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First trimester combined screening for trisomy 21 with different combinations of placental growth factor, free β-hCG and PAPP-A.
MedLine Citation:
PMID:  22611005     Owner:  NLM     Status:  Publisher    
Objective: To examine placental growth factor (PlGF) in euploid and trisomy 21 pregnancies at 11-13 weeks of gestation and to model the impact on first trimester combined screening. Methods: PlGF was measured in the surplus of 509 (409 euploid and 100 trisomic fetuses) serum samples that have been derived from prospective first trimester combined screening for trisomy 21 at 11 to 13 weeks. The serum samples were stored at -80° C following the measurement of free β-hCG and PAPP-A and were only thawed for the measurement of PlGF. In euploid and trisomy 21 pregnancies, the samples were stored for a median time span from 0.9 to 4.1 years. The effect of the additional measurement of PlGF at the time of combined screening was investigated by simulating fetal NT measurements and MoM values for PAPP-A, free β-hCG, and PlGF for 20.000 euploid and 20.000 trisomy 21 pregnancies. Patient specific combined risks were calculated based on maternal age and fetal NT and in addition either free β-hCG, PAPP-A and PlGF, PAPP-A and PlGF or free β-hCG and PlGF. Detection and false-positive rates were calculated as proportion of cases above certain thresholds. Results: In euploid fetuses, median PlGF MoM was 1.0 (95% CI 0.96 - 1.04). In trisomy 21, median PlGF MoM was 0.73 (95% CI 0.70 - 0.80) MoM, which was significantly lower than in euploid pregnacies (p<0.0001). There was no significant dependency neither between PlGF and gestational age at the time of blood sampling (r=0.087; p=0.392) nor between PlGF and the storage time (r=0.028; p=0.785). Modelled detection and false-positive rates for first trimester combined screening (based on maternal and gestational age, fetal NT and maternal serum biochemistry) without PlGF were 85% and 2.7% for a fixed risk cut-off of 1:100. The addition of PlGF incresed the detection rate to 87% and reduced the false-positive rate to 2.6%, respectively. Screening by maternal and fetal NT in combination with PlGF and PAPP-A or in combination with PlGF and free β-hCG provides detection rates of 82% and 79% for false-positive rates of 2.7% and 3.0%, respectively. Conclusion: In pregnancies with trisomy 21 PlGF is reduced. The impact on the overal screening performance for trisomy 21 is low and does not justify the measurement of PlGF solely for trisomy 21. However, as the measurement of PlGF aims to assess the risk for preeclampsia rather than for trisomy 21, a further improvement in screening for trisomy 21 can be considered as a positive side effect. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Ko Kagan; M Hoopmann; H Abele; R Alkier; K Lüthgens
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-18
Journal Detail:
Title:  Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology     Volume:  -     ISSN:  1469-0705     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9108340     Medline TA:  Ultrasound Obstet Gynecol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Department of Obstetrics and Gynaecology. University of Tuebingen. Germany.
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