Publications by authors named "Valerie Désilets"

29 Publications

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Reflecting on professional identity in undergraduate medical education: implementation of a novel longitudinal course.

Perspect Med Educ 2021 Mar 9. Epub 2021 Mar 9.

Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada.

Background: Today's healthcare professionals face numerous challenges. Improving reflection skills has the potential to contribute to the better management of complex patients and healthcare systems, as well as to improve professional practice. However, the question of how reflection skills can inform professional identity development at the undergraduate medical education level remains unanswered.

Approach: The authors developed and implemented a 4-year course that aims to engage students in a reflective process to increase their awareness of their professional identity development. The course is structured around three types of pedagogical activities: workshops, reflections deposited in an electronic portfolio, and individual discussions with mentors.

Evaluation: Sixty-four 1st year students (33%) and 17 mentors (50%) from the 2017-2018 cohort completed evaluation questionnaires. For the 2018-2019 academic year, 73 1st year students (34%) and 27 2nd year students (14%), as well as 20 1st year (59%) and 19 2nd year mentors (57%) replied. Students and mentors considered that the pedagogical activities contributed to the development of students' professional identity through the acquisition of reflection skills, but some elements were perceived as challenging, notably, completing the portfolio, finding a subject to reflect about and the timing of the proposed activities.

Reflection: An important preoccupation when wanting to foster the development of professional identity through the acquisition of reflection skills is the authenticity of students' reflection. We tried to favor authentic reflection, by having a mentee-mentor pair throughout the entire 4‑year course. A rigorous evaluation process helped us identify and promptly correct issues as they surfaced.
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http://dx.doi.org/10.1007/s40037-021-00649-wDOI Listing
March 2021

N° 365 -Autopsies fœtales et périnatales en cas d'anomalies fœtales diagnostiquées avant la naissance avec une analyse chromosomique normale.

J Obstet Gynaecol Can 2018 10;40(10):1367-1377.e6

Montréeal (Qc).

Objectif: Examiner les données sur les autopsies fœtales et périnatales, le processus de consentement et les options de collecte de renseignements à la suite d'un diagnostic prénatal d'anomalies non chromosomiques afin d'aider les fournisseurs de soins à offrir du conseil postnatal au sujet du diagnostic et des éventuels risques de récurrence. RéSULTATS: Offrir de meilleurs conseils sur les autopsies fœtales et périnatales aux femmes et aux familles qui ont reçu un diagnostic prénatal d'anomalie fœtale non chromosomique. ÉVIDENCE: Nous avons examiné des études publiées récupérées au moyen de recherches dans PubMed, Medline, CINAHL et la Bibliothèque Cochrane en 2010, en 2011 et en 2017 à l'aide de mots-clés appropriés (« fetal autopsy postmortem », « autopsy », « perinatal postmortem examination », « autopsy protocol », « postmortem magnetic resonance imaging », « autopsy consent », « tissue retention » et « autopsy evaluation »). Nous n'avons tenu compte que des résultats provenant de revues systématiques, d'essais cliniques, randomisés ou non, et d'études observationnelles. D'autres publications ont été repérées dans les bibliographies de ces articles. Aucune restriction de date ou de langue n'a été employée. Nous avons également tenu compte de la littérature grise (non publiée) trouvée sur les sites Web d'organismes d'évaluation des technologies de la santé et d'autres organismes liés aux technologies de la santé, dans des collections de directives cliniques et dans des registres d'essais cliniques, et obtenue auprès d'associations nationales et internationales de médecins spécialistes. AVANTAGES, DéSAVANTAGES ET COUTS: La présente mise à jour renseigne les lecteurs sur : 1) les avantages de l'autopsie fœtale ou périnatale; 2) le processus de consentement; et 3) les autres options offertes aux familles qui refusent l'autopsie. Elle met également en évidence la nécessité d'adopter une démarche normalisée pour la réalisation des autopsies fœtales et périnatales, et met l'accent sur les prélèvements additionnels qui peuvent être pertinents. Les auteurs sont conscients que l'accès aux ressources et aux services mentionnés varie d'un endroit l'autre au Canada; les recommandations formulées ont donc pour but de promouvoir l'accès et de fournir une norme minimale aux provinces et aux territoires du pays.

Valeurs: La qualité des données a été évaluée au moyen des critères énoncés dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (tableau). RECOMMANDATIONS.
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http://dx.doi.org/10.1016/j.jogc.2018.08.006DOI Listing
October 2018

No. 365-Fetal and Perinatal Autopsy in Prenatally Diagnosed Fetal Abnormalities with Normal Chromosome Analysis.

J Obstet Gynaecol Can 2018 10;40(10):1358-1366.e5

Montréal, QC.

Objective: To review the information on fetal and perinatal autopsies, the process of obtaining consent, and the alternative information-gathering options following a prenatal diagnosis of non-chromosomal anomalies in order to assist health care providers in providing postnatal counselling regarding diagnosis and potential recurrence risks.

Outcomes: To provide better counselling about fetal and perinatal autopsies for women and families who are dealing with a prenatally diagnosed non-chromosomal fetal anomaly.

Evidence: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2010, 2011, and 2017, using appropriate key words (fetal autopsy postmortem, autopsy, perinatal postmortem examination, autopsy protocol, postmortem magnetic resonance imaging, autopsy consent, tissue retention, autopsy evaluation). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Additional publications were identified from the bibliographies of these articles. There were no date or language restrictions. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

Benefits, Harms, And Costs: This update educates readers about (1) the benefits of a fetal perinatal autopsy, (2) the consent process, and (3) the alternatives when the family declines autopsy. It also highlights the need for a standardized approach to fetal and perinatal autopsies, emphasizing pertinent additional sampling when indicated. The authors recognize that there is variability across Canada in access to the cited services and resources. As such, these recommendations were developed in an attempt to promote access and to provide a minimum standard for all provinces and territories across the country.

Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table).

Recommendations:
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http://dx.doi.org/10.1016/j.jogc.2018.05.017DOI Listing
October 2018

No. 363-Investigation and Management of Non-immune Fetal Hydrops.

J Obstet Gynaecol Can 2018 08;40(8):1077-1090

Montréal, QC.

