Overview of prenatal tests
Antenatal care is aimed at ensuring the health of the mother and the baby. Many tests are possible to check this. These include the following:
Routine tests to check the mother’s health and risks to the pregnancy
These are tests commonly requested by your obstetrician, and can include the following:
- Your ABO and Rhesus blood group and antibodies. This is done to see if the baby is at risk of anaemia or jaundice in case your blood group differs from the baby’s father’s blood group;
- Your haemoglobin level (to check whether you are anaemic);
- Whether there are antibodies against rubella (German measles), HIV, hepatitis B and syphilis in your blood. This is done to see if the baby is at risk of sustaining an infection before birth;
- Your blood glucose level to check if you have diabetes. This might be already present but undiagnosed, or be brought on by the pregnancy;
- Your blood pressure (to check if you have hypertension, which might be already present but undiagnosed or be brought on by the pregnancy as in a condition called pre-eclampsia);
- Your urine to check for a bladder infection, or for protein in the urine (which might also indicate pre-eclampsia);
- A swab to check whether a bacterium called group B streptococcus is present in your vagina (this could cause a serious infection in the baby if born vaginally);
- A basic ultrasound scan to determine exactly how far the pregnancy is (and what the due date is), whether there are twins or not, to check the amniotic fluid volume and position of the afterbirth (placenta).
Routine tests to check whether the baby is at increased risk for physical or mental problems.
The vast majority of babies are normal. However, every pregnancy carries a small risk that the baby is not developing normally. It is important to realize that no test or combination of tests can ever guarantee a normal baby.
The following risk factors indicate that the chance of carrying an abnormal baby is higher than average. It is important that the doctor or midwife managing the pregnancy is informed if you have chronic health conditions, if you have taken any medication during or just prior to the pregnancy, if there had been problems with a previous pregnancy,if there are or genetic conditions or inborn abnormalities in your or the baby’s father’s family.
Available tests include prenatal screening tests and prenatal diagnostic tests. These tests are optional, but may provide valuable information for the management of the pregnancy.
Screening and diagnostic tests.
Screening tests are tests that can be done on everyone who wants it, but they do not give a definitive answer about whether a condition (for example Down’s syndrome) is present or absent. They only give an indication of the likelihood, expressed either in numbers (risk of 1 in xxx) or as low, intermediate, or high risk. The majority (but not all) of affected babies would have a “high risk” result on the screening test. The proportion of babies with the abnormality who are identified by the test is called the sensitivity or detection rate. The proportion of normal individuals that received a “high risk” result is called the false positive rate. The abnormal babies that had a “low risk” result are missed by the screening test and called false negative results. Ideally, a screening test needs a high sensitivity (although it is never 100%) and low false positive rate (although it is never 0%).
Diagnostic tests on the other hand give a definitive answer about whether the condition is present or absent. Diagnostic tests have some features that make them unsuitable for use on a wide scale, such as risk, cost, or limited availability. The choice of a specific diagnostic test depends on the specific condition that one wants to detect or exclude. Options for diagnostic tests include ultrasound examinations by an expert (e.g. for physical defects in the baby) or invasive procedures to obtain fetal samples for genetic or infective testing (placental tissue obtained by chorionic villus sampling, amniotic fluid by amniocentesis, fetal blood by cordocentesis). All invasive tests carry a risk of miscarriage (approx. 1:200).
The following screening tests are available.
Screening tests for physical abnormalities:
Maternal serum Alpha-Feto-Protein (MSAFP) is a blood test done between 15 and 19 weeks and helps to detect fetal spina bifida (open spine). It does not add value if the anatomy scan will be performed by an expert but does help when the anatomy scan is done by a general obstetrician. MSAFP can detect 60% of fetuses with spina bifida with a 5% false positive rate. If the MSAFP result is abnormal, it is essential to have a detailed assessment by an expert.
The detailed fetal anatomical evaluation is usually done between 18 and 22 weeks. With the right training and equipment, about 50% of the physical abnormalities that are detectable at 18 – 22 weeks can already be seen at 12 – 13 weeks.
The detection rate for abnormalities of the fetal body parts varies. It strongly depends on the scanning conditions, the expertise of the operator and the time spent. Defects in certain organs are far more difficult to detect than defects in other parts. Some defects only appear late in pregnancy and some can only be seen after birth. The detection rate is considerably lower if technical limitations result in poor image quality. This can be related to maternal overweight, early or late stage of the pregnancy, reduced or increased amount of fluid around the baby, presence of more than one baby, unfavourable fetal or placental position, presence of fibroids or abdominal scars etc.
It is impossible to detect all fetal abnormalities before birth. As a general rule of thumb, only about 50% of serious abnormalities are detected by a routine anatomy scan (and 50% not). When experts perform such a scan, the detection rate is significantly higher (around 75%) as they have undergone extensive special training and therefore are more experienced than general obstetricians. An expert scan is usually more expensive than a routine scan since experts generally have spent more time in training, use more expensive equipment spend more time on the examination. The number of experts in the country is insufficient to cover all pregnancies. It is therefore generally advisable that their services are predominantly used for pregnancies with risk factors or when the routine scan by the obstetrician raises any concern.
