Low PAPP-A and Celiac Disease in Pregnancy
Wednesday, November 26, 2008
Kenneth F. Trofatter, Jr., MD, PhD
Kate said...
Dear Dr.T,
I have been following your site and articles ever since my NT (nuchal translucency - combined first trimester screening) and your information, insight and attentive responses to your readers have been exemplary. Thank you SO much for writing and responding to all of us! I am 36 years old with my first baby and currently 16w3d. No history of smoking or drinking. At my NT everything looked good: my Down’s risk was 1:800 and trisomy 18/13 1:7000. I did not need to do an amnio. However my PAPP-A was .44MOM (10th percentile). I also have "suspected" Celiac disease which I will be retested for later.
I have been concerned with this low PAPP-A and when I asked my OB she was not very helpful. So in reading you articles I have gained insight but have further questions:
1) The report said my .44MOM was at 10th percentile...yet I saw many other readers with .4 etc. and were considered 5th percentile (which is a percentile cited as of concern)...am I marginally at 10th percentile and is there a big difference? Should I be concerned?
2) Is there correlation with celiac disease and placental health or low PAPP-A levels? I have read reports of celiac disease causing many of same risk factors associated with low PAPP-A.
3) The other day, I felt a gush of fluid and went to the OB where she tested me for amniotic fluid. She only did a Nitrazine and "thought" all was fine. I revisited PAPP-A levels and their correlation with PROM (premature rupture of membranes)...do you have any insight or advice on this? As a first time mom, I don't even know what a gush of amniotic at 16 weeks might feel like. But moreover...I am concerned about PAPP-A, celiac disease , and PROM.
Many thanks Dr. T!
To Kate:
Let me briefly answer the first and third questions before spending more time with the second in another post. Multiples of the median (MoM) are a measure of how far an individual test result deviates from the median. The ‘median’ is the middle of a distribution: half the scores are above the median and half are below the median. It is less sensitive to extreme values than the mean and this makes it a better measure than the mean for highly skewed distributions. The median is found by arranging all the observations from lowest value to highest value and picking the middle one. MoM is commonly used to report the results of medical screening tests, as is done with the concentrations of the maternal serum markers in both first and second trimester screening tests during pregnancy, where the median is highly variable and dependent on the gestational age. This allows comparison between laboratories and helps to ‘standardize’ interpretation of tests for sake of comparison that may be performed differently in different laboratories. In your case, the MoM for your PAPP-A value at 16 3/7 weeks is 0.44. This is less than half the median for that gestational age and places you between the 5th and the 10th percentiles, but this is not what we consider to be extremely low as would be the case at the 1st percentile. In your case, I would not see that as cause for panic!
All that said and done, as we have discussed in previous posts, the further the PAPP-A is below the median, the greater the risk is for certain pregnancy-related complications such as intrauterine growth restriction, premature labor, unexplained fetal demise, pregnancy-induced hypertensive disorders, and cesarean delivery. However, on an individual basis, the absolute risk is difficult to predict and some women with extremely low PAPP-A values have none of these complications. In the case of preterm delivery, a recent article by Spencer and colleagues (Ultrasound Obstet Gynecol 2008;31:147-52) concluded that women with PAPP-A levels in the range of yours had about twice the risk of delivery before 37 and 34 weeks.
You do raise an interesting question though and that is related to the risk of premature rupture of membranes (PROM) and low PAPP-A. I had not heard, or even thought, about that association before you raised the question. Certainly, premature labor and delivery in general is often preceded by PROM, but in the case premature delivery in association with a low PAPP-A, we tend to think more in terms of this being necessitated by fetal and/or maternal complications. Interestingly, I did find and article by She and colleagues (Taiwan J Obstet Gynecol. 2007:46:242-7) that reported that low maternal serum levels of pregnancy-associated plasma protein-A during the first trimester are associated with subsequent preterm delivery with preterm premature rupture of membranes and the authors concluded that this may be the result of “a trophoblast invasion defect in the maternal-fetal interface” which sets up the series of events leading to both PROM and preterm labor.
So Kate, thanks for the great questions and we will continue with your concerns related to celiac disease and pregnancy in our next post. And, to all our readers, have a very HAPPY THANKSGIVING!
Labels: celiac disease, PAPP-A
12 Comments:
At Thu Nov 27, 11:44:00 PM 2008,
Anonymous said…
Hi. I am 33 years old, I will be almost 34 when I give birth. I will be 22 weeks on Monday. With my 1rst trimester results I had a 1 in 7,000 chance of having a child with Downs. Both my 12 week sand 20 week ultrasounds were normal. But with my quad screening I have a 1 in 290 chance of having an baby with Downs, I wish my doctor would have informed me of these results earlier, but because the quad results weren't positive, she didn't feel the need. I was VERY concerned with a number like 1 out of 290. My doctor saw I was nervous and suggested I have an amnio. I know it's late, but I am very concerned with both alternatives: having a baby with Downs and miscarrying a healthy baby.
