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.