the amazing support you provide!

best regards, Lana
Perth - Western Australia
At Wed Apr 16, 07:40:00 AM 2008, Rev said…

Thanks Dr.T ! I will get my results of the second trimester blood work next week. I will give you the details then. But I wanted to know more about my current numbers..
At Thu Apr 17, 09:49:00 AM 2008, Anonymous said…

Hello Dr. T, Thank you very much for your comments and help. I like most of the women are paralyzed by the resent news I receieved. I am 28 y/o, have one healthy, active, 15 month old daughter. I had insulin dependent gestational diabetes with her. It runs in my family and likely not b/c I am overweight as my BMI is 21. I only mention that b/c I am not sure if any of those factors are correlated with papp-a or beta HCG levels. She was tiny at birth 6 lbs 1oz. Aside from that I had a healthy pregnancy. I am pregnant again and I just had my first tri screening and the results are
I had the blood test at 9 weeks GA
GA 14 w 3 d (current)
NT 1.4
papp-a .15
beta-HCG 1.6
Increased risk of DS 1 in 74
Trisomy 18 1 in 10,000

I am extremely worried. Particularly about the very low papp-a level. I am going to have an amnio on April 22 at 15 weeks. Just wanted to also mention that I have been very sick this pregnancy with flu type symptoms (fevers, etc.) on 2 separate occasions. Could this have altered my blood serum levels? I would greatly appreciate it if you could shed any light on my results.
Thank you so much for your time,

GD
At Fri Apr 18, 02:58:00 PM 2008, Anonymous said…

I am pregnant with my second baby 13 weeks. All of the ultrasounds show normal development/heart beat, but the PAPP-A result was low.
Nucal Translucency 1.8mm
free beta - HCG .65 MoM
PAPP-A .38 MoM
crown rump length 54mm equivalent to gestational age.
Fetal heart 157bpm.

Some doctors have said that is not too bad and others seem concerned that we need further investigation. They have recommended an Amnio, but I noticed that this doesn't always tell you what the problem is or why the PAPP-A was so low. Please note that the results were very different from my first pregnancy (very positive results in 1st), which is why my OB is concerned, as I am only 2 years older 32.

Could you please advise:
1 Is my PAPP-A results low enough to be concerned? (I note that some people have normal amnio/later scan results and out of the blue something happens).
2 Is there any indication of in advance of still birth?
3 If the amnio results come back normal, do many women with those type of PAPP-A results deliver babies that are developmentally and physically normal?

Thank you
At Sun Apr 20, 05:57:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Sarah Apr 15: ...and thank you, Sarah. Dr T
At Sun Apr 20, 05:58:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Lana Apr 15: You can write back ANYTIME, Lana! If I EVER get to Pert, I want to see her! Dr T
At Sun Apr 20, 06:00:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Rev Apr 16: We will be pulling for you, Rev! Let us know... Dr T
At Sun Apr 20, 06:02:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To GD Apr 17: I too am worried by those numbers. When they do the amnio, ask your doctor to send some of the fluid for CMV PCR. He/she will know what I am talking about. Good luck to you and let us know what you find out. Dr T
At Sun Apr 20, 06:06:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous Apr 18: Bothe serum markers are on the low side, but I have another question. The CRL (crown-rupm length) of the baby is equivalent to that seen in a baby that is only 11 and a half weeks. Are you not quite as far along as you thought and, if so, that could be the reason for the low MoMs on the maternal serum markers? Best wishes and I will try to answer your other questions after you check back with me on the gestational age issue! Dr T
At Mon Apr 21, 11:59:00 AM 2008, Rev said…

Hi Dr.T:
My second trimester screening results came back with increased positive results. Here is the data
NT - 1.25 MoM
PAPP-A - 0.80 MoM
AFP - 0.35 MoM < 2.50
HCG - 4.80 MoM
Inhibin - 3.54 MoM.
UE3 - 0.54 MoM

Down syndrome - 1:5
trisomy 18 - 1:940
ONTD - 1:6000.

I will be going tomorrow for Councelling for Amnio. I would appreciate your input on these numbers. Why my HCG is so high.. Are there any other reasons besides down for HCG to be so high. Please advise.

Thanks,
Rev.
At Mon Apr 21, 05:43:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

Hi Rev: I am very worried by that combination of numbers as well. I would highly recommend the amniocentesis, regardless of what you think you may or may not do if you find out the baby has Down syndrome. The risk of the amnio is less than 1/100 the risk of the baby having trisomy 21. Good luck and stay in touch. Dr T
At Thu Apr 24, 08:33:00 PM 2008, Anonymous said…

Dr. T,
I have been reading these posts for the past week and it has been invaluable in helping me understand my "abnormal" blood results. Thank you so much for your time and insight! I am 35, pregnant with my second child. First child screen was completely normal.

For this screen my blood was taken at 9w 2d and my NT scan at 12w 5d. After hearing these results we went ahead with a CVS abdominally and so thankful we did it since the results just came back normal! Since I had such a low Papp-a result should I still be concerned about other abnormalities that CVS does not pick up and what about premature labor or IUGR? I will be getting an AFP done and 18-20 w hi-res ultrasound. Also my TSH level at 8 weeks pregnant was .35 - should I be concerned and does that have anything to do with low Papp-A?

