Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome and spinal muscular atrophy: patterns of community and healthcare provider participation in a Victorian screening program

Keywords: community health, cystic fibrosis, fragile X syndrome, general practice, genetics, healthcare disparities, reproductive carrier screening, reproductive health services, spinal muscular atrophy.

Reproductive genetic carrier screening (RGCS) provides individuals and couples with information about their chance of having a child affected by a genetic condition and enables them to make informed reproductive decisions (Henneman et al. 2017). Advances in technology have facilitated the development of carrier screening panels that test for multiple autosomal recessive and X-linked conditions from blood or saliva samples (Henneman et al. 2017).

The Royal Australian and New Zealand College of Obstetricians and Gynaecologists and the Royal Australian College of General Practitioners now recommend that information on carrier screening for at least the most common inherited genetic conditions in our population, that is, thalassaemia, cystic fibrosis (CF), spinal muscular atrophy (SMA), and fragile X syndrome (FXS), should be offered to all women planning pregnancy or in early pregnancy regardless of family history or ethnicity (Royal Australian and New Zealand College of Obstetricians and Gynaecologists 2019; Royal Australian College of General Practitioners 2020). Screening for thalassaemia carrier status can be undertaken by full blood examination. Options for RGCS include screening with a three-condition panel for CF, SMA and FXS (prevalences of 1 in 2500, 1 in 10 000 and 1 in 4000–6000 respectively; Archibald et al. 2018) or screening with an expanded panel for many disorders (up to hundreds). At present, RGCS in Australia is generally offered on a user-pays basis, with a 3-panel screen costing approximately between A$350 and A$400 and expanded genetic carrier screening costing between A$579 and A$900.

It is generally recognised that GPs are well placed to offer RGCS (Archibald et al. 2016; Plantinga et al. 2016; Schuurmans et al. 2019) as they already have a role in providing preconception counselling and are often the first healthcare practitioners to see women early in pregnancy. However, it is also recognised that GPs may have limited genetic knowledge (Archibald et al. 2016). Confidence, time, and interest are additional barriers to offering RGCS in general practice (Best et al. 2021).

In this study we investigate community and healthcare provider (HCP) participation in a Victorian RGCS program for CF, SMA and FXS.

This study investigates a 3-panel RGCS program offered by the Victorian Clinical Genetic Services (a not-for-profit, wholly owned subsidiary of the Murdoch Children’s Research Institute) screening for CF, SMA and FXS. This program was available to HCPs across Australia from early 2013, with primarily Victorian practitioners using the service. Obstetricians, fertility specialists, general practitioners, genetic counsellors, and clinical geneticists were notified of the screening program by letter and via newsletters and email bulletins. Education sessions were offered to all HCPs providing this test and involved one-to-one or small group discussions and larger seminars. The program is now recognised as Victoria’s largest RGCS program (Robson et al. 2020). Detection rates are estimated to be 90% for CF, 95% for SMA, and >99% for FXS (Archibald et al. 2018). Screening is offered to women prior to pregnancy or early in pregnancy (recommended ≤12 weeks gestation) by HCPs at a cost of A$389. The purpose of this screening is to identify women and/or couples who have an increased chance of having a child with CF, FXS or SMA. A sequential screening model is generally used, where the female partner is screened first due to the X-linked inheritance pattern of FXS. Information for patients and health professionals is available in an information brochure and on the VCGS website (https://www.vcgs.org.au/tests/prepair). Genetic counselling, offered by trained genetic counsellors from VGCS, is available at any stage in the genetic carrier screening process. All carrier results are discussed with the requesting HCP by telephone and genetic counselling is offered for genetic carriers. Testing of the partner is offered for genetic carriers of CF and SMA. All couples/individuals with an increased chance of having a child with a condition (CF and SMA genetic carrier couples and FXS genetic carrier females) are offered a genetic counselling appointment and an appointment with a paediatric subspecialist with expertise in the relevant condition. Partner screening, genetic counselling and paediatric subspecialist appointments, where required, are provided at no additional charge.

