Prenatal Diagnosis Of Congenital Anomalies

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

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Abstract

A. Fetal intelligent navigation is superior to manual navigation to examine the fetal heart with ultrasound Congenital heart disease (CHD) is the most common birth defect by organ system, and the leading cause of infant morbidity and mortality related to birth defects. In 2013, hospital costs exceeded $6 billion to care for children with CHD. All pregnancies should undergo prenatal sonographic screening for cardiac defects, since up to 90% of cases occur in the absence of risk factors. Moreover, there is evidence that prenatal diagnosis of specific cardiac anomalies improves the survival after surgery, and long-term neurocognitive function and outcome. The overall prenatal detection rate for congenital heart disease with ultrasound remains suboptimal. To address these issues, the PRB successfully developed a novel method known as Fetal Intelligent Navigation Echocardiography (FINE) to interrogate fetal sonographic cardiac volume datasets. This method allows the automatic display of nine standard fetal cardiac views required to diagnose most cardiac defects. The FINE method simplifies examination of the fetal heart and reduces operator dependency. Virtually all ultrasound examinations use manual navigation to examine the fetal heart. We conducted a study to compare the performance between manual and intelligent navigation (FINE) of the fetal heart by non-expert sonologists. This prospective observational study included ten sonologists who underwent formal training on both navigational methods. Subsequently, we tested the ability of participants to obtain nine cardiac views from five STIC volumes of normal fetal hearts (1928 gestational weeks) using such methods. The following parameters were determined for both methods: 1) success rate of obtaining nine cardiac views; 2) mean time to obtain nine cardiac views per sonologist; and 3) maximum number of cardiac views successfully obtained for each STIC volume. All fetal cardiac images were obtained from 100 STIC volumes (50 for each navigational method) and reviewed by an expert in fetal echocardiography. Compared to manual navigation, FINE had a: 1) higher success rate of obtaining eight (excluding the abdomen view) appropriate cardiac views (92100% vs. 5688%; all p<0.05); 2) shorter mean time (minute:seconds) to obtain nine cardiac views (2:11 0:37 vs. 15:49 7:44; p<0.0001); and 3) higher success rate of obtaining all nine cardiac views for a given STIC volume (86% vs. 14%; p<0.001). We conclude that when performed by non-expert sonologists, intelligent navigation (FINE) had a superior performance than manual navigation of the fetal heart. Specifically, FINE obtained appropriate fetal cardiac views in 92%-100% of cases. B. Syndecan-1: a biomarker for fetal growth restriction The identification of fetal growth disorders is an important priority in obstetrics since this condition increases the risk of perinatal morbidity and mortality, as well as adult disease. A subset of small for gestational age (SGA) infants are growth restricted and this is often attributed to placental insufficiency. Syndecan-1, a product of the degradation of the endothelial glycocalyx, has been proposed as a biomarker of endothelial damage in different pathological conditions. During pregnancy, there is a specialized form of the glycocalyx the syncytiotrophoblast glycocalyx which covers the placental villi. We conducted a study to determine whether maternal plasma syndecan-1 concentrations can be used as a biomarker for fetal growth restriction. A cross-sectional study was performed to include women with normal pregnancy (n=130) and pregnant women who delivered SGA neonates (n=50). Doppler velocimetry of the uterine artery and umbilical artery was performed in women with SGA fetuses at the time of diagnosis. Venipuncture was performed within 48 hours of Doppler velocimetry and plasma concentrations of syndecan-1 were determined by a specific and sensitive immunoassay. The results showed that the mothers with pregnancies complicated with an SGA fetus had a significantly lower mean plasma concentration of syndecan-1 than those with an appropriate for gestational age fetus (p=0.005). This difference was attributed to fetal growth restriction as the mean plasma syndecan-1 concentration was significantly lower only in the group of women with SGA fetuses with an abnormal umbilical and uterine artery Doppler velocimetry compared to controls (p=0.00071; adjusted p=0.0028). Among women with SGA fetuses, those with abnormal umbilical and uterine artery Doppler findings had a significantly lower mean plasma syndecan-1 concentration (p=0.02; adjusted p=0.04). A plasma syndecan-1 concentration < 850 ng/mL had a positive likelihood ratio of 4.4 and a negative likelihood ratio of 0.24 for the identification of a mother with an SGA fetus with abnormal umbilical artery Doppler velocimetry (area under the ROC curve 0.83; p < 0.001). The results of this study suggest that plasma syndecan-1 could be used as a biomarker to identify fetal growth restriction.