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Cell-free DNA levels predict pre-eclampsia, small for gestational age

06 Aug 2020

Spikes in cell-free DNA (cfDNA) levels may help predict pre-eclampsia (PE) or having a smaller-for-gestational-age (SGA) neonate, a recent study reports.

Researchers conducted a nested case-control study on 29 women with PE and 12 with gestational hypertension (GH). Levels of cfDNA were measured from maternal blood samples using real-time quantitative polymerase chain reaction, with the methylated HYP2 gene as an epigenetic indicator of cfDNA. A parallel group of 78 controls was also included.

During the third trimester, the levels of HYP2 in PE participants was significantly higher than that in controls (59,488 vs 14,969 copies/mL; Wilcoxon rank sum test p<0.0001). Similarly, HYP2 was significantly elevated in PE vs GH (59,488 vs 28,265 copies/mL; p=0.013).

No such difference was reported for GH patients and controls. Moreover, levels of methylated HYP2 were comparable during the second trimester.

Dividing PE patients according to its time of onset, the researchers found that levels of methylated HYP2 were significantly higher in those who developed early-onset PE than in controls (p=0.042). Further disaggregating according to birth weight percentiles likewise showed that HYP2 levels were significantly predictive of an SGA neonate (p=0.032). No such interactions were reported in GH patients.

Moreover, in patients with PE and PE with SGA, total cfDNA levels were elevated early in the second trimester of pregnancy.

“[B]ased on our findings, efforts should continue toward better prediction of PE and [intrauterine growth restriction] during early pregnancy,” the researchers said.

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