Epigenetic Biomarker Signature Predicts the Likelihood of Premature Birth

Researchers have identified an epigenetic biomarker signature for preterm birth that can be used in a clinical setting to predict the likelihood that a pregnant woman might deliver prematurely.

Preterm birth (earlier than 37 weeks) is the major cause of newborn and infant mortality affecting nearly one in every ten live births. Many premature infants face a number of health issues, including cognitive disabilities and cardiovascular problems. Preterm birth has been linked to risk factors such as a twin or multiple pregnancy and preclampsia. Yet, many early births are unexpected, and having a diagnostic test in the first-term of pregnancy could allow caregivers to take steps to delay or prevent a preterm birth.

A study carried out by investigators at Washington State University Pullman, USA) was designed to develop an epigenetic biomarker for susceptibility of preterm birth using buccal cells from the mother, father, and child (triads). An epigenome-wide association study (EWAS) was used to identify differential DNA methylation regions (DMRs) using a comparison of control term birth versus preterm birth triads.

Cheek swabs were obtained from two groups of mother-father-infant triads shortly after the babies were born. In one set of 19 triads, the infants were born prematurely and in another group of 21 triads, the babies were carried to full term. DNA was isolated from the buccal cell collections and analyzed with a methylated DNA immunoprecipitation (MeDIP) procedure to obtain methylated DNA for subsequent sequencing (Seq) for an MeDIP-Seq protocol. This procedure provides a genome-wide assessment of greater than 90% of the genome, compared to approximately 50–70% for bisulfite sequencing, or less than 1% for array analysis.

Epigenetic DMR associations with preterm birth were identified for both the mother and father that were distinct and suggested potential epigenetic contributions from both parents. The mother (165 DMRs) and female child (136 DMRs) had the highest number of DMRs and were highly similar, suggesting potential epigenetic inheritance of the epimutations. The male child had negligible DMR associations. Clearly the female infants’ epigenetic biomarker signature was not used to predict potential preterm birth, but could potentially be used to assess later life disease susceptibility in the individual.

"The signature we found was present in all the parents we analyzed," said senior author Dr. Michael Skinner, professor of biological sciences at Washington State University. "This is likely to lead eventually to a very useful test. We used buccal cells, which are collected by a cheek swab. It is very non-invasive and easy to do. Although we may not be able to fix the problem, if we know that it is going to develop because of these diagnostics, we can treat it. This could help with the transition from reactionary medicine to preventive medicine."

The study was published in the March 1, 2022, online edition of the journal Scientific Reports.

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