Determining gestational age using genome methylation profile: A novel approach for fetal medicine. (12th August 2019)

• Record Type: Journal Article
• Authors: Falick Michaeli, Tal; Spiro, Adam; Sabag, Ofra; Karavani, Gilad; Yagel, Simha; Eventov‐Friedman, Smadar; Cedar, Howard; Bergman, Yehudit; Gielchinsky, Yuval
• Is Part Of: Prenatal diagnosis. Volume 39:Number 11(2019)
• Page Start: 1005
• Page End: 1010
• Publication Date: 2019-08-12
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.5535
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Gestational age determination by traditional tools (last menstrual period, ultrasonography measurements and Ballard Maturational Assessment in newborns) has major limitations and therefore there is a need to find different approaches. In this study, we looked for a molecular marker that can be used to determine the accurate gestational age of the newborn. To this end, we performed reduced representation bisulfite sequencing (RRBS) on 41 cord blood and matching placenta samples from women between 25 and 40 weeks of gestation and generated an epigenetic clock based on the methylation level at different loci in the genome. We identified a set of 332 differentially methylated regions (DMRs) that undergo demethylation in late gestational age in cord blood cells and can predict the gestational age ( r = −.7, P = 2E‐05). Once the set of 411 DMRs that undergo de novo methylation in late gestational age was used in combination with the first set, it generated a more accurate clock (R = .77, P = 1.87E‐05). We have compared gestational age determined by Ballard score assessment with our epigenetic clock and found high concordance. Taken together, this study demonstrates that DNA methylation can accurately predict gestational age and thus may serve as a good clinical predictor. Abstract : What's already known about this topic? Knowing the accurate gestational age of the newborn is essential for the prediction of its clinical course. Presently, there are two main tools for determining gestational age in antenatal life, the use of the last menstrual period and ultrasonography measurements. These tools have major limitations necessitating the need for different approaches. To date, studies have demonstrated a correlation between gestational age and methylation profile using the Ilumina 450 K array system. What does this study add? Whereas to date, the collection of methylation data had been pooled from various centers and deciphered in a retrospective manner, our study is prospective, employing a novel method (reduced representation bisulfite sequencing [RRBS]) for gestational age determination of a controlled sampling. The RRBS protocol provides comprehensive genomic CpG coverage and is performed using small amounts of DNA, making this a favorable method in the clinical setting. Furthermore, placenta samples were used as added control.