Fruit of the Womb
Fruit of the Womb

Low PAPP-A and Celiac Disease in Pregnancy

One of the reasons I love the comments we get from our readers is that they often make me look at pregnancy-related conditions and complications from a different perspective. I stated from the outset of this blog that I was looking forward to participating in the learning experience with our readers. Such is the opportunity afforded to us by Kate’s concerns below…

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) 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) 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!
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