Prenatal Diagnosis Of Congenital Anomalies

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

Investigators

Linked publications & trials

Abstract

1. Cardiac measurements of size and shape in fetuses with absent or reversed end-diastolic velocity of the umbilical artery and perinatal survival and severe growth restriction before 34weeks' gestation. The purpose of this study was to evaluate the end-diastolic size and shape of the 4-chamber view as well as the right ventricle (RV) and left ventricle (LV) in growth-restricted fetuses before 34 weeks' gestation with absent or reversed end-diastolic velocity of the umbilical artery and compare the results between those with perinatal deaths and those who survived the neonatal period. Of the 49 fetuses, there were 13 perinatal deaths (27%) and 36 (63%) neonatal survivors. Measurements that were unique for neonatal survivors were an increased RV apical transverse width and decreased measurements of the following: LV and RV widths, LV and RV areas, as well as RV sphericity indices. We concluded that fetuses with a smaller RV and LV size and area and those with a globular-shaped RV were at significantly lower risk for perinatal death (2). 2. Crowdsourcing assessment of maternal blood multi-omics for predicting gestational age and preterm birth. Identification of pregnancies at risk of preterm birth, the leading cause of newborn deaths, remains challenging given the syndromic nature of the disease. In this study, we report a longitudinal multi-omics study coupled with a crowdsourcing initiative (DREAM challenge) to develop predictive models of gestational age and spontaneous preterm birth. The computational challenge was based on previously published and new data generated by the Perinatology Research Branch, while incentives for participating in the challenge were funded by Wayne State University and the March of Dimes. The findings indicate that whole blood gene expression predicts ultrasound-based gestational ages at blood draw in normal and complicated pregnancies (r=0.83). Based on samples collected before 33 weeks in asymptomatic women, our analysis suggests that gene expression changes preceding preterm prelabor rupture of the membranes are consistent across time points and cohorts, and involve leukocyte-mediated immunity. Models built from plasma proteomic data predict spontaneous preterm delivery with intact membranes with higher accuracy and earlier in pregnancy than transcriptomic models (AUROC=0.76 vs. AUROC=0.6 at 27-33 weeks of gestation). This work has therefore identified RNAs and proteins in maternal circulation predictive of spontaneous preterm birth in asymptomatic patients that can be further evaluated in larger targeted studies. Early prediction of women at risk could enable preventive strategies. Moreover, a byproduct of this work is a suite of methods and software tools for longitudinal omics data that can be applied to the study of other adverse pregnancy outcomes to identify biomarkers. These methods are available at www.synapse.org/pretermbirth (5).