RANDOMIZED STUDY OF RISK OF FETAL LOSS RELATED TO EARLY AMNIOCENTESISVERSUS CHORIONIC VILLUS SAMPLING

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 comp leted randomised study of fetal safety showed a significant fetal-loss risk related to first-trimester amniocentesis. We assessed fetal safe ty in early amniocentesis and CVS. Methods We assessed early amniocent esis at 11-13 weeks' gestational age compared with the fetal risk asso ciated with CVS at 10-12 weeks. 1160 pregnant women were randomly assi gned one procedure (581 early amniocentesis, 579 CVS) after a baseline ultrasound examination at 10 weeks' gestation and were followed up un til birth. Total fetal loss and neonatal morbidity were the primary ou tcome measures. Sampling success and pregnancy complications were seco ndary outcomes. We used a filter to increase the cell yield in the ear ly amniotic-fluid samples. CVS was transabdominal. Findings We found a significantly increased occurrence of talipes equinovarus in the earl y amniocentesis group (p<0.01), the risk of which was associated with sampling at the earliest gestational ages and with temporary leakage o f amniotic fluid after sampling. Therefore, the trial was stopped earl y, which reduced the power of the safety study, 48% (27) of fetuses in the CVS group and 5.4% (30) in the early amniocentesis group were los t after randomisation (p=0.66). More detailed survival analysis did no t show any significant differences in fetal loss rates. Leakage of amn iotic fluid after sampling occurred significantly more frequently afte r early amniocentesis than after CVS (p<0.001), but we found no other major differences in pregnancy complications. Significantly more CVS t han early amniocentesis procedures were repeated or railed to produce a karyotype (p<0.01). Interpretation Even though the numbers were smal l, we found an association between early amniocentesis and talipes equ inovarus. We believe this association to be true, since it supports a trend in a similar randomised study. Our results show that early amnio centesis, when done with the filter technique, is associated with an a bortion risk similar to CVS, although the limited size of our study po pulation reduced the strength of this conclusion.