First-Trimester Markers of Aneuploidy and the Prediction of Small-for-Gestational Age Fetuses

Abstract

First-trimester estimates of 2 biomarkers of placental origin, pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG), are increasingly used along with ultrasound measurement of nuchal translucency thickness to screen for trisomy 21 and other aneuploidies. There are preliminary indications that reduced levels of these markers—especially PAPP-A—may help to identify at-risk pregnancies including those resulting in delivery of a small-for-gestational age (SGA) infant. The study population included singleton pregnancies with chromosomally normal fetuses that were screened at 11 to 14 weeks’ gestation. Biochemical marker levels were converted to multiples of the expected normal median (MoM) for a pregnancy of the same gestational age. Associations between levels of free β-hCG and PAPP-A and the incidence of SGA were assessed by comparing relative incidence rates at MoM cutoffs and birth weight centile cutoffs. A total of 46,262 pregnancies resulted in live births of infants weighing at or above the 10th centile, whereas 3539 others produced SGA infants weighing less than the 10th centile for gestation. The risk of an SGA infant was significantly and inversely associated with maternal serum PAPP-A MoM, but not with free β-hCG MoM. In pregnancies with PAPP-A levels below the 10th, 5th, and 3rd percentile, the incidence of SGA was 12%, 14%, and 16%, respectively, and the odds ratios for SGA were 2.70, 3.21, and 3.66, respectively. Free β-hCG levels did not predict SGA. The investigators believe that, in the presence of a normal fetal karyotype, low maternal serum levels of PAPP-A are associated with an elevated risk of subsequently delivering a SGA infant. Low levels presumably indicate impaired placentation. Present evidence warrants using low PAPP-A to help identify SGA pregnancies.