First-trimester screening biochemical markers (free beta-subunit human chorionic gonadotropin, pregnancy-associated plasma protein-A) and risk of early fetal loss

Abstract

Aim: The aim of this work was to assess the risk of early fetal loss (first trimester of pregnancy, 8-13 weeks of gestation) using the results of first-trimester screening (FTS) biochemical markers independently and combined.

Methods: FTS results of 152 women who suffered early fetal loss were compared to a control group of 150 women with normal pregnancy outcomes. FTS biochemical markers were measured with a Delfia Xpress 6000 analyzer and biochemical risks for Down's and Edward's syndromes were calculated using Prenatal-Lifecycle version 3.0 software. Marker levels were standardized by calculating the gestational-specific multiple of the medians (MoM), further adjusted by maternal age, maternal weight, cigarette consumption and pre-existing type 1 diabetes mellitus. Receiver-operator curves were built to evaluate each marker and its combination.

Results: Our results show that values of biochemical risk of t21 of more than 1 in 310 have a poor sensitivity to predict early fetal loss (31.4%) with a positive predictive value (PPV) for fetal loss of 67.7%. Values of pregnancy-associated plasma protein A (PAPP-A) MoM of less than 0.48 show a sensitivity of 62.1% and a PPV of 84.5% for early fetal loss; whereas for free β-human chorionic gonadotropin, values of MoM of less than 0.44 have a sensitivity of 66.4% with a PPV of 85.3%. A novel algorithm, consisting in the multiplication of both markers, shows for values of less than 0.48 a sensitivity of 83.1%, a specificity of 78.7% and a PPV of 77.1%.

Conclusion: Combined analysis of PAPP-A and free β-hCG appears to be a potential candidate to predict early fetal loss.

Keywords: fetal loss; first-trimester screening; free beta-subunit human chorionic gonadotropin; pregnancy-associated plasma protein A.