Serum pregnancy-associated plasma protein-A in the three trimesters of pregnancy: effects of maternal characteristics and medical history

Abstract

Objective: To define the contribution of maternal variables which influence the measured level of maternal serum pregnancy-associated plasma protein-A (PAPP-A) in screening for pregnancy complications.

Methods: Maternal characteristics and medical history were recorded and serum PAPP-A was measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of PAPP-A were determined from a linear mixed-effects multiple regression.

Results: Serum PAPP-A was measured in 94,966 cases in the first trimester, 7785 in the second trimester and 8286 in the third trimester. Significant independent contributions to serum PAPP-A were provided by gestational age, maternal weight, height, racial origin, cigarette smoking, diabetes mellitus, method of conception, previous pregnancy with or without pre-eclampsia (PE) and birth-weight Z-score of the neonate in the previous pregnancy. The effects of some variables were similar and those for others differed in the three different trimesters. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured level of serum PAPP-A and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates, both in pregnancies that developed PE and in those without this pregnancy complication.

Conclusions: A model was fitted to express the measured serum PAPP-A across the three trimesters of pregnancy as MoMs, after adjusting for variables from maternal characteristics and medical history that affect this measurement.

Keywords: first-trimester screening; pre-eclampsia; pregnancy-associated plasma protein-A; pyramid of pregnancy care; second-trimester screening; third-trimester screening; trisomy 18; trisomy 21.