Prenatal genetic testing for cystic fibrosis: a systematic review of clinical effectiveness and an ethics review

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We aimed to assess the clinical value of prenatal testing for cystic fibrosis (CF) and whether ethical considerations would affect endpoint selection.


To determine effectiveness, we conducted a systematic literature review whose protocol outlined search strategies across eight databases, study inclusion criteria, and prespecified literature screening, data extraction, and synthesis processes. We conducted a scoping search on ethical considerations.


The genetic test showed good diagnostic performance. A change in clinical management was observed: termination of pregnancy (TOP) occurred in most cases where two pathogenic variants were identified in a fetus of carrier parents (158/167; 94.6%). The TOP rate was lower in pregnancies where CF was diagnosed after fetal echogenic bowel detection (~65%). TOP and caring for a child with CF were both associated with poor short-term parental psychological outcomes. Ethical analyses indicated that informed decisions should have been the main endpoint, rather than CF-affected births prevented.


CF testing leads to fewer CF-affected births. It is difficult to assess whether this means the test is valuable, since patients may not value TOP primarily in terms of maternal or fetal health outcomes, psychological or otherwise. The value of testing should arguably be measured in terms of improving patient autonomy rather than health.

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We thank Judy Morona for analyzing the diagnostic accuracy evidence and Thomas Vreugdenburg for critical revision of the manuscript. Earlier versions of the systematic review and ethics review were previously conducted in 2015 as part of an Australian Department of Health contracted assessment of the technology (Kessels S, Morona J, Mittal R, et al. Testing for hereditary mutations in the cystic fibrosis transmembrane conductance regulator [CFTR] gene. 2015. MSAC application 1216, Assessment Report, Commonwealth of Australia, Canberra, ACT). Any opinions expressed belong to the authors or cited writers alone.

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Correspondence to Drew Carter PhD.

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Kessels, S.J.M., Carter, D., Ellery, B. et al. Prenatal genetic testing for cystic fibrosis: a systematic review of clinical effectiveness and an ethics review. Genet Med (2019) doi:10.1038/s41436-019-0641-8

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