Increased fetal RhD gene in the maternal circulation in early pregnancy is associated with an increased risk of pre-eclampsia

Objective To determine whether the fetal RhD gene is present in the maternal circulation in early pregnancy prior to the clinical manifestation of pre-eclampsia. Design This is a nested case-control study. Setting Blood samples were obtained from patients attending for a first antenatal visit. Sample Cases were asymptomatic RhD negative women (n= 23) who subsequently developed pre-eclampsia matched to RhD negative controls (n= 23) for parity and gestational age. Methods Real time PCR using TaqMan primers and probes directed against the RhD gene quantified fetal DNA in the maternal circulation. Main outcome measures Quantity of RhD gene detected. Results As the copy number of RhD gene per millilitre of whole blood at 15 weeks of gestation increased, there was a significantly increased risk of developing pre-eclampsia. There was a graded association between copy number of RhD gene in early pregnancy and severity of disease with controls having 6942, mild pre-eclamptics 83,273 and severe pre-eclamptics 285,793 copies/mL (logscale 3.6, 4.0 and 4.5, respectively). Conclusion Increased fetal RhD gene is present in the maternal circulation in early pregnancy in women who subsequently develop pre-eclampsia and there appears to be a graded response between the quantity of fetal DNA and severity of pre-eclampsia.