Outcomes of screening of women between 18 September 2013 and 12 October 2018 were analysed. Male results were excluded from the analysis because, in line with the sequential screening model, most males were tested only as a consequence of their female partner being found to be a genetic carrier of CF or SMA. Requesting HCP and patient data were extracted from screening request forms. Data were analysed with respect to profession of requesting HCP, and characteristics of women screened (age, pregnancy status, socioeconomic status, geographic location, and family history of CF, SMA or FXS). Requesting HCPs were categorised into general practitioner, obstetrician, fertility specialist, genetic HCP (clinical geneticist or genetic counsellor), or ‘other’, by using data from the Australian Health Practitioner Registration Agency, Human Genetics Society of Australasia and, for missing data, internet searches on the name of the individual HCP. Where HCPs practised both as fertility specialists and obstetricians, they were categorised as fertility specialists.

Geographical location was identified using the postcode of women screened. For women from Victoria, the postcode was used to categorise their local government authority (LGA). Population data from the Australian Bureau of Statistics (ABS) were used to calculate the rate of screening in each LGA, and the Australian Urban Research Infrastructure Network portal (Australian Urban Research Infrastructure Network 2019) was used to produce a geographical map of screening rates per 10 000 head of population.

Socioeconomic status of women screened in Australia (excluding 391 women screened in New Zealand) were categorised into 10 deciles, with decile 1 being the most disadvantaged and decile 10 being the least disadvantaged, using the SEIFA (Socio-Economic Indexes for Area) Index of Relative Socioeconomic Disadvantage score for Australian postcodes (Australian Bureau of Statistics 2018a). In addition, the socioeconomic status of the subgroup of screened women living in Victoria was analysed. For this analysis, the Index of Relative Socioeconomic Advantage and Disadvantage score for Victorian LGAs was used (Australian Bureau of Statistics 2018a). In order to account for variations in birth rate within different socioeconomic groups, the rate of screening per 100 000 births in each socioeconomic quintile in Victoria was calculated using ABS birth data for LGAs from 2012 to 2018 (Australian Bureau of Statistics 2018b). Socioeconomic data were missing for 65 women because of missing postcodes or postcodes that did not match with SEIFA postcodes. Victorian LGA data were missing for 10 women because of missing postcodes or postcodes that did not match with SEIFA LGAs.

The proportion of women of child-bearing age in Victoria and the proportion of pregnant women in Victoria who undertook screening were calculated using Victorian government statistics on births and population (Births in Victoria 2018). The proportion of Victorian HCPs who requested screening were calculated using data on workforce participation (Australian Government Department of Health 2017, 2020).

Descriptive statistical analysis was undertaken using STATA 16 (StataCorp).

This project was approved by the Royal Children’s Hospital Human Research Ethics Committee in March 2019 (Reference Number: 38158).

A total of 21 172 women was screened between 18 September 2013 and 12 October 2018.

Although tests were requested for people from all states and territories of Australia and from New Zealand, 19 222 (91%) of the women screened were from Victoria (frequencies of screening in other locations were: New South Wales 429, Tasmania 494, Queensland 438 Tasmania 494, ACT 82, South Australia 30, Northern Territory 27, West Australia 37, New Zealand 391, and 22 of unknown location).

The mean age at screening was 33.9 (95% CI 33.9–34.0) years with a range of 18–57 years. Two-thirds of those screened were aged between 29 and 38 years (Table 1).

Table 1.  Screening patterns according to category of requesting healthcare professional (HCP).

The pregnancy status was known in 15 272 of the women screened (72% of the cohort). Among these women, 10 350 (68%) were pregnant at the time of testing (Fig. 1). Among women of known pregnancy status, 7709 (89%) screened by obstetricians were pregnant at the time of testing, compared with 574 (22%) screened by fertility specialists, and 1773 (53%) screened by GPs.

Fig. 1.  Pregnancy status of women screened for each category of requesting healthcare provider.

A family history of one or more of the three conditions was recorded in 331 women (1.6%).

Ten thousand three-hundred and forty-eight women (50%) were in the top quintile for socioeconomic status and 15 643 (75%) in the top two quintiles (Fig. 2).

