Table 1

A summary of general ethical considerations for and against genomic testing in the NICU

In favour of genomic testing in the NICUPoints of concern with genomic testing in the NICU
  • Actionability

    • Genomic testing may yield information that is relevant for medical decision-making in the NICU

    • A test is generally thought to be of value if it generates information that has both clinical utility and validity; providing actionable information11

    • However, it will often be difficult to predict whether genomic testing will lead to actionable information (particularly while genomic knowledge is at an early stage), and it may do so only in a minority of cases

  • Cost-effectiveness

    Genomic testing may save costs by preventing the need for expensive and prolonged diagnostic testing (including traditional Sanger sequencing), as well as by avoiding prolonged, expensive and non-beneficial intensive care treatment.4 The costs of genomic tests have fallen rapidly

    However, the after-sequencing costs, including bioinformatics and interpretation may be substantial12

  • Access to testing

    Genome testing will soon be available to parents prenatally or postnatally from private companies. It would potentially be better to provide information within a healthcare system with access to support and interpretation. It might also be unfair to deny parents (who cannot afford it) the option of testing that might be relevant to clinical management decisions

  • Consistency

    The principles of use of genomic testing in the NICU are similar to more conventional investigations that are widely used, such as karyotype, single-gene sequencing, MRI or metabolic tests

  • False-positive results

    Genomic testing may lead to incorrect diagnoses. Even very accurate tests with high sensitivity and specificity yield significant numbers of false positives when applied to a very large number of genes.13 False-positive results may also arise because variations within or adjacent to disease-causing genes may be predicted by commonly used software packages (PolyPhen, Mutation Taster) to be pathogenic, but in the fullness of time are proven not to be. A significant proportion of mutations that were previously identified in published literature as causative of disease are now believed to be incorrect14

  • Incidental findings

    Testing could reveal genetic mutations that confer risk of adult-onset illnesses such as cancer or neurodegeneration.13 15 16 Release of this information may have no bearing on current clinical decision-making, prevents children deciding whether to undergo testing in the future (removing their right to an ‘open future’) and could lead to psychological harm in the family17

    However, diagnosis of these conditions could be beneficial for the child psychologically and in terms of the child's autonomy (eg, by helping the child make decisions about education and career),18 and could have major implications for the health of the child's parents.16 See also ‘genetic privacy’ below

  • Uncertain results

    Genome testing may identify variants of uncertain significance (VUS).19 A VUS is a DNA sequence alteration or copy number variation (deletion/duplication), which is not common in the general population, but for which a definite link to human disease cannot be made on current data. Some VUS’ will be redefined as pathogenic mutations in the near future as more cases are ascertained; others will be classified as non-pathogenic with time. For this reason, post-test interpretation can be challenging, highly complex, non-definitive and potentially confusing for parents

  • Genetic privacy

    Testing could impact on future employment or ability to access insurance. Identification of genetic abnormalities in the child may also lead, by inference or further testing, to identification of mutations in the parents and extended family

    However, these concerns apply equally to genetic and other tests already in use and accepted in the NICU. Notions of ‘privacy’ with respect to children are also difficult to uphold. In some jurisdictions, these concerns may be partly addressed by existing legislation or regulation19

  • This table necessarily condenses a complex debate, which is discussed in depth elsewhere.6 ,7 ,9 ,10

  • Opposing considerations are shown in italics.

  • NICU, newborn intensive care unit.