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Low PAPP-A during pregnancy – Do you need to be concerned?

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When my wife Kathy was pregnant with our second baby, her OBGYN detected that she had low PAPP-A levels. In this article, I will explain what PAPP-A is and why low levels often result in additional tests and monitoring. None of that should freak you out! Scientific studies have yet to establish a clear connection between low PAPP-A and the increased risk of problems during pregnancy.

Pregnancy-Associated Plasma Protein-A (PAPP-A)

Two weeks ago we learned about a new blood test, called Harmony, that could more reliably detect trisomies 21 (Down syndrome), 18, and 13 starting at week 10. The test would also tell us our baby’s gender long before ultrasound-based gender determination takes place. So we decided to do the test, and fortunately, it came back negative for all tested chromosomal abnormalities. Of course, we also did the regular first-trimester blood screening that checks serum biochemical markers such as Pregnancy-Associated Plasma Protein-A (PAPP-A), human Chorionic Gonadotropin (hCG), Placental Growth Factor (PlGF) and Placental Protein 13 (PP13).

Low PAPP-A during pregnancy - what it means and do you need to be concerned?

Ultrasound of Lucas at week 12

Scientists and doctors measure PAPP-A as Multiples of Median (MOM), and earlier studies have suggested that levels =< 0.5 could lead to any of the following conditions:

  • Pre-eclampsia,
  • Small for gestational age (SGA) and
  • Preterm delivery

Kathy had PAPP-A levels of 0.5 MOM, but our doctor told us not to worry. She didn’t elaborate on what PAPP-A exactly was, what medical consequences low levels could have or what we could do if in fact there was an issue and we didn’t ask. Frankly, we focused more on the fact that we’d be having a boy than on something, our doctor said, we shouldn’t be worried about.

But once the excitement had settled, both Kathy and I did some research, and we got concerned when we read about all the consequences low PAPP-A levels could have. We had just enough information to be worried but not sufficient information to understand the situation fully. But instead of wishing that we had never looked up PAPP-A, I was determined to learn enough to either put our minds at ease or at least come up with a strategy on what to do next.

The following day I spent a couple of hours researching the topic. Similar to my approach to the paleo diet, I tried to steer clear of anything that smelled like an opinion and instead I looked for scientific studies on the subject.

The Scientific Community

I found a couple of studies from the early 2000’s supporting the theory that low PAPP-A levels could lead to adverse pregnancy outcomes. Then I found a study that suggests that there is only limited clinical relevance between low PAPP-A and fβ-hCG levels and adverse pregnancy outcome.

Last but not least, I came across a meta-study (a study of existing studies with the goal of detecting a trend), from August of 2015 that states that there is no connection between low PAPP-A levels and an increased risk of pre-eclampsia, small for gestational age (SGA) and preterm delivery. The conclusion of the study is:

First-trimester screening analytes have low predictive accuracy for pre-eclampsia, small for gestational age and preterm delivery. However, the predicted value of first trimester analytes is not worse than that of the second-trimester markers.

It’s important to understand, however, that the study excluded patients with chromosome aberrations or fetal anomalies. In other words, low PAPP-A levels could still be an indication of chromosomal aberrations, unless otherwise ruled out. Because of the Harmony test and nuchal translucency (NT) screenings we had done, we know that our baby boy doesn’t have any chromosome aberrations (with a 97% certainty) and hence the study’s conclusion would apply.

Low PAPP-A during pregnancy

Despite the lack of evidence that low PAPP-A levels increase the risk of adverse pregnancy outcome, some pregnancies go differently than planned.

Low PAPP-A during pregnancy - what it means and do you need to be concerned?

Lucas at 11 months (corrected)

My wife delivered our baby boy prematurely at 30 weeks and six days. He spent 57 days in the NICU of Northside Hospital. He is healthy and has developed just like a full-term baby. After his delivery, a pathologist inspected my wife’s placenta to confirm if there was anything wrong with it. Unfortunately, all tests were inconclusive, and we don’t know what caused Lucas’ premature delivery. PAPP-A was likely not the cause, but maybe an indication of another problem. I documented his incredible journey in my article Lucas – NICU to seven months (corrected).

If your doctor diagnosed you with low PAPP-A levels, leave a comment and share your story with my readers!

About the Author Michael Kummer

I was born and raised in Austria. I speak German, English, and Spanish. Since moving to the U.S., I have lived and worked in the greater Atlanta area. In my twenties, I was a professional 100m sprinter. These days I do mostly CrossFit. I'm a technologist and Apple fan. I love science and don't believe anything unless there is proof. I follow a Ketogenic Paleo diet and intermittently fast every day. I'm married and have two trilingual kids. My goal with this blog is to share what I learn so that you can spend time on something else. Check out my latest Diet, Fitness, and Technology articles.

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  • Andrea says:

    My Papp-a was extremly low. 0.01 percentil. I gave birth to a healthy girl week 39. She was 5.650 pounds. Little small but she gain way fast.

    • Congratulations! My wife ended up giving birth at almost 31 weeks – but that’s going to be subject of another blog post :)

      • Jo says:

        Is baby and mum ok and why did your wife delivery early ?
        Congratulations !
        In 15 weeks and have been told I have low Papp a . Very worried and scared . Seeing the consultant a week on thurs to discuss it x

        • Hi Jo!

          Both are fine and doing well fortunately. In our case, my wife’s placenta was aging prematurely and wasn’t providing sufficient nutrients. I wouldn’t worry about low PAPP-A too much – our doctors confirmed that it may not mean anything.

          Good luck!

          • Chloe says:

            I’m researching low pappa as three days ago we gave birth to a sleeping baby boy – our scan Monday showed his heart had stopped – I was 30 weeks , we were told at 14 weeks my pappa levels were low that was it

          • Hi Chloe,

            I’m terribly sorry to hear that and wish you all the strength to process such a terrible loss!

            Have you been under close monitoring by perinatal specialists since they detected low PAPP-A levels at week 14?

            Michael

    • Joanne says:

      Hello I hope you don’t mind me asking but with a Papp a that low how was your pregnancy managed?, mine is 0.08 I have been told my baby is going to die, the hospital have even offered me a termination to speed things up, which I’ve declined, I’m. Wondering are you just very lucky or do they really not know much about Papp a’s ?

      • Hi Joanne,

        we had regular (weekly or bi-weekly) ultrasounds and at some point my wife got admitted to the hospital where they kept a closer eye on her and the baby. So for the last few weeks she was mostly on bed rest. Interestingly enough, the pathology report of her placenta didn’t show any issues such as premature aging, which is what doctors thought our issue would be. So nobody knows what caused our premature delivery but low PAPP-A wasn’t the cause.

        I think science doesn’t understand completely yet how low PAPP-A plays into thus. It’s apparently somehow related but it doesn’t appear to be the primary cause of pregnancy issues.

        Good luck!

        • Sara says:

          I’m currently 31 weeks pregnant and have to have an ultra sound every week until he is born. One week is to check his growth, then the next week is to make sure nutrients is flowing from the placenta to the baby. They say i have to deliver at 37 weeks. He currently only weighs 2lbs 6oz when really he should weigh around 3lbs 2oz. He’s very small and I’m very worried there could be more wrong with him. We did do the Down syndrome testing and that came back negative.

    • Linda says:

      OMG this is really a good news . I am currently 20 weeks and in my first trimester my PAAP A result was 0.06. So I have been booked in with more scans to monitor the growth. I am very worried because of the things I read online . This gave me a bit of reassurance.

    • Sandy says:

      Hello, our son was low Papp A as well. We were part of a study. He carried full term plus a week. He was over 8 lbs. We had no issues with him at all. So in a opinion low Papp A is something that could indicate a problem.

    • Karen says:

      Hey Andrea, I was also tested and my Papp-a came back extremely low. Do you guys have any idea if my age have something to do with the low result? I’m 40 y/o and 19 weeks pregnant. I’m worried but trying to stay positive. I have a scheduled ultra sound 5 days from now. I hope to hear from you.

  • Joanne says:

    My Papp a is 0.08. We have a chromosome normal baby, we’ve been told to prepare for late miscarriage, and fetal death in utero. I am 13 weeks 5 days and worried sick .

    • Hi Joanne,

      I’m sorry to hear that and I can imagine how that feels. We felt the same way, but over here doctors confirmed that low PAPP-A with a chromosomal normal baby may not have any negative impact on pregnancy and studies back that up. However there may be other issues such as a problem with your placenta that you likely won’t see on an ultrasound yet. That was the case with our baby boy who was ultimately delivered healthy at almost 31 weeks.

