Ethical issues with regard to PCS include preliminary concerns about eugenics, medicalization, and discrimination, the objectives of offering PCS, and issues arising in view of the normative framework for population screening. We will end this section with a brief discussion of the possible future expansion towards comprehensive PCS.
Eugenics, medicalization, discrimination?
PCS is more controversial than individual genetic counseling. Critics object for different but related reasons to the fact that in this approach genetic preconception care is meant to serve the reproductive health of the population as a whole. Why would that be problematic? Some are concerned about a supposed resurgence of ‘eugenics’ (Scully 2008); others speak of ‘medicalization’ (Verweij 1999). However, as those terms have many different meanings, it seems more fruitful to ask what scenarios people actually fear and to assess the likelihood of those scenarios (Bouffard et al. 2009; Paul 1994). For instance, people may think of government restrictions of reproductive freedom, as in Nazi Germany. That scenario, however, is quite implausible, at least in Western democratic societies. Fears about societal pressure to participate in screening or to choose specific reproductive options seem more realistic. But that should be taken as a reason for developing and implementing an appropriate system of safeguards, not as a ground for categorically opposing this form of preconception care (De Wert and De Wachter 1990). We will return to this when discussing the normative framework for PCS.
Another issue is the ‘disability rights’ critique. The so-called ‘expressivist argument’ states that taking measures to avoid the birth of a child with a specific disorder or disability expresses a discriminatory view regarding the worth of the life of those living with such conditions (Parens and Asch 2000). If taken as a claim about parental motives this cannot be maintained. Prospective parents may want to protect their child from harm, or they may feel that they would not be able to be good parents for a (severely) disabled child. None of these motives expresses a discriminatory attitude towards disabled persons (Knoppers et al. 2006). But the argument may also be directed against the systematic offer of reproductive testing for specific diseases. Does this not send the message that persons with the diseases screened for are a burden to society and would better not be born (Scully 2008)? There is certainly a risk that PCS may lead to reinforcing existing tendencies of stigmatization and discrimination (Wilfond and Fost 1990). Here again, much depends on how the programme is presented and conducted in practice.
Objectives of offering PCS
As a form of reproductive screening, it would seem that PCS is better compared with autonomy-directed prenatal screening for Down syndrome and other foetal anomalies, than with prevention-directed screening for, eg, breast-cancer (Dondorp et al. 2010). Indeed, the arguments behind the strong emphasis on reproductive autonomy in the clinical genetics tradition seem equally relevant when PCS is concerned. However, there may be some room for differentiation between PCS as a top-down initiative from the health care system (as in the case of the recently introduced obligatory offer of PCS for CF in the USA; ACOG 2011) and community-based initiatives targeting high profile genetic risks for serious diseases within that specific community or population. Whereas reduced birth rates of affected children should not be regarded as the measure of success of the former type of programmes, doing so may seem less problematic for programmes of the latter kind (Laberge et al. 2010). The difference being that in programmes set up in answer to a need for prevention as self-defined by a community in which many families are struck by a high burden of disease, most participants will actively support the aim of bringing down the birth-prevalence of the disease, whereas this is less obvious in top-down programmes aimed at populations rather than communities. With regard to this tentative distinction we make the following comments. Firstly, the material (genetic risk and burden of the disease) and procedural (community involvement) criteria would require further exploration. Clearly, a high population frequency of an untreatable, debilitating and lethal disease such as Tay Sachs Disease (TSD) would amount to a high risk of serious harm. And it would seem that the same can also be said of β thalassemia in regions and countries where that disease is highly frequent, even though it is amenable to some form of treatment. But for diseases that are less serious or highly variable or well treatable, enabling autonomous choices rather than prevention should be the objective of PCS. Where the line would have to be drawn is a matter for further debate, involving the participation of the relevant communities themselves. The procedural criterion of bottom-up community involvement and support would also require more precise determination. Secondly, although this brings in the prevention view, it is prevention as primarily motivated by the community’s concern about the suffering of its children and families, rather than by health economic considerations. Finally, to say that prevention may under conditions be a morally legitimate objective of community-based PCS is not to deny that pressure on individuals or couples is a concern also in those contexts. Especially in socially tight communities, pressure to participate in prevention-aimed PCS is far from imaginable, and safeguards are needed to avoid this (see next subsection).
