The 29 scoping review articles indicate the current landscape and status of NIPT in SA and other LMICs. Only 11 articles specifically mention SA, which indicates a gap in the literature for NIPT in SA. Of those 11 articles, only three are South African published articles, specifically discussing SA, NIPT, its clinical use, value, and challenges. (Bhorat et al. 2018; Mnyani et al. 2016; Urban et al. 2014). These articles are outdated and have been published between 2014 and 2018. One of the articles also reiterates the need for more NIPT studies applicable to SA and LMIC to assess the value and role of NIPT (Mnyani et al. 2016).

The identified themes are discussed below in relation to existing challenges, opportunities, and priorities within South Africa’s prenatal care framework. The discussion considers the current state of prenatal screening in SA and situates the findings within the broader South African healthcare landscape.

NIPT is a screening testNIPT's potential role as a screening test in the South African public healthcare sector

In SA, the accessibility to prenatal screening tests is unequal across the public sector. Pregnant women, especially those who reside in rural communities, do not have access to prenatal screening, which includes biochemical screening, ultrasound, and NIPT.

In a South African study, 45% of expectant mothers believed that the only reason they should go to a clinic while pregnant is to get an antenatal card to record essential maternal and fetal health information (Haddad et al. 2016). The most common screening technique in the public sector to determine a high-risk pregnancy is maternal age, since other resources like sonar and biochemical screening are scarce and expensive (Geerts 2008; Urban et al. 2011).

According to the Clinical Guidelines for Genetics Services in SA, published in November 2021, maternal serum screening is only available at district hospitals and not at primary health care level such as in clinics or community health centres. Therefore, an additional screening method, like NIPT, might not be appropriate, justified, or applicable for SA.

However, in a study conducted in SA, the average gestational age at which pregnant women first presented at a public healthcare facility was 19.1 weeks (Haddad et al. 2016), which is considerably later than the recommended 12-week gestation mark for initiating antenatal care (World Health Organization 2016). This delay has been attributed to a variety of factors, including fear of HIV testing, cultural beliefs, and uncertainty regarding the continuation of the pregnancy (Haddad et al. 2016). Other factors contributing to delays may include limited access to clinics, travel-related costs, and the need to take time off work, whether paid or unpaid. Given this delayed presentation, the implementation of biochemical screening would likely be of limited utility in this population, as such screening is typically only possible and accurate up to 20 weeks of gestation (Driscoll & Gross 2009). NIPT does not have a strict gestational age cut-off, which makes it particularly advantageous for women who present later in pregnancy and still require prenatal screening.

Another aspect to consider is that because NIPT is a screening test, positive results should be confirmed with invasive testing. The time frame, gestational age, patient informed consent, follow-up time, availability of resources and results must be considered when choosing the most appropriate prenatal test. For example, if a woman is 18 weeks pregnant and her fetus is determined to be at high risk for aneuploidy, and she would consider termination if the fetus were affected with a common trisomy, invasive testing will give a quicker and definitive answer, compared with NIPT.

The South African Society for Ultrasound in Obstetricians and Gynaecologists (SASUOG) and the South African Society of Obstetricians and Gynaecologists (SASOG) have stated that the majority fetal anomalies in SA are diagnosed after 20 weeks (The South African Society for Ultrasound in Obstetricians and Gynaecologists (SASUOG) & The South African Society of Obstetricians and Gynaecologists (SASOG) 2015).Therefore, it is important to refer to the termination of pregnancy (TOP) act in SA and how it should be applied.

The TOP act in SA specifies that a woman can terminate a pregnancy until 20 weeks of gestational age under specific conditions. The circumstances stipulated include; if the continued pregnancy poses a risk to the woman's physical or mental health, if there is a substantial risk that the fetus would suffer from a severe physical or mental abnormality, if the pregnancy resulted from rape or incest or if continuing the pregnancy would significantly affect the woman's social or economic circumstances. Termination can only occur after 20 weeks under exceptional circumstances, such as if the continued pregnancy would endanger the woman's life, if there is a risk of severe malformation of the fetus, or if there is a risk of injury to the fetus (National Department of Health,RSA 2019). SASUOG, with the endorsement of SASOG, has issued additional guidelines concerning the termination of pregnancy for fetuses affected by anomalies after 20 weeks (The South African Society for Ultrasound in Obstetricians and Gynaecologists (SASUOG) & The South African Society of Obstetricians and Gynaecologists (SASOG) 2015). These guidelines clarify the gestational limits and the severity for which termination is considered appropriate.

