Newborn screening for sickle cell disease: whose reproductive benefit?

The ethics and policy statements about newborn screening (NBS) have routinely stated that the primary goal is to provide clinical benefit to affected children.^{1, 2, 3} Although many policy statements acknowledge that NBS may provide reproductive information to the child and his or her parents, ‘reproductive benefit’ has always been viewed as secondary and not adequate by itself to justify screening of infants.

Bombard et al.⁴ describe the findings from a sample of Canadian healthcare providers (HCPs) who were asked their attitudes towards the reproductive significance of identifying sickle cell carriers (known as sickle cell trait (SCT)) through NBS. Over two-thirds of HCPs who responded in the 2007 survey stated that they either ‘agree’ or ‘strongly agree’ that a purpose of NBS is to provide parents with information about their infant's carrier status (77.9%) of about the parents’ own reproductive risk (68.1%).⁴ The main justifications for this position are that reproductive risk information (1) allows reproductive choice and (2) permits disease prevention, a main goal of NBS.⁴ On the other hand, a minority of health care providers suggested that it would be better to obtain reproductive knowledge in the preconceptional or prenatal rather than the neonatal period and that this should be done with a robust consent process.⁴

These findings are consistent with data from the mid-1990s when Wertz and colleagues⁵ found that 74% of Canadian genetics services providers and 90% of United States primary care providers agreed with the statement ‘An important goal of newborn screening is to identify and counsel parental carriers before the next pregnancy’.

The data show a broad disconnect between HCPs’ goals and the preferences of the general public. Although SCT has been identified by NBS in the United States for over two decades (36 years in New York State), the frequency of sickle cell disease (SCD) among newborns has not appreciably changed.⁶ Although NBS for cystic fibrosis is more recent, early data again show that reproductive information from NBS has had minimal impact,⁷ as distinct from antenatal carrier screening.⁸

Bombard et al.⁴ chose to focus their study on SCD, an autosomal recessive condition found mainly in minority communities in the United States and Canada. NBS for SCD is driven by the opportunity to save lives through penicillin prophylaxis and other clinical measures, and the detection of SCT is an incidental and unavoidable byproduct of screening. Thus, the HCPs may have been expressing a viewpoint that reproductive benefit is a ‘free’ additional benefit rather than expressing the viewpoint that reproductive benefit should be a primary benefit of NBS. If the researchers had truly wanted their respondents to focus exclusively on the legitimacy of reproductive benefits as a rationale for NBS, they should have used a condition like Duchenne muscular dystrophy or Fragile X for which early presymptomatic diagnosis is not known to provide clinical benefit to the infant but does offer reproductive information. Advocates of expanding NBS programs to include such conditions contend that there is benefit to the child—either in the avoidance of the diagnostic odyssey or in the ability to enroll in early research.^{9, 10} However, the same supporters also argue that there is a need to provide these services in the context of a robust consent process.^{9, 10}

The choice of conditions is further complicated by the ‘not so benign’ nature of SCT. Although the authors deliberately attempt to exclude the possible clinical implications of SCT, it is not clear that their respondents did so when answering the survey questions. Individuals with SCT are at increased risk of hematuria, hyposthenuria (decreased ability to concentrate urine), exertional rhabdomyolysis and splenic infarction with high altitude hypoxia.¹¹ These risks are moral justification for informing parents of their child's SCT, regardless of any reproductive benefit to themselves or their child.

Finally, the selection of SCT must be evaluated from a health care disparities perspective. In both Canada and the United States, the vast majority of women and couples with SCT are ethnic minorities. Both the potential benefits and adverse effects of carrier identification through NBS need to be carefully considered through close consultation with both HCPs and lay experts from at-risk communities. Although Bombard et al.⁴ quote one participant who expressed this concern, it does not appear that the researchers specifically sought the opinions of the at-risk community to determine if SCT knowledge is a potentially real reproductive benefit or just a hypothetical reproductive benefit of essentially academic interest. Given the absence of North American data demonstrating that such information is indeed used for reproductive purposes, despite decades of both newborn and antenatal screening, the default assumption should be that this is not a real reproductive benefit. Neither the researchers nor the large majority of HCPs who agreed with the proposition that SCT detection is an important reproductive benefit have considered whether women and couples in at-risk communities would actually use that information in the way that many majority-community researchers and HCPs think that they should.

Bombard et al.⁴ question whether it is appropriate to make reproductive information a primary goal of routine NBS, which is mandatory in most North American jurisdictions. In a previous article, the authors argue that any population screening program developed for reproductive benefit should either (1) incorporate a ‘cascade of choices’ meaning that the participants (or in the case of NBS, the parents) must have opportunities to consent to the testing or at least to decide whether to be informed of the finding or (2) focus on preconception or prenatal screening programs.¹² Assuming that the authors still believe that it is inappropriate to pursue reproductive goals outside of these two screening options, their current study identifies a critical need for educating HCPs about the ethically justifiable public health goals of a universal NBS program. Furthermore, researchers and HCPs must be culturally sensitive about the use of genetic information in reproductive decision making, particularly when the information is more frequently found in ethnic minority communities¹³▪