Researchers isolate the culprit in preterm birth

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University of Adelaide researchers have identified a key sensing molecule that controls the timing of birth. The discovery is expected to generate new therapies to prevent preterm labour.

Published this week in the journal Endocrinology, the laboratory study found that activation of the TLR4 molecule is a trigger common to both preterm and on-time labour. As well, TLR4 is essential for successful progression of labour to maximise the baby’s chance of survival.

“Preterm labour, birth at less than 37 weeks gestation, affects 5-13% of pregnancies worldwide. It accounts for 28% of all neonatal deaths and can result in major health consequences for surviving children,” says Professor Sarah Robertson, Director of the University’s Robinson Research Institute and lead author on the study.

“In order to prevent preterm birth, we need to understand the physiological responses which lead to normal on-time birth, and our new research pinpoints a ‘master switch’ that influences the timing of birth.

“We know that several agents can bind and trigger the molecule TLR4 after release from fetal and maternal tissues in late gestation, including proteins that are released from a baby’s lungs just before birth.

“Other molecules that activate TLR4 are produced in the mother’s tissues due to uterine stretch, or when the placenta begins to reach the end of its life.

“However, a local bacterial infection, damage to the placenta due to inflammation, or even multiple pregnancy can result in a surge of agents that activate TLR4 before the expected end of pregnancy, resulting in premature birth,” she says.

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Professor Robertson says this study will ultimately lead to the development of new drugs to assist women at risk of preterm labour.

“This is a surprising finding because TLR4 is generally thought to be involved in the immune response to infection, and had not previously been linked with normal processes in pregnancy,” says Professor Robertson.

“Now that we know how critical TLR4 is in regulating the timing of birth, we can commence testing drugs that target the TLR4 pathway.

“While this is yet to be looked at in a clinical setting, we believe this finding will ultimately lead to methods to effectively protect women at risk of going into labour early,” she says.

This work was supported by project and fellowship grants from the National Health and Medical Research Council of Australia, the Canadian Institutes of Health Research and the Australian Research Council.

(Source: The University of Adelaide, Endocrinology)

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Date Created: August 3, 2015