The need for invasive testing will decrease

The Green Top Guideline on Amniocentesis and CVS from the Royal College of Obstetricians and Gynaecologists recommends that medical practitioners perform a minimum of 20 invasive procedures per year to maintain competency (Navaratnam et al. 2022). Although NIPT has significantly reduced the need for invasive testing, positive or high-risk NIPT results should be confirmed through diagnostic procedures such as amniocentesis or CVS. With the adoption of NIPT, which has a low false-positive rate, the demand for invasive testing has declined, particularly in HICs where NIPT has been integrated into routine prenatal care. The reduction in the volume of amniocentesis procedures has been linked to an increase in procedure-related complications, including a higher incidence of miscarriage. Studies have demonstrated an inverse correlation between the number of invasive procedures performed and the risk of fetal loss following amniocentesis, suggesting that decreased practitioner experience may contribute to a higher risk of procedure-related miscarriage (Hui et al. 2015).

In SA, particularly within the public healthcare sector, invasive testing, especially amniocentesis, remains the primary method for prenatal diagnosis, largely due to limited or no availability of NIPT (Allyse et al. 2015; Sium et al. 2023).

Invasive procedures like CVS and amniocentesis require expertise, and few doctors are qualified to perform them. In rural areas, access to skilled practitioners is limited, further restricting availability of invasive testing (Allyse et al. 2015). This highlights the need for improved access to NIPT in the public sector.

NIPT is a screening test and requires invasive diagnostic testing for confirmation of a high-risk result. Therefore, invasive testing remains essential. The following quote emphasises this: “The frequency of chromosome abnormalities, which would be missed if invasive prenatal chromosomal microarray-based analysis would be replaced by targeted NIPT, has been estimated to be 16.9%, including 2% of those pregnancies deemed at high risk of aneuploidy based upon abnormal serum screening results.”(Brady et al. 2016). However, chromosomal microarray analysis is not currently available in the public sector in SA and remains limited within the private sector. These findings reinforce the view that NIPT should not replace biochemical screening, as approximately 2% of high-risk pregnancies may go undetected using NIPT alone.

NIPT cannot/should not replace combined first-trimester screening

In SA, biochemical screening has several advantages. Testing is not labour intensive, has a quick turnaround time, the test provides additional information about the pregnancy and the sample is collected in a more easily available sample tube that does not have to reach the laboratory within a set time. Despite these benefits and the reduced costs of reagents, equipment, and technology compared to NIPT, this fundamental screening test, which is routinely available in HICs, remains largely inaccessible within the South African public healthcare sector.

NIPT is advantageous for HIV-positive mothers

HIV remains a significant public health issue in SA, with a prevalence of 13.7%. Almost one in four women of reproductive age (15–49 years) are living with HIV (Statistics South Africa 2022). In this context, NIPT is particularly valuable. Unlike invasive procedures such as CVS or amniocentesis, NIPT does not involve breaching the uterine environment and therefore avoids the risk of transplacental infection and vertical HIV transmission (Hui et al. 2015). NIPT is especially relevant for women who may not yet have achieved full viral suppression or who face barriers to consistent antiretroviral treatment.

Previous studies have shown higher rates of mother-to-child transmission (MTCT) of HIV following invasive procedures such as amniocentesis, particularly when maternal viral load is not well controlled (Mandelbrot et al. 2009). The risk of transmission is closely linked to the viral load, and MTCT becomes very low when the viral load is undetectable (Navaratnam et al. 2022). In SA, the MTCT rate has been reported at around 0.9% (Goga et al. 2018) though this estimate does not account for the potential increase when invasive testing is performed.

Beyond lowering the risk of MTCT, NIPT may also reduce the need for invasive follow-up procedures, support earlier decision-making, and contribute to better prenatal care planning. For HIV-positive pregnant women, particularly in high-prevalence settings like SA, these advantages make NIPT a safer and more accessible option.

