Publications by authors named "Jacques Horovitz"

18 Publications

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Type 3 confined placental mosaicisms excluding trisomies 16 are also associated with adverse pregnancy outcomes.

Genet Med 2020 02 1;22(2):446-447. Epub 2019 Oct 1.

Centre de Médecine Fœtale, Maternité Pellegrin, CHU de Bordeaux, Bordeaux, France.

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http://dx.doi.org/10.1038/s41436-019-0664-1DOI Listing
February 2020

Confined placental mosaicism revisited: Impact on pregnancy characteristics and outcome.

PLoS One 2018 12;13(4):e0195905. Epub 2018 Apr 12.

Université de Bordeaux, Bordeaux, France.

Objectives: We wanted to re-evaluate the influence of confined placental mosaicism subtypes (type 2 and type 3) on pregnancy characteristics and outcome.

Material And Methods: From July 2009 to December 2015, 5512 chorionic villus samplings were performed in our Fetal Medicine Center. Conventional karyotyping was performed after long-term and short-term cultured villi to define type 2 or type 3 confined placental mosaicisms. Karyotype after amniocentesis was performed to exclude true fetal mosaicism, when appropriate. Pregnancy characteristics and outcomes were collected and compared to a control population.

Results: Thirty-six (0.65%) confined placental mosaicisms were observed (13 type 2 and 23 type 3). Nuchal translucency was not increased for type 2 and type 3 confined placental mosaicisms. Pregnancy characteristics and outcomes were comparable between type 2 confined placental mosaicisms and the control population. In type 3 confined placental mosaicisms, median first trimester serum pregnancy-associated plasma protein A was lower than for the control population (p<0.001), preterm births were noticed in 56% (p<0.001), small for gestational age newborns in 74% (p<0.001), and adverse pregnancy outcome was reported in 35% (p<0.01).

Conclusion: Although type 2 confined placental mosaicisms appeared to have no influence on pregnancy characteristics and outcome, type 3 confined placental mosaicisms were associated with low levels of first trimester serum pregnancy-associated plasma protein A, preterm birth, small for gestational age newborns, and adverse pregnancy outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195905PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897023PMC
July 2018

Incidence of obstetrical thrombotic thrombocytopenic purpura in a retrospective study within thrombocytopenic pregnant women. A difficult diagnosis and a treatable disease.

BMC Pregnancy Childbirth 2015 Jun 17;15:137. Epub 2015 Jun 17.

Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.

Background: Thrombotic thrombocytopenic Purpura (TTP) defined as ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin type 1 domain 13) activity <10 % is a rare aetiology of thrombocytopenia during pregnancy, although the precise incidence is unknown. During pregnancy, the diagnosis of TTP is crucial as it has high feto-maternal morbidity-mortality and requires urgent plasma exchange. The purpose of this study was to assess the incidence of TTP retrospectively and to describe case presentations and follow-up.

Methods: A monocentric retrospective study (2008-2009) was conducted among pregnant women followed in a tertiary care obstetrical unit who experienced at least one episode of severe thrombocytopenia (platelets ≤75 G/L) during 2008 and 2009. In cases of uncertain aetiology of thrombocytopenia, ADAMTS-13 activity was assessed by the full length technique.

Results: Among 8,908 deliveries over the 2 year period, 79 women had a platelet count nadir ≤75 G/L. Eighteen had a known aetiology of thrombocytopenia and 11 were lost to follow-up. Among 50 remaining patients, ADAMTS-13 activity was undetectable (<5 %) in 4, consistent with the diagnosis of TTP. Platelet count spontaneously normalized in 3 patients after delivery. None presented focal cerebral involvement. Three of the four, who were primipara patients, had a sustained severe deficiency in the absence of anti-ADAMTS-13 antibodies, and ADAMTS-13 gene sequencing indicated a constitutive deficiency. The fourth, a multipara patient, had an acquired, auto-immune TTP. Placental pathology in the three primipara patients showed severe and non-specific ischemic lesions. Two patients lost their babies shortly after birth. In subsequent pregnancies in these two patients, prophylactic plasma infusion initiated early with increasing volume throughout pregnancy prevented TTP relapse, improved placental pathology, and led to normal delivery.

Conclusions: The prevalence of TTP among thrombocytopenic pregnant women is high, up to 5 % in a tertiary unit. Platelet count normalization after delivery does not eliminate TTP. Clinicians should be aware of TTP during pregnancy, and, even if assessed retrospectively, ADAMTS-13 assessment is of particular importance for identifying patients with congenital TTP. In these patients, preventive plasma infusion and/or exchange can dramatically improve foetal prognosis, resulting in successful childbirth.
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http://dx.doi.org/10.1186/s12884-015-0557-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469004PMC
June 2015

Evaluation of Quantitative Fluorescence in situ Hybridization for Relative Measurement of Telomere Length in Placental Mesenchymal Core Cells.