      I’m surprised that doctors would make such a diagnosis based on just low PAPP-A – but they may see other risk factors. Did you ask them to comment on the study I posted a link to? Mine knew about it…

      Good luck!
      Michael

  • Joanne says:

    To be honest they have stated they really don’t know what the outcome will be for this pregnancy , I have never experienced this before in previous pregnancies. When ever they scan me they said everything is looking as it should , but I still have 6 weeks until my 20 week scan a lot can deteriorate in that time and I’m so scared my baby will just demise which is so sad as its a perfectly healthy baby.but yes they have basically come to this conclusion based on my Papp a level alone. I’ve been told to get on with my life prepare for the worst because if is going to happen it will happen. Are you referring to the link about not worrying about low Papp a levels?

  • Joanne says:

    Also I don’t know if it’s worth mentioning but I came back a high risk for preeclampsia . And that’s also placental issues. I just hope it has the same happy ending that your family has been blessed with.

  • Michelle Korman says:

    Just wanted to add a note of my findings for anyone who is reading this right after they received their results. PAPP-A is a zinc binding protein, and I have not found anyone or any study discussing the possibility of a zinc deficiency effecting either the function of PAPP-A or the blood test result. I am currently speaking to a doctor in Australia to carry out the study. I was breastfeeding my first child when pregnant with my second for 4 months until I received my low PAPP-A result with no other issues, no elevated AFP, no small placenta (if that is the case for you, you may be a real low PAPP-A candidate). I always thought it was the breastfeeding, it was, but my focus was incorrect, the breastfeeding was causing my zinc deficiency that I was unaware of, to get worse. I delivered my 7lb. 13oz daughter naturally at 41.5 weeks against doctors orders, and everything was fine (I even had GBS with no treatment, and she was still fine). If you only have low PAPP-A, buy a zinc tally taste test, or see a naturopath they should have some, it should taste extremely bitter if your zinc levels are normal, for me, it tasted like water, I also have beau’s lines in my nails which is further proof of zinc deficiency. I am now taking 25mg of zinc with a 10th of copper (too much zinc can make you copper deficient). Hope this helps!

    • Hi Michelle!

      That’s mighty interesting! It’s too late for us, but we’ll bring that up next time with our OBYGN.
      Thanks for posting!

    • Beckah N says:

      Hi Michelle,

      I’ve just been told I have low Papp A, only just in the low bracket though at 0.45.
      Im breastfeeding my 21mo and instead of taking my usual pregnancy multi vitamin I’ve been taking a higher dose of folic acid (I’m overweight and my mw recommend it). I’ve not been taking my bf multi vitamins for quite some time, so I’m wondering if this zinc deficiency could be a factor.

      Did you get anywhere with research in to this as I’d be really keen to see how it went/going.

      Many thanks!

      B

    • Mich says:

      I wanted to share my story as I found reading this thread of comments very helpful when I was given my result of low papp-a. At my first trimester screening I had a papp-a of 0.31 MoM, which also caused me to be screen positive for down syndrome. I subsequently had a non-invasive prenatal scan which ruled out downs and a bunch of other genetic abnormalities, but I was still worried about other potential adverse outcomes associated with my low papp-a. After seeing your post about zinc, I started doing some research on zinc deficiency. Although it’s relatively rare in the Western world, apparently it’s more common in vegetarians (I follow a vegetarian diet) because the best sources of zinc are in meat. I then checked the prenatal vitamin I was taking and realized the amount of zinc in it was actually very low, and much lower than the standard multivitamin I had been taking before we started trying to get pregnant. Around 15 weeks pregnant I started taking an additional zinc supplement daily (15mg Zinc + 2mg Copper, as Zinc supplementation can drain your body of copper). I’ll never know if it helped or not, but I’m happy to say that I delivered a healthy baby girl at 41+2 weeks (I had to be induced!), weighing 7 lbs 13 oz. She’s now 6 months old and in the 90th percentile for both height and weight. I hope my story can bring some comfort to people dealing with the stress of a low papp-a diagnosis because things can turn out just fine. It also might be worth trying Zinc supplementation (if your health care provider okay’s it). Good luck to everyone out there.

  • Jo says:

    Just wanted to leave an update as I’m the lady with the low Papp a 0.08. At 19 weeks 4 days my baby was measuring below the 5th percentile, found out we are having a girl but she is showing signs of severe iugr. The consultant said I had done well getting this far in my pregnancy and hopefully the baby can hold on for another 6 weeks , trying to stay positive, but when I read my notes saying fetal demise and miscarriage and early onset iugr. It really isn’t looking good and mine is due to non existent Papp a .

