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Objective: This revised guideline is intended to provide an update on the genetic aspects, prevention, screening, diagnosis, and management of fetal neural tube defects., Target Population: Women who are pregnant or may become pregnant. Neural tube defect screening should be offered to all pregnant women., Options: For prevention: a folate-rich diet, and folic acid and vitamin B 12 supplementation, with dosage depending on risk level. For screening: second-trimester anatomical sonography; first-trimester sonographic screening; maternal serum alpha fetoprotein; prenatal magnetic resonance imaging. For genetic testing: diagnostic amniocentesis with chromosomal microarray and amniotic fluid alpha fetoprotein and acetylcholinesterase; fetal exome sequencing. For pregnancy management: prenatal surgical repair; postnatal surgical repair; pregnancy termination with autopsy. For subsequent pregnancies: prevention and screening options and counselling., Outcomes: The research on and implementation of fetal surgery for prenatally diagnosed myelomeningocele has added a significant treatment option to the previous options (postnatal repair or pregnancy termination), but this new option carries an increased risk of maternal morbidity. Significant improvements in health and quality of life, both for the mother and the infant, have been shown to result from the prevention, screening, diagnosis, and treatment of fetal neural tube defects., Benefits, Harms, and Costs: The benefits for patient autonomy and decision-making are provided in the guideline. Harms include an unexpected fetal diagnosis and the subsequent management decisions. Harm can also result if the patient declines routine sonographic scans or if counselling and access to care for neural tube defects are delayed. Cost analysis (personal, family, health care) is not within the scope of this clinical practice guideline., Evidence: A directed and focused literature review was conducted using the search terms spina bifida, neural tube defect, myelomeningocele, prenatal diagnosis, fetal surgery, neural tube defect prevention, neural tube defect screening, neural tube defect diagnosis, and neural tube defect management in order to update and revise this guideline. A peer review process was used for content validation and clarity, with appropriate ethical considerations., Validation Methods: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations)., Intended Audience: Maternity care professionals who provide any part of pre-conception, antenatal, delivery, and neonatal care. This guideline is also appropriate for patient education. RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES)., (Copyright © 2020 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: To review the approach to prenatal genetic screening and diagnosis for chromosomal abnormalities in pregnancies conceived through in vitro fertilization and following preimplantation genetic testing for aneuploidy., Intended Users: General practitioners, family physicians, obstetricians, midwives, nurses, maternal-fetal medicine specialists, fertility specialists, genetic counsellors, geneticists, and other health care providers involved in prenatal screening., Target Population: All individuals or couples who conceivd through in vitro fertilization and underwent preimplantation genetic testing for aneuploidy., Evidence: Literature published in or before September 2018 was retrieved through searches of Medline, PubMed, and the Cochrane Library. SUMMARY STATEMENTS., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: Yearly, 450 000 pregnant Canadians are eligible for voluntary prenatal screening for trisomy 21. Different screening strategies select approximately 4% of women for invasive fetal chromosome testing. Non-invasive prenatal testing (NIPT) using maternal blood cell-free DNA could reduce those invasive procedures but is expensive. This study evaluated the cost-effectiveness of NIPT strategies compared with conventional strategies., Methods: This study used a decision analytic model to estimate the cost-effectiveness of 13 prenatal screening strategies for fetal aneuploidies: six frequently used strategies, universal NIPT, and six strategies incorporating NIPT as a second-tier test. The study considered a virtual cohort of pregnant women of similar size and age as women in Quebec. Model data were obtained from published sources and government databases. The study predicted the number of chromosomal anomalies detected (trisomies 21, 13, and 18), invasive procedures and euploid fetal losses, direct costs, and incremental cost-effectiveness ratios., Results: Of the 13 strategies compared, eight identified fewer cases at a higher cost than at least one of the remaining five strategies. Integrated serum screening with conditional NIPT had the lowest cost, and the cost per case detected was $63 139, with a 90% reduction of invasive procedures. The number of cases identified was improved with four other screening strategies, but with increasing of incremental costs per case (from $61 623 to $1 553 615). Results remained robust, except when NIPT costs and risk cut-offs varied., Conclusion: NIPT as a second-tier test for high-risk women is