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labor and childbirth - and consultations and education regarding NBS are key topics of conversation that
should happen before the test, in order to understand the process and have the opportunity to ask
[37]
questions . Formal permission or written consent was, however, a secondary priority for parents, while it
was felt more urgent in case NBS was performed with WGS, given the increased complexity of genetic
information. The need for formal parental permission implies the possibility that parents opt out, thus
[34]
altering the universality principle that characterizes NBS .
Genetti et al. in 2018 evaluated parental interest in a randomized trial of GS-NBS, in particular analyzing
causes for declining participation, before and after an enrolment meeting with a genetic counselor. Risk
communication was found to be a key element during the education process for informed consent, given
the sensitivity of genetic information and the apprehension that this information would be recorded in their
infants’ medical documents .
[30]
Psychological distress
Families and professionals involved in newborn genetic screening are challenged with complex and onerous
questions that can lead to an increased amount of new knowledge which can be difficult to deal with.
Parents have the authority, both legal and moral, of making decisions for their newborns, including medical
decisions that are, supposedly, in their child’s best interest. When using GS, a large number of gene variants
are possibly detected, including genes encoding for adult-onset disorders. Such timing of testing, being in
the neonatal period, makes it impossible for the primary beneficiaries, i.e., newborns, to make their own
decisions depriving them of future adult autonomy and confidentiality [11,12,35,37] .

While the use of GS as a diagnostic tool is accepted, the uncertainty and ambiguity of some results of GS as
a screening tool could transform healthy newborns into pre-sick or “patient-in-waiting” , risking
[42]
[34]
premature medicalization of infants and causing significant distress and worry in parents .

Many other potential drawbacks for the screened family are the damage to the child’s self-esteem,
stigmatization, and the sense of guilt of transmitting a pathogenic variant to your child; this information
could also be the cause of discrimination, lack of privacy in different circumstances, with issues accessing
[35]
medical insurance being the first difficulties on a potentially long list .
Genetic professionals and laboratorians are also suffering from potential moral and ethical dilemmas: Ross
et al. in 2019 reported a case in the BabySeq project where the discovery of an actionable adult-onset disease
in a newborn led to a dilemma of the personnel that could not return a result that was widely considered
actionable . On the basis of this case, the BabySeq protocol was then modified, invoking the principle of
[12]
family benefit, for which the best interest of the child includes his parents’ well-being. Following these
modifications, parents could decide whether they wanted to receive information on adult-onset variants,
[43]
even though it is still widely accepted that children should not be tested for adult-onset conditions. For
Ross & Clayton, one solution could have been to modify the BabySeq analytical process in order not to
discover those variants, designing the study to limit the search to relevant genes and reduce the risk of
[12]
finding stress-inducing information .

A survey conducted by Pereira et al. published in 2019 demonstrated that parents and clinicians would
prefer NBS without GS, even though parents showed more trust than clinicians towards GS. This shows that
what is considered a clinical benefit to the clinicians is different from the perception of the parents (i.e.,
parental/personal utility), which might have a broader range of expectations, showing once again how
relevant and crucial the education process is in these circumstances .
[8]