Quadruple Test Results

Why you were offered this test and not the other one

The combined test is the first-trimester test and, as the NHS Fetal Anomaly Screening Programme puts it, is "the test of choice". The quadruple test is what you are offered when the combined test cannot be done, and there are two defined reasons for that in the FASP handbook: the nuchal translucency measurement cannot be obtained, or the crown rump length measurement is greater than 84.0mm, meaning the pregnancy is too far along for the combined test.

Being offered the quad test is therefore usually about timing or about the baby's position during the scan, not about anything being wrong. The handbook describes the process for when nuchal translucency cannot be measured: at least one more attempt is offered, described as "twice on the couch", and if it still cannot be obtained, "the woman must be offered the quadruple test".

What it measures, and what it does not screen for

The FASP handbook says the quadruple test uses maternal age plus four biochemical markers measured between 14 weeks plus 2 days and 20 weeks plus 0 days: alpha-fetoprotein (AFP), human chorionic gonadotropin or free beta hCG, inhibin-A, and unconjugated oestriol (uE3).

The critical difference from the combined test is scope. The FASP programme overview states that "the quadruple test is offered in the second trimester to assess the chance of the baby having Down's syndrome", whereas the combined test assesses the chance of Down's syndrome, Edwards' syndrome and Patau's syndrome. Edwards' and Patau's syndromes are instead screened for at the 20-week scan for women who have the quad test.

The handbook is also honest that this is the weaker test: "this combination of markers has a lower detection rate and a higher screen positive rate than the combined test". You are more likely to get a higher chance result that turns out not to reflect a chromosomal condition.

The timing rules that trip people up

The quad test is tied to head circumference as well as to dates. The handbook says the test is performed when head circumference is between 101.0mm and 172.0mm. If the blood sample is taken on the same day as the scan, head circumference must be in that range; if measured on a different day, the gestational age at the blood test should be between 14 weeks plus 2 days and 20 weeks plus 0 days.

Two hard stops follow. If head circumference is more than 172.0mm, "the quadruple test must not be offered" and you are offered the 20-week screening scan instead. And NIPT cannot be performed after 21 weeks plus 6 days. Between them, these rules mean a delay of a week or two can close options, which is why appointments for this test are not worth postponing.

Reading your result

Results come as a chance, written as 1 in a number, and the direction of the number is the part that is routinely misread. A result of 1 in 5,000 means a lower chance than 1 in 200, because the larger the second number, the smaller the chance.

The NHS cut-off is defined precisely. FASP guidance states that NIPT screening "is offered following a higher chance result (between 1 in 2 and 1 in 150) from either the NHS combined or the quadruple test in both singleton and twin pregnancies". So 1 in 150 or anything more likely than that is a higher chance result; 1 in 151 or less likely is a lower chance result.

That boundary is a policy decision, not a biological one. A result of 1 in 145 and a result of 1 in 160 describe almost identical situations, and land on opposite sides of a line. Understanding that helps if your result sits close to the cut-off in either direction.

The other thing to hold onto: a higher chance result is not a diagnosis. Even at the higher-chance end of the range, most pregnancies do not have the condition being screened for. That is why a further step is offered rather than a decision being asked for.

What happens after a higher chance result

The FASP handbook says that following a higher chance result you must have a discussion with a healthcare professional, and that you can choose no further testing, NIPT screening, or a diagnostic test.

NIPT analyses cell-free DNA in your blood. The handbook explains why it is screening rather than diagnosis: most of that DNA is yours, "usually consisting of approximately 90% DNA from the woman's cells and 10% DNA from the placenta". Within the NHS pathway, NIPT screens only for Down's, Edwards' and Patau's syndromes, does not screen for other chromosomal conditions, and does not assess the baby's sex. It cannot be offered after a lower chance result, in triplet or higher multiple pregnancies, or after 21 weeks plus 6 days.

Diagnostic testing means amniocentesis or chorionic villus sampling, which give a definite answer and carry a small procedure-related risk. From the second trimester, amniocentesis is the relevant option.

Choosing none of these is a legitimate choice, and the handbook lists it first among the options.

What an AFP result on its own means

One of the four markers, AFP, was historically used alone to screen for neural tube defects, and older sources still describe it that way. In the current NHS pathway, structural conditions including open neural tube defects are screened for at the 20-week scan rather than by blood test, so an AFP value from your quad test is not reported to you as a separate neural tube result. If you have been given a raised AFP interpretation from a private test, ask how it fits the NHS pathway you are actually on.

How this compares elsewhere

ACOG's practice advisory on screening for fetal chromosomal abnormalities sets out the US approach, where cell-free DNA screening is offered more broadly rather than only after a higher chance serum result. Neither approach is a correction of the other; they are different national policies about who gets the more expensive test first. If you have had screening in more than one country, expect the sequence, and sometimes the conditions screened for, to differ.