Objective: To describe the current investigation and management of non-immune fetal hydrops with a focus on treatable or recurring etiologies.

Outcomes: To provide better counselling and management in cases of prenatally diagnosed non-immune hydrops.

Evidence: Published literature was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in 2017 using key words (non-immune hydrops fetalis, fetal hydrops, fetal therapy, fetal metabolism). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, observational studies, and significant case reports. Additional publications were identified from the bibliographies of these articles. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to September 2017. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinicalpractice guideline collections, clinical trial registries, and national and international medical specialty societies.

Benefits, Harms, And Costs: These guidelines educate readers about the causes of non-immune fetal hydrops and its prenatal counselling and management. It also provides a standardized approach to non-immune fetal hydrops, emphasizing the search for prenatally treatable conditions and recurrent genetic etiologies.

Values: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care.

Recommendations:
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http://dx.doi.org/10.1016/j.jogc.2017.12.011DOI Listing
August 2018

N° 363 - Évaluation et prise en charge de l'anasarque fœtoplacentaire non immune.

J Obstet Gynaecol Can 2018 08 3;40(8):1091-1107. Epub 2018 Jul 3.

Montréal (Qc).

Objectif: Décrire les méthodes actuelles d'évaluation et de prise en charge de l'anasarque fœtoplacentaire non immune en mettant l'accent sur les étiologies traitables ou récurrentes. RéSULTATS: Offrir de meilleurs services de conseil et de prise en charge en cas d'anasarque fœtoplacentaire non immune diagnostiquée en période prénatale. DONNéES: La littérature publiée a été récupérée au moyen de recherches menées dans PubMed, MEDLINE, CINAHL, et la Bibliothèque Cochrane en 2017 à l'aide de mots-clés (« non-immune hydrops fetalis », « fetal hydrops », « fetal therapy », « fetal metabolism »). Les articles retenus portaient sur des revues systématiques, des essais cliniques contrôlés, randomisés ou non, des études observationnelles et des études de cas importantes. D'autres publications ont été repérées dans les bibliographies de ces articles. Aucune restriction de date ou de langue n'a été employée. Les recherches ont été mis à jour régulièrement, et les résultats ont été incorporés à la directive clinique jusqu'en septembre 2017. Nous avons également tenu compte de la littérature grise (non publiée) trouvée sur les sites Web d'organismes d'évaluation des technologies de la santé et d'autres organismes liés aux technologies de la santé, dans des collections de directives cliniques et des registres d'essais cliniques, et obtenue auprès d'associations nationales et internationales de médecins spécialistes. AVANTAGES, INCONVéNIENTS ET COûTS: La présente directive clinique renseigne les lecteurs sur les causes de l'anasarque fœtoplacentaire non immune ainsi que sur son évaluation et sa prise en charge. Elle propose également une approche standardisée d'évaluation et de prise en charge, et met l'accent sur la recherche des conditions traitables en période prénatale et des étiologies génétiques récurrentes.

Valeurs: La qualité des données probantes a été évaluée en fonction des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs. RECOMMANDATIONS.
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http://dx.doi.org/10.1016/j.jogc.2018.06.005DOI Listing
August 2018

Clinical validity of phenotype-driven analysis software PhenoVar as a diagnostic aid for clinical geneticists in the interpretation of whole-exome sequencing data.

Genet Med 2018 09 1;20(9):942-949. Epub 2018 Feb 1.

Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada.

Purpose: We sought to determine the diagnostic yield of whole-exome sequencing (WES) combined with phenotype-driven analysis of variants in patients with suspected genetic disorders.

Methods: WES was performed on a cohort of 51 patients presenting dysmorphisms with or without neurodevelopmental disorders of undetermined etiology. For each patient, a clinical geneticist reviewed the phenotypes and used the phenotype-driven analysis software PhenoVar (http://phenovar.med.usherbrooke.ca/) to analyze WES variants. The prioritized list of potential diagnoses returned was reviewed by the clinical geneticist, who selected candidate variants to be confirmed by segregation analysis. Conventional analysis of the individual variants was performed in parallel. The resulting candidate variants were subsequently reviewed by the same geneticist, to identify any additional potential diagnoses.

Results: A molecular diagnosis was identified in 35% of the patients using the conventional analysis, and 17 of these 18 diagnoses were independently identified using PhenoVar. The only diagnosis initially missed by PhenoVar was rescued when the optional "minimal phenotypic cutoff" filter was omitted. PhenoVar reduced by half the number of potential diagnoses per patient compared with the conventional analysis.

Conclusion: Phenotype-driven software prioritizes WES variants, provides an efficient diagnostic aid to clinical geneticists and laboratories, and should be incorporated in clinical practice.
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http://dx.doi.org/10.1038/gim.2017.239DOI Listing
September 2018

A Novel PGM3 Mutation Is Associated With a Severe Phenotype of Bone Marrow Failure, Severe Combined Immunodeficiency, Skeletal Dysplasia, and Congenital Malformations.

J Bone Miner Res 2017 Sep 26;32(9):1853-1859. Epub 2017 Jun 26.

Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada.

Congenital disorders of glycosylation (CDGs) affect multiple systems and present a broad spectrum of clinical features, often including skeletal dysplasia. Exome sequencing has led to the identification of new CDG genes. Immune and skeletal phenotypes associated with mutations in PGM3, encoding a protein that converts N-acetyl-glucosamine-6-phosphate into N-acetyl-glucosamine-1-phosphate, were recently reported. Through exome sequencing, we identified a novel homozygous mutation (c.1135T>C; p.Phe379Leu) in PGM3 in two siblings with bone marrow failure, severe combined immunodeficiency, renal and intestinal malformations, and a skeletal dysplasia resembling Desbuquois dysplasia. Severe respiratory compromise secondary to lung hypoplasia and pulmonary hypertension, and intestinal obstruction led to their demise. We thus report the most severe phenotype described so far associated with PGM3 mutations. This CDG should be considered in the presence of skeletal dysplasia associated with severe immunodeficiency. © 2017 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3173DOI Listing
September 2017

Exploration et prise en charge de l'anasarque fœtoplacentaire non immune.

J Obstet Gynaecol Can 2016 Dec 4;38(12S):S311-S325. Epub 2017 Jan 4.

