Inhibin A, activin A, placental growth factor and uterine artery Doppler pulsatility index in the prediction of pre-eclampsia

Abstract

Objectives: To evaluate whether the measurement of maternal serum inhibin A, activin A and placental growth factor (PlGF) at 12 + 0 to 16 + 0 weeks of gestation alone or in combination with second-trimester uterine artery Doppler pulsatility index (PI) is useful in predicting pre-eclampsia.

Methods: This was a case-control study of pre-eclampsia. From pregnant women attending their first antenatal examination at 12-16 weeks we collected serum samples and stored them at - 80 °C. All patients also underwent uterine artery Doppler examination to measure the PI at 22-24 weeks' gestation. We retrieved for analysis frozen samples from women who then developed pre-eclampsia, as well as three control samples per woman, matched for gestational age and storage time. Inhibin A, activin A and PlGF were measured using an enzyme-linked immunosorbent assay (ELISA) by an examiner who was blinded to the pregnancy outcome.

Results: There were 31 cases with pre-eclampsia and 93 controls. Second-trimester uterine artery PI and marker levels were expressed as multiples of the median (MoM). The uterine artery PI was increased in pregnancies with pre-eclampsia compared with controls (mean ± SD, 1.45 ± 0.31 MoM vs. 1.02 ± 0.25 MoM, P < 0.001), as were the level of inhibin A (mean ± SD, 1.57 ± 0.34 MoM vs. 1.08 ± 0.43 MoM, P < 0.001) and the level of activin A (mean ± SD, 1.68 ± 0.38 MoM vs. 1.06 ± 0.42 MoM, P < 0.001). The level of PlGF was decreased in pre-eclampsia compared with controls (mean ± SD, 0.69 ± 0.23 MoM vs. 1.00 ± 0.26 MoM, P < 0.001). Receiver-operating characteristics curves were analyzed for controls and cases and areas under the curve (AUC) were 0.796 (95% CI, 0.712-0.880, P < 0.001) for inhibin A, 0.823 (95% CI, 0.746-0.899, P < 0.001) for activin A, 0.831 (95% CI, 0.752-0.910, P < 0.001) for PlGF and 0.851 (95% CI, 0.783-0.920, P < 0.001) for uterine artery PI. The combination of activin A, inhibin A and PI using logistic regression analysis yielded an AUC of 0.907 (95% CI, 0.830-0.938, P < 0.001) with a sensitivity of 87% and a specificity of 80%. The combination of activin A, PlGF and PI gave an AUC of 0.925 (95% CI, 0.852-0.978, P < 0.001) with a sensitivity of 90% and a specificity of 80%. Combining all four markers gave an AUC of 0.941 (95% CI, 0.891-0.990, P < 0.001) with a sensitivity of 93% and a specificity of 80%.

Conclusion: Early second-trimester serum inhibin A, activin A, PlGF and second-trimester uterine artery Doppler PI may add further information for the prediction of pre-eclampsia. The combination of the three serum markers and uterine artery Doppler PI has the highest prediction value for pre-eclampsia.