QF-PCR: a valuable first-line prenatal and postnatal test for common aneuploidies in South Africa

Abstract

Quantitative fluorescence-polymerase chain reaction (QF-PCR) is useful for the detection of aneuploidies involving chromosomes 13, 18, 21, X and Y. Due to the rapid turn-around time and reduced cost compared to traditional karyotyping, QF-PCR has been used as an alternative test for both pre- and postnatal aneuploidy detection in Johannesburg, South Africa since 2001. An internal review of 13,396 aneuploidy tests processed using QF-PCR between January 2015 and December 2019 was performed, and the results showed that the majority (~ 88%) of cases were postnatal tests, with prenatal samples accounting for only ~ 12% of cases. The most common aneuploidies detected were Trisomy 21 (20.6%), Trisomy 18 (3.7%) and Trisomy 13 (2.4%), while sex chromosome aneuploidies were only detected in < 1% of cases. The average percentage of positive cases over the 5-year period was 32.1% for postnatal samples and 11.3% for prenatal samples. QF-PCR testing of the common aneuploidies is being used appropriately, and the high percentage of positive cases demonstrates the value of QF-PCR as prenatal and postnatal tests, particularly in limited resource settings. The higher proportion of positive postnatal cases suggests that referrals are clinically appropriate. However, there is under- and uneven utilization of genetic services in many provinces in South Africa, and the state of prenatal genetic services is poor, as reflected by the low number of prenatal referrals. These results demonstrate the need for programs which will improve the genetic knowledge of referring doctors and the general public, thereby improving the broader utilisation of QF-PCR aneuploidy diagnostic testing, so that patients receive appropriate diagnoses and subsequent management.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12687-022-00587-y.

Background

Aneuploidy refers to the presence of an abnormal number of chromosomes, with the most common aneuploidies seen in live births involving chromosomes 13, 18, 21, X and Y (Table 1). Although conventional cytogenetic testing for aneuploidies is highly accurate and comprehensive (Turrina et al. 2008), it is labour intensive, time consuming (~ 4 weeks), and costly (~ R34001 based on State costs (2020) in South Africa) and requires short transport times of specimens to achieve live cells for culture (Brown et al. 2006; Muthuswamy and Agarwal 2016). It also requires skilled cytogeneticists for analysis. Therefore, quantitative fluorescence-polymerase chain reaction (QF-PCR) was developed as a way to meet the need for rapid results in prenatal cases (Brown et al. 2006; Allingham-Hawkins et al. 2011; Muthuswamy and Agarwal 2016). By using short tandem repeats across a chromosome, QF-PCR is able to quantify the amount of DNA present, and thus able to detect aneuploidies involving chromosomes 13, 18, 21, X and Y (Hills et al. 2010; Allingham-Hawkins et al. 2011). One of the greatest advantages of QF-PCR is that is does not require cell culture which allows for a shorter turn-around time (TAT) (within 3 days), reduced cost (~ R18002 based on State costs (2020) in South Africa) and the ability to still analyse samples that may have been delayed in transit (Hills et al. 2010; Allingham-Hawkins et al. 2011).

Table 1.

Global and South African birth prevalence for the common aneuploidies

Common Aneuploidies	Worldwide birth prevalence	South African birth prevalence
Trisomy 21	1.25 in 1000 live birthsa	1.33–1.8 in 1000 live birthsb,c
Trisomy 18	1 in 8000 live birthsd	1 in 10,000 live birthse
Trisomy 13	1 in 10 000 live birthsf	1 in 24,000 live birthse
Klinefelter Syndrome	1 in 660 live male birthsd
Turner Syndrome	1 in 2500 live female birthsd

^aGabbe et al. (2017)

^bDelport et al. (1995)

^cChristianson and Kromberg (2008)

^dKumar et al. (2014)

^eParrot (1997)

^fCarey (2005)

The South African health care system consists of a public, state-funded system that serves at least 80% of the population, while the remaining ~ 20% of the population are served by private hospitals and funded by medical aid schemes. Therefore, with the majority of patients relying on state services and the limited funding that is available, the use of tests, such as QF-PCR, that limit costs is extremely important. Additionally, with only a handful of genetic testing centres in the country, it can take days for samples to reach these centres. Therefore, the fact that QF-PCR does not require cell culture and can still be performed following transit delays is beneficial in the South African setting.