Montréal (Québec).

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http://dx.doi.org/10.1016/j.jogc.2016.09.041DOI Listing
December 2016

Diagnosis of late-onset Pompe disease and other muscle disorders by next-generation sequencing.

Orphanet J Rare Dis 2016 Jan 25;11. Epub 2016 Jan 25.

Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, NC, USA.

Background: Late-onset Pompe disease (LOPD) is a rare treatable lysosomal storage disorder characterized by progressive lysosomal glycogen accumulation and muscle weakness, with often a limb-girdle pattern. Despite published guidelines, testing for LOPD is often overlooked or delayed in adults, owing to its low frequency compared to other muscle disorders with similar muscle patterns. Next-generation sequencing has the capability to test concurrently for several muscle disorders. This could potentially lead to increased diagnosis of LOPD, disorders with non-specific muscle weakness or atypical patients.

Methods: We developed a gene panel to further study its clinical utility in a cohort of patients with suspected muscle disorders. We designed a gene panel to analyze the coding sequences and splice site junctions of GAA causing LOPD, along with 77 other genes causing muscle disorders with overlapping phenotypes.

Results: At a median coverage of ~200X (sequences per base), all GAA exons were successfully covered with >20X and only 0.3 % of exons across all genes were <20X. The panel showed an excellent sensitivity (100 %) and specificity (98 %) across all selected genes, using known variations in Pompe patients and controls. We determined its clinical utility by analyzing 34 patients with suspected muscle disorders of undetermined etiology and various muscle patterns, who were referred or followed in neuromuscular and genetics clinics. A putative diagnosis was found in up to 32 % of patients. The gene panel was instrumental in reaching a diagnosis in atypical patients, including one LOPD case. Acid alpha-glucosidase activity was used to confirm the molecular results in all patients.

Conclusion: This work highlights the high clinical utility of gene panels in patients with suspected muscle disorders and its potential to facilitate the diagnosis of patients showing non-specific muscle weakness or atypical phenotypes. We propose that gene panels should be used as a first-tier test in patients with suspected muscle disorders of undetermined etiology, which could further increase overall diagnosis of muscle conditions, and potentially reduce diagnostic delay. Further studies are necessary to determine the impact of first-tier gene panels on diagnostic delay and on treatment outcome for LOPD.
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http://dx.doi.org/10.1186/s13023-016-0390-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727295PMC
January 2016

Loss-of-function de novo mutations play an important role in severe human neural tube defects.

J Med Genet 2015 Jul 24;52(7):493-7. Epub 2015 Mar 24.

CHU Ste-Justine Research Center, Université de Montréal, Montréal, Québec, Canada.

Background: Neural tube defects (NTDs) are very common and severe birth defects that are caused by failure of neural tube closure and that have a complex aetiology. Anencephaly and spina bifida are severe NTDs that affect reproductive fitness and suggest a role for de novo mutations (DNMs) in their aetiology.

Methods: We used whole-exome sequencing in 43 sporadic cases affected with myelomeningocele or anencephaly and their unaffected parents to identify DNMs in their exomes.

Results: We identified 42 coding DNMs in 25 cases, of which 6 were loss of function (LoF) showing a higher rate of LoF DNM in our cohort compared with control cohorts. Notably, we identified two protein-truncating DNMs in two independent cases in SHROOM3, previously associated with NTDs only in animal models. We have demonstrated a significant enrichment of LoF DNMs in this gene in NTDs compared with the gene specific DNM rate and to the DNM rate estimated from control cohorts. We also identified one nonsense DNM in PAX3 and two potentially causative missense DNMs in GRHL3 and PTPRS.

Conclusions: Our study demonstrates an important role of LoF DNMs in the development of NTDs and strongly implicates SHROOM3 in its aetiology.
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http://dx.doi.org/10.1136/jmedgenet-2015-103027DOI Listing
July 2015

Functional zebrafish studies based on human genotyping point to netrin-1 as a link between aberrant cardiovascular development and thyroid dysgenesis.

Endocrinology 2015 Jan;156(1):377-88

Institute of Interdisciplinary Research in Molecular Human Biology (R.O., I.V., A.T., S.C.), Université Libre de Bruxelles, 1070 Brussels, Belgium; Research Center of Centre Hospitalier Universitaire Sainte-Justine (M.-P.H., I.V., R.A.-K., M.S., G.A., J.D.), Department of Pediatrics, Université de Montréal, Montréal, Québec, Canada H3T 1C5; and Department of Medical Genetics (V.D.), Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Canada J1H 1P8.

Congenital hypothyroidism caused by thyroid dysgenesis (CHTD) is a common congenital disorder with a birth prevalence of 1 case in 4000 live births, and up to 8% of individuals with CHTD have co-occurring congenital heart disease. Initially we found nine patients with cardiac and thyroid congenital disorders in our cohort of 158 CHTD patients. To enrich for a rare phenotype likely to be genetically simpler, we selected three patients with a ventricular septal defect for molecular studies. Then, to assess whether rare de novo copy number variants and coding mutations in candidate genes are a source of genetic susceptibility, we used a genome-wide single-nucleotide polymorphism array and Sanger sequencing to analyze blood DNA samples from selected patients with co-occurring CHTD a congenital heart disease. We found rare variants in all three patients, and we selected Netrin-1 as the biologically most plausible contributory factor for functional studies. In zebrafish, ntn1a and ntn1b were not expressed in thyroid tissue, but ntn1a was expressed in pharyngeal arch mesenchyme, and ntn1a-deficient embryos displayed defective aortic arch artery formation and abnormal thyroid morphogenesis. The functional activity of the thyroid in ntn1a-deficient larvae was, however, preserved. Phenotypic analysis of affected zebrafish indicates that abnormal thyroid morphogenesis resulted from a lack of proper guidance exerted by the dysplastic vasculature of ntn1a-deficient embryos. Hence, careful phenotyping of patients combined with molecular and functional studies in zebrafish identify Netrin-1 as a potential shared genetic factor for cardiac and thyroid congenital defects.
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http://dx.doi.org/10.1210/en.2014-1628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272402PMC
January 2015

Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA synthetase IARS2 in patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness, and peripheral neuropathy or with Leigh syndrome.