Gynecol Obstet Invest 2016 20;81(1):54-60. Epub 2015 May 20.

Histologie et pathologie molx00E9;culaire des tumeurs, EA 2406, Universitx00E9; de Bordeaux, Bordeaux, France.

Background: Reduced telomere length in placental mesenchymal core cells has been reported during pregnancies complicated by intrauterine growth restriction. To estimate telomere length, a precise, accurate and reproducible technique must be used.

Objective: We evaluated the characteristics of a quantitative fluorescence in situ hybridization (Q-FISH) technique for measuring relative telomere length in placental mesenchymal core cells.

Methods: From late chorionic villus samplings, telomere length in placental mesenchymal core cells was estimated by a Q-FISH technique using peptide nucleic acid telomere probes. The main characteristics of the Q-FISH technique, such as precision and reproducibility, were evaluated.

Results: The telomere length of the cultured placental mesenchymal cells did not follow a normal distribution. When the Q-FISH technique was performed on interphase nuclei of uncultured mesenchymal core cells, normal telomere length distribution was observed. The precision of the technique when applied to cultured placental mesenchymal core cells was estimated to be <6%, and its reproducibility ranged from to 92.9 to 104.7%.

Conclusion: Our results showed that cell culture of placental villi produced a non-normal telomere length distribution, probably related to telomere DNA replication during the cell cycle. Despite the influence of cell culture, the Q-FISH technique reported herein showed good precision and reproducibility.
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http://dx.doi.org/10.1159/000381896DOI Listing
December 2016

Prenatal diagnosis using array-CGH: a French experience.

Eur J Med Genet 2013 Jul 20;56(7):341-5. Epub 2013 Feb 20.

CHU Bordeaux, Génétique médicale, F-33000 Bordeaux, France.

Array-CGH or Chromosomal Microarray Analysis (CMA) is increasingly used in prenatal diagnosis throughout the world. However, routine practices are very different among centers and countries, regarding CMA indications, design and resolution of microarrays, notification and interpretation of Copy Number Alterations (CNA). We present our data and experience from our Fetal Medicine Center on 224 prospective prenatal diagnoses. Our approach is practical, and aims to propose a strategy to offer Chromosomal Microarray Analysis (CMA) to selected fetuses and to help to interpret CNA. We hope that this publication could encourage development of CMA in centers that have not started yet this activity in prenatal routine, and could contribute to edict guidelines in this field.
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http://dx.doi.org/10.1016/j.ejmg.2013.02.003DOI Listing
July 2013

Reduced placental telomere length during pregnancies complicated by intrauterine growth restriction.

PLoS One 2013 11;8(1):e54013. Epub 2013 Jan 11.

EA 2406 Histologie et pathologie moléculaire des tumeurs, Université Bordeaux Segalen, Bordeaux, France.

Objectives: Recent studies have shown that telomere length was significantly reduced in placentas collected at delivery from pregnancies complicated by intrauterine growth restriction secondary to placental insufficiency. Placental telomere length measurement during ongoing pregnancies complicated by intrauterine growth restriction has never been reported. This was the main objective of our study.

Methods: In our center, late chorionic villus samplings were performed between 18 and 37 weeks of amenorrhea in 24 subjects with severe intrauterine growth restriction (cases) and in 28 subjects with other indications for prenatal diagnosis (controls). Placental insufficiency was assessed by histo-pathological examination. Relative measurement of telomere length was carried out prospectively by quantitative Fluorescent In Situ Hybridization using fluorescent Peptide Nucleic Acid probes on interphase nuclei obtained from long-term cultured villi and with an automated epifluorescent microscope. A quantitative Polymerase Chain Reaction technique was performed to confirm the quantitative Fluorescent In Situ Hybridization results. The number of copies of gene loci encoding the RNA template (hTERC) and the catalytic subunit (hTERT) of the enzyme complex telomerase were also estimated in these placentas by Fluorescent In Situ Hybridization.

Results: Mean fluorescence intensity of telomere probes estimated by quantitative Fluorescent In Situ Hybridization was significantly less for cases compared to controls (p<0.001). This result indicated that mean telomere length was significantly reduced in placentas during pregnancies complicated by intrauterine growth restriction. Reduced telomere length was confirmed by the quantitative Polymerase Chain Reaction technique. No copy number variation of the hTERC and hTERT loci was noticed for cases, or for controls.

