Early Pregnancy Levels of Pregnancy-Associated Plasma Protein A and the Risk of Intrauterine Growth Restriction, Premature Birth, Preeclampsia, and Stillbirth

Abstract

The risk of adverse perinatal outcome among 8839 women recruited to a multicenter, prospective cohort study was related to maternal circulating concentrations of trophoblast-derived proteins at 8-14 wk gestation. Women with a pregnancy-associated plasma protein A (PAPP-A) in the lowest fifth percentile at 8-14 wk gestation had an increased risk of intrauterine growth restriction [adjusted odds ratio, 2.9; 95% confidence interval (CI), 2.0-4.1], extremely premature delivery (adjusted odds ratio, 2.9; 95% CI, 1.6-5.5), moderately premature delivery (adjusted odds ratio, 2.4; 95% CI, 1.7-3.5), preeclampsia (adjusted odds ratio, 2.3; 95% CI, 1.6-3.3), and stillbirth (adjusted odds ratio, 3.6; 95% CI, 1.2-11.0). The strengths of the associations were similar when the test was performed before 13 wk gestation or between 13 and 14 wk gestation. In contrast, levels of free beta-human CG, another circulating protein synthesized by the syncytiotrophoblast, were not predictive of later outcome in multivariate analysis. PAPP-A has been identified as a protease specific for IGF binding proteins. We conclude that control of the IGF system in the first and early second trimester trophoblast may have a key role in determining subsequent pregnancy outcome.

Ultrasound and Biochemical First Trimester Markers as Predictive Factors for Intrauterine Growth Restriction

“…β-hCG is not directly related to fetal growth, but may be reduced due to placental insufficiency. The extent of β-hCG reduction in SGA fetuses is controversial as some studies show a relation and other do not [8,[17][18][19]. The data from this study confirm a relationship between low levels of β-hCG and SGA (p < 0.001).…”

Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

“…There is a modest increase in LR with decreasing levels of PAPP-A and in the presence of a normal karyotype such low levels, in addition to being an indicator of increased risk for preeclampsia, also indicated increased risk for other adverse pregnancy outcomes (Spencer et al, 2006a(Spencer et al, , 2007a. The presentation of data in terms of LR curves at any level of PAPP-A MoM is likely to be a more useful aid to counselling than the point estimates from previous studies Smith et al, 2002;Yaron et al, 2002;Dugoff et al, 2004;Spencer et al, 2005b), which are summarised in Table 2.…”

“…Several recent studies have shown an association between low first-trimester maternal serum pregnancy associated plasma protein-A (PAPP-A) levels and the subsequent development of pregnancy complications, including pre-eclampsia Smith et al, 2002;Yaron et al, 2002;Tul et al, 2003;Dugoff et al, 2004;Krantz et al, 2004;Spencer et al, 2005aSpencer et al, , 2006aSpencer et al, ,b, 2007aCowans and Spencer, 2007).…”

Prediction of the preeclampsia: a view of biochemical markers

“…But the screening performance is extremely low when used as a single biochemical marker and the predictive rate is only about 10-20 % [14]. Several studies denoted low first or second trimester serum PAPP-A value is predictive and diagnostic biochemical marker of preeclampsia [14][15][16][17][18][19][20][21][22][23]. First trimester serum PAPP-A is low also prior to other pregnancy complications, such as in pregnancies developing fetal growth restriction, spontaneous miscarriage placental abruption, preterm birth and stillbirth and gestational diabetes [15,16,20,23].…”