Early Pregnancy Levels of Pregnancy-Associated Plasma Protein A and the Risk of Intrauterine Growth Restriction, Premature Birth, Preeclampsia, and Stillbirth
Gordon C. S. Smith,
Emily J. Stenhouse,
Jennifer A. Crossley,
David A. Aitken,
Alan D. Cameron and
J. Michael Connor
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 recruitedto a multicenter, prospective cohort study was related to maternalcirculating concentrations of trophoblast-derived proteins at8–14 wk gestation. Women with a pregnancy-associated plasmaprotein A (PAPP-A) in the lowest fifth percentile at 8–14wk 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 (adjustedodds ratio, 2.4; 95% CI, 1.7–3.5), preeclampsia (adjustedodds ratio, 2.3; 95% CI, 1.6–3.3), and stillbirth (adjustedodds ratio, 3.6; 95% CI, 1.2–11.0). The strengths of theassociations were similar when the test was performed before13 wk gestation or between 13 and 14 wk gestation. In contrast,levels of free ß-human CG, another circulating proteinsynthesized by the syncytiotrophoblast, were not predictiveof later outcome in multivariate analysis. PAPP-A has been identifiedas a protease specific for IGF binding proteins. We concludethat control of the IGF system in the first and early secondtrimester trophoblast may have a key role in determining subsequentpregnancy outcome.
This article has been cited by other articles:
F. W. Bazer, G. Wu, T. E. Spencer, G. A. Johnson, R. C. Burghardt, and K. Bayless Novel pathways for implantation and establishment and maintenance of pregnancy in mammals
Mol. Hum. Reprod.,
March 1, 2010;
16(3):
135 - 152.
[Abstract][Full Text][PDF]
G. C. S. Smith First-Trimester Determination of Complications of Late Pregnancy
JAMA,
February 10, 2010;
303(6):
561 - 562.
[Full Text][PDF]
J. Wang, Q. Qiu, M. Haider, M. Bell, A. Gruslin, and J. K Christians Expression of pregnancy-associated plasma protein A2 during pregnancy in human and mouse
J. Endocrinol.,
September 1, 2009;
202(3):
337 - 345.
[Abstract][Full Text][PDF]
A. Gruslin, C. E. Cesta, M. Bell, Qing Qiu, M. A. Petre, and A. C. Holloway Effect of Nicotine Exposure During Pregnancy and Lactation on Maternal, Fetal, and Postnatal Rat IGF-II Profile
Reproductive Sciences,
September 1, 2009;
16(9):
875 - 882.
[Abstract][PDF]
H. Nishizawa, K. Pryor-Koishi, M. Suzuki, T. Kato, H. Kogo, T. Sekiya, H. Kurahashi, and Y. Udagawa Increased levels of pregnancy-associated plasma protein-A2 in the serum of pre-eclamptic patients
Mol. Hum. Reprod.,
October 1, 2008;
14(10):
595 - 602.
[Abstract][Full Text][PDF]
H.-w. Yung, S. Calabrese, D. Hynx, B. A. Hemmings, I. Cetin, D. S. Charnock-Jones, and G. J. Burton Evidence of Placental Translation Inhibition and Endoplasmic Reticulum Stress in the Etiology of Human Intrauterine Growth Restriction
Am. J. Pathol.,
August 1, 2008;
173(2):
451 - 462.
[Abstract][Full Text][PDF]
J. Kim, G. Song, H. Gao, J. L. Farmer, M. C. Satterfield, R. C. Burghardt, G. Wu, G. A. Johnson, T. E. Spencer, and F. W. Bazer Insulin-Like Growth Factor II Activates Phosphatidylinositol 3-Kinase-Protooncogenic Protein Kinase 1 and Mitogen-Activated Protein Kinase Cell Signaling Pathways, and Stimulates Migration of Ovine Trophectoderm Cells
Endocrinology,
June 1, 2008;
149(6):
3085 - 3094.
[Abstract][Full Text][PDF]
R. Bukowski, G. C. S. Smith, F. D. Malone, R. H. Ball, D. A. Nyberg, C. H. Comstock, G. D. V. Hankins, R. L. Berkowitz, S. J. Gross, L. Dugoff, et al. Human Sexual Size Dimorphism in Early Pregnancy
Am. J. Epidemiol.,
May 15, 2007;
165(10):
1216 - 1218.
[Abstract][Full Text][PDF]
G. C. S. Smith, I. Shah, I. R. White, J. P. Pell, and R. Dobbie Previous Preeclampsia, Preterm Delivery, and Delivery of a Small for Gestational Age Infant and the Risk of Unexplained Stillbirth in the Second Pregnancy: A Retrospective Cohort Study, Scotland, 1992-2001
Am. J. Epidemiol.,
January 15, 2007;
165(2):
194 - 202.
[Abstract][Full Text][PDF]
V. E. Murphy, R. Smith, W. B. Giles, and V. L. Clifton Endocrine Regulation of Human Fetal Growth: The Role of the Mother, Placenta, and Fetus
Endocr. Rev.,
April 1, 2006;
27(2):
141 - 169.
[Abstract][Full Text][PDF]
Q. Qiu, A. Basak, M. Mbikay, B. K. Tsang, and A. Gruslin Role of pro-IGF-II processing by proprotein convertase 4 in human placental development
PNAS,
August 2, 2005;
102(31):
11047 - 11052.
[Abstract][Full Text][PDF]
G. C. S. Smith, J. A. Crossley, D. A. Aitken, J. P. Pell, A. D. Cameron, J. M. Connor, and R. Dobbie First-Trimester Placentation and the Risk of Antepartum Stillbirth
JAMA,
November 10, 2004;
292(18):
2249 - 2254.
[Abstract][Full Text][PDF]
C. P. Sibley, P. M. Coan, A. C. Ferguson-Smith, W. Dean, J. Hughes, P. Smith, W. Reik, G. J. Burton, A. L. Fowden, and M. Constancia Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta
PNAS,
May 25, 2004;
101(21):
8204 - 8208.
[Abstract][Full Text][PDF]
G. C. S. Smith, J. P. Pell, and R. Dobbie Risk of Sudden Infant Death Syndrome and Week of Gestation of Term Birth
Pediatrics,
June 1, 2003;
111(6):
1367 - 1371.
[Abstract][Full Text][PDF]
