The Science Behind the PreTRM® Test

Until recently, clinicians have had limited resources for predicting the risk of spontaneous preterm birth. Traditional indicators of increased risk — such as short cervical length and a positive history for previous spontaneous preterm birth — fail to detect 80% of spontaneous preterm births.

The Need for an Accurate and Reliable Risk Predictor in the Clinical Setting

Given the limitations of current risk factors to predict the risk of premature birth, scientists at Sera set out to discover biomarker prediction to develop a test that would be:

• Accurate and reliable at identifying pregnancies at increased risk of spontaneous preterm birth
• Performed early enough in pregnancy to be able to improve outcomes
• Minimally invasive
• Timed to coincide with planned obstetrical visits

The PAPR Study: Discovery and Validation

The groundbreaking Proteomic Assessment of Preterm Risk (PAPR) study1, published as an Editor’s Choice article in American Journal of Obstetrics and Gynecology, was conducted to discover, verify, and validate protein biomarkers in the serum of pregnant women. 

Based on best practices for “omics” research, PAPR enrolled 5,501 pregnant women at 11 Institutional Review Board (IRB)-approved sites across the United States. Blood draws were performed weekly at 17-28 weeks’ of gestation and samples were analyzed using proteomics, bioinformatics, and multidimensional data analysis.

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The Value of the PreTRM Test in Prenatal Testing

Background on Proteomics

Proteomics is a rapidly evolving field of systematic, high-throughput protein analysis. Using mass spectrometry to rapidly analyze peptides allows scientists to take a deep dive into the proteins expressed during pregnancy.

Why Proteomics?

Protein expression is the biology of pregnancy.

• Proteins provide a snapshot of the state of each pregnancy. Analyzing expressed proteins provides functional information about each individual pregnancy at a specific point in time. Proteomics goes beyond inheritance (genetics and genetic mutations) to allow direct measurement of protein expression and gain insight into the pathophysiology of preterm birth.

• Proteins are measurable. Unlike other possible analytes, proteins are stable and measurable using a blood draw and analysis with mass spectrometry technology.

• Proteins reflect the functions of specific cells. Proteins regulate all cell functions and may be over- or under-expressed based upon an individual’s health status. This information can be predictive of future health risk, even much earlier than the onset of preterm birth symptoms.

Discovery of Biomarker Prediction

Determining Key Proteins

After a rigorous empirical process, researchers discovered that two proteins combined with biometric variables accurately predict spontaneous preterm birth in asymptomatic singleton pregnancies.

References

1. Saade GR, et al. Development and validation of a spontaneous preterm delivery predictor in asymptomatic women. Am J Obstet Gynecol. 2016 May;214(5):633.e1-633.e24.
2. Sitar T, et al. Structural basis for the inhibition of insulin-like growth factors by insulin-like growth factor-binding proteins. Proc Natl Acad Sci USA. 2006 103: 13028-13033.
3. Grishkovskaya I, et al. Resolution of a disordered region at the entrance of the human sex hormone-binding globulin steroid-binding site. J Mol Biol. 2002 318: 621-626.