OC17.08: Levels of cell free fetal DNA can be used to differentiate between mild and severe pre‐eclampsia, but is not predictive of SGA

Abstract

Objectives: To investigate whether levels of cell free fetal DNA (cffDNA) assessed at 25 weeks gestation when determining fetal RHD status and PAPP-A from the combined first trimester risk assessment for trisomy 21 can identify women at risk of developing pre-eclampsia and SGA neonates. Methods: A population of 964 singleton pregnant RhD negative women with an RHD positive fetus who participated in the antenatal RHD screening programme in the Capital Region of Denmark. All women had a first trimester nuchal translucency scan and a 20 week malformation scan. Gestational age was based on CRL measurement at first trimester screening, PAPP-A was measured at 8–14 weeks. SGA was calculated using the regression equation constructed by Marsal and co-workers. We used a standard dilution curve to calculate the amounts of cffDNA. Results: A total of 38 women developed pre-eclampsia (3.9%), 15 cases of severe and 23 cases of mild pre-eclampsia. The number of neonates born SGA was 51 (5.3 %). The OR of developing mild pre-eclampsia given a cffDNA level below the 5th centile was 4.1 (95% CI: 1.2–13.2) and the OR of developing severe pre-eclampsia given a cffDNA level above the 90th centile was 10.2 (95% CI: 3.4–30.4). SGA was significantly associated with fetal DNA levels above the 90th centile (P = 0.009). Amongst women diagnosed with pre-eclampsia 46% in the group with cffDNA levels above the 90th centile delivered an SGA neonate compared to 7% in the group with cffDNA levels below the 90th centile. Amongst women not developing pre-eclampsia the numbers were 7.1% versus 4.5%. PAPP-A levels below the 5th centile were associated with mild pre-eclampsia, but not with SGA. Conclusions: Cell free fetal DNA is a marker for pre-eclampsia. High levels were associated with severe pre-eclampsia, low levels with mild pre-eclampsia, thus indicating different placental pathologic mechanisms. High levels of cffDNA is a poor marker of SGA independently of pre-eclampsia.