Non-invasive prenatal determination of fetal sex: translating research into clinical practice

Abstract

The effectiveness and clinical utility of non-invasive prenatal diagnosis (NIPD) for fetal sex determination using cell-free fetal DNA (cffDNA) was assessed by undertaking a prospective national audit of UK testing. NIPD was performed using real-time polymerase chain reaction analysis of the DYS14 or SRY gene in cffDNA extracted from maternal plasma. All cases referred for fetal sex determination from 1 April 2006 to 31 March 2009 were ascertained from two laboratories offering the test. Fetal gender determined by NIPD was compared with that based on ultrasound, invasive test or phenotype at birth. Indication and rate of invasive testing was ascertained. In the first year, results were issued in 150/161 pregnancies tested. Of the 135 with outcome data, results were concordant in 130/135 [96.3% (95% CI 91.6-98.8%)]. Reporting criteria were changed and in the subsequent 511 pregnancies the concordancy rate increased to 401/403 [99.5% (95% CI 98.2-99.9%)]. Over the 3 years only 32.9% (174/528) underwent invasive testing. NIPD for fetal sex determination using cffDNA is highly accurate when performed in National Health Service laboratories if stringent reporting criteria are applied. Parents should be advised of the small risk of discordant results and possible need for repeat testing to resolve inconclusive results.

Non-invasive prenatal diagnosis for fetal sex determination: benefits and disadvantages from the service users’ perspective

“…Further, some of the disadvantages raised, such as 'robbed of surprise' , relate to any form of fetal sex determination. In addition to the clinical benefits derived through NIPD including safety, ease of performing the test, early testing and reduction in the number of invasive tests being performed, 20 other psychological benefits were also identified. These included normalization of pregnancy, control and peace of mind.…”

Noninvasive fetal sex determination in maternal plasma: a prospective feasibility study

“…36 Some recently published studies used a combination of the DYS14 and SRY sequences to improve sensitivity and specificity of the assay. 34,37 Determination of fetal sex based on the detection of Y-chromosome-specific markers in maternal plasma is prone to false-negative results because female fetuses are not detected directly but instead are inferred by a negative result for Y-chromosome sequences, which could also be caused by undetectable levels of cffDNA. Because of the higher sensitivity of DYS14, testing for only DYS14 has been suggested.…”

Management of Inherited Bleeding Disorders in Pregnancy

“…Inconclusive results are reported in up to 13% of cases and necessitate repeat testing. 230 Fetal sex should be confirmed by US at 20 weeks of gestation.…”

“…Appendix III: Methods for prenatal diagnosis [228][229][230][231][232][233][234][235][236][237][238] Investigation/ procedure Timing: weeks of gestation Important information Recommendations Noninvasive PND for fetal sex determination > 9 PCR analysis of cffDNA, originating from the placenta and present in maternal blood, permits noninvasive determination of fetal sex early in pregnancy. Overall sensitivity of 95% and specificity of 98% are reported.…”