Towards Early Biochemical Screening for
Fetal Aneuploidy in the First Trimester
Niels Tørring1 , Olav B Petersen2
1. Department of Clinical Biochemistry, Aarhus Universityhospital-Skejby, Denmark
2. Center for fetalmedicine and ultrasound, Aarhus Universityhospital-Skejby, Denmark
Background
Results
In Denmark first trimester seceening for fetal
aneuploidy is implemented as part of the routine
pregnancy screening program since 2003.
The councilling and the blood sampling is often taken
care of by the family G.P. Therefore the majority of
the blood samples received by the labs are taken early
in the first trimester in gestational week 8-10.
At Aarhus Universityhospital-Skejby we have 8 years
of experience with early screening, and the program is
accepted by the pregnant women with a high
participation rate.
The laboratory analyze approximately 15-18.000
samples per year covering a population of
approximately 1.2 mio.
At the Center for fetalmedicine and ultrasound,
Aarhus Universityhospital-Skejby, 90-95% of the
pregnant women participate in the prenatal
screening program including biochemistry, NTmeasurement, and risk assesment.
80% of the blood samples are taken in gestational
week 8 – 10.
The increased sensitivity of the first trimester
screening using early biochemistry is the
impact of an increased discriminatory value
of PAPP-A in gestational week 8-10 as
compared to gestational week 12-14.
In gestational week 12-14 the median MoM of
PAPP-A is 0.5-0.7, but in gestational week 810 the median MoM of PAPP-A is 0.3-0-35.
The median MoM of fβhCG shows the
opposite correlation with a value of 1.3 to 1.4
in week 8-10 and 2.0 to 2.2 in week 12-14.
The linear regressions of log MoMs for PAPPA and fβhCG are shown in figure 3.
Logistics
1. The pregnant women makes an appointment
with the family G.P. for the first pregnancy
examination.
2. The family G.P will give oral and written
information about the prenatal screening
program.
3. The G.P. will take the blood sample, separate the
serum, and send the sample to the lab for analysis
4. The lab runs the analysis for PAPP-A and fβhCG
5. The results are sent to the department of
obstetrics
6. In gestational week 12-14 ultrasound examination
is performed at department of obestetrics, and
the risk for fetal aneuploidy is calculated based
on NT and biochemistry.
7. In case of risk, the CVS can be performed.
Gestational week 8 -9
Gestational week 12-13
Pregnant goes to family
G.P:
Pregnant goes to dept. of
obstetrics
•Information on prenatal
screening program
•Blood sampling
Separation
of serum
•Serum is sent to central lab.
•Ultrasound scanning (CRL and
NT)
•Risk assesment for fetal
aneuploidy
1 laboratory devided into gestational age at day
Figure 2. Blood samples received at the
of sampling.
The false positive rate is not dependent on the
time of blood sampling (1).
The overall sensitivity of the first trimester
screening for fetal trisomy 21 from November
2003 to May 2011 is 92% with a false positive rate
of 4.4%.
Figure 2. Linear regression of long MoM for PAPP-A and fβhCG from
gestational Day 56 (week 8+0) to day 97 (week 13+6)
When the blood sample is taken in gestational
week 10-13+6 the sensitivity is 86%, but when the
blood sample is taken from gestational week 7+6
to 9+6 the sensitivity is significantly increased to
96% (p = 0.026).
For fetal trisomy 13 and 18 there is no difference in
the sensitivity of the screening between early and
late blood sampling. (2).
Gestational
week
7+6 - 13+6
Analysis of PAPP-A and fβhCG
Results are sent electronically to
dept. of Obstetrics
Figure 1. Logistics of first trimester screening for fetal aneuploidy.
Positive
Fetal
trisomy 21
164
Negative
fetal
trisomy 21
14
Sensitivity
103
4
96%
10+0 - 13+6
61
10
86%
The most optimal discriminatory value of
biochemical screening for fetal aneuploidy is
based on two bloodsamples analyzing for
PAPP-A is in gestational week 8-10, and of
fβhCG in week 12-14.
False
positive
References
92%
7+6 - 9+6
Future
4.4%
Table 1. Sensitivity and false positive rate of first trimester screening from 2003
to 2011, at Aarhus University Hospital.
1. Prenatal diagnostics in Aarhus and Viborg Counties after
implementation of first trimester risk assesment.
Tørring N, Jølving LR, Petersen OB, Holmskov A, Hertz JM, Uldbjerg
N. Ugeskr Laeger. 2008; 170(1):50-4. (Danish).
2. Performance of first-trimester combined screening for trisomy 13
and 18 with the double test taken at gestational age 8+0 to 13+6.
Kirkegaard I, Petersen OB, Uldbjerg N, Tørring N. Prenat Diagn.
2009; (6):582-7.