likely to be cost-effective as compared with screening algorithms not involving NIPT., (Copyright © 2018 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: To develop a Canadian consensus document on maternal screening for fetal aneuploidy (e.g., Down syndrome and trisomy 18) in singleton pregnancies., Options: Pregnancy screening for fetal aneuploidy started in the mid 1960s, using maternal age as the screening test. New developments in maternal serum and ultrasound screening have made it possible to offer all pregnant patients a non-invasive screening test to assess their risk of having a fetus with aneuploidy to determine whether invasive prenatal diagnostic testing is necessary. This document reviews the options available for non-invasive screening and makes recommendations for Canadian patients and health care workers., Outcomes: To offer non-invasive screening for fetal aneuploidy (trisomy 13, 18, 21) to all pregnant women. Invasive prenatal diagnosis would be offered to women who screen above a set risk cut-off level on non-invasive screening or to pregnant women whose personal, obstetrical, or family history places them at increased risk. Currently available non-invasive screening options include maternal age combined with one of the following: (1) first trimester screening (nuchal translucency, maternal age, and maternal serum biochemical markers), (2) second trimester serum screening (maternal age and maternal serum biochemical markers), or (3) 2-step integrated screening, which includes first and second trimester serum screening with or without nuchal translucency (integrated prenatal screen, serum integrated prenatal screening, contingent, and sequential). These options are reviewed, and recommendations are made., Evidence: Studies published between 1982 and 2009 were retrieved through searches of PubMed or Medline and CINAHL and the Cochrane Library, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to August 2010. 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. The previous Society of Obstetricians and Gynaecologists of Canada guidelines regarding prenatal screening were also reviewed in developing this clinical practice guideline., Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care., Benefits, Harms, and Costs: This guideline is intended to reduce the number of prenatal invasive procedures done when maternal age is the only indication. This will have the benefit of reducing the numbers of normal pregnancies lost because of complications of invasive procedures. Any screening test has an inherent false- positive rate, which may result in undue anxiety. It is not possible at this time to undertake a detailed cost-benefit analysis of the implementation of this guideline, since this would require health surveillance and research and health resources not presently available; however, these factors need to be evaluated in a prospective approach by provincial and territorial initiatives., (Copyright © 2017. Published by Elsevier Inc.)

Objectif: Offrir aux médecins un survol des troubles génétiques courants qui devraient être pris en considération dans le cadre de l'examen gynécologique annuel d'une patiente, et ce, afin de déterminer le risque que court celle-ci ou d'en venir à procéder à des examens particuliers ou à orienter la patiente vers un autre service de sous-spécialité, en fonction de ses antécédents personnels ou familiaux., Options: Ces renseignements d'ordre génétique peuvent être utilisés aux fins de la sensibilisation des patientes et du dépistage ou du diagnostic de possibles maladies et/ou mutations., Issues: L'utilisation de ces renseignements d'ordre génétique pourrait mener à l'amélioration de l'évaluation des risques et des avantages et à celle de la prise en charge dans le cadre de l'examen gynécologique annuel. RéSULTATS: Les études publiées en anglais, jusques et y compris en mai 2010, ont été récupérées par l'intermédiaire de recherches menées dans PubMed et la Cochrane Library au moyen d'un vocabulaire contrôlé (« gynaecological diagnosis », « genetic inheritance ») et de mots clés (« genetic risk », « genetic mutation », « inheritance », « family history », « uterus », « ovary », « endometrial », « vagina », « colon », « gastric », « renal », « breast », « cardiac », « thrombophilia », « diabetes », « epilepsy », « leiomyomata uteri ») appropriés. D'autres sources ont été identifiées par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales., Valeurs: Le niveau des résultats ne permet pas la formulation de recommandations factuelles. AVANTAGES, DéSAVANTAGES ET COûTS: La présente opinion de comité améliorera l'utilisation de nouvelles connaissances génétiques et leur application aux soins gynécologiques offerts annuellement aux femmes. Les occasions de gestion du risque et de diagnostic, pour ce qui est des troubles gynécologiques génétiques, s'en trouveront améliorées. Une compréhension plus exhaustive des troubles génétiques pourrait entraîner une hausse de l'anxiété et du stress psychologique chez les femmes et les membres de leur famille., Commanditaire: Société des obstétriciens et gynécologues du Canada., Recommandations: Le niveau des résultats ne permet pas la formulation de recommandations factuelles., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To provide updated information on the pre- and post-conception use of oral folic acid with or without a multivitamin/micronutrient supplement for the prevention of neural tube defects and other congenital anomalies. This will help physicians, midwives, nurses, and other health care workers to assist in the education of women about the proper use and dosage of folic acid/multivitamin supplementation before and during pregnancy., Evidence: Published literature was retrieved through searches of PubMed, Medline, CINAHL, and the Cochrane Library in January 2011 using appropriate controlled vocabulary and key words (e.g., folic acid, prenatal multivitamins, folate sensitive birth defects, congenital anomaly risk reduction, pre-conception counselling). