I love PUNS and DENS (Patient Unmet Needs and Doctors Educational Needs). It is something I intend to continue until I stop practising medicine, encourages self-reflection, and is an important part of lifelong learning. I recently had a patient who was having additional screening as they had a low level of PAPP-A discovered at routine antenatal screening. She was consulting about something else, but I wasn’t 100% sure of the role of low PAPP-A levels, and poorer outcomes in pregnancy such as pre-eclampsia and low birth weight. We do very little antenatal care in Defence, it being almost exclusively the preserve of the community midwifery team. I was also unsure of the predictive value of the test so, being inquisitive, did a quick literature review. There were a number of papers I found, but this systematic review and meta-analysis seemed high quality and originated from my affiliated University, Birmingham:
I have read it but for the purposes of this blog, asked ChatGPT to summarise the discussion:
Recent research has explored how a specific protein in early pregnancy, called Pregnancy-Associated Plasma Protein A (PAPP-A), might help predict certain pregnancy complications. PAPP-A levels are measured during the first trimester, and this study found that very low levels of this protein can be linked to a higher risk of complications like preterm birth or having a small baby.
However, it’s important to note that while low PAPP-A levels do indicate a higher risk, the prediction isn’t perfect. Most women with low levels of PAPP-A will still go on to have healthy pregnancies, and many who experience complications will have normal levels of this protein.
The study’s strength lies in its robust and thorough approach to reviewing existing research, but there were some limitations. For example, differences in the studies they analyzed led to some inconsistent results. Additionally, the researchers had to simplify their analysis by treating PAPP-A levels as either “low” or “not low,” which can oversimplify the true relationship between PAPP-A and pregnancy outcomes.
The research highlights that while PAPP-A can be a useful marker, it’s not enough on its own to predict pregnancy outcomes. More research, especially studies that look at individual patients’ data, is needed to fully understand how PAPP-A interacts with other factors throughout pregnancy.
Currently, in the UK, PAPP-A is used as part of screening for Down syndrome, but it’s not yet used to predict other pregnancy risks. Before it could be used in this way, doctors would need to be sure that they can effectively intervene to help women identified as high-risk based on PAPP-A levels. For now, the study helps doctors provide better information and support to expectant mothers who have low PAPP-A levels, ensuring they understand what it might mean for their pregnancy.
So there you have it. As I thought, it’s one of those tests where both the sensitivity and specificity are not amazing, but not bad. Indeed, the relationship between placental thickness and PAPP-A levels demonstrated a sensitivity of around 70% and a specificity of around 50% in one study I found. Another study looked at low PAPP-A levels and risk of pre-eclampsia, finding a significant association with low levels (<10th centile). It should be noted, the analysis in this study was not multivariable so there was a risk of confounding variables also having an effect, a point the authors recognise.
I found this patient information leaflet which summarises it nicely.
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