In a prenatal setting, the shorter TAT associated with QF-PCR may lead to faster reassurance when there are negative results and earlier decisions involving pregnancy management or termination in cases in which an abnormality is detected (Ogilvie 2005). In South Africa, termination of pregnancy (TOP) is governed by the Termination of Pregnancy Act (No. 92, 1996). This Act allows for termination in the presence of foetal anomalies such as aneuploidies throughout pregnancy, with different requirements depending on the stage of pregnancy. During the first 12 weeks of pregnancy, a TOP can be performed without any conditions. Between 13 and 20 weeks, a medical practitioner must find a substantial risk of severe physical or mental abnormality to the foetus in order to perform a TOP. Lastly, after 20 weeks, a TOP must be agreed upon by two medical practitioners in the case that there is a severe malformation of the foetus. Furthermore, postnatal aneuploidy testing is equally as important, and the rapid nature of QF-PCR is beneficial as early interventions can be put in place. Additionally, management and care decisions, including avoiding invasive procedures such as ventilation or surgery, can be made in the case of Trisomy 13 and 18.

While initially developed for prenatal aneuploidy screening, QF-PCR has been used for both pre-and postnatal aneuploidy testing at the Division of Human Genetics (DHG), National Health Laboratory Services (NHLS) and The University of the Witwatersrand since 2001, and is one of the most commonly requested tests with ~ 13,000 tests performed between January 2015 and December 2019. The aim of this research was to perform an internal review of the QF-PCR aneuploidy testing to assess the diagnostic yield and appropriateness of testing, in our limited-resource setting.

Methods

Data collection and analysis

Data for all QF-PCR aneuploidy test requests (n = 13,396) processed between January 2015 and December 2019 were obtained from the Division of Human Genetics (DHG), National Health Laboratory Services (NHLS) and The University of the Witwatersrand, henceforth referred to as the DHG. The DHG is one of the three laboratories in South Africa that provides genetic services for State patients. It is based in Johannesburg, South Africa and receives samples from the Gauteng province, in which it is based, as well as from five other surrounding provinces, where there are no genetics laboratories. The data for all cases were recorded in a Microsoft Excel (v16.35) database, including the case number, sample type received, results of the QF-PCR test, as well as the time and date at which the sample was received, and the results were obtained. The sample type was used to determine whether cases were prenatal or postnatal in nature and the time and date at which the sample was received, and the results obtained were used to calculate the TAT. The referral site for each case was obtained from the DHG’s laboratory information management system (NHLS-LABTRAK) and was used to determine the province and hospital of origin. All the data analyses were performed, and all the figures were generated using Microsoft Excel (v16.35).

Ethics

The analysis was performed under Human Research Ethics Committee (HREC) (Medical) certificate number M180506, from the Faculty of Health Science, University of the Witwatersrand.

Results

Number of samples received per year:

Overall, 13,396 QF-PCR tests were requested over the 5-year period (2015–2019). The number of cases requested per year can be seen in Fig. 1. We observed a steady increase in the number of cases per year from 2160 cases in 2015 to 3597 cases in 2019, with an increase of 66.5% over a 5-year period (Fig. 1). Further in-depth analysis regarding the breakdown of cases into prenatal and postnatal cases can be seen in the ‘Sample type’ section below.

Fig. 1.

Number of cases for QF-PCR aneuploidy testing received per year from 2015–2019 separated into prenatal (n = 1628; blue), postnatal (n = 11,706; orange) and unrecorded samples (n = 62; grey). The total number of cases received per year can be seen in bold above each bar

Referral path (province and hospital)

Over a 5-year period (2015–2019), the majority (68.9%) of QF-PCR tests were requested from Gauteng (the province in which the testing laboratory is based), followed by Limpopo (10.6%), Mpumalanga (5.9%), North West Province (5.2%), KwaZulu-Natal (4.64%) and the Eastern Cape (3.62%) (Fig. 2). In Gauteng, the three centres that contributed the highest number of cases were the central, academic hospitals, namely Chris Hani Baragwanath Hospital (18.1%), NHLS Braamfontein (cases from the genetics clinics performed by doctors of the DHG) (12.9%) and Charlotte Maxeke Academic Hospital (11.0%) (Fig. 2). Almost one-third of cases originating in Limpopo were requested from a single tertiary hospital, Mankweng Hospital (29.2%) (Fig. 2). In Mpumalanga, three centres contributed over half (58.9%) of the cases from this province (Fig. 2). Almost half of the cases originating in the North West were requested from Klerksdorp Hospital (47.9%) which is a tertiary hospital (Fig. 2). Lastly, approximately half of the cases requested from KwaZulu-Natal were requested from Newcastle Hospital (48.7%) which is a regional hospital and in the Eastern Cape the majority of cases (76.7%) were requested from a central, academic hospital, namely Nelson Mandela Academic Hospital. The number of samples referred is not proportionate to the type of hospital (e.g. central, regional or tertiary) or the size of population served.

