Prediction of preeclampsia by a combination of cell-free fetal hemoglobin, cell-free fetal DNA and maternal obstetric history

Background The aim of the study was to investigate the combination of cell-free fetal hemoglobin (cfHbF), total cell-free hemoglobin (tcfHb), cell-free fetal DNA (cffDNA), Pregnancy Associated Plasma Protein A (PAPP-A) and maternal obstetric history as potential markers in first and second trimester, for prediction of preeclampsia (PE) in asymptomatic pregnant women. Methods This was a retrospective case-control study of 589 pregnant women (560 in the control group and 29 with PE in the case group). We used routine blood samples used in screening for chromosomal anomalies and rhesus immunization to analyze the levels of cfHbF, tcfHb, and PAPP-A in gestational weeks 8-14 and levels of cfHbF, tcfHb, and cffDNA in gestational weeks 23-28. Results In first-trimester samples, there was no statistically significant difference between controls, mild PE, and severe PE regarding levels of PAPP-A, cfHbF, tcfHb or cfHbF/tcfHb ratio. In second trimester samples, cfHbF and cffDNA levels were significantly higher in PE cases than in controls. The odds ratio (OR) for developing PE was 4.28 (95%CI: 1.85-9.89) given a cfHbF>90th centile (p<0.001), and 6.55 (95%CI: 2.61-16.46) given a cffDNA level>90th centile (p<0.001). When adjusting for BMI and previous history of PE in a logistic regression analysis, only cffDNA and BMI remained statistically significant (p< 0.001). Conclusion We found a significant association between PE and high levels of cfHbF and cffDNA in second- trimester samples, but no statistically significant difference in first-trimester samples were observed.