Conclusion: This study clearly demonstrates a reduction of placental telomere length in ongoing pregnancies (from 18 to 37 weeks of amenorrhea) complicated by severe intrauterine growth restriction secondary to placental insufficiency.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0054013PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543434PMC
July 2013

The diagnosis of rupture of fetal membranes (ROM): a meta-analysis.

J Perinat Med 2013 May;41(3):233-40

Vivantes Hospital Neukolln, Perinatal Medicine, Rudowerstr. 48, D-12351 Berlin, Germany.

Aim: The aim of this study was to compare the performance of tests based on the detection of insulin-like growth factor binding protein 1 (IGFBP-1) and placental α-microglobulin-1 (PAMG-1) in diagnosing rupture of fetal membranes (ROM) across different patient populations.

Methods: A meta-analysis was conducted on prospective observational or cohort studies investigating ROM tests based on the detection of IGFBP-1 and PAMG-1 meeting the following criteria: (1) performance metrics calculated by comparing results to an adequate reference method; (2) sensitivity thresholds of the investigated tests matching those of the currently available tests; (3) study population, as a minimum, included patients between 25 and 37 weeks of gestation. Sensitivities, specificities, and diagnostic odds ratios were calculated.

Results: Across all patient populations, the analyzed performance measures of the PAMG-1 test were significantly superior compared with those of the IGFBP-1 test. Of particular clinical relevance, PAMG-1 outperformed IGFBP-1 in the equivocal group, which comprised patients with uncertain rupture of membranes (sensitivity, 96.0% vs. 73.9%; specificity, 98.9% vs. 77.8%; PAMG-1 vs. IGFBP-1 tests, respectively).

Conclusions: Compared with its performance in women with known membrane status, the accuracy of the IGFBP-1 test decreases significantly when used on patients whose membrane status is unknown. In this latter clinically relevant population, the PAMG-1 test has higher accuracy than the IGFBP-1 test.
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http://dx.doi.org/10.1515/jpm-2012-0247DOI Listing
May 2013

Proportion of parents agreeing to delay fetal karyotyping until the third trimester of pregnancy in cases with an indication.

Fetal Diagn Ther 2012 31;31(2):115-21. Epub 2012 Jan 31.

Laboratoire de cytogénétique, service de génétique médicale, maternité Pellegrin, CHU de Bordeaux, Bordeaux, France.

Objective: To assess the extent to which couples who could benefit from fetal karyotyping during the first or second trimester would agree to delay the examination until the third trimester.

Methods: In this prospective monocentric study, the same physician suggested to some couples to delay fetal karyotyping until the third trimester.

Results: 458 couples participated in this study. 230 couples (230/458 = 50.2%) refused to delay the examination until the third trimester of pregnancy (group 1). For these patients, four chromosomal abnormalities led to the termination of pregnancy. Fifty-six couples (56/458 = 12.2%) who initially agreed to delay the fetal karyotyping later changed their minds (group 2). 104 couples (104/458 = 22.7%) agreed to delay the examination (group 3). For these patients, one trisomy 21 was diagnosed and led to the subsequent termination of the pregnancy at 33 weeks of amenorrhea. Sixty-eight couples (68/458 = 14.8%) refused any form of invasive prenatal diagnosis (group 4). There was no difference in the rate of preterm premature rupture of membranes, pregnancy term, premature birth rate and birth weight between the four groups.

Conclusions: Our study reports that about a quarter of couples did indeed agree to delay fetal karyotype assessment until the third trimester of pregnancy.
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http://dx.doi.org/10.1159/000334067DOI Listing
July 2012

An unusual chromosome 22q11 deletion associated with an apparent complementary ring chromosome in a phenotypically normal woman.

Eur J Med Genet 2011 May-Jun;54(3):292-4. Epub 2011 Jan 5.

Laboratoire de Cytogénétique, Service de Génétique Médicale, Hôpital Pellegrin (Maternité), CHU de Bordeaux, France.

