Photo Credit: Svitlana Hulko
Findings published in Clinical Epigenetics underscore the impact of differentially methylated regions in pregnancy complications, including preeclampsia.
“Previously, aberrant DNA methylation due to placental hypoxia has been identified as a potential marker of placental insufficiency and, hence, potential (future) pregnancy complications,” researchers wrote in Clinical Epigenetics. “The goal of the Early Prediction of prEgnancy Complications Testing, or the ExPECT study, is to validate a genome-wide, cell-free DNA (cfDNA) methylation strategy to diagnose preeclampsia accurately. More importantly, the predictive potential of this strategy is also explored to reliably identify high-risk pregnancies early in gestation.”
The longitudinal study included sequential blood samples from pregnant people who experienced uneventful as well as complicated gestations to determine the methylation dynamics of cfDNA during the pregnancies.
Impact of Gestational Age on Methylation Patterns
In the symptomatic cohort, which involved a “diagnosing disease approach,” investigators selected 23 samples from 23 cases of severe preeclampsia. All samples were taken 24-37 weeks of gestation (average gestational age (GA), 31.6 weeks). Researchers also selected 49 samples from 49 control patients who had uneventful pregnancies with no heightened risk (average GA, 31.0 weeks).
Following the onset of maternal symptoms, cfDNA blood samples from cases (n=27) were obtained; control samples (n=50) were obtained at a similar GA.
The 4.5 million unique methylation loci identified had an average of 4.01 million unique CpG sites per sample. To increase the overlap in covered methylation loci between samples, methylation values were smoothed. To further improve the power of the analysis, the methylation loci were clustered according to position. A custom coordinate-based clustering method identified 367,429 unique CpG clusters.
Following batch correction, an overall hypomethylation was seen with symptomatic preeclampsia samples versus controls (estimated difference, 0.032; 95% CI, 0.02–0.043).
“We observed a clear impact of the gestational age on the methylation patterns and, therefore, computed [differentially methylated regions (DMRs)] separately in the different groups, using the diagnostic approach using symptomatic samples and the predicting approach using presymptomatic samples,” the study team wrote. “After correcting for batch, fetal sex, and gestational age, 53,994 DMRs between symptomatic preeclampsia patients and controls were discovered (P<0.05).”
Insights Into the Epigenetic Landscape
The results provide insights into the epigenetic landscape of placental development, specifically regarding diagnosing and predicting preeclampsia, according to the study team.
“Our findings offer a significant understanding of DMRs linked to pregnancy complications, providing crucial knowledge about methylation changes at specific genomic regions,” investigators noted.
Further, the findings underscore the potential impact of ctDNA, “suggesting the potential to integrate this non-invasive approach into routine prenatal care.”