For the normative assessment of population screening programmes, a general framework of criteria has been developed (Dondorp et al. 2010; Health Council of the Netherlands 1994). At the core of this framework, there is a requirement of proportionality: there must be a proven positive balance of benefits over harms for those participating. Whether this requirement is met can only be determined on the basis of scientific evidence regarding many separate aspects including the natural history of the disease, how screening may provide meaningful options for changing an otherwise dreadful outcome, and possible psychosocial implications. Further criteria refer to test characteristics, quality issues, cost-effectiveness etc. It is also stressed that participation must be voluntary and based on informed choice.
There is strong consensus that some PCS programmes meet these criteria, whereas some other programmes do not, or less clearly. For instance, with regard to PCS for Fragile-X syndrome (FXS) there are concerns that may affect overall proportionality (De Jong and De Wert 2002; Musci and Moyer 2010). First, it is not always clear as to whether women carry an unstable allele which may cause FXS in offspring—think, for example, of ‘intermediate’ alleles in the grey zone. Such findings change the nature of carrier screening for FXS into a form of risk assessment screening, potentially inducing higher levels of anxiety and complicating decision making. Second, unlike other carrier screening programmes, screening for fragile-X carriers will identify individuals who themselves are at risk for adult-onset disorders, more in particular premature ovarian failure (POF) and fragile-X-associated tremor and ataxia syndrome (FXTAS). And third, phenotype prediction in female foetuses with a full mutation is difficult, if not impossible. Cascade screening may be a more acceptable approach to identify female carriers of FXS (De Jong and De Wert 2002; De Wert 2005). An important advantage being that one starts from (a patient with) a disease-causing allele, allowing for more straightforward genetic counseling.
With regard to PCS for CF, the apparent lack of international consensus is reflected in a recent European consensus document that only provides a template for further debate (Castellani et al. 2010). The reasons behind this include the fact that due to the large number of CFTR mutations, CF carrier tests have a less than perfect sensitivity and also that for many mutations the genotype–phenotype correlation is weak. However, in a Dutch study, it was found that PCS for CF would in principle fulfil the requirements of the normative framework (Henneman et al. 2002).
Screening in the context of reproduction is especially sensitive as it may affect decision making with regard to having or avoiding to have children with a disease or disability. It is far from imaginable that as a result of offering such screening, these choices will come under pressure as to what professionals or society would like to see happen. That is indeed the concern behind the charges of eugenics and medicalization briefly discussed in the beginning of this section. As suggested, the only way to answer this is through safeguards that protect reproductive freedom. Some of those safeguards will need to be integrated in the set-up of the programme. These include adequate provisions for ensuring voluntary, well-informed decision making regarding participation in PCS, the availability of non-directive counseling (within the limits earlier referred to), and a systematic evaluation aimed at identifying and removing elements of unjustified directivity. Other safeguards will have to be of a societal nature, including the continued availability and funding of proper health care services for children born with the diseases targeted in PCS, also when their parents had the option to choose to avoid their birth (Human Genetics Commission 2011).
Modes of offering carrier screening
Carrier screening may be offered either in pregnancy or preconceptionally, and if preconceptionally, either to couples with possible reproductive plans or to all individuals of (pre-)reproductive age. Which of these approaches is more in line with the proportionality requirement of the normative framework will to a large extent also depend on whether prevention or autonomy is taken as the overarching objective.
In terms of enabling reproductive choices, carrier screening in pregnancy is clearly suboptimal. Prenatal carrier screening leaves couples found to be at a 1:4 risk of having a child with a serious disease no other options than either accept that risk or opt for PD and a possible abortion. Moreover, it forces them to start thinking about this under time pressure in what is already an emotionally charged period. Organizationally, however, the preconception approach is more challenging. Pregnant women and their partners are easier to find than couples with possible reproductive plans. As proposed by the Health Council of the Netherlands, the introduction of a general preconception consultation might help to create a context for the offer of PCS (Health Council of the Netherlands 2007). Since not all couples will be reached preconceptionally, a combination of both approaches may be optimal: offering prenatal carrier screening as a back-up to couples who for whatever reason did not participate in PCS.
PCS is usually offered to couples rather than to non-committed individuals. It is couples who have more imminent reproductive plans, and it is as couples that they may be found to be at a high risk of having a child with an autosomal recessive disease. But couples can be regarded and approached in different ways: either as single units or as unions of two separate individuals (Castellani et al. 2010). The single unit approach aims at informing the partners jointly about whether or not they are a carrier couple. In case of a discordant outcome, individual carrier status is not always reported. This deprives a possible carrier of the option of informing his or her relatives and of using this information in a future relation with another partner (Modra et al. 2010). Withholding this information is legally questionable and at odds with the objective of enhancing reproductive autonomy. Nor does it seem that being identified as a carrier has a more than transient psychological impact on well-informed testees (Lakeman et al. 2008).
