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Elevation of total cell-free DNA (cfDNA) in patients with preeclampsia is well-known; however, whether this change precedes the onset of symptoms remains inconclusive. Here, we conducted a nested case–control study to determine the elevation of cfDNA levels in women who subsequently developed preeclampsia. Methylated  HYP2  (m- HYP2 ) levels were determined in 68 blood samples collected from women with hypertensive disorders of pregnancy, along with 136 control samples, using real-time quantitative PCR. The measured m- HYP2  levels were converted to multiples of the median (MoM) values for correction of maternal characteristics. The m- HYP2  levels and MoM values in patients with preeclampsia were significantly higher than in controls during the third trimester ( P  < 0.001, both), whereas those for women who subsequently developed preeclampsia did not differ during the second trimester. However, when patients with preeclampsia were divided based on the onset-time of preeclampsia or 10th percentile birth weight, both values were significantly higher in women who subsequently developed early-onset preeclampsia ( P  < 0.05, both) and preeclampsia with small-for-gestational-age (SGA) neonate ( P  < 0.01, both) than controls. These results suggested that total cfDNA levels could be used to predict early-onset preeclampsia or preeclampsia with SGA neonate.

Maternal total cell-free DNA in preeclampsia with and without intrauterine growth restriction