Anne-Gael Cordier

Genotoxic signature in cord blood cells of newborns exposed in utero to a zidovudine-based antiretroviral combination

BACKGROUND The genotoxicity of zidovudine has been established in experimental models. The objective of the study was to identify genotoxicity markers in cord blood cells from newborns exposed in utero to antiretroviral (ARV) combinations containing zidovudine. METHODS Cells were investigated by karyotyping and gene expression analysis of the CD34(+) hematopoietic stem/progenitor cell (HPC) compartment. RESULTS Karyotyping of the cord blood cells from 15 ARV-exposed newborns and 12 controls revealed a higher proportion of aneuploid cells in the exposed group (median, 18.8% [interquartile range, 10.0%-26.7%] vs 6.6% [interquartile range, 3.1%-11.7%]; P < .001). All chromosomes were involved, with a random distribution of these alterations. Gene expression profiling of CD34(+) HPCs from 7 ARV-exposed and 6 control newborns revealed that >300 genes were significantly upregulated or downregulated by at least 1.5-fold in the exposed group (P < .05 for all comparisons). Significant alterations of genes involved in cell cycle control, mitotic checkpoints, and DNA repair were identified. Although this study does not allow discrimination between the roles of each of the 3 drugs, both cytogenetic and transcriptional findings are similar to those in cellular experiments that used zidovudine alone. CONCLUSIONS The cord blood cells, including hematopoietic stem cells, from newborns exposed in utero to a zidovudine-based ARV combination present cytogenetic and transcriptional abnormalities compatible with DNA damage.

Detailed in utero ultrasound description of 30 cases of congenital cytomegalovirus infection.

The aim of this research was to describe precisely prenatal ultrasound (US) features in congenital cytomegalovirus (CMV) infection.

Stomach position versus liver-to-thoracic volume ratio in left-sided congenital diaphragmatic hernia

Abstract Objective: To describe a new grading method for stomach position (SP) in fetuses with left-sided congenital diaphragmatic hernia (L-CDH) using ultrasound and to correlate SP to liver position and to liver-to-thoracic cavity volume ratio (LiTR) using magnetic resonance imaging. Methods: SP were graded at the level of the 4-chamber view as following: grade 1-to-4 for stomach not visualised, visualised anteriorly at the apex of the heart, stomach showing abdominal structures anteriorly and stomach with its larger part posterior to the level of the atrial-ventricular heart valves, respectively. The LiTR was calculated and correlated to SP using the Mann–Whitney U test. Results: Seventy-four fetuses were included. Median LiTR for grade 1 SP was 0% and was not different from median LiTR for grade 2 SP (0%, p = NS). Median LiTR for grade 3 SP was 14.9% and was significantly higher than for grade 2 SP (p < 0.001). Similarly, median LiTR for grade 4 SP was 20.7% and was significantly higher than for grade 3 SP (p < 0.05). When SP was grade 1 or 2, liver was intra-abdominal in 21 (84%) out of 25 fetuses while it was always intrathoracic for SP 3 or 4. Conclusion: In L-CDH, SP as described represents a simple indirect measurement of intrathoracic position and quantification of liver.

Stomach position in prediction of survival in left‐sided congenital diaphragmatic hernia with or without fetoscopic endoluminal tracheal occlusion

To investigate the value of fetal stomach position in predicting postnatal outcome in left‐sided congenital diaphragmatic hernia (CDH) with and without fetoscopic endoluminal tracheal occlusion (FETO).

Antenatal ultrasound prediction of pulmonary hypoplasia in congenital diaphragmatic hernia: Correlation with pathology

To examine the relationship between observed to expected (o/e) lung to head circumference ratio (LHR) and lung‐to‐body weight ratio (LBWR) in fetuses with congenital diaphragmatic hernia (CDH).

Evaluation of the Cepheid Xpert GBS Assay for Rapid Detection of Group B Streptococci in Amniotic Fluids from Pregnant Women with Premature Rupture of Membranes

ABSTRACT The Xpert GBS real-time PCR assay for the detection of group B streptococci (GBS) in antepartum screening samples was evaluated on amniotic fluid samples collected from 139 women with premature rupture of membrane at term. When any intrapartum positive result from the Xpert GBS or culture was considered a true positive, the sensitivities of the Xpert GBS and culture were 92.3% and 84.6%, respectively. This assay could enhance exact identification of candidates for intrapartum antibiotic prophylaxis.

Comparing genotoxic signatures in cord blood cells from neonates exposed in utero to zidovudine or tenofovir.

Objectives:Zidovudine and tenofovir are the two main nucleos(t)ide analogs used to prevent mother-to-child transmission of HIV. In vitro, both drugs bind to and integrate into human DNA and inhibit telomerase. The objective of the present study was to assess the genotoxic effects of either zidovudine or tenofovir-based combination therapies on cord blood cells in newborns exposed in utero. Design:We compared the aneuploid rate and the gene expression profiles in cord blood samples from newborns exposed either to zidovudine or tenofovir-based combination therapies during pregnancy and from unexposed controls (n = 8, 9, and 8, respectively). Methods:The aneuploidy rate was measured on the cord blood T-cell karyotype. Gene expression profiles of cord blood T cells and hematopoietic stem and progenitor cells were determined with microarrays, analyzed in a gene set enrichment analysis and confirmed by real-time quantitative PCRs. Results:Aneuploidy was more frequent in the zidovudine-exposed group (26.3%) than in the tenofovir-exposed group (14.2%) or in controls (13.3%; P < 0.05 for both). The transcription of genes involved in DNA repair, telomere maintenance, nucleotide metabolism, DNA/RNA synthesis, and the cell cycle was deregulated in samples from both the zidovudine and the tenofovir-exposed groups. Conclusion:Although tenofovir has a lower clastogenic impact than zidovudine, gene expression profiling showed that both drugs alter the transcription of DNA repair and telomere maintenance genes.

Teaching invasive prenatal procedures: effectiveness of two simple simulators in training

Chorionic villus sampling (CVS) and amniocentesis are the major tools of invasive prenatal diagnosis. We studied the effectiveness of two simulators in training in invasive procedures.

Vitamine D et grossesse

Vitamin D insufficiency is characterized, since 2005, by 25(OH)D concentration less than 75 nmol/L (or 30 ng/mL). Vitamin D could interfere with many mechanisms involved in preeclampsias pathogenesis including trophoblastic invasion and immunomodulation as well as blood pressure control and proteinuria. Occurrence of preeclampsia and gestational diabetes seems to be linked to vitamin D deficiency but recent data in the literature are contradictory. Vitamin D supplementation during pregnancy is controversial. Some societies consider it unnecessary and others recommend up to 2000 UI/d. There is no reported case of teratogenicity linked with vitamin D intake.

Pitfalls in the diagnosis of congenital rubella syndrome in the first trimester of pregnancy

A 29-year-old woman, gravida 3 para 0, was referred at19weeks of gestation because of a maternal rubella infectionduring the first trimester of pregnancy. She consulted at5weeks for a rash, which, at that time, was considered tobe urticaria. Her serological status for rubella was unknownat that time, and as rubella infection was not considered,serological investigations were not conducted. At 6weeks,toxoplasma and rubella testings were performed asrecommended by the French High Health Authority [HauteAutorite de Sante (HAS)]. HAS only recommends IgGtesting for routine Rubella screening and both IgG and IgMtestings for toxoplasma.