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from 1985 and June 2014. Searches were updated on a regular basis and incorporated in the guideline to June 2014 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. Costs, risks, and benefits: The financial costs are those of daily vitamin supplementation and eating a healthy folate-enriched diet. The risks are of a reported association of dietary folic acid supplementation with fetal epigenetic modifications and with an increased likelihood of a twin pregnancy. These associations may require consideration before initiating folic acid supplementation. The benefit of folic acid oral supplementation or dietary folate intake combined with a multivitamin/micronutrient supplement is an associated decrease in neural tube defects and perhaps in other specific birth defects and obstetrical complications., Values: The quality of evidence in the document was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (Table 1). Summary Statement In Canada multivitamin tablets with folic acid are usually available in 3 formats: regular over-the-counter multivitamins with 0.4 to 0.6 mg folic acid, prenatal over-the-counter multivitamins with 1.0 mg folic acid, and prescription multivitamins with 5.0 mg folic acid. (III) Recommendations 1. Women should be advised to maintain a healthy folate-rich diet; however, folic acid/multivitamin supplementation is needed to achieve the red blood cell folate levels associated with maximal protection against neural tube defect. (III-A) 2. All women in the reproductive age group (12-45 years of age) who have preserved fertility (a pregnancy is possible) should be advised about the benefits of folic acid in a multivitamin supplementation during medical wellness visits (birth control renewal, Pap testing, yearly gynaecological examination) whether or not a pregnancy is contemplated. Because so many pregnancies are unplanned, this applies to all women who may become pregnant. (III-A) 3. Folic acid supplementation is unlikely to mask vitamin B12 deficiency (pernicious anemia). Investigations (examination or laboratory) are not required prior to initiating folic acid supplementation for women with a risk for primary or recurrent neural tube or other folic acid-sensitive congenital anomalies who are considering a pregnancy. It is recommended that folic acid be taken in a multivitamin including 2.6 ug/day of vitamin B12 to mitigate even theoretical concerns. (II-2A) 4. Women at HIGH RISK, for whom a folic acid dose greater than 1 mg is indicated, taking a multivitamin tablet containing folic acid, should be advised to follow the product label and not to take more than 1 daily dose of the multivitamin supplement. Additional tablets containing only folic acid should be taken to achieve the desired dose. (II-2A) 5. Women with a LOW RISK for a neural tube defect or other folic acid-sensitive congenital anomaly and a male partner with low risk require a diet of folate-rich foods and a daily oral multivitamin supplement containing 0.4 mg folic acid for at least 2 to 3 months before conception, throughout the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues. (II-2A) 6. Women with a MODERATE RISK for a neural tube defect or other folic acid-sensitive congenital anomaly or a male partner with moderate risk require a diet of folate-rich foods and daily oral supplementation with a multivitamin containing 1.0 mg folic acid, beginning at least 3 months before conception. Women should continue this regime until 12 weeks' gestational age. (1-A) From 12 weeks' gestational age, continuing through the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues, continued daily supplementation should consist of a multivitamin with 0.4 to 1.0 mg folic acid. (II-2A) 7. Women with an increased or HIGH RISK for a neural tube defect, a male partner with a personal history of neural tube defect, or history of a previous neural tube defect pregnancy in either partner require a diet of folate-rich foods and a daily oral supplement with 4.0 mg folic acid for at least 3 months before conception and until 12 weeks' gestational age. From 12 weeks' gestational age, continuing throughout the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues, continued daily supplementation should consist of a multivitamin with 0.4 to 1.0 mg folic acid. (I-A). The same dietary and supplementation regime should be followed if either partner has had a previous pregnancy with a neural tube defect. (II-2A).

