Complex congenital malformations and the impact of the plasminogen activator system and beta-hCG in amniotic fluid.
OBJECTIVE
The plasminogen activator system and beta-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.


METHODS
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 approximately PAI-1 and uPA approximately PAI-1 complexes, and beta-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 (> or =19%) and tPA approximately PAI-1 (35%). Cases showed significantly higher adjusted mean levels of beta-hCG (> or =48%) and PAI-2 (10 ng/mL) than controls. Mean PAI-1 and uPA approximately PAI-1 levels were comparable between both groups.


CONCLUSIONS
Disturbances in the plasminogen activator system and beta-hCG levels are suggested to be involved in the pathogenesis of complex congenital malformations by affecting neural crest cell migration and angiogenesis.
Verkleij-Hagoort
Anna C
AC
Department of Obstetrics and Gynaecology, Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Centre, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Ursem
Nicolette T
NT
Hop
Wim C
WC
Geurts-Moespot
Anneke
A
Steegers
Eric A
EA
Sweep
Fred C
FC
Steegers-Theunissen
Régine P
RP
D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000032:analysis*; D000013:Congenital Abnormalities / Q000378:metabolism*; D005260:Female; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis; D011247:Pregnancy; D010959:Tissue Plasminogen Activator / Q000032:analysis*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
D018997:Chorionic Gonadotropin, beta Subunit, Human; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator