ABSTRACT
PURPOSE: We compared the diagnostic yield of fetal clinical exome sequencing (fCES) in prospective and retrospective cohorts of pregnancies presenting with anomalies detected using ultrasound. We evaluated factors that led to a higher diagnostic efficiency, such as phenotypic category, clinical characterization, and variant analysis strategy. METHODS: fCES was performed for 303 fetuses (183 ongoing and 120 ended pregnancies, in which chromosomal abnormalities had been excluded) using a trio/duo-based approach and a multistep variant analysis strategy. RESULTS: fCES identified the underlying genetic cause in 13% (24/183) of prospective and 29% (35/120) of retrospective cases. In both cohorts, recessive heterozygous compound genotypes were not rare, and trio and simplex variant analysis strategies were complementary to achieve the highest possible diagnostic rate. Limited prenatal phenotypic information led to interpretation challenges. In 2 prospective cases, in-depth analysis allowed expansion of the spectrum of prenatal presentations for genetic syndromes associated with the SLC17A5 and CHAMP1 genes. CONCLUSION: fCES is diagnostically efficient in fetuses presenting with cerebral, skeletal, urinary, or multiple anomalies. The comparison between the 2 cohorts highlights the importance of providing detailed phenotypic information for better interpretation and prenatal reporting of genetic variants.
Subject(s)
Exome , Ultrasonography, Prenatal , Chromosomal Proteins, Non-Histone , Exome/genetics , Female , Fetus/abnormalities , Fetus/diagnostic imaging , Humans , Phosphoproteins , Pregnancy , Prenatal Diagnosis , Retrospective Studies , Exome SequencingABSTRACT
OBJECTIVE: to assess whether fetal oxymetry reduces the intervention rate in a "theoretical setting". STUDY DESIGN: Data bank including 93 cases where a fetal oxymetry had been used for suspicion of fetal distress. Subjects-Two sets of labor charts were constructed for each case. One included relevant data with the saturometry, the other included relevant data without the saturometry. INTERVENTION: Theoretical setting: 3 obstetricians, unaware of study aim of the obstetrical outcomes. Each case was presented first without the saturometry; in a second reading, its result was available. OUTCOMES: Number of extractions. Consensus between experts. STATISTICS: descriptive and paired non parametric tests. RESULTS: The global intervention rate was lower (47% versus 52%; p<0.05) and the consensus higher, using monitoring and saturometry than using monitoring only. CONCLUSION: In a theoretical setting, the use of saturometry in suspicious cardiotocography (CTG) may help reduce the risk of invasive procedures.
