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

Abstract

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.

Keywords: amniocentesis; chorionic villus sampling; combined first-trimester screening; fetal loss; invasive prenatal testing; miscarriage; procedure-related risk; stillbirth.