Prenatal exome sequencing, a powerful tool for improving the description of prenatal features associated with genetic disorders.

OBJECTIVE: Prenatal exome sequencing (pES) is now commonly used in clinical practice. It can be used to identifiy an additional diagnosis in around 30% of fetuses with structural defects and normal chromosomal microarray analysis (CMA). However, interpretation remains challenging due to the limited prenatal data for genetic disorders. METHOD: We conducted an ancillary study including fetuses with pathogenic/likely pathogenic variants identified by trio-pES from the "AnDDI-Prenatome" study. The prenatal phenotype of each patient was categorized as typical, uncommon, or unreported based on the comparison of the prenatal findings with documented findings in the literature and public phenotype-genotype databases (ClinVar, HGMD, OMIM, and Decipher). RESULTS: Prenatal phenotypes were typical for 38/56 fetuses (67.9%). For the others, genotype-phenotype associations were challenging due to uncommon prenatal features (absence of recurrent hallmark, rare, or unreported). We report the first prenatal features associated with LINS1 and PGM1 variants. In addition, a double diagnosis was identified in three fetuses. CONCLUSION: Standardizing the description of prenatal features, implementing longitudinal prenatal follow-up, and large-scale collection of prenatal features are essential steps to improving pES data interpretation.

Analysis of the transplacental transmission of SARS CoV-2 virus and antibody transfer according to the gestational age at maternal infection.

To quantify transplacental transmission of SARS-CoV-2 virus and antibody transfer in pregnant women and their newborns according to the gestational age at maternal infection. A prospective observational multicenter study including pregnant women with a positive RT-PCR or a positive serology for SARS-CoV-2 and compatible symptoms, from April to December 2020, in 11 French maternities. The study was designed to obtain a systematic collection of mother-infant dyad's samples at birth. SARS-CoV-2 viral load was measured by RT-PCR. IgG and IgM antibodies against the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed according to the gestational age at maternal infection. The primary outcome was the rate of SARS CoV-2 materno-fetal transmission at birth. The secondary outcome was the quantification of materno-fetal antibody transfer. Maternal and neonatal outcomes at birth were additionally assessed. Among 165 dyads enrolled, one congenital infection was confirmed {n = 1 (0.63%) IC95% [0.02%; 3.48%]}. The average placental IgG antibody transfer ratio was 1.27 (IC 95% [0.69-2.89]). The transfer ratio increased with increasing time between the onset of maternal infection and delivery (P Value = 0.0001). Maternal and neonatal outcomes were reassuring. We confirmed the very low rate of SARS-CoV-2 transplacental transmission (< 1%). Maternal antibody transfer to the fetus was more efficient when the infection occurred during the first and second trimester of pregnancy.