    • Dana says:

      Hi Jo!
      How are you now?

      • Joanne cuzen says:

        Hi Dana not realising what I had done, but I have left a message on Michael kummers website about low Papp a just to update you. Please feel free to message me if you need support . Kind regards Jo. My message has been left under the name of Joanne cuzen

        • maria alvarez says:

          I just got my results also for a low level I think is 5*. I am dying because it is my first baby. I am 17 weeks. the doctor told me not to worried that it could be pre-clancia or something else associated with low grow of my baby. Everything alse is normal. please help

  • Jacquie says:

    Thanks for your research, reading this has put my mind at ease

  • Alonna says:

    Thank you so much for this. I was freaking out, but this was great reassurance that everything will be fine. Thank you again.

  • kelli says:

    Not to panic people but we lost our son last week at 25weeks gestation exactly the day before mothers day and we had a Papp a odlf .25 so it does happen.

    • Hi Kelli,

      I’m very sorry for your loss but appreciate that you shared it with other (expecting) parents by leaving a comment.
      It’s not comparable to your loss, but we too started having issues at week 25, when doctors wanted to deliver our baby. He was ultimately born at 30 weeks and 6 days and surely my wife’s low PAPP-A levels must have gotten something to do with it (I figured), causing the placenta to not provide sufficient nutrients.

      However, the pathology report didn’t indicate any issues with the placenta at all, giving more credibility to the fact that individual cases (like yours and to a degree ours), don’t prove a relationship between low PAPP-A and bad outcomes. That’s were (meta)-studies come in handy, by looking at all studied cases combined.
      Ultimately, it is plausible that low PAPP-A could be an indicator of an underlying problem that could cause bad outcomes, but it doesn’t have to be. There are just as many cases of low PAPP-A that don’t lead to any issues.

      Again, I’m truly sorry for your loss and wish you all the best.
      Michael

  • Dena says:

    I was told that I have a low PAPP-A at my 12 week fetal scan. They said it is a .25 and they want it to be a .5, I am so worried. Everything seemed to check out ok and the baby looked great. Measuring right on schedule. I just want to know what to prepare for and how likely it is for something to happen. I go back to be checked in July and then every 4 weeks after that. I know the chance of something happening is low but I just feel like I am in the dark about it.

  • Joanne cuzen says:

    I just wanted to update the ladies to say I had a Papp a of 0.08 I have previously wrote on here. On the 16 th march we were sent to kings hospital as problems were detected but not only did our baby girl at 21 weeks measure below 3rd percentile but they discovered she had tetralogy of fallot a major congenital heart defect but also that her vermis had not developed so she was diagnosed with dandy walker syndrome , sadly we ended the pregnancy at 22 weeks she was 195 g where most babies her gestation would be 400/450 g. I believe this Papp a testing does have relevance and although my bloods and amnio came back chromosomally normal my babies abnormalities were not detected until a lot later on in the pregnancy. If anyone else is going through this heartbreaking horrendous ordeal please feel free to speak to me on this site.

    • Anna says:

      Hi Joanne, I just read your post and I am so sorry for your loss. I also was told that I had a low Papp-A of .21. I was very worried but by OB seemed to think that there wasn’t much reason to worry because everything else looked fine. Unfortunately, in the 22nd week anatomy scan, my baby girl was also diagnosed with severe Dandy Walker Malformation and a small heart defect. We terminated at 23 weeks. She was just under a pound, so not far from expected weight. Like you, all genetic tests were normal. The Papp-A was the only number that was low. I see your post is over a year old and am wondering how are you doing? Wishing you the best.

  • Zoe says:

    I had low Papp-a and was not offered additional growth scans. My baby died in utero at 36 weeks. I think the main point here is that low Papp-a can be indicative of potential issues later on, and these issues are entirely manageable, particularly by the third trimester, if they are in fact managed. Unfortunately mine were not. So I would encourage all mums with this low papp-a result to push for extra monitoring as sadly not every OB thinks it necessary.

  • RIANNA says:

    Hi Thanks for all your helpful comments and information about low PAPP-A. I have been told I have low PAPP-A and my NIPT test has come back normal. I will be seeing consultant soon to discuss a management plam. Is there anything I can do to increase PAPP-A levels? like change my diet? I am prescribed asprin to take until the end of my pregnancy.