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

Objective: To provide the physician with an overview of common genetic conditions that should be considered during a women's annual gynaecological assessment to determine the patient's risk or to initiate specific testing or referral to another subspecialty service, depending on personal or family history., Options: This genetic information can be used for patient education and possible disease and/or mutation screening or diagnosis., Outcomes: The use of this genetic information may allow improved risk-benefit assessment and management at the annual gynaecological examination., Evidence: Studies published in English up to and including May 2010 were retrieved through searches of PubMed and the Cochrane Library, using appropriate controlled vocabulary (gynaecological diagnosis, genetic inheritance) and key words (genetic risk, genetic mutation, inheritance, family history, uterus, ovary, endometrial, vagina, colon, gastric, renal, breast, cardiac, thrombophilia, diabetes, epilepsy, leiomyomata uteri). Other literature sources were identified through searching the web sites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies., Values: The levels of evidence are not adequate for evidence-based recommendations to be made., Benefits, Harms, and Costs: This committee opinion will enhance the use of new genetic knowledge and its application to the annual gynaecological care of women. Risk management and diagnostic opportunities for genetic gynaecological conditions will be improved. A more complete understanding of genetic conditions may increase anxiety and psychological stress for women and their families., Sponsors: Society of Obstetricians and Gynaecologists of Canada., Recommendations: The levels of evidence are not adequate for evidence-based recommendations to be made.

Objective: To summarize for obstetrical care providers the current literature on array genomic hybridization in prenatal diagnosis and to outline the recommendations of the Canadian College of Medical Geneticists regarding the use of this new technology with respect to prenatal diagnosis., Evidence: PubMed and Medline were searched for articles published in English between 2004 and 2010, using the key words DNA QF-PCR, quantitative fluorescent polymerase chain reaction, fetal chromosomal abnormalities, prenatal diagnosis, array genomic hybridization, fetal structural anomalies, and copy number variants. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis, and articles were incorporated in the guideline to September 2011. 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., 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. Array genomic hybridization is not recommended in pregnancies at low risk for a structural chromosomal abnormality; for example, advanced maternal age, positive maternal serum screen, previous trisomy, or the presence of "soft markers" on fetal ultrasound. (III-D) 2. Array genomic hybridization may be an appropriate diagnostic test in cases with fetal structural abnormalities detected on ultrasound or fetal magnetic resonance imaging; it could be done in lieu of a karyotype if rapid aneuploidy screening is negative and an appropriate turnaround time for results is assured. (II-2A) 3. Any pregnant woman who qualifies for microarray genomic hybridization testing should be seen in consultation by a medical geneticist before testing so that the benefits, limitations, and possible outcomes of the analysis can be discussed in detail. The difficulties of interpreting some copy number variants should also be discussed. This will allow couples to make an informed decision about whether or not they wish to pursue such prenatal testing. (III-A).

Objective: To provide Canadian health care providers with current information on the use of quantitative fluorescent polymerase chain reaction (QF-PCR) or equivalent technology in the prenatal diagnosis of fetal chromosomal abnormalities., Options: Over the last few decades, prenatal diagnosis of fetal chromosomal abnormalities has relied on conventional cytogenetic analysis of cultured amniocytes, chorionic villi, or fetal blood. In the last few years, the clinical validity of a newer technique, QF-PCR, to detect the common aneuploidies has been reported by a number of investigators. This technique has the advantage of providing rapid results for the diagnosis or exclusion of aneuploidy in chromosomes 13, 18, 21, X or Y. It is now possible to choose standard chromosome analysis or QF-PCR for the prenatal diagnosis of chromosomal abnormalities, or to perform both tests, depending on the clinical indication for testing. This document reviews the clinical utility of QF-PCR and makes recommendations for its use in the care of Canadian patients., Evidence: Medline and PubMed were searched for articles published in English between January 2000 and December 2010 that presented data on the use of QF-PCR versus standard cytogenetic analysis of prenatal samples. A second search was done to identify publications in English that provided results of cytogenetic analysis performed on prenatal samples for women at an increased risk of fetal aneuploidy because of maternal age, abnormal prenatal screening results, or fetal soft ultrasound markers suggestive of an increased risk of aneuploidy. Publications were included if they provided detailed information on the abnormalities detected, regardless of whether or not rapid aneuploidy screening was undertaken. Results were restricted to systematic reviews, randomized controlled trials, and relevant observational 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 national and international medical