Risk of Down: 1 in 40
Trisomy 18/13 1 in 9,081.
Papp-a (mom): .24
Beta HCG (mom:) 1.32
NT(mm): .9
CRL (mm): 70
GA: 13.2

Thank you again,
MM
At Sat Apr 26, 12:05:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To MM: You had your PAPP-A done so early that it may simply be due to that. Since you had a good result by CVS (congratulations!), I would simply recommend the MSAFP at 16 weeks and the targeted scan at 18-20 weeks. Your TSH is abit on the low side, but this is not uncommon in pregnancy due to cross-reactivity with hCG and pituitary suppression. It is unlikely this represents true 'hyperthyroidism'. Good luck, thanks for reading and let us know how things turn out. Dr T
At Mon Apr 28, 02:45:00 AM 2008, Anonymous said…

Hi Dr T,
I am having trouble getting anyone to take my numbers seriously. The NT scan showed up a low PAPP-A result and the sonographer consultant told me to ask my GP to watch this and to make sure my Obs Consultant knew about it. My GP wrote to the Obs consultant and she has just told me this morning that "Don't worry - they are not concernced as the PAPP-A result is low which is good!" Even I know that this does not make sense. Can you please help me by giving your opinion as most info I have read on this amazing site seems to point towards a possible problem:

CRL:57.9mm
NT: 1.6mm
Placenta:posterior high
Free B-hcg: .956(MoM)
PAPP-A: .269 (MoM)
Egg was IVF donor egg -maternal age 21 yrs.
I was 11weeks and 6 days when the scan was done.

I look forward to hearing from you.Many thanks. Jackie
At Wed Apr 30, 05:05:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Jackie Apr 28: I wish I knew how old you are, what sort of medical problems you have, what was the cause of your infertility, and have you ever had any pregnancies (successful or not)? Barring that, it would be helpfyul to know what the calculated risk assessment result for Down syndrome and trisomies 18/13 based on your test results. Regardless, the low PAPP-A may not be good, but it may not be bad either! If you have read the posts I have written on this subject, and some of the comments from our readers and my responses, you will better appreciate why I seem to be talking out of both sides of my mouth. The reassuring components of your screen are the normal NT and hCG measurements. With a "21 year old egg", I doubt your calculated risk for aneuploidy was very high. You are probably at modest risk for a small baby and the things that might go along with that, such as early delivery, preeclampsia, and cesarean section, but there might be other factors you have not told me about (or are not aware of) that might also put you at risk for these. My bet right now is that you will do fairly well with the pregnancy and nothing is wrong with your baby! Let us know how things turn out. Dr T
At Thu May 01, 03:16:00 AM 2008, Anonymous said…

hi again Dr T,

I am so grateful for your reply and apologies for omitting some of the info. I am 44 years old with no medical problems except a fibroid which has appeared with this pregnancy. The infertility was unexplained, save for a mild endometriosis. I had one pregnancy last year (natural) which ended after just 6 weeks with no explanation. I have had 2 previous rounds of IVF - the first produced 4 follicles and 2 embryos were implanted but did not take. The second produced no follicles.
Tha adjusted risk for Downs was 1:1804 and for Trisomy 18+13 was 1:18628. I was advised that no amnio or CVS would be necessary.
My main concern is the IUGR/stillbirth scenario which seems to go hand in hand with a low PAPP-A result. Do you imagine that my doctors would keep a closer eye on me - in your opinion what should I be pushing for at my 20 week scan? Will the AFP result throw anything in to the mix as I am yet to receive that?
Thank you again.Jackie
At Thu May 01, 10:49:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

Hello again Jackie: When the PAPP-A is low, the women at risk for complications are those that have a placenta that is smaller than normal and/or did not have normal growth into the lining of the uterus (specifically into the uterine spiral arterioles). The MSAFP test at 16 weeks can sometimes provide an insight to that as a possibility. If the AFP is abnormally high, and there are no apparent abnormalities of the baby to be seen, then that "false positive" result may actually reflect an underlying placental problem (that may not manifest itself as a problem such as fetal growth restriction or maternal preeclampsia until later in the pregnancy).

The other procedure we use that can also anticipate risks down the line is Doppler flow velocimetry. This is an ultrasound technique that can help us to detect degrees of 'resistance' to blood flow. If you and/or the baby are found to have trouble pushing blood through the placenta by virtue of increased resistance in the uterine or umbilical arteries, respectively, this can be another reason to keep a closer eye on the baby's growth, development and overall well-being. Still, do not panic at this point! Again, thanks for your questions and let us know how things turn out! Dr T
At Tue May 06, 10:15:00 AM 2008, katie said…

Hi Doctor Trofatter

Thank you for the time you take to answer these questions. I am really worried baout my Ultrascreen results:
Here are my statistics
Age :30
BMI: 21
Non smoker and drinker
PAPP-A = 0.42
HcG= 0.29
NT = 0.7
Nasal bone present
Trisomy 21 1/10,000
Trisomy 18 and 13 1/173
Ultrascreen was at 13 weeks

I am worried to death about the trisomy 18. I don know what I shoudl do and my doctor has not really had time to talk to me. She did mention that possibly I might have low amniotic fluid or placental problems.

I also want to know what are "normal" values for HcG, PAPP-A and NT. I cant find the values anywhere.

Please can you shed some light on my figures. I need something to get my through the next 3 weeks before my ultrasound and possible amnio.

Many thanks

Katie
At Tue May 06, 04:33:00 PM 2008, katie said…

Sorry about my spelling mistakes! I also forgot to mention that although my thyroid test prior and before becoming pregnant were normal I am on 25 mcg of synthroid. My doctor thought that this might be affecting my irregular menstrual cycle. Could my thyroid have affected my Ultrascreen result?