Fig. 2.

Number of QF-PCR aneuploidy test requests originating from each province in South Africa. The hospitals from which testing was most commonly requested in Gauteng, Mpumalanga, Limpopo and North West can be seen in the blocks. There were 113 cases where the origin could not be ascertained

Sample type

Over the 5-year period (2015–2019), the vast majority (87.8%) of cases received were postnatal, with prenatal samples accounting for only 12.2% of cases (Fig. 1). The number of prenatal cases did increase over the 5-year period, with 281 prenatal samples received in 2015 and 501 prenatal samples received in 2019, an increase of 78.3%. For prenatal samples, amniotic fluid was the most common sample type (1594/1628; 97.9%), with very few chorionic villus samples (CVS) (27/1628; 1.7%) or cord blood samples (7/1628; 0.4%) received. For postnatal samples, blood samples were the most common sample type received (10,329/11,706; 88.2%), followed by skin/tissue samples (1019/11,706; 8.7%) and products of conception (POC)/foetal samples (269/11,706; 2.3%). Other sample types included DNA (35/11,706; 0.3%), placenta (26/11 706; 0.2%), muscle tissue (15/11,706; 0.1%) and urine (3/11,706; < 0.1%). In seven cases (0.1%) a combination of sample types was received. Furthermore, one cerebrospinal fluid sample, one umbilical cord sample and one foetal ascitic fluid sample were received.

Results of QF-PCR tests

Overall, the most common result returned from the QF-PCR tests was no aneuploidy detected (NAN) (66.6%) (Fig. 3a). The most common aneuploidy detected was Trisomy 21 (20.6%) which was followed by Trisomy 18 (3.7%) and Trisomy 13 (2.4%) (Fig. 3a). Sex chromosome aneuploidies were only identified in 0.9% of cases (Fig. 3a), and the most common sex chromosome aneuploidy that was detected was Turner Syndrome (X0) which accounted for 60.3% of the sex chromosome aneuploidies (Fig. 3b). Furthermore, in 2.0% of cases, a result other than the common aneuploidies mentioned above was obtained (Fig. 3a). A detailed breakdown of these results is reported in the supplementary material (Supplementary Table 1). Lastly, in 518 cases (3.9%), no result or no conclusive result was obtained for various reasons (Fig. 3a). Unsuccessful tests accounted for the majority (373/518; 72.0%) of cases in which no result was obtained. This was followed by maternal cell contamination (MCC) (90/518, 17.4%) and tests with unreliable results (n = 43; 8.3%). MCC occurred most commonly in amniotic fluid samples (35/90, 38.9%), followed by skin/tissue samples (25/90, 27.8%) and POC/foetal samples (21/90, 23.3%).

Fig. 3.

a Results obtained from the QF-PCR aneuploidy tests performed over a 5-year period. b Further breakdown of the sex chromosome aneuploidies that were detected (X0, Turner Syndrome; XXX, Triple X Syndrome; XXY, Klinefelter Syndrome; XXXXY, XXXXY Syndrome; and XYY, XYY Syndrome)

For cases in which a positive result was obtained, we looked at the contribution of each common aneuploidy in prenatal versus postnatal samples (Fig. 4). Clear differences can be seen for the following aneuploidies: (1) Trisomy 21 was detected in 71.3% of positive postnatal cases as opposed to 35.7% of positive prenatal cases, (2) Trisomy 18 was detected in 11.3% of positive postnatal cases compared to 35.7% of positive prenatal cases, and (3) Trisomy 13 was detected in 7.7% of positive postnatal cases as opposed to 13.2% of positive prenatal cases (Fig. 4).

Fig. 4.

