Background: Several cohort studies have shown the feasibility of early amniocentesis (between 11 and 13 weeks of gestation) as an alternative to chorionic villus sampling (CVS) for karyotyping, but the only completed randomised study of fetal safety showed a significant fetal-loss risk related to first-trimester amniocentesis. We assessed fetal safety in early amniocentesis and CVS.
Methods: We assessed early amniocentesis at 11-13 weeks gestational age compared with the fetal risk associated with CVS at 10-12 weeks. 1160 pregnant women were randomly assigned one procedure (581 early amniocentesis, 579 CVS) after a baseline ultrasound examination at 10 weeks' gestation and were followed up until birth. Total fetal loss and neonatal morbidity were the primary outcome measures. Sampling success and pregnancy complications were secondary outcomes. We used a filter to increase the cell yield in the early amniotic-fluid samples. CVS was transabdominal.
Findings: We found a significantly increased occurrence of talipes equinovarus in the early amniocentesis group (p < 0.01), the risk of which was associated with sampling at the earliest gestational ages and with temporary leakage of amniotic fluid after sampling. Therefore, the trial was stopped early, which reduced the power of the safety study. 4.8% (27) of fetuses in the CVS group and 5.4% (30) in the early amniocentesis group were lost after randomisation (p = 0.66). More detailed survival analysis did not show any significant differences in fetal loss rates. Leakage of amniotic fluid after sampling occurred significantly more frequently after early amniocentesis than after CVS (p < 0.001), but we found no other major differences in pregnancy complications. Significantly more CVS than early amniocentesis procedures were repeated or failed to produce a karyotype (p < 0.01).
Interpretation: Even though the numbers were small, we found an association between early amniocentesis and talipes equinovarus. We believe this association to be true, since it supports a trend in a similar randomised study. Our results show that early amniocentesis, when done with the filter technique, is associated with an abortion risk similar to CVS, although the limited size of our study population reduced the strength of this conclusion.