The alternative approach of regarding the couple as a union of two individuals entails simultaneous testing of both partners and providing information about all individual outcomes. Drawbacks are that this doubles the costs of testing and leads to the identification of twice-as many discordant couples. In PCS for CF, this outcome requires careful counseling in the light of the fact that the risk for these couples has increased as a result of testing (Ten Kate et al. 1996).
PCS is sometimes also offered in non-clinical settings (workplace, school) to individual adults or to adolescents, as candidate participants may thus be more easily and effectively reached. It has been argued that from an ethical point of view, this approach has the benefit of ensuring equity of access (Modra et al. 2010). Offering PCS to adolescents means educating their parents as well, leading to an increased awareness in the population as a whole.
One concern with addressing individuals is that it might lead to stigmatization and lack of self-esteem of those found to be carriers within the community. That this is not unimaginable has been illustrated in a recent analysis of the orthodox Jewish Dor Yeshorim PCS programme (Raz and Vizner 2008). However, much seems to depend on how the screening is offered and what information is given (Modra et al. 2010). Proper education about the meaning of being a carrier is of course crucial. This should also include the fact that in terms of carrier status for recessive disease, we are indeed all ‘fellow mutants’. Clearly, society needs to be educated about this as well: identification of carriers and patients led to the erroneous rejection of carriers by American insurance companies in the early 1970s.
Another concern regards the voluntariness of participation, especially when PCS is offered to adolescents (Barlow-Stewart et al. 2003). The UK Human Genetics Commission recently recommended that offering PCS to adolescents may be acceptable under strict conditions protecting their autonomy rights (Human Genetics Commission 2011). Still, one may object that the trade-off between the relevance of testing to the young person (increasing as they grow and come closer to the time that they may wish to start a family) and the ease of population coverage (becoming progressively less complete, or more costly, as the age of the target group increases) is risky in view of less favourable conditions for voluntary and truly informed participation.
Traditionally, PCS regarded one single disease. In the last years, however, there is a tendency of using test panels for several diseases. A recent PCS pilot in Quebec, Canada, is directed at four diseases with a high frequency in the population (1:5) due to a historic founder effect (Charlevoix–Saguenay spastic ataxia; peripheral neuropathy with or without agenesis of corpus callosum; lactic acidosis COX deficiency; and hereditary tyrosinemia type 1) (personal communication Dr. Claude Laberge, Quebec). The best example of expansion of traditional programmes is PCS offered to the Ashkenazi community; originally focused on TSD only, it presently includes up to 16 genetic disorders, an expansion which seems to be strongly supported by the community (Scott et al. 2010). Expanding testpanels with diseases that, although less frequent in the relevant population, are serious and without meaningful treatment options sounds reasonable, provided that genotype–phenotype relations are well understood and good-quality tests are available. However, there is debate about whether expanded panels should also include lower-penetrance mutations, where disease severity is difficult to predict and homozygotes may well remain asymptomatic. An example from the group of 16 diseases just referred to is type 1 Gaucher Disease (GD), which not only has a low-penetrance and variable expression, but for which effective treatment is also available (Zuckerman et al. 2007). It is clear that if PCS is to be offered for such diseases, the rationale will have to be the provision of autonomous choice rather than the prevention perspective governing traditional PCS in the Ashkenazi community. Mixing the two perspectives in one programme is morally risky as this might send the message that also minor health problems are to be avoided by responsible reproductive decisions (Raz and Vizner 2008).
Driven by technological developments, expansion of PCS seems unavoidable. New techniques, such as the use of DNA chips and next generation sequencing, will allow carrier status to be simultaneously determined for many more recessive conditions than are included in current screening programmes, without significantly increasing the costs. American researchers recently reported to have developed a PCS test for no less than 448 severe recessive childhood diseases (Bell et al. 2011). The question is whether such ‘comprehensive’ PCS will fulfill the criteria for responsible screening. For each of the separate conditions this will depend on whether the relevant mutations are known, on what is known about the disease and genotype–phenotype correlations, and whether a good quality diagnostic test is available. Introducing carrier screening that would lead to couples making far-reaching reproductive decisions on the basis of test results of which the implications are not yet fully understood is morally unacceptable. Another concern regards the quality of informed consent. The introduction of genome-wide testing questions the feasibility of informed consent as traditionally understood and urges society to consider the acceptability of so-called generic consent, where applicants are only more generally informed about types of possible test outcomes and their implications (Dondorp and De Wert 2010).