BACKGROUND: Cell-free fetal DNA (cffDNA) can be detected in maternal blood 
during pregnancy, opening the possibility of early non-invasive prenatal 
diagnosis for a variety of genetic conditions. Since 1997, many studies have 
examined the accuracy of prenatal fetal sex determination using cffDNA, 
particularly for pregnancies at risk of an X-linked condition. Here we report a 
review and meta-analysis of the published literature to evaluate the use of 
cffDNA for prenatal determination (diagnosis) of fetal sex. We applied a 
sensitive search of multiple bibliographic databases including PubMed (MEDLINE), 
EMBASE, the Cochrane library and Web of Science.
RESULTS: Ninety studies, incorporating 9,965 pregnancies and 10,587 fetal sex 
results met our inclusion criteria. Overall mean sensitivity was 96.6% (95% 
credible interval 95.2% to 97.7%) and mean specificity was 98.9% (95% CI = 98.1% 
to 99.4%). These results vary very little with trimester or week of testing, 
indicating that the performance of the test is reliably high.
CONCLUSIONS: Based on this review and meta-analysis we conclude that fetal sex 
can be determined with a high level of accuracy by analyzing cffDNA. Using 
cffDNA in prenatal diagnosis to replace or complement existing invasive methods 
can remove or reduce the risk of miscarriage. Future work should concentrate on 
the economic and ethical considerations of implementing an early non-invasive 
test for fetal sex.