Abstract
Objectives. The primary aim was to evaluate which investigation performed after sonographic detection of central nervous system (CNS) or skeletal anomalies that had highest diagnostic yield. The secondary aim was to estimate recurrence risk. Design. Retrospective review of patients’ records. Setting. Tertiary fetal medicine referral center. Sample. Pregnancy terminations (n=97) because of CNS or skeletal anomalies during a 17-year period, within 12–24 weeks gestation. Methods. Two medical geneticists and one genetic counselor reviewed charts independently. Main outcome measures. Primary ultrasound diagnosis, change in diagnosis following supplementary examinations in addition to prenatal ultrasound (medical history, autopsy, post-mortem X-ray, karyotyping, targeted DNA analysis and investigations for infection), the most useful method to determine diagnosis, and recurrence risk estimate including inter-rater agreement. Results. Mean gestational age was 19.8 weeks. All three investigators agreed in each case on which investigation constituted the best basis to determine the most precise diagnosis. The examinations performed in addition to prenatal ultrasound provided important diagnostic information in 54 cases (56%) and altered recurrence risk in 22 (23%) cases; in eight of these cases the risk estimate was increased. In nine cases (9%) the investigators disagreed in their estimates of recurrence risk. Kappa for inter-rater agreement was >0.90. Conclusions. A panel of diagnostic investigations, depending on the organ system involved, allows for a more precise diagnosis and a more reliable estimate of recurrence risk than prenatal ultrasound alone. In some instances, recurrence risk estimation is not straightforward as evidenced by lack of consensus.