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