Proteinuria and Hypertension Are Independent Factors Affecting Fetal DNA Values: A Retrospective Analysis of Affected and Unaffected Patients

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Abstract
Cell-free fetal DNA circulates in the plasma of pregnant women (1)(2)(3). Increased concentrations of fetal DNA have been reported in the plasma of pregnant women with various complications of pregnancy, including preeclampsia (PE) (4)(5)(6), preterm labor (7), invasive placenta(8), hyperemesis gravidarum (9), and aneuploidy(10)(11)(12). We recently reported that fetal DNA in maternal plasma is derived primarily from villous trophoblasts bordering the intervillous spaces, which are filled with maternal blood (13). Because trophoblast damage may be involved in the pathogenesis of PE, it may be possible to use fetal DNA as a marker to monitor the severity of PE. In this study, we assessed the relationship between fetal DNA concentrations in maternal plasma and clinical evidence of PE, such as proteinuria and/or hypertension. We conducted a retrospective study in which the control group included 116 women with uncomplicated male pregnancies between 28 and 40 weeks of gestation. Controls were matched with 45 consecutive pregnancies in which different grades of proteinuria and/or hypertension were observed at the time of blood sampling (28–40 weeks). PE was defined as gestational hypertension (systolic pressure >140 mmHg or diastolic blood pressure >90 mmHg on at least two occasions after 20 weeks of gestation) with proteinuria (>0.3 g/day). Severe PE (SPE) was defined as severe gestational hypertension (systolic pressure >160 mmHg or diastolic blood pressure >95 mmHg on at least two occasions after 20 weeks of gestation) with severe proteinuria (>3 g/day). Fetal growth restriction was defined as an estimated fetal weight 2.0 SD below the mean expected weight for gestational age (GA), as determined by ultrasonographic evaluation. None of the pregnant women had fetal aneuploidy, abnormalities of cord insertion, and/or maternal complications such as systemic lupus erythematosus, diabetes mellitus, or hyperthyroidism. All …