Original Title: Ikke-invasiv prenatal testing (NIPT) for kjønnsbestemmelse av foster. Metodevurdering

Authors' objectives: This health technology assessment summarizes research findings on diagnostic accuracy of NIPT for fetal sex determination, and discusses clinical, health economic and ethical consequences related to NIPT. The purpose of using NIPT for fetal sex determination is to reduce the number of invasive tests, as only pregnant women who, according to a NIPT result, carry a male fetus, will be referred to invasive testing.

Authors' results and conclusions: RESULTS: Diagnostic accuracy We identified four systematic reviews that met our inclusion criteria. We chose to re‐ port results of a systematic review of high methodological quality that was published in 2016. The systematic review was based on 60 studies, including altogether results from 11,179 NIPT samples. Another systematic review from 2011 was used to report diagnostic accuracy of NIPT related to gestational age and sample type. Due to inadequate reporting of inconclusive results across studies, we chose to refer to the results from all four systematic reviews when reporting this outcome. Diagnostic accuracy of NIPT for fetal sex determination is very high. The sensitivity of the test is 98.9% and the specificity 99.6%. The positive and negative predictive values are correspondingly high, 99.6% and 98.8% respectively. Diagnostic accuracy of NIPT increases with gestational age. While sensitivity before week 7 is 74.5%, it is 94.8% in the gestational weeks 7‐12 and 99.0% after week 20. Diagnostic accuracy using plasma and serum are equally high. The sensitivity of NIPT is 95.6% using plasma and 96.6% using serum, and the specificity 98.8% using plasma and 98.2% using serum. Based on the test's sensitivity and specificity, in the Norwegian population with 48.6% female births, 490 of 1,000 invasive tests will be avoided if NIPT is used to determine fetal sex prior to a referral to invasive testing. However, this calculation does not take into account inconclusive results. 13 Some NIPT tests will result in inconclusive results. Inconclusive results were poorly re‐ ported across studies. Based on the identified systematic reviews, we estimate that inconclusive results will occur in approximately 10‐20% of NIPT samples. Health economic evaluation In our cost analysis, we assume that approximately 50 pregnant women in Norway are eligible for fetal sex determination each year. The proportion of inconclusive NIPT results is assumed to be 15%. Based on these assumptions, we estimate that 21 pregnant women will avoid invasive testing. The total annual costs of such a program for the Norwegian health care system is calculated to be 197,000 Norwegian kroner. The incremental costs per tested pregnant woman is approximately 3,900 Norwegian kroner compared with current practice. This means an incremental cost of approximately 9,400 Norwegian kroner per avoided invasive test. However, due to uncertainty related to NIPT prices, these results should be interpreted with caution. The costs will not differ substantially from the above estimates when the test is delivered abroad to a commercial laboratory for analysis. Ethical aspects Fetal sex determination may be carried out for two purposes. Firstly, determination of fetal sex may be used to identify fetuses at increased risk for severe hereditary dis‐ eases. Secondly, one may seek this information to select the gender of a child. Our re‐ port deals solely with the first alternative, where NIPT presumably will not bring along any new ethical challenges compared to current practice. CONCLUSION: NIPT is a test that can be used to identify fetal sex in pregnancies at increased risk of X‐ linked recessive diseases. Diagnostic accuracy of NIPT for fetal sex determination is very high. Testing in 7th gestational week or later provides more reliable results than testing before week 7. Implementation of NIPT will potentially reduce 42% of invasive tests carried out in this group of pregnant women. With the assumption of 50 pregnant women eligible for testing, the total costs of introducing NIPT for fetal sex determination in the health care system is 197,000 Norwegian kroner per year.

Authors' methods: Diagnostic accuracy. We conducted systematic literature searches for systematic reviews. Individual search strategies were designed for selected relevant databases. Search strategies were based on a combination of subject headings and text words for NIPT. Searches were limited to the period of 2010 to February 2016. Two reviewers independently screened all identi‐ fied records and critically appraised the selected publications. The following outcomes were included: sensitivity and specificity, predictive values, likelihood ratio, inconclu‐ sive results, and the number of avoided invasive tests compared with current clinical practice. By inconclusive results, we mean cases where the laboratory cannot tell whether the fetus is a girl or boy. Health economic evaluation We performed a cost analysis where two alternative scenarios were considered: cur‐ rent practice for fetal sex determination by means of invasive tests, and a program where NIPT is used for fetal sex determination. We calculated total costs of introducing NIPT, incremental costs per pregnant woman who is tested, and incremental costs per avoided invasive test.

Project Status: Completed

Year Published: 2016

URL for published report: https://www.fhi.no/en/publ/2016/ikke-invasiv-prenatal-testing-nipt-for-kjonnsbestemmelse-av-foster.-metodev/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Norway

Pubmed ID: 29553638

Organisation Name: Norwegian Institute of Public Health

Contact Address: P.O. Box 222 Skoyen, N-0123, Oslo