I have also felt that I have very very slight cramping sensation for the last few weeks.
At Wed May 07, 01:46:00 AM 2008, Anonymous said…

Dear Dr T,

I wrote to you a month ago regarding a high PAPP-A result from a double test performed at 12w 3d. I will be 35 when the baby is born.

My results were:-
HCGb 1.20 mom
NT 0.69 mom
PAPP-A 2.76 mom
My downs risk was 1:13000 but my doctor was concerned about high PAPP-A

You advised me that I was at very low risk for Downs syndrome and I had decided to put the test out of my mind and get on with enjoying my pregnancy. Since then, the two doctors I have seen are insisting on the triple test as they are still concerned. The whole thing is stressing me out and I cant understand why they are so concerned if my risk result came back so good. I live in Turkey and the doctors tend to be a little alarmist compared to the doctors back home in th UK. Do you see any advantage for me doing the triple test when I have already done the double test and received these results? I just want to be able to put the whole thing out of my head.

Once again thanking you in advance of your response.
At Wed May 07, 09:34:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Katie: The low hCG and the low PAPP-A were driving your risk for trisomy 18. I am very curious about something. You say you have irregular cycles and that usually means your ovulation is delayed. What was the crown-rump length of your baby on the day the first trimester screening was done and what did they use for your gestational age? Was there a difference in the ultrasound dating and your last period dating and which did they use? The reason I am asking is that if you were really a week behind because of delayed ovulation and they used your period, then that alone could account for the low hCG and PAPP-A and perhaps your rsik for trisomy 18. I doubt that low dose of thyroid hormone will be an issue, but why are you on it if you don't need it? Dr T
At Wed May 07, 09:36:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

P.S. Katie: BOTH your serum markers would be below the 5th percentile for multiples of the median (MoM) at 13 weeks. Dr T
At Wed May 07, 11:37:00 AM 2008, Katie said…

Dear Doctor Trofatter

Thanks again for your response. I can’t tell you how reassuring it is not know there is experienced help and support.

In answer to your questions:

My last period was at the beginning of January and it finished on the 13th of Jan. This was the first period I had had since September. I told them this at the doctors and initially they tried to tell me that my baby was way older then it possibly could be. I told them that I was pretty certain that my baby was conceived on the 19th or 20th of February because my partner had been working nights. Also I had a yeast infection about a weekend a half before that and I took a pregnancy test, just to be sure before taking a Diflucan. Because my periods are so irregular I tend to take a test just to be on the safe side.

So I believe I conceived on the 20th of Feb. On the 25th I started to have some strange cramps and a lot of pain. On the 26th I did a test and it was very faintly positive. I went to the OBGYN to tell them of the test result and also of the terrible pain I had that night. They gave me an ultra sound and could not see anything at all in my uterus but saw that I had two large cysts on my right ovary. They found my HcG was 380 and two days later after another blood test it was over 1000. A week or so later we saw on the ultra sound the yolk sac (a big raisin).

I just called my perinatologist to ask for the crown to rump length on the day of my ultra screen (April 28th). There was no-one there today but from my notes they said that the baby was 7.5cm although I am not sure if that is crown to rump…. Could it be its full length?

I also asked what age they used and again they can’t tell me today because no-one is there. My OBGYN gave me a due date of Nov 5th based on the baby’s measurements at around 5 weeks gestation. The ultra screen people thought the baby looked 13.5 weeks so I am now wondering if they used that date. Maybe this is the problem because when I calculated my due date based on my date of conception I got November 12th!!!!!!!

I will call again tomorrow and get their exact figures used.
In respect to the synthroid they thought that even though my profile looked normal I was very tired all the time and had such irregular cycles, despite a very good diet and activity regime. I started to take it in January 2008.

Apologies for this almost essay like response. I wanted to give you the most precise information I could.

I also wanted to mention that in terms of my family medical history all my paternal relatives have type II diabetes (Indian origin) and my mother had pre-eclampsia during pregnancy.
At Wed May 07, 04:29:00 PM 2008, katie said…

I also meant to ask if one dose of Diflucan (150mg) could have caused trisomy 18 or other problems. I took it around conception time I guess even though I took a pregnancy test before hand to check and the test was negative.

Thanks
At Fri May 09, 07:24:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous May 7: I do not see the advantage of doing the 'triple test' or 'quad screen' at this time with those initial results. It will only confuse the issues. I would suggest that you consider ONLY the MSAFP part of those tests and then a good ultrasound at 18-20 weeks. Good luck and please let us know how things turn out. Dr T
At Fri May 09, 07:28:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Katie: So perhaps there is a discrepancy in dating that gave you those test results. Still not sure what to think, but it sounds like things are going well to this point otherwise. I am not aware of ANY association between Diflucan and chromosomal abnormalities in babies. Dr T
At Sun May 11, 11:42:00 PM 2008, Lana said…

Dear Dr T - I just wanted to give you an update on Imani... she was diagnosed with moderate (about 50dB) unilateral hearing loss in her left ear...

Without a family history of hearing problems, I was wondering if the low PAPP-A could be associated with the hearing loss somehow?

Also - with hearing loss, could there be any other abnormalities that I should look out for?

Thanks again!!

Lana
At Tue May 13, 05:50:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

Lana: The only thing I would suggest at this time is that they screen her for evidence of a congenital cytomegalovirus (CMV) infection. That is the most common infectious cause of congenital sensorineural hearing loss. Other than that, if they find something else out, please let me know. I am here to learn too! Good luck to ALL of you. Dr T
At Wed May 14, 09:24:00 AM 2008, Anonymous said…

Dr. T,

Thank you again for your comments. I just wanted to give follow up which could help the other readers out there.