The process of implementing NIPT is multifaceted and challenging

Some of the limitations to implementing NIPT in SA include the viability of the sample, expensive collection tubes with short expiry dates, transport and cost.

The Clinical Guidelines for Genetic Services in South Africa recommend offering NIPT to all women with high-risk pregnancies (National Department of Health: Pretoria, South Africa 2021). This includes cases of AMA, previous pregnancies affected by chromosomal abnormalities, ultrasound-detected abnormalities or pregnancies showing an increased biochemical risk. However, the guidelines also state that NIPT should first be introduced as a pilot study before widespread implementation. While these recommendations indicate that the South African government has considered the integration of NIPT, to the author’s knowledge, no studies have been conducted to date to explore its feasibility or implementation.

Several articles debate when and how NIPT should be implemented, as it is a more expensive test than biochemical screening. Most studies focused on high-risk pregnancies, skewing the results of the positive predictive value of the test. Women with a high-risk biochemical screen have previously been offered NIPT in SA. However, the uptake was low, with only 2.3% of women participating in this study (Mnyani et al. 2016). One possible reason for the low uptake of NIPT is that, in 2016, samples were sent overseas for analysis, resulting in delayed turnaround times. It is also assumed that patients had to pay out of pocket, when potentially few expectant couples could afford this.

A South African article suggests that NIPT screening should be extended to pregnant women in the intermediate-risk category (Bhorat et al. 2018). The intermediate risk group consists of women with a first-trimester biochemical screening risk score of between 1:300 and 1:1000. Testing for women in this group will eliminate the discrepancy between absolute and relative risk. This is important since the odds of a positive result vary with maternal age (Bhorat et al. 2018). However, first-trimester screening needs to be offered first to determine intermediate risk. As discussed previously, most of the South African population does not undergo biochemical prenatal screening beyond maternal age assessment, or previous history of an abnormal child or pregnancy. This raises concerns about the feasibility and practicality of implementing NIPT within the current South African healthcare system. First-trimester screening would have to be integrated universally into the state healthcare system before NIPT should be considered in this scenario.

NIPT testing is expensive and complex

When comparing the cost of NIPT with the average household income/expenditure in SA, it becomes evident that NIPT is a significantly expensive prenatal screening option. In 2024, the average price for NIPT in SA was between R5500-R6500 ($300-$330) for standard NIPT screening. According to Statistics SA, in 2022, 63% of SA households had an expenditure of less than R5000 ($270) per month (Statistics South Africa 2023a). This emphasises the cost of NIPT versus the average income in the South African population.

The SA unemployment rate in 2024 was 32% (Statistics South Africa 2024), and 49.5% of the population received government grants (Statistics South Africa 2023a). Over 9 million people in SA were medical aid beneficiaries in 2023 (CMS 2023; Statistics South Africa 2023a) with 15.7% of the South African population having medical aid. Medical aid will generally only cover the cost of NIPT when it is a high-risk pregnancy. These figures show that NIPT is only available to a minority of the South African population, as most people do not have medical aid and cannot afford it.

NIPT is a complex and resource-intensive procedure compared with other prenatal screening methods. It relies on advanced NGS technology, specialised glass collection tubes, and timely pre-sample processing. A significant limitation to the process of testing is the short viability of the cffDNA in the maternal blood sample, which must be processed within five days of blood draw to extract sufficient cffDNA for accurate testing (Diaz et al. 2016). These requirements, combined with the need for sophisticated equipment and highly trained laboratory personnel, present logistical and financial challenges, particularly in resource-constrained settings.

NIPT is usually performed at centralised laboratories because of batching requirements, expensive equipment and skills required, making it, in many cases, inaccessible in LMICs (Sium et al. 2023). NIPT is available in SA, however, samples must be sent to processing laboratories in Gauteng or abroad. Sample transportation presents a significant challenge, particularly if NIPT is to be implemented in the public healthcare sector, due to the sample's limited viability. Timely delivery to a processing laboratory is essential, yet this may be difficult to achieve in SA, where vast geographical distances and numerous small towns with limited healthcare access pose logistical obstacles. Furthermore, the transportation system itself presents constraints; for instance, it has been reported that the National Health Laboratory Service (NHLS) courier service typically collects specimens only once per day, meaning that patients still waiting to have their blood drawn at the time of collection may miss the opportunity for sampling that day (Girdwood et al. 2022).