We report an unusual chromosome 22q11 deletion associated with an apparent complementary ring chromosome in a phenotypically normal woman with a family medical history of 22q11 deletion. Using peripheral blood samples, conventional karyotyping, Fluorescence In Situ Hybridization (FISH) analysis on metaphase spreads and oligo array-based comparative genomic hybridization (oligo array-CGH) were performed. After conventional cytogenetic examination, the chromosome formula was as follows: 47,XX,+r(?)[16]/46,XX[6]. The FISH analysis revealed that this patient had a rearranged chromosome 22 with decreased centromeric fluorescence intensity and deletion of the 22q11.2 locus. She also had a supernumerary ring chromosome composed of an alpha-satellite centromere of 22 origin and 22q11.2 locus. The oligo array-CGH profile showed a deletion of approximately 4.18 Mb on chromosome 22 with a log 2 intensity ratio mean deviation of the deleted region of about -0.29. The 22q11 deletion associated with a complementary ring chromosome described in our patient could be consistent with a centromere misdivision mechanism, with one chromosomal break occurring in the alpha-satellite array and a second one in the 22q11 locus, a mechanism which has recently been referred to as the McClintock mechanism.
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http://dx.doi.org/10.1016/j.ejmg.2010.12.005DOI Listing
September 2011

Confined placental mosaicism and pregnancy outcome: a distinction needs to be made between types 2 and 3.

Prenat Diagn 2010 Dec;30(12-13):1155-64

Department of Medical Genetics, Pellegrin University Hospitals (Maternity), Bordeaux, France.

Objective: To study the influence of types 2 and 3 confined placental mosaicism (CPM) on pregnancy outcome.

Method: From 13 809 chorionic villus samplings (CVSs), karyotype after long-term cultured villi (LTC-villi) was systematically performed. Next, in case of suspicion of CPM, karyotype after short-term cultured villi (STC-villi) was established to define type 2 CPM (chromosomal abnormality limited to the mesenchymal core) or type 3 CPM (chromosomal abnormality found both in the cytotrophoblast and the mesenchymal core). Confirmatory amniocentesis was performed to exclude fetal mosaicism. Uniparental disomy (UPD) testing was carried out when the abnormal cell line involved chromosomes 5, 6, 7, 15 or 16.

Results: Fifty-seven CPM cases were observed (57/13 809 = 0.41%) and of these, 37 were type 2 and 20 were type 3 CPM. Incidence of preterm infants, neonatal hypotrophy and adverse pregnancy outcome were comparable between patients in whom type 2 CPM was demonstrated and the control population. In contrast, for the type 3 CPM the incidence of these factors was higher than for the control population.

Conclusion: When a CPM is suspected, it appears essential to determine type, since type 2 has no effect on fetal development and type 3 is associated with preterm infants, low birth weight and adverse pregnancy outcome.
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http://dx.doi.org/10.1002/pd.2631DOI Listing
December 2010

[Advantages and limitations of chorionic villous sampling].

Bull Acad Natl Med 2009 Mar;193(3):675-89; discussion 689-90

Unité de Pathologie Foetoplacentaire, Service d'Anatomie Pathologique, Hôpital Pellegrin, 33076 Bordeaux.

Chorionic villous sampling (CVS) has been available for more than twenty years. Together with amniocentesis, it helps the cytogenetician to determine the fetal karyotype for prenatal diagnosis. The choice between these two methods depends on the team and the indication. CVS can now provide sufficient material for both histopathologic and cytogenetic analyses. We evaluated the accuracy of microscopic examination of CVS for detecting primary ovular, uteroplacental vascular (preeclampsia) and inflammatory disorders. Four hundred CVS were examined in the pathology laboratory of Pellegrin Hospital, Bordeaux, France, from January 1995 to February 2008. The results were analyzed according to the indication, the karyotype, the results of placental examination, pregnancy outcome and, when available (following spontaneous or medical termination), fetoplacental findings. The sample was representative of patients requiring CVS for prenatal diagnosis, with respect to maternal age, the stage of pregnancy, and the indications. When used to screen for preeclamsia (prevalence 29.6% in the sample), the sensitivity and specificity of placental biopsy were respectively 56.8% and 87.2% (76.9% in case of intra-uterine growth retardation). When used to screen for chromosomal aberrations (prevalence 7.4%), the specificity was 14.3% and the sensitivity 93.2%. The prevalence of other disorders, and particularly chronic intervillitis, was too low for meaningful analysis. This study shows that histopathologic analysis of chorionic villous samples is useful for detecting the utero-placental vascular origin of intrauterine growth retardation in the absence of other clinical, biological or ultrasound signs, and that it is complementary to cytogenetic analysis. Being a simple and inexpensive examination, histopathologic analysis of CVS could be performed systematically in this indication. Its value and diagnostic signs in other settings need to be determined in larger series.
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March 2009

Prenatal diagnosis and management of sex chromosome aneuploidy: a report on 98 cases.

Prenat Diagn 2004 Mar;24(3):213-8

Maternal and Fetal Medicine Unit, Pellegrin University Hospital, Bordeaux, France.

