The present study provides detailed neonatal and congenital malformation follow-up from 695 women enrolled in a prospective randomized multicenter study comparing the safety and accuracy of early (11-12 weeks of gestation) and midtrimester amniocentesis (15-16 weeks of gestation). No differences were found for total pregnancy loss (difference 0.4%; CI -3.6 to 4.4%), obstetrical or neonatal outcome. The incidence of congenital anomalies was 2.4 and 2.6% for the early amniocentesis and midtrimester amniocentesis groups, respectively. Respiratory problems were present in 2.1 and 1.6%, respectively. Musculoskeletal problems were present in 0.9 and 2.4%, respectively. It must be emphasized that before early amniocentesis can be considered as an alternative to midtrimester amniocentesis or chorionic villus sampling, careful evaluation of any fetal effects must be considered and further large randomized trials are necessary.