Methods	Telephone randomisation interactive voice response computer-based system
Participants	14 clinical centres. Inclusion criteria: age of mother more than 34 years, previous affected child, positive screening test. Exclusion criteria: multiple pregnancy, familiar chromosome rearrangements, inherited enzyme disorders, serious maternal illnesses (insulin-dependent diabetes, severe hypertension, HIV), bleeding equal menstruation, IUD in situ, oligohidramnios, recognised fetal abnormalities. Total number of patients = 3775 (CVS group = 1914 and EAC group = 1861)
Interventions	EAC group: 22 G spinal needle, 1 ml for each week. - CVS - single (19 to 20 G) and double needle technique (18 to 20 G). Larger guide needle to the margin of the chorion
Outcomes	Primary outcome: fetal loss less than 28 weeks. Secondary outcome: all fetal loss, all neonatal death, oligohydramnios, gestational age at the delivery, IUGR, respiratory distress syndrome, limb reduction defects, talipes equinovarus, other congenital anomalies
Notes
Risk of bias
Item	Authors’ judgement	Description
Allocation concealment?	Yes	A - Adequate