Breakdown of the type of aneuploidy detected in a prenatal samples and b postnatal samples. Only the most common sex chromosome aneuploidies (Turner Syndrome (X0), Triple X Syndrome (XXX) and Klinefelter Syndrome (XXY)) were included specifically in this figure

Proportion of positive cases and TAT

The average proportion of positive cases over the 5-year period was 32.1% for postnatal samples and 11.3% for prenatal samples. A subset of postnatal samples, including skin, tissue, placenta, muscle and POCs, were classified as post-mortem samples. These samples were most likely collected after miscarriages, still births, pregnancy terminations and postnatal deaths. The average proportion of positive cases for these post-mortem samples over the 5-year period was 8.6%.

The mean TAT for each case over the 5-year period was 5.2 days from the date that the sample was received to the date that the result was returned. The median was 5 days, and the mode was 3 days. It is important to note that the calculated TAT includes weekends, and therefore the true TAT is likely to be shorter.

Discussion

Historically, diagnosis of chromosomal abnormalities has been performed by conventional cytogenetic testing (Langlois et al. 2011). However, the need for rapid and affordable, culture-independent testing has led to the development and use of rapid aneuploidy tests (RATs), including QF-PCR (Badenas et al. 2010). Due to the lower cost, robustness and short TAT (Cirigliano et al. 2005; Hills et al. 2010), QF-PCR is the preferred method for aneuploidy testing at the DHG, in Johannesburg South Africa, where it is used for both prenatal and postnatal detection of the common aneuploidies. The postnatal use of QF-PCR seems to be an uncommonly reported practice elsewhere in the world as no publications could be found in which QF-PCR was used for the postnatal testing of aneuploidies; however, the European cytogenetics guidelines does suggest that QF-PCR is performed on newborn blood samples (Silva et al. 2019). With aneuploidy testing being one of the most commonly requested tests at the DHG, the aim of this study was to perform a 5-year internal review of QF-PCR aneuploidy tests performed between January 2015 and December 2019.

Underutilization of genetic services in some provinces

The majority of cases were requested from Gauteng (68.9%) (Fig. 2), which is to be expected due to the larger population size and proximity of these populations to the hospitals and the testing laboratory. According to the “Human Genetics Policy Guidelines for the management and prevention of genetic disorders, birth defects and disabilities”, Gauteng provides genetic services to the North West, Limpopo, Mpumalanga and KwaZulu-Natal (National Department of Health 2003). However, the number of requests originating from the North West, Limpopo, Mpumalanga and KwaZulu-Natal is low (Fig. 2). While there may be some referrals from these provinces to other laboratories, very few other laboratories serve State patients. Therefore, the lack of requests may be because genetic testing is not being offered consistently throughout these provinces. This may be due to a lack of awareness of both the health professionals and the public regarding the genetic services that are available and, additionally, due to issues surrounding transport and access (Kromberg et al. 2013). Interestingly, utilization is not always related to the size of the facility or proximity to Gauteng which suggests that there is uneven use of these services, perhaps related to knowledge or activity of particular clinicians. It is likely that patients are not receiving confirmatory diagnoses, limiting their access to downstream management and appropriate counselling. These findings emphasize the need to improve genetic awareness, particularly in provinces which are not making full use of the available genetic services, and to interrogate the reasons for poor utilisation further.

Lack of prenatal genetic services or uptake of these services

Over the 5-year period, prenatal samples accounted for only 12.2% of QF-PCR tests requested, despite this being the original reason for the introduction of the test (Fig. 1). This indicates that QF-PCR is probably being underutilized for prenatal aneuploidy testing. Even though South Africa has prenatal screening policies in place (Bryant et al. 2006), the lack of financial resources means that prenatal diagnostic procedures as well as foetal ultrasound are limited to tertiary centres only, and biochemical screens as well as non-invasive prenatal screening (NIPS) are only available in the private sector (Urban et al. 2011; Scott et al. 2013). Furthermore, even though invasive prenatal procedures have been available in South Africa since 1979, these services, where available, are underutilized due to limited knowledge, late initiation of antenatal care, and low uptake of amniocentesis in the public sector (Urban et al. 2011; Scott et al. 2013). Furthermore, only 27 cases over a 5-year period were CVS samples which suggests that early pregnancy testing is very limited within the public sector in South Africa. The limited access to prenatal services is also reflected in the high number of postnatal diagnoses of common aneuploidies. The results of this study reflect the limited prenatal genetic services, as well as a lack of uptake of the available services, in the northern part of South Africa and indicate the need for educational programs, for both health care professionals and the public, regarding the importance of early pregnancy evaluation and testing.