Hum Mutat 2014 Nov 18;35(11):1285-9. Epub 2014 Oct 18.

McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.

Mutations in the nuclear-encoded mitochondrial aminoacyl-tRNA synthetases are associated with a range of clinical phenotypes. Here, we report a novel disorder in three adult patients with a phenotype including cataracts, short-stature secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral sensory neuropathy, and skeletal dysplasia. Using SNP genotyping and whole-exome sequencing, we identified a single likely causal variant, a missense mutation in a conserved residue of the nuclear gene IARS2, encoding mitochondrial isoleucyl-tRNA synthetase. The mutation is homozygous in the affected patients, heterozygous in carriers, and absent in control chromosomes. IARS2 protein level was reduced in skin cells cultured from one of the patients, consistent with a pathogenic effect of the mutation. Compound heterozygous mutations in IARS2 were independently identified in a previously unreported patient with a more severe mitochondrial phenotype diagnosed as Leigh syndrome. This is the first report of clinical findings associated with IARS2 mutations.
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http://dx.doi.org/10.1002/humu.22629DOI Listing
November 2014

In response.

J Obstet Gynaecol Can 2014 Feb;36(2):115

Department of Obstetrics and Gynaecology, University of Calgary, Calgary AB.

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http://dx.doi.org/10.1016/s1701-2163(15)30655-1DOI Listing
February 2014

Investigation and management of non-immune fetal hydrops.

J Obstet Gynaecol Can 2013 Oct;35(10):923-38

Montreal QC.

Objective: To describe the current investigation and management of non-immune fetal hydrops, with a focus on treatable or recurring etiologies.

Outcomes: To provide better counselling and management in cases of prenatally diagnosed non-immune hydrops.

Evidence: Published literature was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in 2011 using key words (non-immune hydrops fetalis, fetal hydrops, fetal therapy, fetal metabolism). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, observational studies, and significant case reports. Additional publications were identified from the bibliographies of these articles. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2012. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

Benefits, Harms, And Costs: These guidelines educate readers about the causes of non-immune fetal hydrops and its prenatal counselling and management. It also provides a standardized approach to non-immune fetal hydrops, emphasizing the search for prenatally treatable conditions and recurrent genetic etiologies.

Values: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).

Recommendations: 1. All patients with fetal hydrops should be referred promptly to a tertiary care centre for evaluation. Some conditions amenable to prenatal treatment represent a therapeutic emergency after 18 weeks. (II-2A) 2. Fetal chromosome analysis and genetic microarray molecular testing should be offered where available in all cases of non-immune fetal hydrops. (II-2A) 3. Imaging studies should include comprehensive obstetrical ultrasound (including arterial and venous fetal Doppler) and fetal echocardiography. (II-2A) 4. Investigation for maternal-fetal infections, and alpha-thalassemia in women at risk because of their ethnicity, should be performed in all cases of unexplained fetal hydrops. (II-2A) 5. To evaluate the risk of fetal anemia, Doppler measurement of the middle cerebral artery peak systolic velocity should be performed in all hydropic fetuses after 16 weeks of gestation. In case of suspected fetal anemia, fetal blood sampling and intrauterine transfusion should be offered rapidly. (II-2A) 6. All cases of unexplained fetal hydrops should be referred to a medical genetics service where available. Detailed postnatal evaluation by a medical geneticist should be performed on all cases of newborns with unexplained non-immune hydrops. (II-2A) 7. Autopsy should be recommended in all cases of fetal or neonatal death or pregnancy termination. (II-2A) Amniotic fluid and/or fetal cells should be stored for future genetic testing. (II-2B).
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http://dx.doi.org/10.1016/s1701-2163(15)30816-1DOI Listing
October 2013

Mutations in TMEM231 cause Joubert syndrome in French Canadians.

J Med Genet 2012 Oct 25;49(10):636-41. Epub 2012 Sep 25.

Centre of Excellence in Neurosciences of Université de Montréal and Sainte-Justine Hospital Research Center, Montreal, Quebec, Canada H3T 1C5.

Background: Joubert syndrome (JBTS) is a predominantly autosomal recessive disorder characterised by a distinctive midhindbrain malformation, oculomotor apraxia, breathing abnormalities and developmental delay. JBTS is genetically heterogeneous, involving genes required for formation and function of non-motile cilia. Here we investigate the genetic basis of JBTS in 12 French-Canadian (FC) individuals.

Methods And Results: Exome sequencing in all subjects showed that six of them carried rare compound heterozygous mutations in CC2D2A or C5ORF42, known JBTS genes. In addition, three individuals (two families) were compound heterozygous for the same rare mutations in TMEM231(c.12T>A[p.Tyr4*]; c.625G>A[p.Asp209Asn]). All three subjects showed a severe neurological phenotype and variable presence of polydactyly, retinopathy and renal cysts. These mutations were not detected among 385 FC controls. TMEM231 has been previously shown to localise to the ciliary transition zone, and to interact with several JBTS gene products in a complex involved in the formation of the diffusion barrier between the cilia and plasma membrane. siRNA knockdown of TMEM231 was also shown to affect barrier integrity, resulting in a reduction of cilia formation and ciliary localisation of signalling receptors.

Conclusions: Our data suggest that mutations in TMEM231 cause JBTS, reinforcing the relationship between this condition and the disruption of the barrier at the ciliary transition zone.
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http://dx.doi.org/10.1136/jmedgenet-2012-101132DOI Listing
October 2012

Mutations in C5ORF42 cause Joubert syndrome in the French Canadian population.

Am J Hum Genet 2012 Apr 15;90(4):693-700. Epub 2012 Mar 15.

Centre of Excellence in Neurosciences, Université de Montréal and Sainte-Justine Hospital Research Center, Montréal, QC, Canada.