Fig. 2.  (a) Socioeconomic status of women screened in Australia. Frequency of screening in each Australian socioeconomic quintile (using SEIFA 2016 Index of Relative Socioeconomic Disadvantage score for Australian postcodes). (b) Socioeconomic status of women screened in Victoria. Frequency of screening and rate of screening per 100 000 births in each Victorian socioeconomic quintile (using SEIFA 2016 Index of Relative Socioeconomic Advantage and Disadvantage score for Victorian local government areas).

Obstetricians, fertility specialists, GPs and genetics HCPs made up >99% of all requests (Table 1). Obstetricians made 11 241 requests (53%), whereas GPs made 4277 requests (20%). However, of the 1288 requesting HCPs, 860 (67%) were GPs. The median number of requests per GP was 1 compared with 6 for obstetricians and 9 for fertility specialists. There were 670 HCPs who requested a single test, of whom 538 (80%) were GPs. Thirty-eight (17%) requesting obstetricians made over 100 requests compared with two (0.2%) requesting GPs (Fig. 3).

Fig. 3.  Number of screening requests per requesting healthcare provider for each category of requesting healthcare provider.

Within Victoria, 10 415 (54%) women screened were in the highest socioeconomic quintile (Fig. 2b). This was a slightly higher number than found in the highest socioeconomic quintile in the total Australian data, and is likely to be due to differences in how the data were derived; Victorian data were derived using SEIFA 2016 Index of Relative Socioeconomic Advantage and Disadvantage score for Victorian local government areas whereas the total Australian data were derived using SEIFA 2016 Index of Relative Socioeconomic Disadvantage score for Australian postcodes. The frequency of screening per 100 000 births was 11 414 women screened per 100 000 births in the highest quintile compared with 1407 women per 100 000 births in the lowest quintile (i.e. the screening rate was approximately eight-fold higher in the highest socioeconomic quintile than the lowest socioeconomic quintile). By calculating this measure, the effect of any variations in birth rate with socioeconomic status was accounted for.

Within Victoria, the highest screening rate was in the inner eastern suburbs of Melbourne, where between 117 and 134 per 10 000 population were screened, whereas the lowest rate of screening was in rural areas, with between 0 and 17 per 10 000 population screened (Fig. 4).

Fig. 4.  Screening rates per 10 000 population for each local government area in Victoria (on the left is a map of the whole of Victoria; on the right is an enlarged map of the Metropolitan Melbourne area only).

Approximately 1.5% of Victorian women of child-bearing age and approximately 3% of pregnant Victorian women were screened by this program over the period of this study. There were 49 women screened by this program per 1000 births in Victoria over the time of this study. Approximately 9% of GPs and approximately half of all obstetricians and fertility specialists in Victoria made at least one screening test request over the study period.

This study of Victoria’s largest RGCS program (Robson et al. 2020) highlights the unequal participation in RGCS by the community and HCPs. Steep socioeconomic and geographic gradients were identified, such that those in more affluent and inner metropolitan areas were much more likely to be screened than those in less affluent and outer metropolitan and regional areas.

This study also highlights the importance of GPs in preconception care by revealing the larger proportion of non-pregnant women screened by GPs compared with obstetricians (47% vs 11%). Although this finding is expected, as few women see their obstetrician prior to pregnancy, it confirms that GPs are indeed undertaking preconception screening at a greater rate than obstetricians. It is widely accepted that preconception carrier screening is preferable to prenatal screening because it offers a wider range of reproductive options including preimplantation genetic testing using IVF (Archibald et al. 2016; Delatycki et al. 2019). Preconception care in general practice is encouraged by GP professional bodies (Royal Australian College of General Practitioners 2016), but participation is not high (Mazza et al. 2013; Kizirian et al. 2019). Barriers to preconception care delivery include time constraints, lack of knowledge and lack of resources for patients (Kizirian et al. 2019). Increasing rates of GP preconception care, which includes RGCS, provides a model by which screening could be offered to all people of reproductive age (Delatycki et al. 2019).