    • According to our OBGYN, there is nothing you can do to influence your PAPP-A levels but it doesn’t hurt to double check with your doc.

      • Diana says:

        That is not true . my doctor advise to take a low dose of aspirin until baby is born. Please discuss this with your doctor .

        • Hi Diana,

          And I recommend following your doctor’s orders as it probably won’t hurt. But I haven’t seen any peer-reviewed studies that suggest Aspirin has a positive impact on your low PAPP-A.

          I wish you certainly all the best for you and your baby Diana! Remember, your low PAPP-A may not have any negative impact on your pregnancy.

          Michael

          • Erica Lasky says:

            Aspirin wont impact the low papp-a however it will aid in keeping.you bp inder control reducing your risk for pre clampsia

        • Samantha says:

          I was informed that there is nothing you can do to change the low Pappa (I was diagnosed at 12 weeks with it and now 33 weeks pregnant) I was prescribed low dose aspirin during this pregnancy but the aspirin is to help with the chance of pre-clamsia and not the levels of Pappa. There isn’t anything you can do with the Low Pappa except go for regular growth scans and if they find an issue then, then they can address it accordingly.

          And a side note I’m 33 weeks pregnant now and my little guy is growing perfectly so far. I start weekly scans after next weeks appointment as they believe at 34 weeks is when issues can start arising, but the doctors still keep telling me not to worry.

        • Felicia says:

          Aspirin reduces the chances of preeclampsia. I know this because I’m Type 1 Diabetic and high risk for preeclampsia and that’s what I’ve been prescribed.

  • Danielle says:

    I just got diagnosed with low PAPP-A levels today so this is all very new to me, and I found your post very helpful. However, if I am reading this correct from above (“earlier studies have suggested that levels => 0.5 could lead to any of the following conditions:”), doesn’t this say that levels equal to or greater than 0.5? Isn’t it supposed to say less than (=<)? Or is this a fancier symbol for something I'm not familiar with?
    If it's a typo, I just wanted to point it out, if not I apologize and keep up the great writing!

  • Jose A Lopez-Zeno says:

    Fantastic conversation! My two cents are the following:

    1. The most widely accepted cut off for a PAPP-A to be considered low is 5.0 MOM. As with any other screening test in medicine, there will be false positive and negatives when trying to correlate a low PAPP-A with a poor pregnancy outcome.

    2. Any patient with a low PAPP-A and/or a low free BHCG (both are measured for the first trimester screening but not for the Harmony test) should consider requesting a consult with a Maternal-Fetal Medicine (aka perinatologist or high risk obstetrician) for additional evaluation and counseling. There are many really good general Ob/Gyn that promote their practices as also being capable of managing high risk pregnancies and they do so really well, but in this case you want to see a fellowship-trained sub specialist. You can search for one here: https://www.smfm.org/members/search?miles=&page=2&q%5Blast_name_start%5D=&q%5Bsearchable_addresses_city_cont%5D=&q%5Bsearchable_addresses_state_eq%5D=Georgia&utf8=✓&zip_code=

    3. Do not freak out. The great majority of patients with a low PAPP-A will do fine, however the additional consultation with an MFM doctor will help assessing objectively the level of concern.

    4. Do not seek an online consultation nor value online opinions above and beyond the real thing. Go and see a doctor. Yes, everybody can use the available online resources to learn more about a health problem but many times the information obtained will be biased and could lead to assuming the wrong posture. Michael did the right thing by quoting a meta-analysis. Although not without potential statistical problems, meta-analysis are thought to be the best way of assessing the published medical literature. Be aware that meta-analysis are not all-encompassing. The authors decide what papers are to be included in the analysis, which by itself could introduce selection bias.

    5. Do not stay quiet. If you have questions or if you do not understand the problem, say so and keep asking your doctors until you are satisfied with the answers.

    • Thanks Doctor Lopez-Zeno for your medical insight that I am confident, my readers appreciate as much as I do!

      • Jose A Lopez-Zeno says:

        Michael:

        My pleasure! I always look forward reading your blog updates. BTW, the triplets are getting iPhones for their birthday presents. At school, the daughters are using Chromebooks (aka Crummy Books!). They absolutely hate them. Last weekend I took them to the Apple Store and the girls loved the 12″ MacBook in the rose-gold finish. I guess I should be happy I have an all Apple-loving household.