Joubert syndrome (JBTS) is an autosomal-recessive disorder characterized by a distinctive mid-hindbrain malformation, developmental delay with hypotonia, ocular-motor apraxia, and breathing abnormalities. Although JBTS was first described more than 40 years ago in French Canadian siblings, the causal mutations have not yet been identified in this family nor in most French Canadian individuals subsequently described. We ascertained a cluster of 16 JBTS-affected individuals from 11 families living in the Lower St. Lawrence region. SNP genotyping excluded the presence of a common homozygous mutation that would explain the clustering of these individuals. Exome sequencing performed on 15 subjects showed that nine affected individuals from seven families (including the original JBTS family) carried rare compound-heterozygous mutations in C5ORF42. Two missense variants (c.4006C>T [p.Arg1336Trp] and c.4690G>A [p.Ala1564Thr]) and a splicing mutation (c.7400+1G>A), which causes exon skipping, were found in multiple subjects that were not known to be related, whereas three other truncating mutations (c.6407del [p.Pro2136Hisfs*31], c.4804C>T [p.Arg1602*], and c.7477C>T [p.Arg2493*]) were identified in single individuals. None of the unaffected first-degree relatives were compound heterozygous for these mutations. Moreover, none of the six putative mutations were detected among 477 French Canadian controls. Our data suggest that mutations in C5ORF42 explain a large portion of French Canadian individuals with JBTS.
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http://dx.doi.org/10.1016/j.ajhg.2012.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322222PMC
April 2012

Fetal and perinatal autopsy in prenatally diagnosed fetal abnormalities with normal karyotype.

J Obstet Gynaecol Can 2011 Oct;33(10):1047-57

Montreal QC.

Objective: To review the information on fetal and perinatal autopsies, the process of obtaining consent, and the alternative information-gathering options following a prenatal diagnosis of non-chromosomal malformations, and to assist clinicians in providing postnatal counselling regarding fetal diagnosis and recurrence risks.

Outcomes: To provide better counselling about fetal and perinatal autopsies for women and families who are dealing with a prenatally diagnosed non-chromosomal fetal anomaly.

Evidence: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2009 and 2010, using appropriate key words (fetal autopsy, postmortem, autopsy, perinatal postmortem examination, autopsy protocol, postmortem magnetic resonance imaging, autopsy consent, tissue retention, autopsy evaluation). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Additional publications were identified from the bibliographies of these articles. There were no date or language restrictions. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

Benefits, Harms, And Costs: This update educates readers about (1) the benefits of a fetal perinatal autopsy, (2) the consent process, and (3) the alternatives when the family declines autopsy. It also provides a standardized approach to fetal and perinatal autopsies, emphasizing pertinent additional sampling when indicated.

Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Recommendations 1. Standard autopsy should ideally be an essential part of fully investigating fetal loss, stillbirths, and neonatal deaths associated with non-chromosomal fetal malformations. (II-3A) 2. Clinicians and health care providers approaching parents for autopsy consent should discuss the options for a full, limited, or step-wise postmortem examination; the issue of retained fetal tissues; and the value of autopsy and the possibility that the information gained may not benefit them but may be of benefit to others. This information should be provided while respecting the personal and cultural values of the families. (III-A) 3. If parents are unwilling to give consent for a full autopsy, alternatives to full autopsy that provide additional clinical information must be presented in a manner that includes disclosure of limitations. (III-A) 4. External physical examination, medical photographs, and standard radiographic or computed tomography should be offered in all cases of fetal anomaly(ies) of non-chromosomal etiology. (II-2A) 5. Well-designed, large prospective studies are needed to evaluate the accuracy of postmortem magnetic resonance imaging. It cannot function as a substitute for standard full autopsy. (III-A) 6. The fetal and perinatal autopsies should be performed by trained perinatal or pediatric pathologists. (II-2A) 7. The need for additional sampling is guided by the results of previous prenatal and/or genetic investigations, as well as the type of anomalies identified in the fetus. Fibroblast cultures may allow future laboratory studies, particularly in the absence of previous karyotyping or if a biochemical disorder is suspected, and DNA analysis. (II-3A) 8. In cases requiring special evaluation, the most responsible health care provider should have direct communication with the fetopathologist to ensure that all necessary sampling is performed in a timely manner. (II-3A) 9. The most responsible health care providers must see the families in follow-up to share autopsy findings, plan for the management of future pregnancies, obtain consent for additional testing, and offer genetic counselling to other family members when appropriate. (III-A).
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October 2011

Preimplantation genetic testing.

J Obstet Gynaecol Can 2009 Aug;31(8):761-75

The Society of Obstetricians and Gynaecologists of Canada (SOGC), Montreal, QC.

Objective: To review the techniques and indications of preimplantation genetic testing, including preimplantation genetic diagnosis and screening.

Options: Limited to an introductory discussion about the genetic aspects of preimplantation reproductive techniques.

Outcomes: This update does not discuss in detail the adverse outcomes that have been recorded in association with assisted reproductive technologies.

Evidence: The Cochrane Library and Medline were searched for articles relating to preimplantation testing that were published from 1990 to February 2008, using the following terms: preimplantation genetic diagnosis, preimplantation genetic screening, and in vitro fertilization. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Additional publications were identified from the bibliographies of these articles. Randomized controlled trials were considered evidence of the highest quality, followed by cohort studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and from national and international medical specialty societies.

Values: This update is a consensus of the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada. The recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care.

Benefits, Harms, And Costs: This update educates readers about new genetic concepts, directions, and technology. The major harms and costs identified are those of assisted reproductive technologies.

Sponsor: The Society of Obstetricians and Gynaecologists of Canada.

Conclusions: Preimplantation genetic diagnosis is an alternative to prenatal diagnosis for the detection of genetic disorders in couples at risk of transmitting a genetic condition to their offspring. Preimplantation genetic screening has been proposed to improve the effectiveness of in vitro fertilization in women of advanced maternal age or in couples with recurrent miscarriage or implantation failure, but the benefits of this approach are debated.