I am 'anonymous' from Apr 3, 2008.
PAPP 0.57 MoM (20th%ile)
free hCG 2.20 MoM (90th%ile)
NT 1.7 mm

Risk of Down's 1:86.

Thankfully, the amniocentesis came back negative for Down's. I do have placenta previa and I did have borderline elevated AFP from the amnio fluid. But the level I ultrasound showed no signs for neural tube defects. I am due for a level II ultrasound today.

Thanks again.
At Thu May 15, 05:43:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous May 14: Congratulations on the normal test results! I have seen MANY 'abnormalities' of maternal serum screening (elevated hCGs, and AFPs) associated with placenta previas. The uterine arteries enter the uterus at the junction of the cervix and the uterus and I have to wonder if that facilitates placental growth (associated with the higher hCG) and also transfer of AFP from the baby into the maternal circulation. Anyway, best of luck for the rest of the pregnancy and thanks for sharing! Dr T
At Wed May 21, 10:45:00 PM 2008, sarah said…

Dr. T.-

Good news from Sarah, April 12.

[to recap: I'm the 37-year old that had low PAPP-A and high hcg despite a good NT measurement]

After a failed FISH test and an entire 14-day wait for the amnio results, we found out today that the baby is "just fine," just as you predicted! And it's a girl to boot -- a bit of a surprise after two boys!

You make such a difference to so many worried moms with your thoughtful replies. You remind me of the story of the boy who threw starfish back into the ocean one at a time (an internet search will reveal the entire story too lengthy to include here).

Thanks again so much Dr. T!
Sincerely, Sarah
At Thu May 22, 10:44:00 AM 2008, elisa said…

Hi Dr. T & Sarah,

First, I want to say to Sarah, I'm so happy to hear that your baby is fine. Congratulations on your littler girl!! I went through a similar experience in April (failed FISH test and lots of waiting on pins and needles). I'm also having a girl and everything is fine with her. I know you probably have felt like your life has been on hold and now you feel liberated and alive again. :-) Fantastic!

Also, Dr. T, I made this point earlier, but you never commented on it. I'm noticing a pattern on this site (and in other women I know & on other sites) where the higher hcg level simply means the woman is carrying a girl baby. I also read a few studies that concluded this to be true. What's your opinion on this?

Btw--I'm in my 20th week. I had my 2nd trimester ultra sound last week and everything is right on track with my little girl. :-)

Thanks Dr. T~

Elisa
At Thu May 22, 11:25:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

Hi Sarah: CONGRATULATIONS andt hank YOU so much for the kind words and the feedback. It is readers like you that keep me going at this and I wish I could spend more time doing it! Come back and let us know how your delivery turns out! Dr T
At Thu May 22, 11:28:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Elisa: I guess CONGRATULATIONS are in order all around. I have wondered if gender could affect the test results so I will ask other folks about. At this point, no 'correction' is made for gender and that would be hard to do considering the early gestational age at which first trimester screening is done. I appreciate your thoughts and remind all my readers that I am here to learn too! Best wishes for the rest of your pregnancy. Dr T
At Fri May 23, 11:41:00 AM 2008, Anonymous said…

Dear Dr. T,
I am so happy I found your website. It is so full of great information. Here is my situation:
I am 41 years old. On the day of the screening, I was at 12w 0d. Here are the results:
Free Beta HCG 1.26
PAPP-A .38
NT .69
CRL 63 mm
Downs risk factor before test: 1/54
Risk after test: 1/71
Combined risk for Trisomy 13 & 18 before test: 1/98
Risk after test: 1/1900
Based on the CRL, they said the baby's age would appear to be 12w 5d but they are leaving the due date as originally calculated.
The concern I have is that they told me due to my elevated HCG level and low PAPP-A level along with the 1/71 risk for Downs that the baby is at a higher risk for having Downs. I have an amnio scheduled for June 17 which seems so far away. What can you tell me about these results? I am very worried and would like to get your opinion.
Thank you very much!
AB
At Fri May 23, 07:03:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To AB: Your age and the relatively low PAPP-A are driving your Down's risk which isn't much different from your 'age alone' risk as a result. So, yes with a 1 in 71 risk for having a baby with Down syndrome you are considered to be "risk positive" - most laboratories use a cut-off of about 1 in 270 as the line above and below which they will call you risk positive. BUT, that number is fairly arbitrary. You need to deal with the 1 in 71 chance that your baby has Down syndrome (and the 70 out of 71 chance it does not). The number is what it is and is based on data from 10's of thousands of women in the databank that is used to calculate your risk based on the combination of all the fetal measurements, the hCG and PAPP-A, your age, your weight, etc. An amniocentesis is a reasonable option under these circumstances and the risk is low in experienced hands. It will also be safer in 3 weeks than if it were to be done today. Good luck and let us know how things turn out. Dr T
At Wed May 28, 11:12:00 AM 2008, Anonymous said…

I wrote to you about an abnormally high PAPP-A result some time ago. I have since had the AFP test done, but dont fully understand what the two results combined mean regarding the downs risk.

