South African researchers have suggested that the rate of prenatal screening for trisomy 21 (the chromosomal defect that leads to the condition Down’s syndrome) is lower than it should be, urging more emphasis on this vital process in the public and private healthcare system.
The researchers say despite the availability of the latest screening programmes, only a minority of infants with trisomy 21 are detected prenatally, raising questions about the effectiveness of screening.
The procedure is integral to antenatal care, the first screening method being an amniocentesis for foetal karyotyping, offered to pregnant women of advanced maternal age, write L Pretorius, CA Cluver, I Bhorat and L Geerts in the SA Medical Journal. Subsequently, biochemical tests were developed that could be done in the first or second trimester (biochemical screening) to identify pregnancies at high risk of foetal trisomy 21.
Ultrasound markers on their own (ultrasound screening), and in combination with biochemical tests (combined screening), were then shown to improve the accuracy of screening, while non-invasive prenatal testing (NIPT) is the most recent development, measuring the free foetal DNA circulating in maternal blood to detect trisomy 21.
It is the most sensitive and specific screening test for trisomy 21.
The development of more sophisticated screening tests has increased the accuracy, but also the costs, of screening for trisomy 21.
In South Africa, as in other low- and middle-income countries, the expense precludes the general availability of NIPT, with screening being largely prompted by maternal age, with ultrasound used in selected patients in the public health sector.
In the private sector, biochemical and combined first trimester screening are available, and NIPT has also recently become available.
Efficient screening for trisomy 21 should be feasible in the private sector, however, an audit demonstrated a low prenatal detection rate (39%) in private healthcare.
We therefore aimed to determine the percentage of pregnant women undergoing screening, and to determine the sensitivity and screen positive rates by linking screening and confirmatory data from different biochemical laboratories and FMF accredited practitioners.
After ethical approval was obtained, a retrospective audit of SA women receiving private healthcare was conducted.
The lead authors approached the three major laboratories performing prenatal screening (Ampath, Lancet and PathCare) and practitioners on the FMF database, which provided data on prenatal screening throughout SA for foetal aneuploidy between January 2011 and December 2015, and pre- and postnatal genetic testing between January 2011 and December 2016. The SA FMF practitioners provided data for the same time period.
We found that a third of women accessing private healthcare in SA from 2011 until 2016 underwent prenatal screening for trisomy 21.
Only 35% of trisomy 21 diagnoses were made prenatally, with 22% after screening. Most screenings were performed with inferior tests.
If prenatal detection is to be improved, more effective screening methods such as combined first trimester screening using FMF software or NIPT should be used.
Research exploring reasons for not having screening, or not proceeding with confirmatory testing after a screen positive result, is needed, and hopefully, the results can counter the equanimity with which obstetrical care givers and laboratories providing prenatal screening in SA have ignored the calls for accreditation and regular audit of NT measurements.
User-friendly audit systems should be developed and implemented, as evaluating screen positive and detection rates should be straightforward and performed at least annually.
Trisomy 21 screening with αlpha software and the Foetal Medicine Foundation algorithm
L Pistorius, C Cluver, I Bhorat, L Geerts.
Published in SA Medical Journal in November 2023
Screening for trisomy 21 provides pregnant women with accurate risk information. Different algorithms are used to screen for trisomy 21 in South Africa (SA). The Foetal Medicine Foundation (FMF) provides software to screen for trisomy 21 in the first trimester by ultrasound or a combination of ultrasound and biochemistry (combined screening), and requires regular and stringent quality control. With αlpha software, first trimester combined screening and screening with biochemistry alone in the first or second trimester are possible.
The αlpha screening requires quality control of biochemical tests, but not of ultrasound measurements. Ideally, a screening test should have a high detection and a low screen positive rate. Despite the availability of these screening programmes, only a minority of infants with trisomy 21 are detected prenatally, raising questions about the effectiveness of screening.
To determine the screen positive and detection rates of prenatal screening for trisomy 21 in the SA private healthcare system
Data from the three largest laboratories collected between 2010 and 2015 were linked with genetic tests to assess screen positive and detection rates. Biochemical screening alone with αlpha software (first or second trimester) and combined screening using either FMF or αlpha software were compared.
One-third of an estimated 675 000 pregnancies in private practice in the six-year study period underwent screening. There were 687 cases of trisomy 21 in 225 021 pregnancies, with only 239 (35%) diagnosed prenatally. The screen positive rates were 11.8% for first trimester biochemistry, 7.6% for second trimester biochemistry, 7.3% for first trimester FMF software ultrasound alone, 3.7% for combined first trimester screening with FMF software, and 3.5% for combined first trimester screening with αlpha software.
The detection rates for a 5% false positive rate were 63% for first trimester biochemistry, 69% for second trimester biochemistry, 95% for combined first trimester screening with FMF software and 80% for combined first trimester screening with αlpha software. Detection and confirmation rates were highest with FMF software.
Screening with FMF software has a similar screen positive rate and better detection rate than screening with αlpha software. The low prenatal detection rate of trisomy 21 is mainly due to a low prevalence of screening. More research is needed in the SA setting to explore why screening and confirmatory testing after high-risk results are not performed in many pregnancies.
L Pretorius, CA Cluver – Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University; Panorama Perinatology, Mediclinic Panorama, Cape Town.
G Geerts – Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University.
I Borat – Department of Obstetrics and Gynaecology,College of Health Sciences, University of KwaZulu-Natal.
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