specialty societies., 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)., Benefits, Harms, and Costs: This guideline promotes the use of a rapid aneuploidy DNA test for women at increased risk of having a pregnancy affected by a common aneuploidy. This will have the benefit of providing rapid and accurate results to women at increased risk of fetal Down syndrome, trisomy 13, trisomy 18, sex chromosome aneuploidy or triploidy. It will also promote better use of laboratory resources and reduce the cost of prenatal diagnosis. However, a small percentage of pregnancies with a potentially clinically significant chromosomal abnormality will remain undetected by QF-PCR but detectable by conventional cytogenetics. Recommendations 1. QF-PCR is a reliable method to detect trisomies and should replace conventional cytogenetic analysis whenever prenatal testing is performed solely because of an increased risk of aneuploidy in chromosomes 13, 18, 21, X or Y. As with all tests, pretest counselling should include a discussion of the benefits and limitations of the test. In the initial period of use, education for health care providers will be required. (II-2A) 2. Both conventional cytogenetics and QF-PCR should be performed in all cases of prenatal diagnosis referred for a fetal ultrasound abnormality (including an increased nuchal translucency measurement > 3.5 mm) or a familial chromosomal rearrangement. (II-2A) 3. Cytogenetic follow-up of QF-PCR findings of trisomy 13 and 21 is recommended to rule out inherited Robertsonian translocations. However, the decision to set up a back-up culture for all cases that would allow for traditional cytogenetic testing if indicated by additional clinical or laboratory information should be made by each centre offering the testing according to the local clinical and laboratory experience and resources. (III-A) 4. Other technologies for the rapid detection of aneuploidy may replace QF-PCR if they offer a similar or improved performance for the detection of trisomy 13, 18, 21, and sex chromosome aneuploidy. (III-A).

Objective: To develop a Canadian consensus document on maternal screening for fetal aneuploidy (e.g., Down syndrome and trisomy 18) in singleton pregnancies., Options: Pregnancy screening for fetal aneuploidy started in the mid 1960s, using maternal age as the screening test. New developments in maternal serum and ultrasound screening have made it possible to offer all pregnant patients a non-invasive screening test to assess their risk of having a fetus with aneuploidy to determine whether invasive prenatal diagnostic testing is necessary. This document reviews the options available for non-invasive screening and makes recommendations for Canadian patients and health care workers., Outcomes: To offer non-invasive screening for fetal aneuploidy (trisomy 13, 18, 21) to all pregnant women. Invasive prenatal diagnosis would be offered to women who screen above a set risk cut-off level on non-invasive screening or to pregnant women whose personal, obstetrical, or family history places them at increased risk. Currently available non-invasive screening options include maternal age combined with one of the following: (1) first trimester screening (nuchal translucency, maternal age, and maternal serum biochemical markers), (2) second trimester serum screening (maternal age and maternal serum biochemical markers), or (3) 2-step integrated screening, which includes first and second trimester serum screening with or without nuchal translucency (integrated prenatal screen, serum integrated prenatal screening, contingent, and sequential). These options are reviewed, and recommendations are made., Evidence: Studies published between 1982 and 2009 were retrieved through searches of PubMed or Medline and CINAHL and the Cochrane Library, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to August 2010. 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. The previous Society of Obstetricians and Gynaecologists of Canada guidelines regarding prenatal screening were also reviewed in developing this clinical practice guideline., Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care., Benefits, Harms, and Costs: This guideline is intended to reduce the number of prenatal invasive procedures done when maternal age is the only indication. This will have the benefit of reducing the numbers of normal pregnancies lost because of complications of invasive procedures. Any screening test has an inherent false-positive rate, which may result in undue anxiety. It is not possible at this time to undertake a detailed cost-benefit analysis of the implementation of this guideline, since this would require health surveillance and research and health resources not presently available; however, these factors need to be evaluated in a prospective approach by provincial and territorial initiatives. RECOMMENDATIONS 1. All pregnant women in Canada, regardless of age, should be offered, through an informed counselling process, the option of a prenatal screening test for the most common clinically significant fetal aneuploidies in addition to a second trimester ultrasound for dating, assessment of fetal anatomy, and detection of multiples. (I-A) 2. Counselling must be non-directive and must respect a woman's right to accept or decline any or all of the testing or options offered at any point in the process. (III-A) 3. Maternal age alone is a poor minimum standard for prenatal screening for aneuploidy, and it should not be used a basis for recommending invasive testing when non-invasive prenatal screening for aneuploidy is available. (II-2A) 4. Invasive prenatal diagnosis for cytogenetic analysis should not