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Next generation sequencing (NGS) is the collective term for some new methods developed in recent years that makes it possible to analyse large amounts of genetic material within the same analysis.
NGS can be used to analyse the presence of a number of predetermined genetic changes, referred to as targeted analysis. NGS can also be used to analyse an individual’s entire genome, referred to as whole genome sequencing. When used for whole genome sequencing, NGS can identify genetic changes without any predetermined objective.
Targeted analysis with NGS can focus on trisomies (where an individual has three copies of a chromosome instead of the normal two), sex chromosome aneuploidies (one, three, or more sex chromosomes instead of two), microdeletions (where a copy of a chromosomal region is missing), or microduplications (one or more extra copies of a chromosomal region). Fetal DNA analysis with NGS can be performed on a blood sample taken from the pregnant woman, referred to as non-invasive prenatal testing or NIPT. In Sweden, targeted NGS analysis of NIPT samples to detect trisomy 13, 18, 21 or sex chromosome aneuploidy is offered in a few regions.
This report evaluates the reliability of the results obtained through NGS of noninvasive samples compared to karyotyping, QF-PCR or FISH analysis for trisomies (other than trisomy 13, 18 or 21), sex chromosome aneuploidies, microdeletions and microduplications.
The report also evaluates the reliability of the results obtained when NGS is used for whole genome sequencing of both invasive (amniotic fluid or placenta samples) and non-invasive samples.
The report highlights ethical aspects of using NGS for prenatal diagnosis, and how expectant parents perceive the value of the information. Health economic aspects are not addressed in this report.
This evaluation was performed following SBU’s method.
Prenatal diagnosis involves issues relating to human dignity, parental autonomy, and the health of both the fetus and the parents. This SBU report presents some of the ethical issues associated with the NGS analysis method as compared to karyotyping.
The main advantage to using NGS for prenatal diagnosis is that NGS can be used to analyse non-invasive samples. Another possible advantage is the ability to detect microdeletions and other smaller chromosomal abnormalities.
An ethical problem with NGS is that it is often provided in the form of a predesigned analysis package that includes elements that may not be of interest. For instance, this packaging has led to NGS already being used to analyse the incidence of sex chromosome aneuploidies in conjunction with analysis for trisomy 13, 18 and 21. Since NGS of non-invasive samples does not increase the risk of miscarriage, expectant parents could perceive it as difficult to turn down. Depending on which genetic changes are included for analysis in the future, use of the method may contribute to a shift of focus to include low or medium-level indications, i.e. that healthcare professionals will gradually begin to look for what are currently perceived as less serious conditions. NGS could also contribute to the stigmatisation of individuals with conditions linked to genetic abnormalities that can be identified using NGS.
An introduction of NGS for prenatal whole genome sequencing may introduce ethical problems regarding how to sufficiently explain the method and the expected results, how to determine who should be analysed and what kind of information should be provided to whom.
How to cite this report: SBU. Prenatal Diagnosis through Next Generation Sequencing (NGS). Stockholm: Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU); 2016. SBU report no 247 (in Swedish).
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