Objectives: To analyse the management of pregnancy after prenatal diagnosis of sex chromosome aneuploidy (SCA) and the factors influencing genetic counselling and parental decision.

Methods: Between 1991 and 2001, 73 non-mosaic fetal SCA were diagnosed in our centre and 25 were referred to us from outside institutions. The same geneticist carried out genetic counselling. The outcome of pregnancies and the termination trend over time were determined according to the type of SCA. Clinical parental data were analysed in order to assess whether they influenced genetic counselling.

Results: 45,X was diagnosed in 41 fetuses. The main indication for karyotyping was abnormal ultrasound (83%). The termination rate was 93%. Sex chromosome polysomies (SCP) including 47,XXY, 47,XXX, and 47,XYY were diagnosed in 31, 16, and 10 fetuses respectively. The main indication for karyotyping was advanced maternal age (60%). The termination rate was 32, 25, and 20% respectively. The difference between the termination rate for local cases (25%) and referred cases (33%) was not significant. The termination rate for pregnancies with SCP was 38% in 1991 to 1994, 34% in 1995 to 1998, and 12% in 1999 to 2001. The parents' characteristics did not influence the outcome of pregnancy.

Conclusions: The relatively low termination rate (28%) in pregnancies where the fetus was affected by SCP and the decreasing termination trend over time in our centre suggest an improved knowledge of the pathological conditions associated with SCP, influencing genetic counselling.
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http://dx.doi.org/10.1002/pd.834DOI Listing
March 2004

Craniofacial dysmorphology and three-dimensional ultrasound: a prospective study on practicability for prenatal diagnosis.

Prenat Diagn 2003 Oct;23(10):810-8

Centre de diagnostic prénatal, CHU Bordeaux, France.

Objective: The aim of this study is to compare two-dimensional and three-dimensional ultrasound for the visualization and diagnosis of craniofacial dysmorphism.

Methods: In this prospective study, we performed three-dimensional (3D) ultrasound following good-quality two-dimensional (2D) ultrasound in an at-risk population. Findings from 2D and 3D examination were noted.

Results: Our series included 41 patients. In 20 cases, 3D performed better than 2D, and in two cases 2D was more informative. In 9 cases, there was no difference between the performance of the two, and in two cases both 2D and 3D gave inadequate results. However, in 7 cases 3D images could not be obtained.

Conclusion: Although it is rarely decisive, 3D ultrasound is of interest when it comes to the precise description of craniofacial dysmorphisms and the study of the fetal ears.
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http://dx.doi.org/10.1002/pd.681DOI Listing
October 2003

Feasibility, accuracy and safety of chorionic villus sampling: a report of 10741 cases.

Prenat Diagn 2003 Apr;23(4):295-301

Maternal and Fetal Medicine Unit, Pellegrin University Hospital, Bordeaux, France.

Objectives: To evaluate the feasibility, accuracy and safety of chorionic villus sampling (CVS).

Methods: Ten thousand seven hundred and forty one singleton pregnancies at risk of chromosome abnormalities (96.3%) and gene disorders (2.8%) were referred from 1990 to 1999 to the fetal medicine unit of a teaching hospital. CVS was performed transabdominally after 11 weeks, using a modified freehand ultrasonographically guided technique by 5 operators. Fetal karyotyping was obtained using a direct method before 1995 and was completed by cell culture after 1996. Failed results, feto-placental discrepancy and fetal loss were assessed.

Results: Villi were sampled using extra-amniotic puncture (89.4%) and one sampling-device insertion (92.3%). The mean weight of the specimen was 15.2 +/- 6.0 mg. All attempts at sampling were successful, except eight (0.07%). The number of failed results following direct preparation, cell culture and both methods was 20 (0.19%), 23 (0.21%) and 2 (0.02%), respectively. Light maternal cell contamination occurred in less than 1% of the samplings after microscopic selection of the villi, and never interfered with the assessment of karyotyping. All 3 false-negative results (0.03%) were recorded after direct preparation and 2 were corrected by culture. The rate of chromosomal abnormalities confined to the placenta decreased from 1.08% before 1995 to 0.73% after 1996. True fetal mosaicisms were recorded in 7 cases (0.06%). The rate of fetal loss at <28 weeks was 1.64% in all pregnancies and 1.92% when CVS was performed before 13 weeks. Advanced maternal age was the single factor significantly associated with fetal loss.

Conclusions: CVS was feasible, accurate and safe in our institution, as a result of the increasing experience of the operators and the cytogeneticists.
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http://dx.doi.org/10.1002/pd.578DOI Listing
April 2003