Screening tests for genetic diseases.
The main aim is to detect fetuses at high risk of Down syndrome as this is the most common of the genetic conditions with significant consequences. A host of different tests are available and they can also be used in a variety of combinations. In general, you get what you pay for: the more expensive the tests, the higher the detection rate AND the lower the false positive rate. This translates in a lower chance of a missed diagnosis of Down syndrome AND a lower chance of receiving a “high risk” result which raises the need for further tests, possibly even invasive diagnostic procedures.
1. Blood tests:
· Maternal blood test for PAPP-A and free β-HCG, done at 8-12 weeks (early is best).
· Maternal blood test for AFP, HCG and estriol (Triple test), done at 15-20 weeks.
· An ultrasound scan is needed before any of these blood tests to check exactly how far you are pregnant and to exclude twins or miscarriage. These blood tests have a 60% sensitivity and a 5% false positive rate for Down syndrome, at a risk cut-off of 1:300.
· Cell free DNA testing, also called NIPT (Non-Invasive Prenatal Testing). This test is very accurate (more than 99% sensitivity and less than 1% false positive rate). It can be performed any time after 10 weeks, but also requires a scan beforehand to exclude problems such as a major physical fetal abnormality, a multiple pregnancy or miscarriage. NIPT is currently very expensive and not covered by most medical schemes. It can test for many other genetic conditions apart from Down syndrome and therefore requires quite extensive counselling beforehand.
- “Simple NT scan”, done at 11 – 13 weeks and 6 days. The name “NT” refers to the measurement of the nuchal translucency thickness, a fluid collection in the fetus’ neck which is thickened in most fetuses with Down syndrome. This has a 70% detection rate and a 5% false positive rate at a risk cut-off of 1:300 when done by an experienced and practitioner. Practitioners accredited by the Fetal Medicine Foundation (https://fetalmedicine.org/lists/map/certified/NT-specialist) submit themselves to external quality control.
- “Extended NT scan”, done at 11 – 13 weeks and 6 days. This includes not only the NT measurement but also assessment of the nasal bone, fetal blood flow patterns and detailed fetal anatomy. The sensitivity of this sort of scan for Down syndrome is about 85% and the false positive rate 5% for a risk cut-off of 1:100 to 1:200. There are very few people in this country trained to do this.
- “Routine fetal anatomy scan” by a general obstetrician, done at 18 – 22 weeks. This has only about 40% sensitivity for Down syndrome.
- “Genetic sonogram” by an expert, done at 18-22 weeks. This is a more detailed ultrasound examination including a long list of subtle ultrasound markers of a fetal chromosomal abnormality. This has roughly 75% sensitivity and a 10% false positive rate.
- Maternal blood test in the first and second trimester. The detection rate is 80-85% and false positive rate 5% for a risk cut-off of 1:300 after the second sample (if the two samples are seen as independent tests however, the false positive rate would double to 10%).
- Maternal blood test in the first trimester together with a “simple NT” scan”. This is called “the early combination test” and has a sensitivity of 85% for Down syndrome and 5% false positive rate at a risk cut-off of 1:300.
- Maternal blood test in the first trimester together with an “extended NT scan” by an expert. This can have a sensitivity of 95% for a false positive rate of around 3%.
If money wasn’t an issue and there were more than enough experts on the country, the very best test would be a combination of NIPT at 10-12 weeks WITH an expert NT scan AND an expert fetal anatomy scan AND a repeat expert scan in the last trimester. This combination could theoretically detect 99% of all Down syndrome fetuses, a whole list of other genetic conditions as well as the majority of physical fetal abnormalities. This approach, even though some patients may choose this, is however very expensive (costs amounting to more than R15000 per pregnancy) and is simply not available for all pregnancies for the foreseeable future. This is not only the situation in South Africa but also in many developed countries. For this reason, alternative screening strategies according to the background risk can be considered as acceptable.
In low risk pregnancies: First and second trimester blood test (with Down syndrome risk recalculated after the second one) PLUS a first AND second trimester scan by the general obstetrician. Referral to an expert is recommended if the first or combined blood test results show a high risk of Down syndrome, if the MSAFP level is raised or if the obstetrician is concerned about anything on the scan. The expert will then reassess all findings and advise on further testing or management, as indicated.
In high risk pregnancies: First trimester blood test + extended NT scan if available. If this demonstrates a low risk (<1:1000), no further testing is recommended. If it indicates a high risk for Down syndrome (>1:100), an invasive test (usually amniocentesis or chorionic villus biopsy) is offered. If an intermediate risk (1:100 – 1:1000) is found, the possibilities would include a diagnostic test, NIPT or reassessment by an expert genetic sonogram. If the high risk patient has no access to an extended NT scan, then NIPT can be considered with an expert second trimester scan if needed.
These options can be confusing and a session with a genetic counselor can be valuable to provide more information, especially if there is a family history of abnormalities.