Proteomics: How Proteomics Can Predict Preterm Birth Through the PreTRM Test^®

The PreTRM Test for Risk Management is a simple blood test that was developed using proteomics. It is now available to most pregnant women during weeks 18 through 20 of pregnancy.

Learn more about preterm birth.

What is proteomics?

Proteomics is—as one might guess—the study of proteomes. A proteome is a collection of all proteins found in a cell, tissue, or organism at a given snapshot in time. For example, a proteome may be the collection of proteins in a tumor, and another proteome in adjacent normal tissue. A different example of a proteome would be all the proteins found in a sample taken for blood work during a routine doctor’s visit.

Proteins are the building blocks of all organisms needed for cells, tissues, and organs to work properly and work together. They are made up of chains of amino acids and are encoded by the blueprints found in our DNA. Proteins are made by cells in response to changing signals. Signals can come from outside our bodies, such as the “sugar rush” one can get from eating a candy bar. They also happen internally, passing between cells, tissues, and organs, such as your nerve cells communicating the pain of that stubbed toe to your brain.

Why study proteins?

Proteins not only make up our cells, tissues, and organs, they control the functions within and among them. They are constantly being built, changed, broken down, and recycled as part of normal life. Studying the proteome gives us clues about how our bodies are working at any given time. By studying proteins and how they change, we can explore medicine with more precision, getting insights into how the cells in our bodies work and what treatments might help if they are needed.

Our DNA genome contains around 22,000 protein-coding genes. The machinery in our cells that reads and translates gene information into proteins can mix and match it, much in the way we copy and paste text to change a sentence or paragraph. Through mixing and matching, anywhere from 80,000 to 400,000 proteins are made from the information in those 22,000 genes!

What are the three main activities of proteomics?

In proteomics, there are three types of analysis that scientists use:

• Protein-expression proteomics compares different proteomes to see how they vary – for example, comparing proteomes in a tumor versus adjacent normal tissue.
• Structural proteomics looks at the actual structure of proteins and groups proteins into families with similar structures. (The amino acid chains that make up proteins bend and fold into all different kinds of shapes, and these shapes determine how they will work. Think about a hammer versus a chainsaw and the different functions each has.)
• Functional proteomics places proteins into the pathways that carry out the jobs needed by our cells to function properly, much like an assembly line. If a protein isn’t working properly, it can disrupt the entire assembly line. Most of the time, the cells can fix these problems, but sometimes they can result in disease.

What is proteomics used for?

Many areas of medicine use proteomics. Here are just a few:

• Understanding how illnesses develop by identifying protein biomarkers (specific proteins detected in blood or tissue) at each stage of disease
• Making an early diagnosis by finding changes in proteins before any symptoms of illness appear
• Finding targets for new drugs to treat diseases
• Screening patients before treatment to understand how they will respond to drugs
• Developing personalized treatments based on each person’s genetic makeup

For a more detailed explanation of proteomes and proteomics, check out this educational series from the European Molecular Biology Laboratory.

How do researchers do proteomics?

A technique called “mass spectrometry” (MS) is considered the “gold standard” for proteomics research. MS can measure up to hundreds of thousands of proteins from a sample—such as a blood sample from a doctor’s visit—all at once. First, the proteins in the sample are cut up into smaller amino acid chains, called peptides. The MS instrument then arranges the peptides into a readable array, in which each peptide has its own unique spot. When a researcher is studying a protein of interest, she can find and measure that protein by locating its component peptides in their unique spots.

How was a proteomic approach used to develop the PreTRM Test?

Learn more about the limitations of traditional preterm birth risk assessments.

Scientists at Sera wanted to develop a diagnostic tool that would be accurate, reliable, easy to use, and available early enough in pregnancy with the goal of reducing the number of babies born too soon.

Researchers performed an analysis of proteins in the blood serum of 5,501 pregnant women. They discovered that two proteins were linked to a higher risk of preterm birth. The PreTRM Test grew out of this research. It uses this proteomics discovery to assess the risk of preterm birth in singleton pregnancies (pregnancies of only one baby, not multiples) using the ratio of these proteins in the blood.

What proteins does PreTRM measure?

PreTRM measures two proteins that were found to be active early in pregnancy in women who later experienced preterm birth:

• Insulin-like Growth Factor Binding Protein (IBP4): This protein is connected to pathways of fetal growth restriction, placental growth, and nutrient uptake
• Sex Hormone Binding Globulin (SHBG): This protein is connected to steroid levels, stress, and inflammation pathways

Read more about the science behind the PreTRM Test here.