Our finding that obstetricians are requesting RGCS more frequently than GPs suggests that obstetricians have incorporated RGCS into their routine practice more readily. It is likely that the vast majority of screening requested by obstetricians is in the private sector rather than in the public hospitals. This is because these women are likely to be able to afford screening, but also, importantly, because private obstetricians often see women in the first trimester whereas in public hospitals, women are usually seen later, by which time screening has lower utility. This means that for women receiving maternity services in the public sector, it is particularly important that their GP is aware of, and has adequate education about RGCS. Limited genetics education among GPs (Archibald et al. 2016; Houwink et al. 2011) may be contributing to low GP participation. There is currently an education and awareness program being offered by the Royal Australian College of General Practitioners to Australian GPs, which may result in more women and couples being offered RGCS by their GPs (https://bewaretherare.com.au/).

A family history of one or more of the three conditions was recorded in only 1.6% of those screened. Although this suggests that most requesting HCPs were not offering screening on the basis of family history, these data should be interpreted cautiously as practice may have varied regarding whether patients were asked about their family history at the offer of screening and whether this information was included on the test request form.

Understanding the test uptake; that is, the number of people who take up the test as a proportion of all who are offered it, is important. A limitation of this study is that it only looks at those who underwent screening, as it is complex and resource-intensive to determine the total number of women being offered screening. Where possible, future research should investigate RGCS uptake.

Another limitation of this study is that it looked at only one RGCS program and participation rates in other RCGS programs are unknown. However, it is recognised that over this time period, most RGCS in Victoria was undertaken by the Victorian Clinical Genetics Services (VCGS) (Robson et al. 2020). The generalisability of the findings for Victoria and nationally is also strengthened by its concordance with other studies, which have shown a similar RGCS socioeconomic gradient outside Victoria (Robson et al. 2020), and reduced provision of other medical services in rural areas compared with metropolitan areas (Alston et al. 2020). Similarly, a study investigating non-invasive pregnancy testing (NIPT) in Victoria found a socioeconomic gradient in those who took up screening (Hui et al. 2018).

The frequency of missing data relating to socioeconomic status (65 women or 0.3% for Australia-wide analysis and 10 women or 0.05% for the Victorian analysis) and relating to geographic location (22 women or 0.1% for Australia-wide analysis and 10 women or 0.05% for the Victorian analysis) was low and so was unlikely to affect findings.

This study mainly looked at outcomes related to equity and access. Attitudes of patients and HCPs to RGCS were not explored and reproductive outcomes were not measured. These outcomes would be important to explore in future research.

Only 1.5% of Victorian women in their childbearing years were screened by this program. In view of this low percentage, while taking into account that this figure only represents those that undertook screening rather than all those who were offered screening, and it only represents those screened by this program (albeit the largest in Victoria (Robson et al. 2020)), it appears likely that The Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) and the Royal Australian College of General Practitioners(RACGP) recommendations for carrier screening (i.e. that information on carrier screening should be offered to all women planning pregnancy or in early pregnancy) are far from being implemented. The time span of this study covers the time over which RANZCOG produced their recommendations (2017) and before RACGP recommended offering screening (Royal Australian College of General Practitioners 2020), so it is possible that screening has increased in the wake of these recommendations. Interestingly, in comparison, the use of NIPT as a genetic screen for aneuploidy was becoming firmly established over this period (Hui et al. 2017).

The Medical Services Advisory Committee has recently supported public funding for reproductive carrier testing to detect CF, SMA and FXS (Medical Services Advisory Committee 2020) and the Australian Federal Government has committed to start funding a Medicare item number for this test from November 2023. Removing the out-of-pocket cost barrier will be crucial to improving equity of access.

In conclusion, this study has identified marked inequity of access to RGCS, with very low rates of screening among socioeconomically disadvantaged women and women from rural and regional areas. Additionally, participation in RGCS has been found to be much higher among obstetricians than GPs. Increased participation by GPs could improve community access to RGCS and improve access to preconception screening. Addressing the causes of inequity of access, particularly the out-of-pocket cost of screening, will allow more women and couples the opportunity to make informed choices about participation in screening.

The data that support this study will be shared upon reasonable request to the corresponding author.

Martin Delatyki, Alison Archibald and Melanie Smith are paid employees of the Victorian Clinical Genetics Services.

Ruth Leibowitz received a Research Training Program Scholarship (Fee offset) – 2018 from The University of Melbourne. This research did not receive any other specific funding.