Late first-trimester invasive prenatal diagnosis: results of an international randomized trial.
OBJECTIVE
To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11-14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening.


METHODS
We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies.


RESULTS
We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P =.07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P =.02) overall and in week 13 (P =.03, relative risk = 4.65), but data were insufficient to determine this risk in week 14.


CONCLUSIONS
Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss.


METHODS
I
Philip
J
J
Rigshospitalet, Copenhagen, Denmark.
Silver
R K
RK
Wilson
R D
RD
Thom
E A
EA
Zachary
J M
JM
Mohide
P
P
Mahoney
M J
MJ
Simpson
J L
JL
Platt
L D
LD
Pergament
E
E
Hershey
D
D
Filkins
K
K
Johnson
A
A
Shulman
L P
LP
Bang
J
J
MacGregor
S
S
Smith
J R
JR
Shaw
D
D
Wapner
R J
RJ
Jackson
L G
LG
D000028:Abortion, Induced; D000022:Abortion, Spontaneous / Q000453:epidemiology; D000649:Amniocentesis; D015193:Chorionic Villi Sampling; D003025:Clubfoot / Q000453:epidemiology; D005260:Female; D005313:Fetal Death / Q000453:epidemiology; D005317:Fetal Growth Retardation / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D008423:Maternal Age; D007752:Obstetric Labor, Premature / Q000453:epidemiology; D016104:Oligohydramnios / Q000453:epidemiology; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D011261:Pregnancy Trimester, First; D018566:Pregnancy, High-Risk; D012449:Safety; D013997:Time Factors; D014314:Trisomy; D016216:Ultrasonography, Prenatal