My double test [performed at 12w 3d] results were as follows:-

HCGb 1.20 mom
NT 0.69 mom
PAPP-A 2.76 mom
My downs risk was 1:13000 but my doctor was concerned about Downs Syndrome due to the high PAPP-A

My AFP result [performed at 18w 3d] was:-

0.69 mom
NT risk: 1/8100

The doctor didnt say anything about the afp result in relation to my babies downs risk. I would really appreciate it if you could tell me what the two test results mean in regards to the Downs risk

Thanking you in advance

Becky
At Wed May 28, 05:21:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Becky: All the tests to date indicate that you are at VERY LOW RISK for having a baby with Down syndrome. I would have been more worried if the PAPP-A was LOW! If you have any doubt about what I am telling you, ask your doctor for a 'second opinion' with a genetic counselor or a specialist in maternal-fetal medicine. RELAX Girl and let us know how things tuurn out! Dr T
At Mon Jun 02, 09:02:00 PM 2008, Naty said…

Dear Dr. T, I'm 41 y.o. This is my 4th pregnancy, My first 2 pregnancies were normal, on the 3rd one I had a pPROM at 23 weeks, stay at he hospital for 2 weeks, had a detachment of the placenta, an emergency c-section, the baby was very premature and he didn't make it.
This pregnancy has been normal so far, but the integrated test shows these results:
N.T:1.6 (Dr. says is above average)
PAPP-A:0.25
HCG:0.93 (Is it normal?)
Dr says my risk of having a baby with a trisomy is 1/9 (I'll be 42 when the baby is born).
I would really appreciate your opinion on these results.
Thank you so much.

Natalia Castano
At Tue Jun 03, 09:05:00 PM 2008, Naty said…

Dear Dr T., I wrote you yesterday regarding the results of my Integrated test. Today I went to the Dr. and I was able to get a copy of them. Those results were given to me by phone and it seems that in my confusion I didn't write them down well.
These are de correct results:
N.T: 1.6
PAPP-A: 0.35 mlU/ml
hCG: 69833 mlU/ml

I would really appreciate your opinion on These results.
We are vey worried.

Thank you so much and God bless you!

Natalia Castano
At Wed Jun 04, 05:50:00 AM 2008, Anonymous said…

Dear Dr T,
I am wondering if you can shed some light on my situation
Age: 26
Natural Conception
Papp-A 0.43 IU/mL
BMI 26.5
HCG's: 3w 6d - 58
4w 1d - 140
All of my u/s have dated me correctly with an EDD of Oct 2/08
All tests for abnormalities have come back negative with very low risk.
I had a lot of first trimester bleading and some second trimester bleeding with large clots.
I am supposed to start u/s every two weeks starting at week 28 (I am 23w now). That seems so far away, should I have them sooner?
What are the complications associated with the low Papp-A now that abnormalities are pretty much ruled out.
Thanks for your help,
Erin
At Wed Jun 04, 01:55:00 PM 2008, Anonymous said…

What a blessing that you attend to the many questions we have at a very confusing and scary time. Thank you in advance. Just got my results from a Sequential Screen today and have not had genetic counseling yet. This is my first pregnancy a month after a chemical pregnancy. I am 37 and will be 38 when the baby is born. Here are my results:
Gest. age- 11.3 week
NT- 1.08 MoM
PAPP-A .26 MoM
hCG- .87 MoM
DS screening risk- 1:46
age risk- 1:97
Trisomy risk- 1:215
age rist- 1:340
I was told that they are not concerned about trisomy. Does that seem right? They are concerned about DS though. We have tried for 2 years to get pregnant and finally did through IUIs with injectibles. The risk of the amnio scares me after all we have been through. I had a surgury to remove 12 fibroids 8 months ago. None were internal. I can see that I do have a fibroid again. Would the surgery or the fibroid affect the low PAPP-A? Do you think an amnio is warranted or should I look into other testing? Did I go in too early?
Thank you so much for your help Dr. You are so kind to be of help to so many you don't even know.
Laura
At Wed Jun 04, 06:58:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Natalia: The NT measurement is perfectly normal as is the hCG. The PAPP-A is low and that combined with your age will probably give you an increased risk for Down syndrome. Let us know what the final result of the risk assessment is and I will give you my thoughts at that time. Best of luck to you! Dr T
At Wed Jun 04, 07:04:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Erin: The low PAPP-A may reflect some abnormality of placentation that has contributed to your bleeding throughout the pregnancy. This could lead to placental insufficiency and growth restriction (and even preeclampsia) earlier than 28 weeks and I would suggest an earlier assessment of the baby's growth with Doppler flow studies under these circumstances by 26 weeks. Ongoing bleeding also increases your risk for an ascending infection that can lead to premature rupture of membranes and/or chorioamnionitis with placental abruption. So the low PAPP-A in early pregnancy may only now be getting you into the problems for which it put you at risk. Best wishes and please let us know how things turn out! Dr T
At Wed Jun 04, 07:13:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Laura: The low PAPP-A and your age are the factors contributing to the increased risk for Down syndrome, BUT as you point out, this does NOT necessarily mean the baby has Down syndrome and the surgery and/or new fibroids might also have contributed to the low PAPP-A if they resulted in a suboptimal place for the placenta to grow. This is a VERY important pregnancy for you and no one can make you have any testing you are afraid of at this point. You are weel within your prerogative to "wait and see", have some other ultrasound studies done later in midtrimester (16 and 20 weeks) before making your final decision regarding an amniocentesis. Best wishes my friend and thank you for your kind comments. Let us know how things turn out! Dr T
At Thu Jun 05, 07:30:00 PM 2008, Naty said…

Dear Dr. T, This is Natalia Castano again. Thank you so much for you opinion on my results.
I have an appointment for an amnio in 5 days (It'll be week 15). Do you think that it is worth the risk?, Shoult I wait to see the results of the second trimester screening and then take the decision of the amnio?. I'm very nervous and I really want to know the health status of my baby.
I appreciate your opinion very much.

