Study suggests simple way to predict preterm births
Massachusetts Institute of Technology Research News Sep 13, 2017
Test of cervical mucus may reveal pregnant womenÂs risk of going into labor too early.
The researchers found that cervical mucus from women who delivered their babies before 37 weeks was very different from that of women who delivered later. This type of analysis could offer an easy way to calculate the risk of early labor, potentially allowing doctors to try to intervene earlier to prevent preterm births.
ÂOur prediction is that we might be able to identify risk for preterm birth ahead of time, before labor sets in, said Katharina Ribbeck, an associate professor of biological engineering at MIT and the senior author of the study. ÂDiagnostic tools for this are missing.Â
Ribbeck worked on the study with Michael House, an associate professor at Tufts University School of Medicine. MIT postdoc Kathryn Smith-Dupont is the first author of the paper, which appeared in the September 4 issue of the journal Scientific Reports.
RibbeckÂs lab at MIT investigates the distinctive chemical and mechanical properties of mucus, and how those properties help it to perform many critical roles as part of the bodyÂs first line of defense against infection. Several years ago, Ribbeck began exploring whether changes in cervical mucus might play a role in preterm births. Between 25 and 40 percent of early births are believed to be caused by infections that occur when microbes reach the uterus through the cervical plug, which is made of mucus and normally blocks access to the uterus.
In a study published in 2013, Ribbeck found that cervical mucus from pregnant women at high risk of early labor was mechanically weaker and more elastic than that of low-risk pregnant women. For the new study, she and her colleagues decided to investigate the mucusÂs permeability to small particles. Mucus is formed from polymers known as mucins, and the composition and arrangement of these mucins determine how porous the gel is.
The researchers collected samples from two groups of patients. The low-risk group included pregnant women who came in to their doctors offices for routine visits around 30 weeks and ended up giving birth after 37 weeks. The high-risk group included women who went into labor early, between 24 and 34 weeks. Doctors were able to halt labor in these women, and the samples were taken after they were stabilized. They all ended up giving birth before 37 weeks.
The researchers tested the ability of negatively charged spheres about 1 micron in diameter to travel through the mucus, and found a small but statistically insignificant difference in porosity between the high- and low-risk samples. They then decided to do the same test with charged peptide probes, which are small enough to avoid getting stuck in the mucus network but are sensitive to the biochemical modifications of the mucus. With these peptide probes, the researchers found a significant differences in mucus permeability and adhesiveness: The peptides were able to pass through samples from high-risk women much more easily.
This suggests that cervical mucus from women at high risk for early labor, for reasons not yet known, may be more susceptible to invasion by potentially harmful bacteria and microbes, making it more likely that those women will experience an infection that leads to preterm birth, Ribbeck said. In addition, the altered mucus may be less able to retain helpful immune system components such as antibodies or antimicrobial peptides, which would normally help to combat infection.
ÂMucins display all sorts of immunologically active factors that you may also lose when the adhesive properties change, Ribbeck said.
She suspects that this loss of adhesion might be caused by changes in molecular structure of the mucins, in particular, changes in the number and types of sugar molecules that comprise part of their structure.
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The researchers found that cervical mucus from women who delivered their babies before 37 weeks was very different from that of women who delivered later. This type of analysis could offer an easy way to calculate the risk of early labor, potentially allowing doctors to try to intervene earlier to prevent preterm births.
ÂOur prediction is that we might be able to identify risk for preterm birth ahead of time, before labor sets in, said Katharina Ribbeck, an associate professor of biological engineering at MIT and the senior author of the study. ÂDiagnostic tools for this are missing.Â
Ribbeck worked on the study with Michael House, an associate professor at Tufts University School of Medicine. MIT postdoc Kathryn Smith-Dupont is the first author of the paper, which appeared in the September 4 issue of the journal Scientific Reports.
RibbeckÂs lab at MIT investigates the distinctive chemical and mechanical properties of mucus, and how those properties help it to perform many critical roles as part of the bodyÂs first line of defense against infection. Several years ago, Ribbeck began exploring whether changes in cervical mucus might play a role in preterm births. Between 25 and 40 percent of early births are believed to be caused by infections that occur when microbes reach the uterus through the cervical plug, which is made of mucus and normally blocks access to the uterus.
In a study published in 2013, Ribbeck found that cervical mucus from pregnant women at high risk of early labor was mechanically weaker and more elastic than that of low-risk pregnant women. For the new study, she and her colleagues decided to investigate the mucusÂs permeability to small particles. Mucus is formed from polymers known as mucins, and the composition and arrangement of these mucins determine how porous the gel is.
The researchers collected samples from two groups of patients. The low-risk group included pregnant women who came in to their doctors offices for routine visits around 30 weeks and ended up giving birth after 37 weeks. The high-risk group included women who went into labor early, between 24 and 34 weeks. Doctors were able to halt labor in these women, and the samples were taken after they were stabilized. They all ended up giving birth before 37 weeks.
The researchers tested the ability of negatively charged spheres about 1 micron in diameter to travel through the mucus, and found a small but statistically insignificant difference in porosity between the high- and low-risk samples. They then decided to do the same test with charged peptide probes, which are small enough to avoid getting stuck in the mucus network but are sensitive to the biochemical modifications of the mucus. With these peptide probes, the researchers found a significant differences in mucus permeability and adhesiveness: The peptides were able to pass through samples from high-risk women much more easily.
This suggests that cervical mucus from women at high risk for early labor, for reasons not yet known, may be more susceptible to invasion by potentially harmful bacteria and microbes, making it more likely that those women will experience an infection that leads to preterm birth, Ribbeck said. In addition, the altered mucus may be less able to retain helpful immune system components such as antibodies or antimicrobial peptides, which would normally help to combat infection.
ÂMucins display all sorts of immunologically active factors that you may also lose when the adhesive properties change, Ribbeck said.
She suspects that this loss of adhesion might be caused by changes in molecular structure of the mucins, in particular, changes in the number and types of sugar molecules that comprise part of their structure.
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