Droplet digital PCR (ddPCR) presents a viable alternative to NGS-based NIPT, particularly in the South African context, as it is more cost-effective and offers a shorter turnaround time while maintaining comparable sensitivity and specificity (Haidong et al. 2020). Additionally, ddPCR has a simpler workflow, and both the equipment and reagents are less expensive than those required for NGS. The technology can detect subtle changes in DNA amplification, making it sufficiently sensitive for use in NIPT (El Khattabi et al. 2016).

Screening for other genetic disorders might be more relevant in LMICs compared with trisomy 13, 18 and 21

Some LMICs, have a higher prevalence of hemoglobinopathies including sickle cell anaemia. The prevalence of sickle cell anaemia in Nigeria is 20 per 1000 births, substantially higher than that of common trisomies. In SA the prevalence of sickle cell anaemia is less than 1% (World Health Organization 2006). One of the most common single-gene disorders that has a high prevalence in SA is Oculocutaneous albinism, which has a prevalence of 0.25 per 1000 births (Kromberg & Kerr 2022). Although the prevalence is high, it is not higher than trisomy 21. The burden of disease should guide how public health resources are allocated, with each country making decisions based on the specific health needs and conditions most common in its population.

A South African study examined the prevalence of congenital abnormalities among live births in KwaZulu-Natal Province. Among the observed abnormalities, 12.8% were chromosomal (Trisomy 13, 18 and 21). Down Syndrome (trisomy 21) had the highest prevalence of 1.73 per 1000 births, while trisomy 13 and 18 were each observed at a prevalence of 0.13 per 1000 births (Saib et al. 2021). Approximately 18% of pregnancies in SA are considered AMA (Statistics South Africa 2023b), which increases the risk for trisomy 21. Therefore, taking everything into consideration, screening for chromosome abnormalities in the SA population is reasonable and justified.

Ethical, legal, and social issues

The ethical, legal, and social implications of NIPT are increasingly complex, particularly in a resource-constrained and socio-economically unequal setting such as SA.

NIPT should not be regarded as ‘just another blood test’. Informed consent is critical, and pregnant women must be provided with comprehensive counselling by an appropriate healthcare professional to understand the potential outcomes, implications, and limitations of the test. This includes the right to decline testing, thereby preserving patient autonomy (Smith et al. 2018). As NIPT can be performed from as early as 10 weeks’ gestation, the receipt of abnormal results may place additional emotional and ethical burdens on expectant mothers. In some cases, the availability of early information may lead to difficult decisions around termination, decisions that may not have arisen if a spontaneous miscarriage were to occur later in the pregnancy (Haidar et al. 2018). This highlights the psychological impact of early screening and the essential role of both pre- and post-test counselling.

Sex selection is a further area of legal and ethical concern. In countries where sex-selective practices are prevalent, policies have been implemented to prevent the disclosure of fetal sex following NIPT (Jayashankar et al. 2023; Ravitsky et al. 2021). In SA, however, fetal sex is disclosed if requested on NIPT screening. Although sex-selective termination is prohibited, the Choice on Termination of Pregnancy Act permits termination of pregnancy for any reason during the first trimester (Thaldar 2023) effectively creating a legal grey area around sex selection. Legislation regarding termination of pregnancy varies significantly between countries. Since NIPT offers early and reliable information about the fetus, it may facilitate decisions regarding termination within the legally permitted timeframe (Minear et al. 2015a).

Another legal issue surrounding NIPT includes its commercialisation (Griffin et al. 2018). The commercialisation of NIPT has given rise to marketing campaigns that often prioritise the interests of test providers over those of patients (Haidar et al. 2018). These campaigns tend to emphasise convenience, speed, and accuracy while downplaying the complexity of the test and its associated ethical and medical implications.

The social implications of NIPT access are also profound. There is potential for increased disease burden within disadvantaged populations, groups that often lack adequate resources to support individuals with special needs (Allyse et al. 2015). These disparities stem from broader systemic issues, including socio-economic inequality, institutional racism, and geographic inaccessibility, as well as barriers related to communication, cultural safety, and awareness of services (Ladak et al. 2024). As Ventura et al. cautioned, “This advanced technology should not be allowed to widen the gap between countries, or worse still between people of the same country.” (Ventura et al. 2013).

