Benefits and Burdens of Newborn Screening: Public Understanding and Decision-making

Stuart G Nicholls; Brenda J Wilson; Holly Etchegary; Jamie C Brehaut; Beth K Potter; Robin Hayeems; Pranesh Chakraborty; Jennifer Milburn; Daryl Pullman; Lesley Turner; June C Carroll


Personalized Medicine. 2014;11(6):593-607. 

In This Article

Where are we, What do we Still Need to Learn & Why?

Despite research indicating parental support for screening, and variation in parental knowledge and understanding of different aspects of newborn screening, there is still a paucity of research regarding the determinants of parent understanding and factors that influence individual decisions. Most notably, we know very little about why some parents decline newborn screening and whether these parents differ in some substantial way from those who accept screening. There is, however, burgeoning research that points to broader influences on parental decisions; research that may point to systemic differences.

In Canada, a recent review by Newborn Screening Ontario revealed that uptake of NBS is extremely high, but that the majority of active 'declines' came from parents under the care of midwives.[140] These descriptive data point to the need for more research on the relationship between professional and parent attitudes and experiences in relation to consent practices for NBS. For instance, do individuals who choose midwifery care have different attitudes toward screening than those who choose obstetricians for their prenatal care? Do midwives have substantially different opinions to other healthcare professionals? Are there system-level issues in play that somehow generate these differences?

There is a need for educational research regarding NBS, in relation both to parents and professionals. In a Canadian study by Hayeems et al., different healthcare providers reported differing views with respect to their own role in the education of parents, as well as barriers to informing parents.[141] Notably, the majority of family physician respondents and obstetricians indicated they had insufficient training to educate parents, while over half of these same groups agreed to some degree that they were not up to date on the conditions being screened and that they lacked confidence in their ability to explain newborn screening to parents.

While research has, understandably, focused on parents and healthcare professionals in relation to newborn screening, a third – and yet unstudied – stakeholder group also exists and warrants further study: those involved in policy development. While the exemption of policy makers might reflect the fact that they are seemingly far removed from the clinical encounter,[142] if policy decisions are incongruent with clinical routines, then parents may suffer through inconsistent practice. Indeed, given the jurisdictional variations in newborn screening consent models, it is important to explore the rationale behind screening policy decisions to identify areas of commonality and difference. At present, no research has explored the perspectives of policy decision-makers with respect to consent processes for newborn screening and the implications for professional practice or parent understanding.

Furthermore, while there has been increasing debate about criteria for expanded screening leading to broader definitions of benefit, far less attention has been paid to how burdens of newborn screening should weigh into these equations and how programs should seek to balance the potential burdens with the benefits offered. Moreover, there are a lack of criteria for decision-making around the exclusion or removal of conditions within existing panels (although processes are currently under review[143]). Recent discussion in the field of implementation science has explicitly raised this issue and called for greater exploration of issues pertaining to the de-implementation of technologies.[144] This is highly relevant given the experiences with screening for Krabbe disease in New York, and which underline the need for the development and evaluation of de-implementation criteria.[55–57,145]

Concerns regarding overdiagnosis also require further consideration. For example, diagnostic testing may be unable to confirm whether a baby has cystic fibrosis when the significance of an identified mutation is unclear and sweat testing is borderline. Does this differ to the situation where diagnostic testing establishes the targeted disease but where it is uncertain whether the baby is at risk of developing the clinical phenotype because it is so clinically heterogeneous and/or dependent on environmental conditions (e.g., 'non-classic' cases of MCADD)? In both cases there are different facets of overdiagnosis that present similar challenges for families, but require different solutions from the perspective of providing care, changing the screening program, or mitigating harms.

Questions of how benefits and burdens should be balanced will be even more pertinent given the potential for whole-exome or whole-genome sequencing (WES/WGS) within newborn screening programs.[146,147] Given current concerns regarding variants of uncertain clinical significance, analytic and clinical validity will be hugely important. How well does sequencing measure the intended target? What is the accuracy with which sequencing predicts the presence, absence or predisposition to a condition[148]? A recent study found substantial differences between sequencing platforms[149,150] and several studies point to a lack of understanding with respect to the interpretability of WES/WGS information.[151,152] Yet even if the implications of variants are understood, significant practical issues of data management and communication remain. Feero, for example, notes that a recent sequencing study identified approximately three million unique variants per individual who underwent sequencing.[150] Each variant required collating, tracking, analyzing and then communicating. The possibility of vast amounts of information, including cumulative risks derived from multiple low-penetrance variants, potentially expands definitions of the meaning of an asymptomatic individual, but may also exacerbate existing issues such as anxiety and stress, especially if parents do not feel informed or do not understand newborn screening.[74–77] There is a need for ongoing research to explore the potential for inequitable experiences of newborn screening and the development of evidence-based communication strategies that seek to mitigate the potential for negative psychological sequelae. These communication approaches will require ongoing evaluation and will remain an important area of research as newborn screening moves forward.