Point-of-care screening for chromosomal anomalies in the first trimester of pregnancy.

Abstract

Since the serendipitous finding almost 20 years ago of a reduced concentration of maternal serum α-fetoprotein (MSAFP) in an index case of a second-trimester pregnancy complicated by trisomy 18 (1) and the subsequent confirmation of this finding in other pregnancies complicated by trisomy 21, there has been a gradual improvement in trisomy 21 screening efficiency as better markers have been identified. Screening using a combination of maternal age, MSAFP, and maternal serum free β-human chorionic gonadotropin (β-hCG) or total hCG has enabled trisomy 21 detection rates of 65–70% (for a 5% screen-positive rate) to be achieved in second-trimester prospective screening (2)(3). Although the use of additional markers such as unconjugated estriol and dimeric inhibin-A have been proposed, modeling predicts only an additional 5% detection (4), and no large-scale prospective data have been published with a four-marker combination. In the past decade, research energies have largely focused on the first trimester of pregnancy. The identification of suitable maternal serum biochemical markers such as free β-hCG (5) and pregnancy-associated plasma protein A (PAPP-A) (6) led this advance. The development of improved ultrasound imaging techniques, however, allowed the identification of nuchal translucency thickness as the major marker of chromosomal anomalies in the first trimester. With measurements performed in a standardized way (defined by the Fetal Medicine Foundation; www.fetalmedicine.com) by suitably trained sonographers, trisomy 21 detection rates in combination with maternal age have reached 73% (for a 5% screen-positive rate) in multicenter prospective intervention studies (7). A combination of nuchal translucency and the two first-trimester serum markers has been shown to increase this detection rate to 89% for …