Prediction of pre-eclampsia combining NGAL and other biochemical markers with Doppler in the first and/or second trimester of pregnancy. A pilot study.

Grigorios A. Karampas a,1,*, Makarios I. Eleftheriades a,b, Konstantinos C. Panoulis a, Myrto D. Rizou c, Alexander D. Haliassos c, Dimitra K. Metallinou d, George P. Mastorakos e, Demetrios A. Rizos a,f

a Second Department of Obstetrics & Gynecology, Medical School, University of Athens ‘‘Aretaieio’’ Hospital, Athens, Greece
b ‘‘EmbryoCare’’, Fetal Medicine Unit, Athens, Greece
c ‘‘Diamedica SA’’, Clinical Chemistry Laboratory, Athens, Greece
d Department of Midwifery, Faculty of Health and Caring Professions, Technological Educational Institute of Athens, Athens, Greece
e Endocrine Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, University of Athens, Athens, Greece
f Hormone Laboratory, ‘‘Aretaieio’’ Hospital, Athens, Greece

Objective: To determine the performance of maternal characteristics, Doppler and a set of biochemical markers for pre-eclampsia (PE) screening at 11 + 0 to 13 + 6 and 20 + 1 to 25 + 6 weeks’ gestation. Study design: Prospectively enrolled women at 11 + 0 to 13 + 6 and 20 + 1 to 25 + 6 weeks. Maternal characteristics, uterine artery pulsatility index (UtA-PI), ductus venosus pulsatility index (DV-PI) and serum biomarkers including pregnancy associated plasma protein – A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), s-Flt-1/PLGF ratio, asymmetric dimethylarginine (ADMA), matrix metalloproteinase 9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and MMP-9/NGAL complex were recorded. Results: Combination of NGAL and BMI in a logistic regression model detected 70% of PE in the first trimester (p = 0.001). Including UtA-PI and DV-PI in the model sensitivity reached 77.8% with 96.6% specificity (p = 0.004). Combination of second trimester NGAL and s-Flt-1/PLGF ratio yield specificity 100% (p = 0.001). Combination of second trimester UtA-PI with first trimester NGAL, BMI and age detected 80% of PE with specificity 91.9% (p = 0.001). Conclusion: Combination of NGAL, maternal characteristics and Doppler parameters in the first and/or second trimester can detect a consistent number of PE pregnancies. NGAL is a potent new biomarker for the prediction of preeclampsia.

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