Thank you!

Natalia
At Fri Jun 06, 07:17:00 PM 2008, Lana said…

Dear Dr T - more bad news...

Her urine sample tested positive at 7 weeks and I have just signed a consent to recheck her Guthrie test for evidence of CMV antibodies at birth.

She has diagnosed with a mild-moderate unilateral hearing lost during hospital screening and other that. I have not had ANY suspicious syptoms suggestive of any infections during pregnancy.

She scored 9 and 10 on her APGAR and was born at 36 5/7 gestation at 2.2kg. Other than that, she has no syptoms however she is going to a liver US today.

Perhaps we should have screening for CMV - maybe that could have helped?? I am devastated and my husband doesnt want to discuss it until the diagnosis has been confirmed.

If you are able to let me know what knowledge/support base is available that would be great. My paeditatrician doesnt want to discuss the details with me until things are confirmed but with a scientific mind, I want to know the facts and worst case scenarios so I can start to get my head around things.

If it turns out the Guthrie test is negative I can breathe a sigh of relief but until then, I want to be informed.

Thanks in advance, Lana
At Sat Jun 07, 10:02:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Natalia: What did they give as your risk for having a baby with Down syndrome? If I knew that I would be in a better position to make a recommendation regarding the amniocenesis. Dr T
At Sun Jun 08, 11:16:00 PM 2008, Anonymous said…

Thank you Dr. T for your response. So much to consider. After meeting with the genetic counselor, we were reassured some about the risks of the amnio and have not ruled it out. We will wait for the level 2 ultrasound and see if there are any markers.
Do you have any recommendations of questions or things to look for during this scan?
How much stock can we put in the results?
If there are any positive markers we will likely do the amnio. If not, we may not.
Thanks again for your help with this. You are the best.
Laura
At Mon Jun 09, 12:36:00 AM 2008, Sue said…

Dear Dr T,

I am 31 years old, this is my second pregnancy and I did my first trimster scan/test at 12 weeks and the result was horrible to me.
NT: 2.8mm
free beta-hcg: 3.7843 MoM
PAPP-A: 0.4065 MoM
Risk for trisomy 21=1:2
Risk for trisomy 13/18 =1: 1466

I have never seen such a high result and it is very scary. Could it be something wrong with it? I had significnat bleeding at 8weeks (placenta dettachmeent was seen) and then resolved. I have been taking dydrogesterone for 5 weeks. Besides, I was also having a flue during the test. Do all these affects the result of the test?
At Mon Jun 09, 12:38:00 AM 2008, Sue said…

Dear Dr T,

I am 31 years old I did my first trimester scan for my second pregnancy at 12 weeks and the result was very scary:
NT: 2.8mm
free-beta-hcg: 3.7843 MoM
PAPP-A: 0.4065 MoM
Risk for Trisomy 21= 1:2
Trisomy 13/18= 1:1466
I could not believe this as I never seen such a high risk! Does it mean I have 50% chance of having a DS baby?

I had significant bleeding (due to placenta deattachement) at 8 weeks and later resolved and I have been taking dydogesterone for 5 weeks. I was also having flue while doing this test. Could all these affects the result as well? My husband and I are very worried.
At Mon Jun 09, 03:45:00 AM 2008, Sue said…

Hi Dr T,

I am 31 yrs old and I did my first trimester screen at 12 weeks (second pregnancy) and the result shows below.
NT: 2.8mm
Free beta-hcg: 3.784 MoM
PAPP-A: 0.4065 MoM
Risk for Trisomy=1:2
Risk for trisomy 18/13=1:1466
I was terrified with this result as I never seen such a high risk. Does it mean the chance of false positive is low as well?
I had significant bleeing at 8 weeks (Porb due to low placenta) and was then recovered. I was dydrogesterone for 5 weeks and I was having a cold when I did the test. Could all these affect the result as well? Look forard to your advise I am realy terrified by the result.
At Tue Jun 10, 06:47:00 AM 2008, katja said…

Hello dr.T and everyone,

I'm from Belgium and after some researching i'm so glad i finally found a site where women have the same problem as myself.
I'm 35, 14 weeks pregnant now through ivf. I was tested at 12 weeks with what they call over here 'the combined test' for Down first trimester screening, which includes an echo (NT), PAPP-A and free b-HCG, and age risk for Down. These 3 factors are thrown into a computer and then you get a risk factor.
These were the findings :
- CRL : 48 mm
- NT : 1 mm
- NT MoM : 0,77
- b HCG free : 57 mIU/mL
- b HCG free MoM : 1,2
- PAPP-A : 0,565
- PAPP-A MoM : 0,4
- Tris 21(Down)combined risk:1/549
- Tris 21 doubletest (blood) : 1/84
- Tris 18 risk : <1/1000
- Down age risk : 1/212
Last week he did another echo and also saw a nasal bone present.