The scientific study to develop the PreTRM Test was called the Proteomic Assessment of Preterm Risk (PAPR) study, which was published in the American Journal of Obstetrics and Gynecology. You can read the full article here.

How can a protein analysis help predict preterm birth through the PreTRM Test?

Several studies tested the protein ratio discovered in the PAPR Study—IBP4/SHBG—to show that this protein analysis can help doctors predict which pregnancies have a higher risk of early delivery.

Performance of a Proteomic Preterm Delivery Predictor in a Large Independent Prospective Cohort (TREETOP)

• TREETOP included 5,011 pregnant patients in 18 sites in the US.
• Researchers confirmed that the IBP4/SHBG ratio was able to predict very early preterm deliveries.

You can read the full article from the TREETOP study here.

Prediction and Prevention of Preterm Birth: A Prospective, Randomized Intervention Trial (PREVENT-PTB)

• 1,191 pregnant women were randomized to receive testing with the PreTRM Test or not be tested.
• Patients whose PreTRM Test showed them to be at higher risk of preterm birth were given special care to prevent serious consequences of early delivery. Those who were found to be at an average level of risk, and patients in the control group, were given standard pregnancy care.
• For the group that received testing, there was a statistically significant reduction in length of stay in the newborn intensive care unit (NICU) – from 45.5 to 6.8 days (an 85% reduction).

Read more about the PREVENT-PTB trial.

Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study

• Researchers analyzed data from patients in the PAPR and TREETOP studies.
• They found that patients found to be at higher risk by the PreTRM Test are at higher risk for a spontaneous preterm birth, longer hospital length of stay, and severe adverse outcomes.

The full results of this study can be found here.

Read more about the clinical studies that support the use of proteomics in preterm birth prevention here.

Why care about proteomics and the PreTRM Test?

Unfortunately, preterm birth is a common and sometimes life-threatening outcome of pregnancy. Thanks to advances in proteomics, the PreTRM test helps women and doctors understand and prepare for the possibility of a premature delivery.

The problem of preterm birth

In the United States, 10% of all babies are born prematurely. While not all preemies have complications, there are a variety of medical risks involved in preterm birth that can last throughout life. Premature birth is the leading cause of infant death and hospitalization.

Often, preterm birth occurs spontaneously, with no clues available in a woman’s medical history or pregnancy exam to signal a higher risk of premature delivery. Recent developments in proteomics have given scientists a new tool to predict the risk of preterm birth.

For more information on preterm birth and its impact on health, check out Premature Birth 101.

How the PreTRM Test provides a new level of information for parents and doctors

The availability of the PreTRM Test for risk management means that many more women and their doctors can find out early in pregnancy if they have an increased risk of premature delivery. With the information from PreTRM, women and their doctors can take action to prolong pregnancy and reduce the negative health consequences.

What can I do to reduce the impact of preterm birth?

There are several steps that doctors can take to help prolong pregnancy and to reduce the risk of serious consequences if your baby needs to be born early. If your PreTRM Test shows a higher than average risk of preterm birth, your doctor will evaluate your pregnancy and find the therapies that are best for you and your baby. Some of the steps may include:

• More frequent appointments with medical team members
• Preterm birth prevention clinic visits
• Ultrasound measurements of cervical length
• Progesterone injections
• Low-dose aspirin
• Corticosteroid treatment
• Cervical cerclage
• Antibiotics
• Tocolytics

Learn more about the steps you can take to prevent preterm birth.

How can proteomics work for my baby and me?

Most pregnant women are candidates for PreTRM. This test can be taken by women who:

• Are 18 years old or older
• Are pregnant with a single baby
• Are not currently in preterm labor
• Are not on progesterone therapy after the first trimester of pregnancy
• Have a pregnancy that is not affected by a genetic condition that is associated with a shortened pregnancy

The test requires a simple blood draw during the 18th week of your pregnancy through week 20. If you qualify for the test, you can ask your doctor to order it for you.

Within about a week of your blood test, Sera will send your doctor a report with information on your individual risk for early delivery. They can discuss your risk with you and recommend steps to modify your pregnancy plans if needed.

For more information on how the PreTRM Test works, check out PreTRM FAQs for parents.

Proteomics is an exciting new field of medicine that is changing many people’s lives for the better. One of the most useful proteomic advances for pregnant women is the identification of the IBP4/SHBG protein ratio and its incorporation into a risk prediction tool for preterm birth.

With the PreTRM Test for Risk Management, pregnant women and their doctors have access to a new level of information to help babies get the best start in life.

To learn more about how PreTRM can offer you and your doctor valuable insight, talk to your doctor today.