Is the number 1 out of 290 high for my age?
Is it worth having an amnio to alleviate my worry?
I obviously have to make a decision right away.
Thank you for your thoughts,
Cammy
At Thu Dec 04, 07:19:00 PM 2008,
Anonymous said…
Dear Dr. Trofatter,
I am 33 years ago. I have a lovely 6-year old daughter. Now I am 16-week pregnant. I had a missed miscarriage 3.5 years ago and I had a D&E afterwards. Before the surgery, I had amnio done. They found the diseased fetus had down syndrome. During that pregnancy, I could feel there was something wrong. For my current pregnancy, I have been felt all well from the first day. But the first trimester screen gave me a risk of 1:60 for DS. The genetic counselor told me the factored into my previous down syndrome pregnancy. I had my 2nd –level ultra-sound done yesterday. They did not find any markers. I was wondering it is true I have such a big risk? Should I have amnio done? I really don't want loose this baby. Looking forward to your response.
At Sun Dec 07, 07:16:00 AM 2008,
Anonymous said…
Dear dr. T,
I had a misscariage at 1st of May 2008. I was pragnant for about 2,5 months and there was no heart beats.
I am now pregnant for 3 months and I made CMV and HERPES SIMPLEX 1 and it was upper limits. I had some brown blood (some drops) in 6th and 9th week and I had some drug of progesteron.
My first trimestre screening are:
- fb-hCG 1.12 MoM
- PAPP-A 0.58 MoM
- Nuchal translucency 1.3 mm
- CRL 51mm
- Gestational age by CRL 11+4
RISK AT TERM
- Biochem risk + NT 1:4615
- Double test 1:954
- Age risk 1:701
- Trisomy 18 + NT <1:10000
Nasal bone seen and other organs are all right.
I will be 32 years of february 2009.
I have a question for You because I am not sure if I need to do AMNIO because here in Serbia doctors are saying there is no need for AMNIO in my case.
Thank you in advance and I am looking forward to hearing from You (neja@neobee.net).
At Mon Dec 08, 03:22:00 PM 2008,
Anonymous said…
Dear Dr. T,
I am 35 and will deliver the baby with 36 yrs. I just did my ultra-screen test and the ultra came back normal (NT=1.5mm), so as the HCG MOM (0.81), but the PAPP-A was very low (0.17). So, they put me in a bracket of increased risk for down syndrome (1:110) where the Trisomy 18/13 was 1:2128 and I am terrified. I don't know what do next and I have not seen my doctor yet (will soon). I am originally from Brazil and my best friend there is an OBGYN and tells me to don't worry with the blood test, he said as long as the NT, nasal bone and venus duct were OK, I should not worry. But that did not help. What do you suggest I do?
Thanks.
Danielle.
At Mon Dec 08, 08:03:00 PM 2008,
Anonymous said…
Dr. Trofatter,
I am currently 14 weeks, 4 days along. I am writing because of a couple of concerns that my OB did not address.
(1) I am 35, and have a history of first trimester miscarriages. I am also suspected to be Type II diabetic.
(2) This is my 5th pregnancy and I have one living child, induced at 39 weeks due to GD. Despite this, she was a small baby, weighing 6 lbs at birth.
(3) My NT scan at 11 weeks, 4 days (which showed fetal age as actually 12 weeks, 1 day) was 1 mm. However, my PAPP-A was 0.44 MoM and Beta-HCG was 1.9 MoM. This put my risk for Trisomy 21 at 1:128 and T-13 and T-18 at 1:9000. I have been told to have the amnio. However, I am wondering if the difference in my due date and the fetal age by ultrasound could have bumped my risk up?
(4) Can diabetes (gestational or Type II) affect PAPP-A or Beta HCG levels?
I have an amnio scheduled for Dec 19, 2008 (at 16 weeks) but am TERRIFIED of losing the pregnancy to miscarriage following the procedure. I am a wreck... this is only the second of my 5 pregnancies to have come this far and I would be DEVASTATED if I lost a "normal" baby because of the amnio.
Do you have any advice for me? I am an EMOTIONAL mess. The procedure will be done by a perinatologist who seems to be pretty experienced but the director of the clinic apparently told my "regular" OB that in their "WORST" year, their risk of amnio related miscarriage was 1:200.
What would you advice me to do if I were a friend or a family member?
Thank you SO much.
-Emotional mess in California
At Tue Dec 16, 03:31:00 AM 2008,
Anutalkies said…
Dear Dr. T
I saw your response to Kate. I have just got my blood test reports wich state that my PAPP-A levels are 0.230MoM and Free B-HCG is 1.210 MoM. The fetal scan was normal. This is my second pregnancy. I did not do this blood test during my first pregnancy so I do not know if my PAPP-A levels were low then. My first pregnancy was a normal delivery and I had no high blood pressure. My baby weighed 2.8kgs at birth. Should I be concerned and should I take any preventive measures ? My fetal medicine doctor who did the scan suggested I take 75 mg of asprin everyday till 34 weeks. My gynacoelogist said it is better to avoid asprin and since my first pregnancy was normal, she told me not to worry. Please advise.