Appropriateness of QF-PCR as an aneuploidy test

Most prenatal diagnosis services offer a RAT, such as QF-PCR, as a first-line screen which is then followed by karyotyping as a confirmatory test (Leung et al. 2008; Badenas et al. 2010). However, this is an expensive and time-consuming approach, which is impractical in a resource-limited public health care system (Badenas et al. 2010) such as the one in South Africa. Therefore, at the DHG, QF-PCR is used as a stand-alone diagnostic test for the common aneuploidies, and the results are not routinely confirmed with karyotyping, an approach which has been shown to be appropriate in a study performed by Badenas and colleagues (2010). Furthermore, the European cytogenetic guidelines also recognize QF-PCR as a diagnostic, targeted test that does not require confirmation in most cases (Silva et al. 2019). The high proportion of prenatal and postnatal tests with a positive result, discussed in the following paragraphs, in combination with the rapid TAT, lower cost, ability to perform testing on samples that have been delayed in transit, and the fact that this test can be used as a stand-alone test, suggest that QF-PCR is an appropriate first-line test for prenatal and postnatal aneuploidies in a low-and-middle-income country (LMIC) such as South Africa and can assist in the appropriate use of scarce antenatal and neonatal resources. Even though karyotyping provides value in terms of being able to determine recurrence risks and mechanisms (distinguishing between aneuploidies caused by non-disjunction versus a translocation), as well as provides a better indication of mosaicism and partial abnormalities, QF-PCR provides sufficient information for a confirmation of diagnosis of one of the common aneuploidies, allowing for routine management particularly within LMICs, where cytogenetics skills may be very limited and access to cytogenetics laboratories is challenging.

Proportion of prenatal cases with a positive result

The average proportion of prenatal samples with a positive result in this study was found to be 11.3%. This is comparable to a study performed by Voglino and colleagues (2002) in which the proportion of cases which tested positive for the common aneuploidies was 11.5%, but higher than a study performed by Badenas and colleagues (2010) in which the proportion of positive QF-PCR tests was only 4.4%. While the positivity percentage of QF-PCR aneuploidy testing for prenatal diagnosis varies from study to study, a positivity percentage of over 10% for prenatal samples in our study is comparable, if not higher, than other studies, suggesting that testing in prenatal cases is being performed appropriately. However, the high proportion of positive postnatal cases in combination with the low number of prenatal cases received confirms that prenatal testing is not being performed enough and suggests that it is probably being performed in high-risk cases only, and less in moderate risk cases. This is evident by the relatively higher proportion of Trisomy 18 detected compared to Trisomy 21 (Fig. 4) which suggests that many women at risk for Trisomy 21 are not being tested prenatally. Although not assessed in this study, future evaluation of the indication for testing provided by clinicians may provide insight into this trend and could help to improve the use of QF-PCR in a prenatal setting in South Africa. QF-PCR is extremely valuable in prenatal cases due to the short TAT. This is particularly important in our setting as we have observed that the majority of testing does not occur during early pregnancy, leaving little time for decision making.

Proportion of postnatal cases with a positive result

The average proportion of postnatal samples with a positive result in this study was 32.1%. No publications were available that provided a comparative positivity percentage for QF-PCR performed on postnatal antemortem samples (blood); however, when karyotyping was used to detect Trisomy 21 postnatally in a study performed by Zhao and colleagues (2015), only 2.9% of cases had a positive result. While this study is not directly comparable, the proportion of positive cases was significantly lower than what was seen in this study. The high numbers of postnatal diagnoses in this study may be a reflection of the poor prenatal services that are available, with cases not being detected prenatally and thus requiring postnatal diagnosis. This also highlights the importance of clinical awareness of the features of the common aneuploidies, so that prompt postnatal diagnosis can be performed. This may impact on management decisions in the immediate postnatal period. Furthermore, the high positivity rate suggests that the use of QF-PCR for the postnatal testing of common aneuploidies is not only appropriate, but also extremely valuable, especially considering the poor prenatal programs that are available in South Africa. The short TAT and reduced processing workflow, in combination with the high postnatal positivity rate, suggests that QF-PCR should be considered and set up as a first-line postnatal test for the common aneuploidies elsewhere, particularly in other resource-limited LMICs.

A subset of the postnatal samples in this study was post-mortem samples consisting of miscarriages, still births, pregnancy termination and postnatal deaths. The average positivity rate for this subset of samples (skin, tissue, placenta, muscle and POCs) was found to be 8.6%. Pregnancy losses are often caused by aneuploidies involving chromosomes other than 13, 18, 21, X and Y (Hassold and Hunt 2001). The QF-PCR test offered by the DHG may not be extensive enough for POC testing, which may explain the relatively low positivity rate. In view of the low number of post-mortem samples and poor clinical information received by the DHG, extension of this testing has not been a focus.

