title: 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.
authors.affiliation: Department of Obstetrics and Gynaecology, Cambridge University, CB2 2QQ, United Kingdom. gcss2@cam.ac.uk
authors.forename: Gordon C S
authors.initials: GC
authors.lastname: Smith
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Stenhouse
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Crossley
authors.forename: David A
authors.initials: DA
authors.lastname: Aitken
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cameron
authors.forename: J Michael
authors.initials: JM
authors.lastname: Connor
mesh_terms: D000328:Adult; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005313:Fetal Death / Q000209:etiology*; D005317:Fetal Growth Retardation / Q000209:etiology*; D006801:Humans; D015999:Multivariate Analysis; D007752:Obstetric Labor, Premature / Q000209:etiology*; D009994:Osmolar Concentration; D011225:Pre-Eclampsia / Q000209:etiology*; D011237:Predictive Value of Tests; D011247:Pregnancy / Q000097:blood*; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A