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- Title
First-trimester combined screening for trisomy 21 with different combinations of placental growth factor, free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A.
- Authors
KAGAN, K. O.; HOOPMANN, M.; ABELE, H.; ALKIER, R.; LÜTHGENS, K.
- Abstract
Objective To examine placental growth factor (PIGF) in euploid and trisomy 21 pregnancies at 11-13 weeks' gestation and to model the impact on first-trimester combined screening. Methods PIGF was measured in 509 (409 euploid and 100 trisomic) fetal serum samples derived from prospective first-trimester combined screening for trisomy 21 at 11-13 weeks' gestation. The serum samples were stored at -80°C, following the measurement of free β-human chorionic gonadotro pin (β-hCG) and pregnancy- associated plasma protein-A (PAPP-A) levels, for median time spans of 0.9 and 4.1 years in the euploid and trisomy 21 pregnancies, respectively. The effect of additional PIGF measurement at the time of combined screening was investigated by simulating fetal nuchal translucency (NT) measurements and multiples of the median (MoM) values for PAPP-A, free β-hCG and PIGF for 20000 euploid and 20 000 trisomy 21 pregnancies. Patient-specific combined risks were calculated based on maternal age and fetal NT in addition to free β-hCG, PAPP-A and PIGF, PA PP-A and PIGF or free β-hCG and PIGF, and detection and false-positive rates were calculated. Results Median PIGF-MoM was 1.0 (95% confidence interval (Cl), 0.96-1.04) in euploid fetuses and significantly lower, at 0.73 (95% Cl, 0.70-0.76), in trisomy-21 fetuses (P <0.0001). There was no significant dependency between PIGF-MoM and either gestational age at the time of blood sampling (r = 0.087, P = 0.392) or sample stor- age time (r = 0.028, P = 0.785). Modeled detection and false-positive rates for first-trimester combined screening (based on maternal and gestational age, fetal NT and maternal serum biochemistry) without PIGF were 85% and 2.7% for a fixed risk cut-off of 1:100. The addition of PIGF increased the detection rate to 87% and reduced the false-positive rate to 2.6%. Screening by maternal age and fetal NT in combination with PIGF and PAPP-A or in combination with PIGF and free β-hCG provided detection rates of 82% and 79%, with false-positive rates of 2.7% and 3.0%, respectively. Conclusion In pregnancies with trisomy 21 P1GF is reduced. The impact on the overall screening performance for trisomy 21 is low and does not justify the measurement of PIGF solely for trisomy 21 screening. However, as PIGF is measured with the aim of assessing the risk for pre- eclampsia, further improvement in screening for trisomy 21 can be considered as an added benefit.
- Subjects
FIRST trimester of pregnancy; DOWN syndrome; PLACENTAL growth factor; PREGNANCY; CHORIONIC gonadotropins; MEDICAL screening; BLOOD proteins
- Publication
Ultrasound in Obstetrics & Gynecology, 2012, Vol 40, Issue 5, p530
- ISSN
0960-7692
- Publication type
Article
- DOI
10.1002/uog.11173