Gene expression analysis of amniotic fluid: New biomarkers and novel antenatal treatments

Abstract

Over the past thirty years there has been a significant increase in the use of prenatal diagnosis to improve perinatal outcome. Frequently, at least in developed countries, this involves prenatal sonography to image fetal anatomy and detect congenital anomalies. This has led to a primarily surgical approach to fetal and neonatal treatment. While effective, this strategy has revealed little about fetal functional development. Since 2005, our laboratory has explored the hypothesis that valuable fetal developmental gene expression information is present in amniotic fluid (AF). In pilot studies performed using large quantities of amniotic fluid obtained from pregnancies complicated by polyhydramnios, we showed that cell-free fetal messenger RNA (cff mRNA) could be successfully hybridized to gene expression microarrays. Comparative analyses of the arrays from different subjects demonstrated that fetal gene expression changes could be detected as a result of fetal sex, gestational age, and disease status [1]. Furthermore, we showed that cff mRNA in AF originated from the fetus and not the placenta, which suggested that AF could be used directly to analyze fetal development and well-being. AF is widely available but generally under-utilized [2]. It is obtained primarily for fetal chromosome analysis and alpha-fetoprotein measurement to diagnose open neural tube defects. AF is an excellent source of material for research, as large quantities of supernatant are obtained for clinical diagnosis and then discarded, samples generally have correlated medical record and karyotype information available, and there is no contamination by maternal nucleic acids [2]. AF provides a way to directly query fetal development from as early as 15 weeks of gestation. We have used cff mRNA in AF to identify new biomarkers of fetal disease, develop new insights into fetal pathophysiology, and to suggest new approaches to fetal treatment.