Objective: The plasminogen activator system and β-hCG may affect neural crest cells and angiogenesis, and thereby embryogenesis. Therefore, we investigated these parameters in amniotic fluids of pregnancies with a complex congenital malformation. Study design: In a case-control study amniotic fluid samples were collected from 62 pregnancies with a complex congenital malformation and from 110 healthy control pregnancies at an obstetric department of a large university hospital in the Netherlands. We determined concentrations of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitors (PAI-1, PAI-2), tPA∼PAI-1 and uPA∼PAI-1 complexes, and β-hCG with enzyme-linked immunosorbent assays. Mann-Whitney U-tests and analysis of covariance, adjusting for gestational and maternal age, were performed for data comparisons. Results: Compared with controls, cases demonstrated significantly lower adjusted geometric mean levels of uPA (24%), tPA (≥19%) and tPA∼PAI-1 (35%). Cases showed significantly higher adjusted mean levels of β-hCG (≥48%) and PAI-2 (10 ng/mL) than controls. Mean PAI-1 and uPA∼PAI-1 levels were comparable between both groups. Conclusions: Disturbances in the plasminogen activator system and β-hCG levels are suggested to be involved in the pathogenesis of complex congenital malformations by affecting neural crest cell migration and angiogenesis.

Additional Metadata
Keywords Amniotic fluid, Angiogenesis, Congenital malformation, Neural crest cells
Persistent URL dx.doi.org/10.1016/j.ejogrb.2006.10.033, hdl.handle.net/1765/36009
Verkleij-Hagoort , A.C., Ursem, N.T.C., Hop, W.C.J., Geurts-Moespot, A., Steegers-Theunissen, R.P.M., Sweep, F.C., & Steegers-Theunissen, R.P.M.. (2007). Complex congenital malformations and the impact of the plasminogen activator system and β-hCG in amniotic fluid. European Journal of Obstetrics & Gynecology and Reproductive Biology, 135(1), 47–52. doi:10.1016/j.ejogrb.2006.10.033