So, with these findings my Dr suggested i do an amnio, mainly caus of my low PAPP-A and the 1/84 risk. He leaves the choice up to me, which is hard because i don't want to risk harming the baby, we had to go through a lot getting pregnant, and eventhough there is only an 1/200 chance for miscarriage after amnio, there IS a chance. I know it's the only way to rule out the chromosomal abnormalities, but now i learned that a low PAPP-A can mean many other risks as preeclampsia etc, which my Dr even didn't mention!
So now i wonder what i should do best, go through with the amnio or just have regular echo's and follow ups (or both)?
I also had some 'difficulties' in the first weeks, i had an echo at 6w6d, and only an empty sac was seen but no embryo. So my Dr said it wasn't possible nothing was there at that term, and the next week i should return for a curretage, but to his surprise (and mine), something was there after all, 8mm with heartbeat. It kept on growing good since then, so from then on he took the measurements of the foetus to determine the age, and not the actual days i was pregnant. It's been a real rollercoaster ride for me since the beginning, i'm unable to be 'happy' and excited about my pregnancy because of all these factors and i'm just thinking what can go wrong next, but i know i'm not alone..
Anyway Dr, I hope you or anyone can shed some light on this or give me some advice, i would be very grateful!
Greetings from Belgium, Europe
Kat
At Tue Jun 10, 04:52:00 PM 2008, Amy L. said…

Hi Dr. T,

I just got my first trimester screen back (12 weeks) and it is as follows:

NT - .84 (.5 MoM)
HCG - 1.02 MoM
PAPP-A - .65 MoM
My risk ratio by age for DS is 1:330 and after testing is 1:1900.
My risk ratio by age for T-18 is 1:1100 and after testing is 1:10,000.

I am not concerned at this point about DS or T-18, but am wondering about the PAPP-A result. I know a "low" result can indicate promlems with the placenta, but don't know what a "low" result is! Is .65 considered low?

I ask b/c I am already at increased risk for preeclampsia b/c I developed it with my first child. (At 38 weeks and was induced, but BP was extremely high postpartum). I'm just curious about the PAPP-A result increasing my risk of PE even further.

Thanks in advance for your help!!!
Amy L.
At Wed Jun 11, 06:39:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Lana June 6: The important thing at this point is that the hearing loss was recognized. Here is a link to the Center for Disease Control and Prevention website on CMV. It contains a lot of good information - http://www.cdc.gov/cmv/

I have written several posts on CMV over the year and yo might want to check out a few of those. Give little Imani a hug and a kiss for me! Dr T
At Wed Jun 11, 06:44:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Laura June 8: There are many things we look for under these circumstances - major anomalies that are typical of Down syndrome such as an endocardial cushion defect in the heart and duodenal atresia in the bowel - and "soft markers" - the most significant of which are thickened nucahl skin-fold, nasal bone hypoplasia, and hypoplasia of the middle bone of the small finger, as well as, abnormal ratios of head to long bone measurements, renal pyelectasis, and echogenic bowel, among others. I am sure you will be evaluated thoroughly and what that involves is well-known and widely performed. Keep us updated, please, and as always, best wishes. Dr T
At Wed Jun 11, 06:50:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Sue: The results are also sacry to me. The high NT measurement combined with the very high hCG and low PAPP-A are driving your 50:50 chance of having a baby with Down syndrome. All the other things that have happened could affect the results somewhat, but this is one of those circumstances where we would strongly advise an invasive diagnostic study. The bleeding that you had earlier in the pregnancy could have been the result of an attempted miscuarriage of a chronosomally abnormal baby as well. Most babies with chromosomal abnormalities, including Down syndrome, miscarry before the end of first trimester. Good luck to you and let us know what you find out. Dr T
At Wed Jun 11, 06:56:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Kat: If I am reading your test results correctly, your COMBINED risk for Down syndrome is only 1 in 549! That is less than half your age alone risk. I would not recommend the amnio based on the serum markers alone under these circumstances - that's why we do the COMBINED risk assessment, but te choice, in the end is yours. My suggestion would be simply to have a high level ultrasound done at about 18 weeks. If that is reassuring, your risk (based on the combined test result) is halved again (about 1 in 1000)! Best wishes and let us know what happens. Dr T
At Wed Jun 11, 06:58:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Amy L: The results are wonderful. Don't try to second guess the individual components' results. It is the COMBINEF result that is the most reliable estimate of your risk. Besides, the PAPP-A is just fine. Best wishes and get some rest! Dr T
At Fri Jun 13, 04:28:00 AM 2008, Debs said…

Dear Doctor,
I am 34 year old , of Asian ethnicity (Indian) and expecting my second child. My first is healthy 4 yr old boy.
My results for First Tri screening

b-HCG - 1.397 MoM
PAPP-A - 0.357 MoM
My ultrasound was perfect with NT 1.2 mm. My adjusted risk for Trisomy 21 is 1:641 ( due 1:51 for the Biochemical risk).
Should I go for an amnio?
My doctor suggested that for all preactical purposes baby could be without Downs , but I am extremely worried. What is the impact of my having a low PAPP-A.
Thanks
Debanjana
At Fri Jun 13, 08:01:00 AM 2008, Amy L. said…

Just curious ~ how common is it to have a negative screen in the first trimester sequential screen, and then a positive screen when the second part of the sequential is done around 16 weeks?

Is that something you see often?

In my case, 1:1900 for DS and 1:10,000 for T18.
At Fri Jun 13, 08:53:00 PM 2008, Anonymous said…

I just went for my NT test today and my results are a little scary. I am 30yrs old - first pregnancy, normal weight, normal blood pressure, great health with no medical problems or history of birth defects on either side of the family. The measurements of our baby during the ultrasound were all great - nasal bone was seen. The doctor was sure the baby was perfectly normal until my bloodwork came back and my Papp-A level was very low. This has changed our results so drastically of have having a baby with abnormalities.

