Integrated pregnancy test: what is it for, when is it done, who is it recommended for?

By Cristiano Antonino On Aug 31, 2022

An ‘integrated test’, or integrated prenatal screening, in medicine refers to a set of three tests that are carried out on the pregnant woman to assess the risk of the foetus having certain diseases, such as Down syndrome

The integrated test is a safe test for both mother and foetus

It is painless as it consists of two simple maternal venous blood samples taken about a month apart and an ultrasound scan that measures nuchal translucency.

The integrated test, while increasing the accuracy of the duo test, quad test and nuchal translucency taken individually, does not allow a diagnosis to be made, but only expresses the statistical risk that the foetus has an abnormality: if this risk is high – and in the presence of risk factors such as age over 35 – the woman is advised to have other more invasive and risky, but also more accurate tests, such as amniocentesis and chorionic villus sampling.

What is the purpose of the integrated test?

The purpose of the integrated test is to quantify the risk of foetal malformations (neural tube defects such as spina bifida or certain heart diseases) or chromosomal abnormalities in the foetus, such as in Down syndrome (trisomy 21) or Edwards syndrome (trisomy 18) or Patau syndrome (trisomy 13).

The integrated test is carried out at three different times

the first sample is usually taken between the 9th and 11th week of gestation;
the ultrasound for measurement of nuchal translucency is generally carried out between the 11th and 14th week of gestation;
the second sample is generally taken between 15 and 17 weeks’ gestation.

It is not necessary to coincide the ultrasound with the first sampling, but the two examinations are often performed together (usually in week 11).

The nuchal translucency value must be provided at the second sampling.

The exact dates for the first blood test are indicated by the attending gynaecologist on the basis of the last menstruation and/or the 1st trimester ultrasound.

The effectiveness of the integrated test is based on the correct determination of the time of pregnancy: without such correctness, the test becomes statistically less accurate.

The three different tests analyse different data:

the first test analyses a specific substance present in the pregnant woman’s blood, PAPP-A (pregnancy-associated plasma protein A). In the presence of a high risk of Down syndrome, PAPP-A tends to decrease;
the ultrasound scan, which measures nuchal translucency, analyses nuchal translucency. Nuchal translucency is a fluid-filled translucent fissure that appears on ultrasound at the level of the fetus’ nuchal skin and is observed in all fetuses in the first trimester of pregnancy. Its measurement is important because, an increase in its thickness indicates an increased risk of chromosomal abnormalities, such as Down’s syndrome, or fetal malformations;
the second test is essentially a quad test and analyses four substances present in maternal blood:

A) AFP (or ‘α-fetoprotein’, alpha-fetoprotein). In the presence of Down syndrome, alpha-fetoprotein decreases by approximately 25-30%. An increase in alpha-fetoprotein may instead suggest an increased risk of neural tube closure defects (e.g. spina bifida);

B) beta-hCG (or ‘β-hCG’, beta portion of human chorionic gonadotropin). In the presence of Down syndrome, beta-hCG reaches values approximately twice as high as normal;

C) uE3 (free or ‘unconjugated’ estriol). In the presence of Down’s syndrome unconjugated estriol decreases by approximately 25-30%;

D) inhibin A. In the presence of Down syndrome, inhibin A is elevated.

The integrated test is therefore basically a combined test (consisting of duo test and nuchal translucency) combined with a quad test.

In which patients is it recommended?

By virtue of the absence of the risks associated with both ultrasound and blood sampling, the integrated test is proposed to all pregnant women, particularly in cases where risk factors are present, including:

age of the patient over 35
parents who are carriers of chromosomal alterations (translocations, inversions, aneuploidies)
fetal defects suspected or detected by ultrasound or other examinations;
one or more previous children affected by a chromosomal abnormality.

The integrated test is performed on an outpatient basis

The nuchal translucency takes about 10 minutes, while the two samples take a couple of minutes each.

Anaesthesia and pain

The examination does not require any anaesthesia and is not painful.

Some more anxious patients may find the gel applied to the skin of the abdomen and/or the pressure of the ultrasound probe on the abdomen annoying, while others may find the simple puncture of the blood sample painful, but we are talking about objectively minor discomforts.

What to do before the examination?

Unless otherwise medically indicated, no preliminary examination is necessary before the ultrasound scan (except in the case of a combined test, in which case the blood sample necessary for the duo test must be taken).

Ask your doctor if fasting is necessary before taking the blood sample.

Nuchal translucency requires a simple ultrasound scan

The patient is on the couch and the doctor, after spreading the ultrasound gel on the abdomen, passes the ultrasound probe over the skin.

The two samples require two simple venous blood draws from the arm.

What to do at the end of the examination?

At the end of the examination you can safely and independently return to your work or home activities.

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Risks

In contrast to amniocentesis and villocentesis, which have an abortion risk of approximately 0.1% and 1.8% respectively, nuchal translucency and the two samples do not pose any risk to either mother or foetus.

Results of the integrated test

The results are usually delivered the week after the last blood test.

It is important to remember that the integrated test does not allow a diagnosis to be made, but expresses the statistical risk that the foetus has an abnormality.

It is a ‘suggestive’ investigation for pathology but – on its own – has no certain diagnostic meaning and expresses only a probability of disease:

a negative result does not guarantee the birth of a normal foetus;
a positive result does not indicate the presence of an affected foetus, but only an increased risk.

In short, the test result expresses a probability:

if the probability is between 1/1 and 1/250, the risk that the foetus is affected with trisomy 21 or trisomy 18 is considered to be higher;
if the probability is greater than 1/250 (e.g. 1/500) the risk is considered lower.

If the risk is high, especially if several risk factors are present (e.g. a woman over 35 and other children with genetic abnormalities), then other more invasive and risky, but also more accurate tests, such as amniocentesis and chorionic villus sampling, are recommended.

In the event of a high risk of an abnormal foetus, 2nd level screening examinations are also recommended: evaluation of the presence of the nasal bone, measurement of the facial angle, evaluation of blood flows in the Arantius venous duct and tricuspid heart valve.

Accuracy of results

The nuchal translucency test alone detects 60-70% of fetuses with Down syndrome (this variability also depends on the skill of the doctor performing the ultrasound scan).

It therefore means that among all Down’s syndrome fetuses, nuchal translucency will fail to detect 3 or 4 out of 10.

By way of comparison, let us recall that amniocentesis and villocentesis succeed in detecting the presence of genetic abnormalities in practically all fetuses examined (approximately 99%).

This is why nuchal translucency is combined with the duo test and the quad test to form the integrated test.

The latter, if it detects a high risk of a foetus with abnormalities, should be supplemented with other tests such as the quad test, or with more invasive tests such as amniocentesis and villocentesis (chorionic villus analysis): the latter, however, have an abortifacient risk for the foetus of about 0.1% and 1.8% respectively.

Notwithstanding the above, it must be said that the overall assessment of risk factors and the integrated test allows satisfactory reliability: the sensitivity of an integrated test is in fact 90-95%.

So to sum up:

nuchal translucency 60-70%
duo test: 80%
quad test: 85%
duo test plus nuchal translucency (‘combined test’): 85-90%
integrated serum test (or ‘integrated serum test’, it is essentially an integrated test, but without nuchal translucency): 85-90%
duo test plus nuchal translucency and quad test (“integrated test”): 90-95%
amniocentesis and villocentesis: 99% (but with a much higher risk of miscarriage than the tests listed above, which are much less invasive).