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

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Abstract
The risk of adverse perinatal outcome among 8839 women recruited to a multicenter, prospective cohort study was re- lated to maternal circulating concentrations of trophoblast- derived proteins at 8 -14 wk gestation. Women with a preg- nancy-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 deliv- ery (adjusted odds ratio, 2.9; 95% CI, 1.6 -5.5), moderately pre- mature delivery (adjusted odds ratio, 2.4; 95% CI, 1.7-3.5), pre- eclampsia (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 -human CG, another cir- culating 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. (J Clin Endocrinol Metab 87: 1762-1767, 2002)

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