Recommendations: The recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. 1. Before preimplantation genetic diagnosis is performed, genetic counselling must be provided to ensure that patients fully understand the risk of having an affected child, the impact of the disease on an affected child, and the benefits and limitations of all available options for preimplantation and prenatal diagnosis. (III-A) 2. Couples should be informed that preimplantation genetic diagnosis can reduce the risk of conceiving a child with a genetic abnormality carried by one or both parents if that abnormality can be identified with tests performed on a single cell. (II-2B) 3. Invasive prenatal testing to confirm the results of preimplantation genetic diagnosis is encouraged because the methods used for preimplantation genetic diagnosis have technical limitations that include the possibility of a false negative result. (II-2B) 4. Before preimplantation genetic screening is performed, thorough education and counselling must be provided to ensure that patients fully understand the limitations of the technique, the risk of error, and the lack of evidence that preimplantation genetic screening improves live-birth rates. (III-A) 5. Available evidence does not support the use of preimplantation genetic screening as currently performed to improve live-birth rates in patients with advanced maternal age, recurrent implantation failure, or recurrent pregnancy loss. (I-D).
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http://dx.doi.org/10.1016/s1701-2163(16)34284-0DOI Listing
August 2009

New molecular techniques for the prenatal detection of chromosomal aneuploidy.

J Obstet Gynaecol Can 2008 Jul;30(7):617-21, 622-7

Calgary AB, Canada.

Objective: To review the molecular genetic techniques currently available for rapid prenatal diagnosis of fetal aneuploidy, as well as those still under investigation.

Options: Limited to introductory discussion of rapid aneuploidy detection methods.

Evidence: Medline was searched for articles related to the topic that were published after 1992. This document represents an abstraction of the information.

Values: This update was prepared by the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada approved by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada.

Benefits, Harms, And Costs: This update provides information about methods of rapid aneuploidy detection using molecular techniques and the evidence supporting their use in prenatal diagnosis. These methods are reliable and cost-effective for detecting the targeted fetal aneuploidies, but are limited in their ability to detect non-aneuploid chromosome abnormalities, some of which are clinically significant.
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http://dx.doi.org/10.1016/s1701-2163(16)32896-1DOI Listing
July 2008

Caudal dysgenesis, sirenomelia, and situs inversus totalis: a primitive defect in blastogenesis.

Am J Med Genet A 2008 Jun;146A(11):1470-6

Department of Pathology, CHU Sainte-Justine, Montreal, Quebec, Canada.

Caudal dysgenesis (CD) constitutes a heterogeneous spectrum of congenital caudal anomalies, including varying degrees of agenesis of the vertebral column, as well as anorectal and genitourinary anomalies. Sirenomelia, characterized by a fusion of the lower limbs, could represent the most severe end of this spectrum. The two main debated pathogenic hypotheses are an aberrant vascular supply versus a primary axial mesoderm defect. We present the autopsy findings of two fetuses of non-diabetic mothers, with normal karyotype. Both fetuses presented situs inversus associated with a CD, in one case consisting of sirenomelia, establishing a very rare association profile that might be random. This association also suggests the occurrence of a common pathogenic mechanism, in accordance to recent genetic data, such as displayed in the Kif3A murine mutation phenotype. Some cases of sirenomelia and CD could represent developmental field defects of blastogenesis involving the caudal mesoderm, rather than being related to vascular insufficiency.
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http://dx.doi.org/10.1002/ajmg.a.32081DOI Listing
June 2008

Present role of stem cells for fetal genetic therapy.

J Obstet Gynaecol Can 2005 Nov;27(11):1038-47

Objective: To provide a Committee opinion on the present status and role of stem cells in fetal genetic therapy.

Options: Limited to discussion of new genetic information and technology related to stem cell therapy.

Evidence: MEDLINE search to identify publications related to this topic after 1980. This document represents an abstraction of the information. VALUE: This Committee opinion is a consensus of the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC).

Benefits, Harms, And Costs: The benefit of this update is to educate the reader about genetic stem cells and their use in fetal therapy. At present there is no harm or cost (research with limited clinical application) identified.

Conclusions: 1. Stem cell therapy has the potential to be a powerful and successful therapy for certain human conditions. 2. There are significant ethical issues related to the use of stem cells derived from embryonic tissue. 3. Fetal therapy using stem cell replacement has been successful for immunodeficient conditions following early prenatal diagnosis for the "at risk" fetus. 4. Other conditions such as hemoglobinopathies, inborn errors of the metabolism and hemophilia require more research to overcome biological barriers.
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http://dx.doi.org/10.1016/s1701-2163(16)30504-7DOI Listing
November 2005

A fragile site at 10q23 (FRA10A) in a phenytoin-exposed fetus: a case report and review of the literature.

Prenat Diagn 2005 Apr;25(4):318-21

F. Clarke Fraser Clinical Genetics Unit, Division of Medical Genetics, Department of Pediatrics, Montreal Children's Hospital, Montreal, Québec H3H 1P3, Canada.

Objective: To report fragility at 10q23.3 in a fetus exposed to phenytoin during pregnancy. Review of the literature.

Methods: Amniocytes were cultured in A10 (WISENT) culture medium. Molecular polymorphism studies of MTHFR gene using PCR were performed on fetal tissues.

Results: The fragile site was expressed in all 22 amniocyte colonies analyzed. Analysis of fetal blood showed 46,XX[98]/46,XX,fra(10)(q23.3)[3]/46,XX,del(10)(q23.3) [1]. Molecular studies of the MTHFR (methylenetetrahydrofolate reductase) gene identified a compound heterozygote genotype for two polymorphisms, 677C>T and 1298A>C.

Conclusion: The fragility at 10q23.3 is unlikely to be due to culture condition-induced folic acid deficiency (medium contains folate). It is possible that this finding represents a previously undescribed folic acid-insensitive fragile site in the region of 10q23.3. Alternatively, the fetal cells may have had decreased folate metabolism, and the fragile site was the known folate-sensitive FRA10A. Since phenytoin has been shown to decrease MTHFR activity in mice, we postulate that the fragile site at 10q23.3 in this fetus may have arisen secondary to a combination of the polymorphisms in MTHFR and exposure to this drug, and is indeed FRA10A.
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http://dx.doi.org/10.1002/pd.1134DOI Listing
April 2005

The use of folic acid for the prevention of neural tube defects and other congenital anomalies.

J Obstet Gynaecol Can 2003 Nov;25(11):959-73

Objective: To provide information regarding the use of folic acid for the prevention of neural tube defects (NTDs) and other congenital anomalies, in order that physicians, midwives, nurses, and other health-care workers can assist in the education of women in the preconception phase of their health care. OPTION: Folic acid supplementation is problematic, since 50% of pregnancies are unplanned and the health status of women may not be optimal.