Sex chromosome aneuploidies

Aneuploidies involving the sex chromosomes occur more frequently than those involving the autosomes (Kumar et al. 2014); however, sex chromosome aneuploidies were only identified in 0.9% of cases in this study (Fig. 3). Karyotyping remains the gold standard for the detection of sex chromosome aneuploidies and, therefore, QF-PCR is not usually indicated for cases involving ambiguous genitalia or disorders of sexual development (Nagy et al. 2015). Our results confirm the limitations of using QF-PCR for sex chromosome aneuploidies as it is unable to detect structural abnormalities and mosaicism of the sex chromosomes reliably and we recommend that karyotyping be performed in cases where a sex chromosome aneuploidy is suspected or ambiguous genitalia are present.

Criteria for referral for QF-PCR aneuploidy testing

With the increasing availability of genetic tests, primary care physicians and non-genetic specialists are requesting a greater number of genetic tests (Christian et al. 2012). This leads to a significant risk for inappropriate testing due to incomplete request forms without proper clinical information and improper ordering of tests (Goodenberger et al. 2018). According to the DHG guidelines (NHLS communication, 29/03/2019), QF-PCR should only be requested in prenatal cases if there is a clear indication of Trisomy 21, Trisomy 18 or Trisomy 13, the mother is of advanced maternal age (AMA) or soft markers are observed on ultrasound. If multiple foetal/congenital abnormalities are observed, or there has been a non-trisomy chromosome abnormality such as a structural chromosomal abnormality in a previous pregnancy, karyotyping should be requested. In postnatal cases, QF-PCR should only be requested if Trisomy 13, Trisomy 18 or Trisomy 21 is suspected clinically. If any other chromosomal abnormality is suspected, karyotyping or microarray, which assesses all of the chromosomes, should be requested instead. Furthermore, QF-PCR is not considered an adequate investigation for the determination of sex in suspected disorders of sexual differentiation or the detection of sex chromosome aneuploidies; therefore, these cases should be sent for karyotyping. Lastly, a limitation of QF-PCR is that the mechanism of the aneuploidy and thus recurrence risk cannot be determined. Therefore, in carefully evaluated circumstances, for example a woman planning future pregnancies with a family history of an aneuploidy and thus a concern about a translocation, karyotyping may be offered.

Conclusion

Overall, the use of QF-PCR as a first-line test for the common aneuploidies at the DHG appears appropriate. The results of this study have shown that the current prenatal genetic services are underutilized and suggest that the prenatal programs in the State hospitals need to be up-scaled significantly in order to identify more aneuploidies prenatally. In addition to QF-PCR being used for prenatal testing, we have shown that there is also a great value in using it as a rapid and accurate test for detecting the common aneuploidies postnatally, when resources are limited. This allows for early postnatal diagnosis, genetic counselling and management. The results of this study have also shown that there is limited and uneven use of genetic services in several provinces in the northern part of South Africa, and that programs to improve the genetic knowledge of both referring doctors and the general public, as well as to investigate the reasons behind the limited use of available services, are desperately needed. Lastly, while there is currently limited availability in State hospitals, the use of ultrasound and biochemical testing, as well as non-invasive prenatal screening (NIPS), should lead to increased and more appropriate referrals for prenatal QF-PCR testing. Furthermore, the study demonstrates the value of QF-PCR as a prenatal and, particularly, a postnatal test for aneuploidies in LMICs. This test could be used by other LMICs to provide a large group of patients with confirmed diagnoses, thus reducing uncertainty and providing directed management and counselling.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contribution

Laura Cottino led the writing of the paper. Laura Cottino, Maria Mudau and Nakedi Lekgate were responsible for the data analysis. All the authors contributed to the writing of the manuscript, and read and approved the final manuscript.

Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval

This study was performed under Human Research Ethics Committee (HREC) (Medical) certificate number M180506, from the Faculty of Health Science, University of the Witwatersrand. This study was performed in line with the principles of the Declaration of Helsinki.

Consent to participate

The ethics certificate (M180506) under which this study was performed allows for anonymized retrospective internal reviews to be performed without consent.

Conflict of interest

The authors declare no competing interests.