Efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12, pregnancy-associated plasma protein A, and maternal characteristics in the prediction of preeclampsia

OBJECTIVE: To estimate the efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A) and maternal characteristics in the prediction of pre-eclampsia. METHODS: This is a prospective cohort study of patients presenting for first-trimester aneuploidy screening between 11-14 weeks’ gestation. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices (PI) were calculated. Outcomes of interest included pre-eclampsia, early pre-eclampsia, defined as requiring delivery at <34 weeks’ gestation, and gestational hypertension. Logistic regression analysis was used to model the prediction of pre-eclampsia using ADAM12 multiples of the median (MoM), PAPP-A MoM, and uterine artery Doppler PI MoM, either individually or in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves (AUC) were used to compare the screening efficiency of the models using non-parametric U-statistics. RESULTS: Of 578 patients with complete outcome data, there were 54 (9.3%) cases of preeclampsia and 13 (2.2%) cases of early pre-eclampsia. Median ADAM12 levels were significantly lower in patients who developed pre-eclampsia compared to those who did not. (0.81 v. 1.01 MoMs; p<0.04) For a fixed false positive rate (FPR) of 10%, ADAM12, PAPP-A, and uterine artery Doppler in combination with maternal characteristics identified 50%, 48%, and 52% of patients who developed pre-eclampsia, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. CONCLUSION: First-trimester ADAM12, PAPP-A, and uterine artery Doppler are not sufficiently predictive of pre-eclampsia. Combinations of these parameters do not further improve their screening efficiency