be performed without multiple marker screening results except for women who are at increased risk of fetal aneuploidy (a) because of ultrasound findings, (b) because the pregnancy was conceived by in vitro fertilization with intracytoplasmic sperm injection, or (c) because the woman or her partner has a history of a previous child or fetus with a chromosomal abnormality or is a carrier of a chromosome rearrangement that increases the risk of having a fetus with a chromosomal abnormality. (II-2E) 5. At minimum, any prenatal screen offered to Canadian women who present for care in the first trimester should have a detection rate of 75% with no more than a 3% false-positive rate. The performance of the screen should be substantiated by annual audit. (III-B) 6. The minimum standard for women presenting in the second trimester should be a screen that has a detection rate of 75% with no more than a 5% false-positive rate. The performance of the screen should be substantiated by annual audit. (III-B) 7. First trimester nuchal translucency should be interpreted for risk assessment only when measured by sonographers or sonologists trained and accredited for this service and when there is ongoing quality assurance (II-2A), and it should not be offered as a screen without biochemical markers in singleton pregnancies. (I-E) 8. Evaluation of the fetal nasal bone in the first trimester should not be incorporated as a screen unless it is performed by sonographers or sonologists trained and accredited for this service and there is ongoing quality assurance. (II-2E) 9. For women who undertake first trimester screening, second trimester serum alpha fetoprotein screening and/or ultrasound examination is recommended to screen for open neural tube defects. (II-1A) 10. Timely referral and access is critical for women and should be facilitated to ensure women are able to undergo the type of screening test they have chosen as first trimester screening. The first steps of integrated screening (with or without nuchal translucency), contingent, or sequential screening are performed in an early and relatively narrow time window. (II-1A) 11. Ultrasound dating should be performed if menstrual or conception dating is unreliable. For any abnormal serum screen calculated on the basis of menstrual dating, an ultrasound should be done to confirm gestational age. (II-1A) 12. The presence or absence of soft markers or anomalies in the 18- to 20-week ultrasound can be used to modify the a priori risk of aneuploidy established by age or prior screening. (II-2B) 13. Information such as gestational dating, maternal weight, ethnicity, insulin-dependent diabetes mellitus, and use of assisted reproduction technologies should be provided to the laboratory to improve accuracy of testing. (II-2A) 14. Health care providers should be aware of the screening modalities available in their province or territory. (III-B) 15. A reliable system needs to be in place ensuring timely reporting of results. (III-C) 16. Screening programs should be implemented with resources that support audited screening and diagnostic laboratory services, ultrasound, genetic counselling services, patient and health care provider education, and high quality diagnostic testing, as well as resources for administration, annual clinical audit, and data management. In addition, there must be the flexibility and funding to adjust the program to new technology and protocols. (II-3B).

With a growing understanding of genetic disorders in the scientific and lay literature, it is becoming increasingly important to consider risk factors based on family history and ethnicity for identifying individuals for whom genetic testing is indicated and will be most beneficial. A pedigree helps to identify patients and families who have an increased risk for genetic disorders, to optimize counselling, screening, and diagnostic testing, with the goal of disease prevention or early diagnosis and management of the disease. Information should be updated periodically as new information regarding family history is acquired. This review was designed to provide a rationale for and an approach to obtaining a three-generation pedigree for patients who are seen as new assessments or those under ongoing care by primary care or specialist physicians, as well to summarize some resources available for constructing a useful pedigree.

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).

We reviewed the available molecular cytogenetic techniques and their potential use in prenatal diagnosis of fetuses with multiple congenital anomalies and a "normal" standard chromosomal karyotype. We searched Medline to identify reports published after 1995 that were related to molecular prenatal diagnosis. After review, we reached the following conclusions: 1. In fetuses with a normal standard karyotype result, common chromosomal microdeletion syndromes may be suspected based on the pattern of congenital anomalies seen on prenatal ultrasound. 2. When a microdeletion syndrome is suspected based on the pattern of fetal anomalies, FISH testing for the specific molecular locus should be undertaken. 3. Routine chromosome analysis, which has been the gold standard for prenatal cytogenetic diagnosis, may in the future be replaced by microarray technology with increased diagnostic capability for smaller, submicroscopic genetic alterations associated with postnatal morbidity. 4. Microarray technology has been shown to increase our ability to make a diagnosis of known or new chromosomal deletion syndromes in pediatric populations with developmental delay. The use of this technology for prenatal diagnosis is currently limited but is likely to expand.

