Use of cell-free signals as biomarkers for early and easy prediction of preeclampsia

IntroductionPreeclampsia (PE) is a leading cause of maternal and perinatal morbidity worldwide. However, current methods of screening are complicated and require special skill sets. In this observational study of prospectively collected samples, we wanted to evaluate if cell-free (cf) DNA could be an efficient biomarker for identification of at-risk patients.MethodsOne hundred patients attending a private prenatal clinic in Canada were enrolled in their first trimester of pregnancy and a blood draw was carried out at 11 + 0 to 14 + 2 weeks’ (timepoint A) and 17 + 6 to 25 + 5 weeks of gestation (timepoint B). CfDNA signals, namely concentration, fetal fraction, and fragment size distribution, were correlated with clinical outcomes in the test population to develop the logistic regression model.ResultsTwelve patients developed PE—four early-stage and eight late-stage PE. Significant differences were observed between PE patients and control cases for all three cfDNA signals at timepoint A, while both fetal fraction and concentration were significantly different between PE patients and control cases at timepoint B. Overall, the model had a sensitivity of up to 100% and specificity of up to 87.5% at Timepoint A.ConclusionThis proof-of-principle study showed that use of this logistic regression model could identify patients at risk of preeclampsia in the first trimester of pregnancy

Rapid testing versus karyotyping in Down's syndrome screening: cost-effectiveness and detection of clinically significant chromosome abnormalities

In all, 80% of antenatal karyotypes are generated by Down's syndrome screening programmes (DSSP). After a positive screening, women are offered prenatal foetus karyotyping, the gold standard. Reliable molecular methods for rapid aneuploidy diagnosis (RAD: fluorescence in situ hybridization (FISH) and quantitative fluorescence PCR (QF-PCR)) can detect common aneuploidies, and are faster and less expensive than karyotyping

A collaborative model to implement flexible, accessible and efficient oncogenetic services for hereditary breast and ovarian cancer : the C-MOnGene study

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants' understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics

RETARDS MENTAUX IDIOPATHIQUES ET UTILISATION DU CARYOTYPE SPECTRAL DANS UNE ETUDE PROSPECTIVE

AMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Patient attitudes and preferences about expanded noninvasive prenatal testing

Introduction: Noninvasive prenatal testing (NIPT) using cell-free DNA (cfDNA) is typically carried out to screen for common fetal chromosomal anomalies, with the option to screen for a wider range of chromosomal changes (expanded NIPT) becoming increasingly available. However, little is known about pregnant patients’ attitudes and preferences regarding expanded NIPT.Methods: To address this gap, we surveyed general-risk patients having first-tier cfDNA screening at a private prenatal clinic on their expectations for expanded NIPT. Patients were asked questions regarding their current pregnancy and previous pregnancy history, their opinions on fetal DNA screenings during pregnancy and incidental findings, information and opinions on financial resources for NIPT, as well as socio-cultural questions to determine patient demographics.Results: Of the 200 survey participants, the majority were educated, self-reported as white, had a higher than average income, and reported no aneuploidy risk factors. When asked what information they would like to receive from cfDNA screening, the vast majority of participants wanted all information available that could have an immediate impact on fetal health (88%) or an immediate impact on infant health from birth (82%). Many participants also wanted information that could have a future impact on the child’s health or an immediate or future impact on the pregnant woman’s own health. Most participants wanted information about the sex of fetus (86%) and common trisomies (71%), with almost half of participants desiring information about rare autosomal aneuploidies and/or all genetic information that may affect the baby. In addition, participants were found to be comfortable screening for conditions that are well-known, influence care during pregnancy, and are treatable. Finally, while most respondents either had insurance coverage for NIPT or were able to afford NIPT out of pocket, the majority of our participants felt that expanded NIPT should be either free for everyone or for those considered high risk.Discussion: Our findings suggest that with appropriate pre-test counseling, pregnant patients may choose NIPT for an expanding list of conditions

Molecular prenatal diagnosis of a sporadic alobar holoprosencephalic fetus: genotype-phenotype correlations

Objective: holoprosencephaly is the most common forebrain malformation syndrome with a multifactorial etiology. Currently, mutations are identified in 5-10% of non syndromic, non-chromosomal cases in at least 12 genes. We report the molecular prenatal diagnosis of a fetus with alobar holoprosencephaly. Methods: CTG band karyotyping and array CGH genome-wide cytogenetic screenings were done, in conjunction with DNA sequence analyses of the SHH, ZIC2, SIX3 and TGIF genes in search of a molecular etiology and with comparison of findings to prior cases. Results: standard CTG band karyotyping and array CGH genome-wide screening failed to identify plausible chromosome imbalances or structural anomalies. However, extensive sequencing of the genomic DNA from the fetus and both parents on all exon and exon-intron boundaries of the four most commonly mutated genes: SHH, ZIC2, SIX3 and TGIF, identified codon 100 of the sonic hedgehog (SHH) gene having a hotspot for loss-of-function mutations in our case and others. Conclusion: mutations in codon 100 of SHH were discovered in both sporadic and autosomal dominant inherited cases with evidence of variable expressivity and penetrance. Collectively, this study reinforces the complexity of genotype-phenotype correlations in the prenatal diagnosis of holoprosencephalic fetuses