PAPP-A = 0.19
hcG= 0.92
NT= 1.8 and nasal bone was present
CRL= 64.5mm
Fetal heart rate=159
amniotic fluid=normal

Before the blood work our risk of T.21 was 1:5776 and risk of T.13+18 was 1:8430. The results of my bloodwork have changed those results to T.21 is now 1:75 and T.13+18 is now 1:236.

Can you please let me know what you think? Would you reccomend having an amnio? HELP!! Any advice would be great.
At Sun Jun 15, 08:58:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Debs: I would not recommend an amnio based on the composite test results, but that is entirely your choice. It is the COMBINATION of factors that provdies the most reliable risk assessment, not any one individial parameter. Other reasons for an apparent low PAPP-A are detailed in the above post and numerous responses to comments above as well. But, again, I would not dwell on that alone. There are factors such as ethnicity and diet that probably play into the maternal serum marker results as well. Best wishes and let us know what you decide to do! Dr T
At Sun Jun 15, 09:02:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Amy: It happens often enough that I recommend either you send only the AFP test at 16 weeks (in your case because of your previous history of preeclmapsia) or consent at the outset to a true integrated screen (where you do not get the results from the screening tests until you have had BOTH of them done) - this actually provides a very high predictive value and very low false positive rate. Best wishes for the rest of the pregnancy! Dr T
At Sun Jun 15, 09:58:00 PM 2008, Debs said…

Thanks so much Doctor for taking your and respond. Yes I am not going for the amnio test , rather my doctor said she will be monitoring the fetal growth more closely. I am still worried a bit and praying for the best.

Debs
At Mon Jun 16, 10:44:00 AM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Debs: Thanks for letting us know. My bet is that averything will turn out just fine. Best wishes for the rest of your pregnancy! Write back and tell us about your delivery. Dr T
At Mon Jun 16, 05:38:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To anonymous June 13: I think the results are scary too and I would offer you either a chorionic villus sampling or an amniocentesis depending on how far along you are in the pregnancy. Do you have any other nedical conditions or early pregnancy complications that might have contributed to the low PAPP-A? Best of luck and please let us know what you find out. Dr T
At Wed Jun 18, 09:01:00 PM 2008, Anonymous said…

I am 45 y.o. with a 13 month old healthy baby who had normal NT, 1.12 HcG and 1.1 PAPP-A.

I currently got results at 11 wks 4 days:
NT .85 MoM (1.09mm)
HcG .92 MoM
PAPP-A .70 MoM

This put my age related risk of 1:18 to a 1:150 for DS (good, they thought). I thought the risk would improve MORE given the "normal" results but it is "SCREEN POSITIVE"> Do you recommend a CVS? Or amnio? I seem to see people with worse results with much better risk odds.

Thanks for your help, Susan
At Thu Jun 19, 07:21:00 PM 2008, Anonymous said…

Hello from Canada. What a wonderful resource, thank you Dr T for taking the time to help us all sort things out, I have learned so much from reading all of the posts! So, I just had my FTS, after the ultrasound portion I was told everything looked great, and then like so many others, I was shocked and scared when my blood results and final risk assessment came in. I will turn 40 3 weeks before my due date, and have had 2 healthy past pregnancies (2 amazing daughters!)

12 weeks + 2 days
CRL 71.0
NT 2.3mm
hCG .64 MoM
PAPP-A .26 MoM
nasal bone present

My risk was calculated as Trisomy 21: 1/53 Trisomy 13+18 1/56. This pregnancy has been a bit different than my others. I had what I thought was a miscarriage (bleeding, strong cramping, tissue) at 5 weeks, but a week later to everyones surprise I was still pregnant, an 8 week ultrasound confirmed this. My doctor told me it was possible that I miscarried a twin. Things settled down and then I had some spotting again at 12 weeks. Now I am worried with these results that it may have been an attempted miscarriage due to a chromosomal abnormality. I know I should have the amnio, but I am also worried that if I do, because of all of the bleeding,(already suffered through a miscarriage??) I will be at a higher risk to miscarry after the procedure. Is there a "safer" time to have an amnio? is 16weks better than 15wks; 17wks better than 16wks? This will be my last chance at having another baby and the thought of losing a healthy child from Amnio is frightening. How successful is the 18 week ultrasound in detecting Trisomy? Will a 16wk ultrasound be of any help?
Thanks in Advance, Sorry for the long post
Alberta
At Thu Jun 19, 10:39:00 PM 2008, Yvonne said…

Hi Dr. T ~ it's been helpful today to read your blog after the scary news I received this morning. I would really appreciate your advice esp. since I haven't seen any info on your blog about twin pregnancies and low papp A levels.

Here are my stats:
first pregnancy
fraternal twins via IVF
date of fertilization 4/6
due date 12/28
age 34 (will be 35 at birth)
currently 12.5 weeks

Had sequential screen done last Friday with following results:
beta HCG .79
papp A .15
NT 1.0, .93

The genetic counselor called today with the results and said I had extremely low papp A levels and my risk for Downs Syndrome has gone from 1/200 to 1/25. They recommend an amniocentesis but I'm really scared b/c of the risks associated with twins amnios. What should I do? Can I retest the seq screen in 2nd trimester to see if results improve rather than amnio? Are these results alarming esp with twins? Are there other things that could contribute to my low papp A levels? I have endometriosis and 1 fibriod at the base of my uterus.

Please help me with some data and insight! YS

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Low Pregnancy-Associated Plasma Protein A (PAPP-A) and Pregnancy Outcome

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