Objective: To provide recommendations to physicians, midwives, genetic counsellors, and clinical laboratory scientists involved in pre-conceptional or prenatal care regarding carrier screening for thalassemia and hemoglobinopathies (e.g., sickle cell anemia and other qualitative hemoglobin disorders)., Outcomes: To determine the populations to be screened and the appropriate tests to offer to minimize practice variations across Canada., Evidence: The Medline database was searched for relevant articles published between 1986 and 2007 on carrier screening for thalassemia and hemoglobinopathies. Key textbooks were also reviewed. Recommendations were quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on Preventive Health Care., Values: The evidence collected from the Medline search was reviewed by the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG) and the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC)., Benefits, Harms, and Costs: Screening of individuals at increased risk of being carriers for thalassemia and hemoglobinopathies can identify couples with a 25% risk of having a pregnancy with a significant genetic disorder for which prenatal diagnosis is possible. Ideally, screening should be done pre-conceptionally. However, for a significant proportion of patients, the screening will occur during the pregnancy, and the time constraint for obtaining screening results may result in psychological distress. This guideline does not include a cost analysis., Recommendations: 1. Carrier screening for thalassemia and hemoglobinopathies should be offered to a woman if she and/or her partner are identified as belonging to an ethnic population whose members are at higher risk of being carriers. Ideally, this screening should be done pre-conceptionally or as early as possible in the pregnancy. (II-2A) 2. Screening should consist of a complete blood count, as well as hemoglobin electrophoresis or hemoglobin high performance liquid chromatography. This investigation should include quantitation of HbA2 and HbF. In addition, if there is microcytosis(mean cellular volume < 80 fL) and/or hypochromia (mean cellular hemoglobin < 27 pg) in the presence of a normal hemoglobin electrophoresis or high performance liquid chromatography the patient should be investigated with a brilliant cresyl blue stained blood smear to identify H bodies. A serum ferritin (to exclude iron deficiency anemia) should be performed simultaneously. (III-A) 3. If a woman's initial screening is abnormal (e.g., showing microcytosis or hypochromia with or without an elevated HbA2, or a variant Hb on electrophoresis or high performance liquid chromatography) then screening of the partner should be performed. This would include a complete blood count as well as hemoglobin electrophoresis or HPLC, HbA2 and HbF quantitation,and H body staining. (III-A) 4. If both partners are found to be carriers of thalassemia or an Hb variant, or of a combination of thalassemia and a hemoglobin variant, they should be referred for genetic counselling. Ideally,this should be prior to conception, or as early as possible in the pregnancy. Additional molecular studies may be required to clarify the carrier status of the parents and thus the risk to the fetus. (II-3A) 5. Prenatal diagnosis should be offered to the pregnant woman/couple at risk for having a fetus affected with a clinically significant thalassemia or hemoglobinopathy. Prenatal diagnosis should be performed with the patient's informed consent. If prenatal diagnosis is declined, testing of the child should be done to allow early diagnosis and referral to a pediatric hematology centre, if indicated. (II-3A) 6. Prenatal diagnosis by DNA analysis can be performed using cells obtained by chorionic villus sampling or amniocentesis. Alternatively for those who decline invasive testing and are at risk of hemoglobin Bart's hydrops fetalis (four-gene deletion alpha-thalassemia), serial detailed fetal ultrasound for assessment of the fetal cardiothoracic ratio (normal < 0.5) should be done in a centre that has experience conducting these assessments for early identification of an affected fetus. If an abnormality is detected, a referral to a tertiary care centre is recommended for further assessment and counselling. Confirmatory studies by DNA analysis of amniocytes should be done if a termination of pregnancy is being considered. (II-3A) 7. The finding of hydrops fetalis on ultrasound in the second or third trimester in women with an ethnic background that has an increased risk of alpha-thalassemia should prompt immediate investigation of the pregnant patient and her partner to determine their carrier status for alpha-thalassemia. (III-A) VALIDATION: This guideline has been prepared by the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG) and the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and approved by the Board of Directors of the CCMG and the Executive and Council of the SOGC.

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.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.