Outcomes: Folic acid supplementation has been proven to decrease or minimize specific birth defects.

Evidence: A systematic review of the literature, including review and peer-reviewed articles, government publications, the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of March 1993, and statements from the American College of Obstetrics and Gynecology, was used to develop a new clinical practice guideline for the SOGC.

Values: Peer-review process within the committee structure.

Benefits, Harms, And Costs: The benefit is reduced lethal and severe morbidity birth defects and the harm is minimal. The personal cost is of vitamin supplementation on a daily basis and eating a healthy diet.

Recommendations: 1. Women in the reproductive age group should be advised about the benefits of folic acid supplementation during wellness visits (birth control renewal, Pap testing, yearly examination), especially if pregnancy is contemplated. (III-A) 2. Women should be advised to maintain a healthy nutritional diet, as recommended in Canada's Food Guide to Healthy Eating (good or excellent sources of folic acid: broccoli, spinach, peas, Brussels sprouts, corn, beans, lentils, oranges). (III-A) 3. Women who could become pregnant should be advised to take a multivitamin containing 0.4 mg to 1.0 mg of folic acid daily. (II-1A) 4. Women taking a multivitamin with folic acid supplement should be advised not to take more than 1 daily dose of vitamin supplement, as indicated on the product label. (II-2A) 5. Women in intermediate- to high-risk categories for NTDs (NTD-affected previous pregnancy, family history, insulin-dependent diabetes, epilepsy treatment with valproic acid or carbamazepine) should be advised that high-dose folic acid (4.0 mg-5.0 mg daily) supplementation is recommended. This should be taken as folic acid alone, not in a multivitamin format, due to risk of excessive intake of other vitamins such as vitamin A. (I-A) 6. The choice of a 5 mg folic acid daily dose for women considering a pregnancy should be made under medical supervision after minimizing the risk of undiagnosed vitamin B12 deficiency (hypersegmentation of polymorphonuclear cells, macrocystic indices, large ovalocytes, leukopenia, thrombocytopenia, markedly elevated lactate dehydrogenase level, confirmed red blood cell folate level). (II-2A) 7. Signs or symptoms of vitamin B12 deficiency should be considered before initiating folic acid supplementation of doses greater than 1.0 mg. (III-A) 8. A three-generation pedigree on the families of both the pregnant woman and the biological father should be obtained to identify increased risk for congenital birth defects (i.e., NTD, cardiac, chromosomal, genetic). (III-A) 9. Women who become pregnant should be advised of the availability of noninvasive screening tests and invasive diagnostic tests for congenital birth defects (including NTDs): maternal serum "triple marker screen" at 15 to 20 weeks, ultrasound at 16 to 20 weeks, and amniocentesis after 15 weeks of pregnancy if a positive screening test is present. (I-A) VALIDATION: This is a revision of a previous guideline and information from other consensus reviews from medical and government publications has been used.
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http://dx.doi.org/10.1016/s1701-2163(16)30248-1DOI Listing
November 2003

Prevention of Rh alloimmunization.

J Obstet Gynaecol Can 2003 Sep;25(9):765-73

Objective: To provide guidelines on use of anti-D prophylaxis to optimize prevention of rhesus (Rh) alloimmunization in Canadian women.

Outcomes: Decreased incidence of Rh alloimmunization and minimized practice variation with regards to immunoprophylaxis strategies.

Evidence: The Cochrane Library and MEDLINE were searched for English-language articles from 1968 to 2001, relating to the prevention of Rh alloimmunization. Search terms included: Rho(D) immune globulin, Rh iso- or allo-immunization, anti-D, anti-Rh, WinRho, Rhogam, and pregnancy. Additional publications were identified from the bibliographies of these articles. All study types were reviewed. Randomized controlled trials were considered evidence of highest quality, followed by cohort studies. Key individual studies on which the principal recommendations are based are referenced. Supporting data for each recommendation is briefly summarized with evaluative comments and referenced.

Values: The evidence collected was reviewed by the Maternal-Fetal Medicine and Genetics Committees of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on the Periodic Health Exam.

