Risk of fetal loss associated with invasive testing following combined first-trimester screening for Down syndrome:a national cohort of 147 987 singleton pregnancies

OBJECTIVE: To assess prospectively the risk of fetal loss associated with chorionic villus sampling (CVS) and amniocentesis (AC) following combined first-trimester screening (cFTS) for Down syndrome.METHODS: This was a nationwide population-based study (Danish Fetal Medicine Database, 2008-2010) including 147 987 women with singleton pregnancy who underwent cFTS. Propensity score stratification was used to assess the risk of fetal loss with and without invasive testing. Analyses were performed between 3 and 21 days after cFTS for CVS and between 28 and 42 days after cFTS for AC. Results are reported as average risk differences with 95% CIs.RESULTS: The risks of miscarriage and stillbirth were not higher in women exposed to CVS or AC compared with unexposed women, independent of the analysis time-point. The average effect of CVS on risk of miscarriage was -0.08% (95% CI, -0.64; 0.47) at 3 days and -0.21% (95% CI, -0.58; 0.15) at 21 days after cFTS, while the effect on risk of stillbirth was -0.18% (95% CI, -0.50; 0.13) at 3 days and -0.27% (95% CI, -0.58; 0.04) at 21 days after cFTS. Regarding the effect of AC on risk of miscarriage, the analysis at 28 days after cFTS showed an average effect of 0.56% (95% CI, -0.21; 1.33), while the effect on risk of stillbirth was 0.09% (95% CI, -0.39; 0.58) at 42 days after cFTS.CONCLUSION: Neither CVS nor AC was associated with increased risk of miscarriage or stillbirth. These findings indicate that the procedure-related risk of CVS and AC is very low.