Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies

<div><p>Data linking assisted reproductive technologies (ART) with aberrant DNA methylation is limited and inconclusive. In addition, most studies to date have analyzed only a small number of CpG sites and focused on methylation changes in placentas, while data on cord blood are scarce. Our aim was to compare DNA methylation in cord blood samples from ART (N = 10) and control pregnancies (N = 8) using a genome-wide approach with the Illumina® Infinium Human Methylation27 array, which interrogates 27,578 CpG sites. A total of 733 (2.7%) of the CpG sites were significantly differentially methylated between the 2 groups (<i>P</i> < 0.05), with an overall relative hypomethylation in the ART group (<i>P</i> < 0.001). Differences in DNA methylation were more pronounced for CpG sites in certain types of genomic locations and were related to baseline methylation levels and distance from CpG islands and transcription start sites. ART was associated with significantly higher variation in DNA methylation, suggesting that differences in DNA methylation between cases and controls may result from stochastic (or random) genome-wide changes in DNA methylation in ART pregnancies. We identified 24 candidate genes with 2 or more CpG sites that were significantly different between the IVF and control groups. The current study provides support for the hypothesis that ART or associated subfertility may be associated with genome-wide changes in DNA methylation, and these changes appear to be, at least in part, due to epigenetic instability in ART pregnancies. Further studies are required in order to determine the extent to which such ART-related epigenetic instability may have phenotypic consequences.</p></div

General practitioners’ knowledge about pregnancy complications associated with long-term cardiovascular risk

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality in women; preeclampsia (PE) and gestational diabetes mellitus (GDM) are associated with an increased risk of CVD. Objective: To evaluate general practitioners (GP) knowledge about complicated pregnancies and their association with CVD. Methods: An anonymous case-based electronic questionnaire designed to assess the level of understanding on the influence of a history of pregnancy complications on longterm cardiovascular risk and general knowledge about CVD risk was sent to GPs. Results: The response rate was 35 % (161/465). The participants recognized that PE and GDM are risk factors for CVD (98 and 83 %, respectively), and reported the following CVD screening strategies in women with a history of PE and GDM: blood pressure monitoring (PE 100 %, GDM 46 %), body mass index calculation (PE 68 %, GDM 57 %), lipid profile evaluation (PE 71 %, GDM 57 %), glycated hemoglobin (PE 26 %, GDM 92 %), and fasting glucose (PE 28 %, GDM 91 %). Conclusion: GP-reported screening strategies to identify CVD in women with a history of PE and GDM were variable

Biological explanations for discordant noninvasive prenatal test results: Preliminary data and lessons learned.

OBJECTIVE: Maternal plasma cell-free DNA (cfDNA) analysis is a powerful screening tool for Down syndrome. In a pilot series, we examined biologic causes of discordance between the cfDNA test results and the fetal karyotype. We also explored the feasibility of obtaining trio biospecimens by using parental engagement. METHODS: A convenience sample of women with discordant cfDNA results were recruited by their care providers. We provided shipping materials and instructions for biospecimen collection. Maternal, newborn, and placental samples were examined with droplet digital PCR. RESULTS: Thirteen of 15 women successfully had biospecimens obtained remotely. High-quality DNA was extracted in 12 of 13 women. Presumed biologic etiologies for discordance were identified in 7 of 12 women: 3 cases from additional clinical review (male renal transplant, vanishing twin, and colon cancer) and 4 cases from additional laboratory investigation using droplet digital PCR (3 with confined placental mosaicism and 1 with true fetal mosaicism). CONCLUSIONS: Understanding the biology behind cfDNA-fetal karyotype discordancy is useful for follow-up clinical care. Our study suggests that most cases could be resolved by using a trio biospecimen protocol and parental involvement. To improve accuracy, additional sequencing of biospecimens will be required

International Society for Prenatal Diagnosis Position Statement: cell free (cf)DNA screening for Down syndrome in multiple pregnancies

status: publishe