Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis

Objectives: To estimate the procedure-related risks of miscarriage after amniocentesis and trans-abdominal chorionic villus sampling (CVS) based on a systematic review of the literature and an updated meta-analysis.

Methods: A search of MEDLINE, EMBASE, and The Cochrane Library was carried out to identify studies reporting complications following CVS or amniocentesis. The inclusion criteria for the systematic review were studies reporting results from large controlled studies and those reporting data for pregnancy loss prior to 24 weeks’ gestation. Study authors were contacted when required to identify additional necessary data. Data for cases that had invasive procedure and controls groups were inputted in contingency tables and risk of miscarriage was estimated for each study. Summary statistics based on a fixed and random effects model were calculated after taking into account the weighting for each study included in the systematic review. Procedure-related risk of miscarriage was estimated as a weighted risk difference from the summary statistics for cases and controls. A subgroup analyses according to the similarity risk levels in the invasive testing and control groups was performed. Heterogeneity was assessed using Cochrane’s Q and I2 statistic. Egger Bias was estimated to assess reporting bias in published studies. Summary statistics for procedure-related risk of miscarriage were graphically represented in Forest plots.

Results: The electronic search from the databases yielded 2,943 potential citations, from which, we selected 20 controlled studies for inclusion in the systematic review to estimate the procedure-related risk of miscarriage from invasive procedures. There were a total of 580 miscarriages from 63,273 amniocentesis procedures with a weighted risk of pregnancy loss of 0.91% (95%CI: 0.73 to 1.09). In the control group, there were 1,726 miscarriages in 330,469 pregnancies with a loss rate of 0.58% (95CI%: 0.47 to 0.70). The weighted procedure-related risk of miscarriage was 0.30% (95%CI: 0.11 to 0.49, I2=70.1%). There were a total of 163 miscarriages from 13,011 CVS procedures with a risk of pregnancy loss of 1.39% (95%CI: 0.76 to 2.02). In the control group, there were 1,946 miscarriages in 232,680 pregnancies with a loss rate of 1.23% (95CI%: 0.86 to 1.59). The weighted procedure-related risk of miscarriage following CVS was 0.20% (95%CI: -0.12 to 0.52, I2=51.9%). However, when only studies with similar risk profiles between the intervention and control groups were considered, the procedure related risk for amniocentesis became 0.03% (95%CI -0.08 to 0.14, I2=0%) and for CVS -0.38 (95% CI -1.12 to 0.36, I2=0%).

Conclusion: The procedure-related risks of miscarriage following amniocentesis and CVS are lower than currently quoted to women. The risk appears to be negligible when these interventions are compared to control groups of the same risk profile.