The decision-making process has reduced the differences in testing between states. However, the variation has not been eliminated. Not all states have chosen to test all the conditions recommended by universal screening panels, and some states have added conditions to their testing panels that have not been approved by the CCHDC. The debate on the extent to which newborn screening should be prioritized given the limited resources available for child health is ongoing. In today`s health system, there is no institutional structure that imposes opportunity costs to be taken into account and ensures good governance. Without accountability, special interest groups such as health associations, consumer groups and manufacturers of screening technologies can exert disproportionate influence on policy. Even suppliers are not immune to problems. GP assessments with standardised patients suggest that conversations run the risk of being too complex and jargon rich to be understood by patients (15). Perhaps more troubling is that in a recent national survey, physicians were less likely to believe that a sickle cell carrier required formal genetic counseling than a cystic fibrosis carrier (32). Finally, the majority of newborn screening programs offer genetic counseling services to carriers of sickle cell disease and cystic fibrosis, but do not assess the quality of counselling (14).

Recommendation 5: Newborn screening by next-generation sequencing or other genomic methods should only be considered as a complement to existing first-level screening programs. Second, parents are emotionally and physically exhausted after the birth of their child, making it difficult for them to learn and retain information about newborn screening. Parents reported a preference for receiving information about newborn screening before birth (12, 26). In the past, the obstetric community has resisted the responsibility of educating parents about newborn screening, claiming that they are already tasked with discussing many prenatal tests with parents (13, 18). However, this perspective seems to be changing; The American College of Obstetricians and Gynecologists recently recommended that prenatal providers provide their patients with information about newborn screening through information brochures, electronic sources, or discussions at prenatal visits (4). In the context of population-based infant screening, the ethical and political concerns raised by the return of random genomic results are, if at all, even greater than with genome-wide diagnostic sequencing. Some have even questioned whether decisions about the return of genomic information discovered during newborn screening should even be made by public health officials or decision-makers, arguing that all genomic data belongs to the child and that parents believe they are acting most effectively in the best interests of the child. should decide what is important and what is not [114-117].

These recommendations are consistent with Wilson and Jungner`s criteria (Table 2) and recent reviews of their application to genome screening at the current stage of clinical trial development [22, 122]. Some conditions for which newborn screening is performed on a large scale cannot be effectively identified by any genetic or genomic testing method, as many cases do not have a genetic cause. For example, congenital hypothyroidism can be caused by maternal iodine deficiency or the transmission of maternal antithyroid antibodies through the placenta. In other circumstances, although genetic factors usually cause the disease, genetic heterogeneity and complexity mean that genetic testing is unlikely to be as sensitive or as specific as current screening methods. Newborn screening for congenital hearing loss by testing for otoacoustic emissions is a clear example. Replacing genomic methods with methods currently used to screen for such conditions would jeopardize the health or development of some children identified by current newborn screening programs. Childbirth HL. Newborn screening: the genomic challenge.

Mol Genet genomic Med. 2014;2:81–4. doi:10.1002/mgg3.74. As noted earlier, the success of current newborn screening programs depends on the systematic screening, diagnosis and management of affected infants through established policies and protocols. Effective management and governance, as well as ongoing monitoring and evaluation, are also needed. Genomic screening of newborns would likely be more complex than current screening programs and would therefore need to build on the strengths of current programs and function as a comprehensive system accessible to every infant. Berry Ltd. Newborn screening. Clin Perinatol. 2015;42:441–53. doi:10.1016/j.clp.2015.03.002. x.

Participants noted the need for further discussion on how the context surrounding screening, including the existing legal context and funding structures, practice models and available human resources, influences health policy decisions about whether and how prenatal/preconception and neonatal screening technologies should be implemented. There is also a need to examine how these contextual factors relate to ELSI. While clinical and technical outcomes in HTA may be relatively generalizable for some technologies, participants noted that ELSI is more contextual. The use of policy-making frameworks that specifically include context [52] could help clarify this. In accordance with the Wilson and Jungner criteria, newborn screening has begun in all provinces and territories where life-threatening or potentially severely disabled conditions are found, are easily detectable and are effectively treated. In their landmark paper on support for mandatory PKU screening, Faden, Holtzman, and Chwalow [33] highlighted the harms that can occur in a newborn who has not been screened, arguing that this far outweighs the benefits of parental decision regarding screening. As it became possible to screen for other conditions, similar criteria were required to complete the selection panel. The association between disease severity and treatability among all conditions tested provided the moral justification for making newborn screening mandatory in many countries. Howard HC, Knoppers BM, Cornel MC, Wright Clayton E, Sénécal K, Borry P. Whole genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programs. Eur J Hum Genet. 2015;23:1593–600.

doi:10.1038/ejhg.2014.289. The success of a newborn screening system must be measured not only by its ability to detect potential disorders, but also by its ability to communicate results effectively and sensitively. There is a clear need to improve the way parents are educated and counselled on screening outcomes, which only becomes more difficult when programs are faced with the prospect of genome-wide sequencing. Therrell BL, Johnson A, Williams D. Status of newborn screening programs in the United States. Paediatrics. 2006;117:S212–52. doi:10.1542/peds.2005-2633C. “Currently, the integration of next-generation NGS into newborn screening is not possible due to the high cost of genomic sequencing and difficulties in interpreting results. It takes weeks to report NGS results, and NGS must be performed reliably using DNA extracted from the dried blood sample needed for newborn screening.

In addition, a major challenge would be the required bioinformatics, which analyzes the huge amounts of data associated with rare or novel nucleotide changes. With the further reduction of WES or WGS costs, the improvement of bioinformatics techniques and once technical (analytical and bioinformatics), ethical and legislative issues (e.g. Communication of results, ownership of data), economic issues (analysis and calculation costs, data storage costs) and data security (adequate encryption systems), it is expected that NGS could be used in newborn screening programs” [51]. Reporting positive newborn screening results presents another challenge. Many of the disorders studied are rare, and primary care physicians have expressed a lack of comfort in explaining them to parents (32). Scenario-based studies of doctor-patient newborn screening have confirmed these concerns, showing that GP conversations did not contain a significant amount of content deemed necessary for parental understanding and sometimes contained misleading content (16, 39). In one study that asked parents to rate the extent to which their primary care physicians explained the results, less than half said it was done “well” or “very well,” and parents with low health literacy were more likely to rate their primary care physicians favorably (17).