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

Department of Obstetrics and Gynaecology (G.C.S.S.), Cambridge University, CB2 2QQ, United Kingdom; Department of Fetal Medicine (E.J.S., A.D.C.), The Queen Mother’s Hospital, Glasgow, G3 8SJ, United Kingdom; and, Institute of Medical Genetics (J.A.C., D.A.A., J.M.C.), Yorkhill National Health Service Trust, Glasgow, G3 8SJ, United Kingdom

Address all correspondence and requests for reprints to: Prof. Gordon C. S. Smith, Department of Obstetrics and Gynaecology, Cambridge University, Rosie Maternity Hospital, Cambridge, CB2 2QQ, United Kingdom. E-mail: . gcss2{at}cam.ac.uk

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 ß-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.

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