VALUE OF THE COMBINED TEST
IN PRENATAL DIAGNOSTICS
Lončar D
*Corresponding Author: Dragan Lončar, Gynecology and Obstetrics Clinic, Clinical Center
Kragujevac , Vojislava Kalanovića 1A/3, 34000 Kragujevac, Serbia; Tel.: +381-64-616-8999;
E-mail: drloncar@sezampro.rs
page: 53
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RESULTS
After conducting the combined test in the total
sample of pregnant women, we found the following
individual values of the examined parameters (see
Table 1): the statistically significant difference
in values of free β-HCG and NT in the examined
group of pregnant women was p <0.05. Parameter
PAPP-A does not show any statistically significant
difference in the examined group of pregnant
women. We also found the same characteristics
of the examined parameters in the receiver
operating characteristic (ROC) curve analyses in
the examination of predictive characteristics of the
specified parameters (Figures 1 and 2).
Analysis of the value distribution of the NT
thickness measurement showed that the distribution
was regular and that measurements were being set
regularly around the median (44.0% below and
56.0% above median), which was in accordance
with the criteria for quality control established by the Fetal Medicine Foundation (London, UK) and
was supposed to be 40.0-60.0% above the median.
The distribution of fetal NT for given CRL in
examination was no different from the established
distribution of the Fetal Medicine Foundation used
as a standard. On the basis of that, our measurements
of NT thickness can be considered to be regularly
conducted and usable in further examination.
The diameter of NT did significantly statistically
differ in the examined group of pregnant women
(p <0.05). Crown-rump length and gestational age
were not different statistically (p >0.05). Using the
contingency table (Table 2), we set the predictive
value of the combination of ultrasonographic and
biochemical markers after taking over the results of
amniocentesis.
Estimation of probability that some disease is
present before testing is called pretest probability (“a
priori probability”). Pretest probability is received
on the basis of available information about the
patient, also including testing previous to the actual
one. Estimation of the probability of disease after
testing is called posttest probability (“a posteriori
probability”). Posttest probability is less or higher
than pretest probability depending on the test results.
Measures of diagnostic accuracy (sensitivity,
specificity) cannot directly answer the following
important clinical questions: 1) if the disease pretest
probability is known, and the examinee is positive
on the test, what is the probability that he/she really
has the disease? 2) If the disease pretest probability
is known, and the examinee is negative on the test,
what is the probability that he/she really does not
have the disease?
These questions can be answered by
application of the pretest odds of the disease and
the credibility ratio. Disease odds ratio is the ratio
of probability that the disease is present (p) and
probability that is not present (1-p): odds = p/1-p.
According to that, pretest disease odds are: pretest
odds = pretest probability/1-pretest probability.
Likelihood ratio (LR) is the probability ratio of the
certain test result (+ or –) of the examinee who
has the disease divided with the probability of the
same result of the person who does not have the
disease. Two types of likelihood can be calculated:
1) likelihood ratio of the positive test (LR+) is
the ratio of sensitivity and false positive ratio
(1–specificity): LR+ = sensitivity/1-specificity;
2) likelihood ratio of the negative test (LR–) the
ratio of sensitivity and false negative ratio (1–
sensitivity) and specificity: LR– = 1-sensitivity/
specificity. The likelihood ratio shows how the
test result can alter the pretest disease probability.
The LR+ shows how much the test result increases
disease probability, LR– shows how much the test result decreases disease probability. The likelihood
ratios are not under the influence of the disease
prevalence.
Likelihood ratios can help measuring the
posttest probability. How big the change from pretest
to posttest probability depends considerably on the
values of the likelihood ratio. It is desirable for (LR+)
to have the highest values and (LR–) to have values
closest to 0. For calculating the posttest disease
probability, posttest odds are first to be calculated.
1) For positive test result: posttest odds = pretest
odds × LR+; 2) for negative test result: posttest
odds = pretest odds × LR–. Posttest probability
is obtained by the formula: posttest probability
= posttest odds/1+ posttest odds. According to
the literature data, the diagnostic accuracy of the
combined test, in relation to the result of the early
amniocentesis (referral standard) is: sensitivity
0.88, specificity 0.90. In our sample sensitivity is
0.94 and specificity 0.99. Likelihood ratios: LR+
= 0.94/1-0.99 = 94.00; LR– = 1-0.94/0.99 = 0.06.
Pretest probability that the pregnant woman carries
the fetus with the chromosomal abnormality is
1:250 = 0.004. Pretest odds = 0.004/0.996 = 0.004.
If the test is positive: posttest odds = pretest odds ×
LR+ = 0.004 × 94 = 0.3760; posttest probability =
posttest odds/1+ posttest odds = 0.3760/1+0.3760
= 0.2732. If the test is negative: posttest odds
= pretest odds × LR– = 0.004 × 0.06 = 0.00024.
Posttest probability = posttest odds/ 1+posttest odds
= 0.00024/1+0.00024 = 0.00024.
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