Finally, there are wider societal risks associated with NIPT, including reduced tolerance for individuals living with disabilities and increased stigma towards pregnant women based on their decisions, to terminate or not to terminate a pregnancy (Griffin et al. 2018). These issues underscore the need for policies that promote equity, ensure informed choice, and protect against discrimination, while also recognising the complex emotional and social landscape within which such decisions are made.

Pre- and post-test counselling and informed consent are essential for NIPT

General pre- and post-test counselling for NIPT can be provided by an appropriate healthcare professional. However, when cases become more complex, such as when a high-risk result is obtained or when greater genetic expertise is required, a trained genetic counsellor or medical geneticist should be involved to interpret the results and provide appropriate counselling. SA lacks sufficient resources for pre- and post-test counselling, with only 28 genetic counsellors nationwide (Gomes et al. 2024). The recommended target is 0.84 genetic counsellors per 100,000 population, meaning SA meets just 5% of this benchmark (Gomes et al. 2024; National Department of Health: Pretoria, South Africa, 2021). A 2017 study reported that SA had approximately one genetic counsellor per 8.4 million individuals and one medical geneticist per 4.9 million individuals (Mozersky et al. 2017). This severe shortage highlights genetic counselling as a significant limitation within the South African healthcare context. Without access to trained professionals, patients may struggle to understand, interpret, or act on their NIPT results, leaving them uncertain about the appropriate next steps.

Culture and religion play a significant role in shaping counselling practices. African proverbs, for example, often reflect the view that every child is a blessing and that children are regarded as wealth, progenitors of lineage, and an investment for the future (Musie et al. 2022). Each culture holds distinct beliefs and values concerning pregnancy, screening, invasive testing, and termination, underscoring the importance of pre- and post-test counselling, informed consent, and respect for autonomy. This is particularly pertinent in SA, a country characterised by a rich diversity of religions and cultures, where such cultural considerations must be carefully integrated into healthcare practices.

Unequal accessibility of NIPT

NIPT provides a reliable, non-invasive option for prenatal screening with high sensitivity and specificity; however, its accessibility remains unequal. This inequality raises important concerns regarding justice and fairness in access to reproductive healthcare.

Ventura et al. (2013) argue that “There is no reason to offer an invasive test with subsequent risk of miscarriage when there is the option of a non-invasive diagnosis with no risk. Withholding this current option from pregnant women during counselling is unethical, even for low-income families. A choice of currently available options should be offered to pregnant women regardless of the social, cultural, or economic conditions, and whether or not the test is performed in their town or country.” (Ventura et al. 2013). Although this statement was made in the context of non-invasive prenatal diagnosis (NIPD), rather than NIPT, its ethical implications remain highly relevant. It is difficult to justify offering invasive testing in the state sector, which carries a risk to the pregnancy, when a safer alternative exists, particularly if the only barrier to access is financial.

In SA, NIPT is currently accessible only to pregnant women who pay out-of-pocket or those with high-risk pregnancies covered by private medical aid. Therefore, pregnant women in the public sector cannot access this test unless they pay out of pocket. In the public sector, a pregnancy that is deemed high risk due to AMA, blood tests, previously affected pregnancy or ultrasound assessment will receive an invasive test if required and provided that resources are available (Bhorat et al. 2018).

Accessibility is also dependent on location. Since NIPT technology is expensive, the test is centralised at specific laboratories. Therefore, NIPT might not be offered in small towns in SA, as they will not have the correct collection tube and/or transport necessary to ensure the sample reaches the laboratory promptly.

The South African Society of Obstetricians and Gynaecologists (SASOG) and the Gynaecology Management Group (GMG) stated the following:

“If money wasn’t an issue and there were more than enough experts in the country, the very best screening would be a combination of NIPT with an expert Nuchal Translucency (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 very expensive and will not be available for all pregnancies soon. This is not only the situation in SA but also in many developed countries. For this reason, alternative screening strategies can be considered acceptable, with some form of triaging according to risk.”(The South African Society of Obstetricians and Gynaecologists & Gynaecology Management Group 2018)