title: Late first-trimester invasive prenatal diagnosis: results of an international randomized trial.
abstract: 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
authors.affiliation: Rigshospitalet, Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Philip
authors.forename: R K
authors.initials: RK
authors.lastname: Silver
authors.forename: R D
authors.initials: RD
authors.lastname: Wilson
authors.forename: E A
authors.initials: EA
authors.lastname: Thom
authors.forename: J M
authors.initials: JM
authors.lastname: Zachary
authors.forename: P
authors.initials: P
authors.lastname: Mohide
authors.forename: M J
authors.initials: MJ
authors.lastname: Mahoney
authors.forename: J L
authors.initials: JL
authors.lastname: Simpson
authors.forename: L D
authors.initials: LD
authors.lastname: Platt
authors.forename: E
authors.initials: E
authors.lastname: Pergament
authors.forename: D
authors.initials: D
authors.lastname: Hershey
authors.forename: K
authors.initials: K
authors.lastname: Filkins
authors.forename: A
authors.initials: A
authors.lastname: Johnson
authors.forename: L P
authors.initials: LP
authors.lastname: Shulman
authors.forename: J
authors.initials: J
authors.lastname: Bang
authors.forename: S
authors.initials: S
authors.lastname: MacGregor
authors.forename: J R
authors.initials: JR
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Shaw
authors.forename: R J
authors.initials: RJ
authors.lastname: Wapner
authors.forename: L G
authors.initials: LG
authors.lastname: Jackson
mesh_terms: 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