Recommendations: 1. Anti-D Ig 300 microg IM or IV should be given within 72 hours of delivery to a postpartum nonsensitized Rh-negative woman delivering an Rh-positive infant. Additional anti-D Ig may be required for fetomaternal hemorrhage (FMH) greater than 15 mL of fetal red blood cells (about 30 mL of fetal blood). Alternatively, anti-D Ig 120 microg IM or IV may be given within 72 hours of delivery, with testing and additional anti-D Ig given for FMH over 6 mL of fetal red blood cells (12 mL fetal blood). (I-A) 2. If anti-D is not given within 72 hours of delivery or other potentially sensitizing event, anti-D should be given as soon as the need is recognized, for up to 28 days after delivery or other potentially sensitizing event. (III-B) 3. There is poor evidence regarding inclusion or exclusion of routine testing for postpartum FMH, as the cost-benefit of such testing in Rh mothers at risk has not been determined. (III-C) 4. Anti-D Ig 300 microg should be given routinely to all Rh-negative nonsensitized women at 28 weeks' gestation when fetal blood type is unknown or known to be Rh-positive. Alternatively, 2 doses of 100-120 microg may be given (120 microg being the lowest currently available dose in Canada): one at 28 weeks and one at 34 weeks. (I-A) 5. All pregnant women (D-negative or D-positive) should be typed and screened for alloantibodies with an indirect antiglobulin test at the first prenatal visit and again at 28 weeks. (III-C) 6. When paternity is certain, Rh testing of the baby's father may be offered to all Rh-negative pregnant women to eliminate unnecessary blood product administration. (III-C) 7. A woman with "weak D" (also known as Du-positive) should not receive anti-D. (III-D) 8. A repeat antepartum dose of Rh immune globulin is generally not required at 40 weeks, provided that the antepartum injection was given no earlier than 28 weeks' gestation. (III-C) 9. After miscarriage or threatened abortion or induced abortion during the first 12 weeks of gestation, nonsensitized D-negative women should be given a minimum anti-D of 120 microg. After 12 weeks' gestation, they should be given 300 microg. (II-3B) 10. At abortion, blood type and antibody screen should be done unless results of blood type and antibody screen during the pregnancy are available, in which case antibody screening need not be repeated. (III-B) 11. Anti-D should be given to nonsensitized D-negative women following ectopic pregnancy. A minimum of 120 microg should be given before 12 weeks' gestation and 300 microg after 12 weeks' gestation. (III-B) 12. Anti-D should be given to nonsensitized D-negative women following molar pregnancy because of the possibility of partial mole. Anti-D may be withheld if the diagnosis of complete mole is certain. (III-B) 13. At amniocentesis, anti-D 300 microg should be given to nonsensitized D-negativeesis, anti-D 300 microg should be given to nonsensitized D-negative women. (II-3B) 14. Anti-D should be given to nonsensitized D-negative women following chorionic villous sampling, at a minimum dose of 120 microg during the first 12 weeks' gestation, and at a dose of 300 microg after 12 weeks' gestation. (II-B) 15. Following cordocentesis, anti-D Ig 300 microg should be given to nonsensitized D-negative women. (II-3B) 16. Quantitative testing for FMH may be considered following events potentially associated with placental trauma and disruption of the fetomaternal interface (e.g., placental abruption, blunt trauma to the abdomen, cordocentesis, placenta previa with bleeding). There is a substantial risk of FMH over 30 mL with such events, especially with blunt trauma to the abdomen. (III-B) 17. Anti-D 120 microg or 300 microg is recommended in association with testing to quantitate FMH following conditions potentially associated with placental trauma and disruption of the fetomaternal interface (e.g., placental abruption, external cephalic version, blunt trauma to the abdomen, placenta previa with bleeding). If FMH is in excess of the amount covered by the dose given (6 mL or 15 mL fetal RBC), 10 microg additional anti-D should be given for every additional 0.5 mL fetal red blood cells. There is a risk of excess FMH, especially when there has been blunt trauma to the abdomen. (III-B) 18. Verbal or written informed consent must be obtained prior to administration of the blood product Rh immune globulin. (III-C) VALIDATION: These guidelines have been reviewed by the Maternal-Fetal Medicine Committee and the Genetics Committee, with input from the Rh Program of Nova Scotia. Final approval has been given by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada.
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http://dx.doi.org/10.1016/s1701-2163(16)31006-4DOI Listing
September 2003

Congenital epulis: prenatal imaging with MRI and ultrasound.

Pediatr Radiol 2003 Nov 5;33(11):800-3. Epub 2003 Sep 5.

Department of Diagnostic Radiology, CHUS-Hôpital Fleurimont, 3001 12 Ave Nord, Fleurimont, Quebec, J1H 5N4, Canada.

Congenital epulis is an uncommon benign tumor that originates from the alveolar ridge in newborns. It is also known as congenital gingival granular cell tumor. Although there have been around 200 reports of its postnatal diagnosis, this oral tumor has rarely been diagnosed prenatally. We present fetal MRI and Doppler prenatal imaging of an infant with two congenital epulides (simultaneous involvement of superior and inferior maxillas).
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http://dx.doi.org/10.1007/s00247-003-1024-4DOI Listing
November 2003

Amniocentesis and women with hepatitis B, hepatitis C, or human immunodeficiency virus.

J Obstet Gynaecol Can 2003 Feb;25(2):145-48, 149-52

Objective: To review the risk of in utero infection through amniocentesis in women with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).

Outcomes: Fetal and neonatal morbidity and mortality.

Evidence: Review articles, meta-analyses, and MEDLINE searches from 1966 to 2002 for English-language articles related to amniocentesis, fetal and neonatal infection, and hepatitis B, hepatitis C, or HIV.

Values: The evidence collected was reviewed by the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on the Periodic Health Exam.

Recommendations: 1. The risk of fetal hepatitis B infection through amniocentesis is low. However, knowledge of the maternal hepatitis B e antigen status is valuable in the counselling of risks associated with amniocentesis. (II-1C) 2. Amniocentesis in women infected with hepatitis C does not appear to significantly increase the risk of vertical transmission, but women should be counselled that very few studies have properly addressed this possibility. (II-2C) 3. In HIV-positive women all noninvasive screening tools should be used prior to considering amniocentesis. (II-2D) 4. For women infected with hepatitis B, hepatitis C, or HIV, the addition of noninvasive methods of prenatal risk screening, such as nuchal translucency, triple screening, and anatomic ultrasound, may help in reducing the age-related risk to a level below the threshold for genetic amniocentesis. (II-2C) 5. For those women infected with hepatitis B, hepatitis C, or HIV who insist on amniocentesis, every effort should be made to avoid inserting the needle through the placenta. (II-1B) VALIDATION: These guidelines have been approved by the SOGC Genetics Committee, SOGC Executive, and SOGC Council.

Sponsors: The Society of Obstetricians and Gynaecologists of Canada.
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http://dx.doi.org/10.1016/s1701-2163(16)30211-0DOI Listing
February 2003

Cystic fibrosis carrier testing in pregnancy in Canada.

J Obstet Gynaecol Can 2002 Aug;24(8):644-51

Objective: To assess the role of cystic fibrosis (CF) testing within the Canadian health care environment.

Methods: The Genetics and Maternal Fetal Medicine Committees of the Society of Obstetricians and Gynaecologists of Canada (SOGC) reviewed Preconception and Prenatal Carrier Screening for Cystic Fibrosis Clinical and Laboratory Guidelines produced by the American College of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics (ACMG) and other educational material from ACOG and ACMG.

Results: Background information related to cystic fibrosis, genetic mutation analysis, and one large clinical cystic fibrosis screening trial are reviewed.

Evidence: The quality of evidence reported in this document has been described using the Evaluation of Evidence criteria outlined in the report of the Canadian Task Force on the Periodic Health Exam.

Recommendations: 1. CF testing in pregnancy is indicated for individuals who may be at increased risk for CF due to considerations of family history or clinical manifestations. (II-2A). 2. Before CF screening could be undertaken, each province/territory would have to review the ethnic diversity of its reproductive population to ensure that CF screening would be appropriate. (III-C). 3. Screening of all women during pregnancy for CF carrier status cannot be recommended at this time. (III-C).
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http://dx.doi.org/10.1016/s1701-2163(16)30196-7DOI Listing
August 2002