  • Kristen says:

    I was diagnosed with low PAPP-A during my second pregnancy. It was like 0.1 mom. I worried the entire pregnancy. We did many ultrasounds. Everything else was normal with my son. I read so many horror stories about it. My result was normal blood pressure, giving birth after 41 weeks, and having a super healthy 9lb 5oz baby boy. I realize that not all low papp-a women have healthy outcomes, but I wanted to share my own experience to give hope to women who have low papp-a. My husband wonders about the accuracy of the test.

  • Tracy says:

    I also wanted to share that I had low PAPP-A with my pregnancy (my first) 0.22 mom, we did a NIPT (as also had slightly high B-HCG) which showed no chromosomal abnormalities. Had additional scan at 23 weeks which showed “possible notching” on the blood flow of one of my uterine arteries and was recommended to have another 4 scans & possible induction at 37 weeks. After a lot of research and consideration, we declined most of the additional scans, (mainly due to the stress & worry they were causing & given everything else was fine) opting only for one at 36 weeks to check growth & size which was fine, as well as blood flow to the placenta (again fine). my BP was excellent throughout so at 36 weeks we requested and were discharged back to community midwife team & ended up having an awesome home birth at 43 weeks (yes – 3 weeks post EDD!). Our boy was a happy healthy 7lb4oz & is now 5 months and doing fab – Just got his first 2 teeth too!!

    • Hi Tracy,

      I’m glad to hear that you had a good pregnancy and your boy is healthy! Good luck with the teething, our baby boy just started teething as well.

      Cheers

      Michael

  • Jose A Lopez-Zeno says:

    In medicine, we have diagnostic and screening tests. The diagnostic tests are more more expensive, invasive and could lead to procedure-related complications. They are thought to be conclusive for the presence of a medical condition. They are highly impractical to be applied to the general population. They are usually ordered for patients who have had either an abnormal diagnostic test or the presence of multiple risk factors for the condition or disease in question.

    Screening tests are usually inexpensive, easy to perform, not associated to test-related complications and recommended as a test to be performed in the general populations. These tests are supposed to have a high sensitivity and specificity but suffer on their predictive values.

    An example of the above is the Pap smear. It can identify pre-cancerous or cancerous cervical abnormalities. Depending on the type of abnormalities detected on a Pap smear, a diagnostic test could be a biopsy of the cervix, or even a more invasive surgical procedure. As you can see, this is an excellent example of how a diagnostic test would be highly impractical as a substitute to a screening test.

    What is the main limitation of screening test? The false positive rate, meaning the likelihood that the test would be abnormal in the absence of a problem. Back to the example of the Pap smear, many ladies will have abnormal Pap smears during their life but very few will have actual cervical cancer, but still we use Pap smears universally for the cervical cancer screening. The incidence of death due to cervical cancer is currently just a small fraction when compare to what it was before the availability of the Pap smear.

    Now, back to the PAPP-A, it is part of the serology component of the first trimester screening which is used for the risk ascertainment of three trisomies (13, 18 and 21). As outcome data accumulated, researchers realized that in a subgroup of patients with a low PAPP-A (<5 MoM) and/or low freeBHcG (< 0.5 MoM) would be at an increased risk for perinatal complications including gestational hypertensive disorders, fetal growth restriction and other conditions suggestive of "placental problems". Some of these patients also do have abnormalities of uteroplacental blood flow which can be detected by Doppler interrogation of the uterine arteries. The frustrating aspect of the issue at hand is that although low PAPP-A and/or low free BHcG can be used as a screening test for a poor pregnancy outcome, we can not further evaluate such patient with a diagnostic test which will then identify those that for sure will get into trouble, hence the recommendation of serial sonography for monitoring of fetal growth and other parameters.

    Of interest, in England and other countries were the first trimester screening is also offered, as part of the report they not only provide a risk assessment for a trisomy but also a risk assessment for poor pregnancy outcome as suggested by an abnormal PAPP-A and/or free BHcG (abnormal analytes).

    Bottom line, this is all a risk vs. benefit analysis which also should include a cost determination. Back to the Pap smear protocol example, we know that the cost related of these screening and diagnostic tests are completely cost effective and justifiable and clearly live-saving. Maybe in the near future we'll have increased accuracy for the detection of patients at an increased risk for an adverse prenatal outcome, but we should not ignore current abnormal reports on the basis of "a friend who had similar results and everything was fine".