At Tue Dec 16, 03:35:00 PM 2008,
Anonymous said…
Hi Dr. Trofatter,
I am 36 yr old and pregnant second time. I will be 37 yrs 3 months at the term. Right now I am almost 14 weeks. At 12.5 weeks, I went for sequential screening first trimester test and here are the results (not good):
NT = 1.4 mm, CRL=61mm, weight =183, asian
Nuchal trans= 0.87 MOM, PAPP-P =0.39 MOM and hCG=2.52 MOM
Due to high level of hCG, my down syndrome risk is 1 in 17 and trisomy 18 is 1 in 3200. I am very sad and scared. Why hCG levels are high , could it be due to infertility trt i took till 11 weeks and this test was just after 1 week of that? Does that suggest down syndrome really? please help me, advise me...my doctor suggested amnio , want to know ur expert opinion?
At Fri Jan 16, 03:52:00 AM 2009,
OVADUE said…
Dr. T,
Her questions do raise great points!
As you posted with me and others on the "Abnormal Screen Results" and I shared that I had a 0.46 Pappa-A.
I did develop pregnancy related hypertension forcing me into the hospital at 29 weeks til I delivered early due to sudden no growth at 35 weeks.
I would like to find out if I had a low Pappa-A with my son as I had PROM with him and delivered him at 31 weeks.
Keep up the great work, Dr. T! I recommend you to every scared mom I meet!
At Thu Mar 19, 05:33:00 AM 2009,
khadjia said…
Dear Dr.T, I am new to this site. i have always had problems with my pregnancys.out of 11 pregnancys i have 2 children my son was born full term and my daughter was born at 6 months 2 pounds and 6 ounces. in all my pregnancys i have to have a cerclage put in place.in 2007 my water broke at 19wks i was passing large blood clots and had a foul oder. i was put on antibiotics that did not work. in2008 i had another loss at 21 weeks my water broke again. i am currently seeing a specialist he mtold me that a lot of times there is no answer for this problem (there has to be something someone can do) in my pregnancys i also experience a lot of pressure in my abdominal area at or around 3 to 4 months. the doctor i have is o.k but i need someone who is willing to listen to my symptoms and work with me in trying to find a soultion. can you please
help me
At Sun Mar 29, 03:25:00 PM 2009,
tracey said…
Dr. T,
I'm not sure where to email you a question, so I'm hoping you'll see it here.
I gave birth to a healthy baby boy in October 2008.
My prenatal screening had come back looking good, except my PAPP-A level was low.
PAPP-A: 0.34 MoM
Other results were as follows:
NT: 0.62 MoM
AFP: 1.53 MoM <2.50
HCG: 1.13 MoM
UE3:.91 MoM
Inhibin: .79 MoM
My question for you is: I'm 32 and I'd like to have another child. Will the PAPP-A levels continue to drop the older I get? Would it be wise to try sooner than later?
Thank you for your time,
Tracey
At Fri Apr 17, 11:06:00 PM 2009,
BonkersMummy said…
Hello Dr T,
Firstly, It is amazing to see how much time you give to all of us worried mums, thankyou so much. I hope I am approaching you through the right avenues but I am hoping you can give me some information that I am struggling to find.
My recent 12 week combined screening came back as:
Free Beta HCG .48 MoM
Papp A .29 MoM
Which translates to 1:2338 rate for trisomy 21 and a 1:264 for Trisomy 18. My OB discussed the elevated trisomy 18 risk with me and was happy with my decision to wait for morphology scan at 19 weeks. Since recieving a copy of the report I have been delving further into the results and was suprised that he didnt mention the other risks that the Low Papp A can indicate. Can you please tell me from these numbers what percentile I am in and how much the increased risk is for other issues (restricted growth, pre ecplamsia etc)
With sincere thanks,
Michelle-Sydney Aus
At Mon May 11, 10:50:00 PM 2009,
Anonymous said…
Hi Dr T,
I don't know if you are still answering queries on this site, but I hope so. I am 28yo and currently 15wks pregnant. It's my first pregnancy. I belatedly got the detailed results of my Nuchal Translucency and Blood tests and was shocked to find that my odds of having a baby with Trisomy 21 are 1:584. I realise that this result is usually assessed as 'low risk' but I want to know why my chances are worse than other people my age (I was expecting at least 1:1000)
The details are:
12wk1d
CRL 57.8mm
NT 2.0mm
free Beta HCG - 1.3400 MoM
PAPP-A - 0.5000 MoM
All I can see is that perhaps my PAPP-A results are a bit low?
I have been sick with worry since I have gotten these results and am considering having an amnio but frightened by the risks. What is your opinion?
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