    Footnote #1: All tests do have accuracy, specificity, sensitivity, positive and negative predictive values. There are well established ways of calculating all of these parameters. All of these parameters can have completely different results based on the incidence of the disease that is under consideration. These concepts can be challenging to understand, even to healthcare professionals. Misunderstanding of these concepts can lead to a lot of pain.

    Footnote #2. Biological variability. Not all small people are dwarfs. Not all tall people suffer of giantism. We all nature's manifestation of a Gaussian or normative distribution ("Bell-shaped curve"). The performance of a screening test will depend on the arbitrary assignment of a limit or "cut off" in the Gaussian distribution. So, if we have a Gaussian distribution of adults' heights, people who are under the second or third standard deviation from the mean will include plenty of normal short people but also the majority of skeletal dysplasia that cause dwarfism. Same story with the abnormal analytes of the first trimester screening.

    So, the bottom line is that somebody who had an abnormal screening test but the disease never develop should not become a paladin against the implications of an abnormal test. All abnormal screening tests require additional ascertainment. Such additional evaluation could require additional consultation with a sub-specialist.

    Disclaimer: Any typos are the responsibility of the auto-spell check.

    ;-)

    • Sarah says:

      This is the most helpful comment I have come across and beats the real life explanations I have been given. Thank you!

  • Viki says:

    My doctor told me I have 0.2 PAPP-A, it’s extremely low :( ,
    I am just 14 weeks ,
    I have one healthy son and had one miscarriage as well ,
    Do not know what to expect , just crying…

  • Ruth says:

    my 12 week bloods came back with high risk for Downs, we had Amnio and all was clear (or so I was led to believe). Had 20 week scan, all ok. I was booked in for growth scans due to high BMI and at 28 weeks it was discovered that my baby was very small. It was then they advised me that in fact the flag for Downs was due to Low Papp-A…. I was monitored constantly for 2 weeks and eventually my baby was delivered at 30 weeks weighing 835grams!

    I’m pleased to say nearly a year on and he’s doing so well! We will forever be grateful to the person who booked me in for growth scans – the alternative doesn’t bear thinking about.

    What i’m interested in, is it likely to happen again on my next pregnancy? According to the nurses in NICU if you’ve had one prem, it’s highly likely to happen again. But then a midwife doubted that, as I never actually went into premature labour and it was in fact my placenta that was the issue.

    Just wondered if anyone has any info on future pregnancies?
    Thanks
    Ruth

  • Jose A Lopez-Zeno says:

    Viki:

    Ask your Ob/Gyn to refer you to a board certified Maternal-Fetal Medicine for a consultation regarding the low PAPP-A. Where are you at?

  • Jose A Lopez-Zeno says:

    Ruth:

    Multiple comments:

    1. The amniocentesis screens for chromosomal abnormalities. It can also screen for some genetic disorders depending on the indication for the procedure. You can have a growth restricted baby with a normal amniocentesis. So you were clear for the reason you had the amniocentesis.

    2. The low PAPP-A is a risk factor for Down syndrome but in some patients it can be a marker for poor pregnancy outcome (low birthweight, preeclampsia, etc.).

    3. You did not have preterm labor, therefore you do not have an increased risk for prematurity. You were delivered early because your baby was in trouble. Your pregnancy had reached a point in which your baby was going to do better in the NICU than in the womb.

    4. In a few patients, this issue of low PAPP-A, low birthweight, etc. can happen again in a later pregnancy. A consultation with a Maternal-Fetal Medicine specialist would be advisable for any future pregnancy. You should still have the first trimester screening. If the low PAPP-A were to be present in any later pregnancy, it could help your doctors determine your level of risk.

    5. Please note that in many patients the low PAPP-A can be a “one pregnancy problem”. It is not a contraindication to try again but before doing so, get a preconceptions consult with the M-FM doctor to go over all the potential risks.

  • Ruth says:

    Jose, thank you so much for your response :)

  • Vidya says:

    Hi all,

    Today I went to hospital for my sister 5th month check up. Today our docter recognized that she is having low PAPP-A level of 0.35 .
    We both worried a lot ..kindly help with this . Our doctor gave aspirine tablet,some vitamin d capsule,accu Cal capsule,and some iron tablets..

    Kindly let us know whether this will not lead to anymore problems once we started diagnosing it.

  • Jose A Lopez-Zeno says:

    Vidya:

    You are asking for specific medical advice. I would recommend requesting a consultation with a Maternal-Fetal Medicine specialist to review your very appropriate concerns.

    https://www.smfm.org/members

    Please let me know if I can be of further assistance.