Chromosomal microarray analysis is a high-resolution, whole-genome technique used to identify chromosomal abnormalities, including those detected by conventional cytogenetic techniques, as well as ...small submicroscopic deletions and duplications referred to as copy number variants. Because chromosomal microarray analysis has a greater resolution than conventional karyotyping, it can detect deletions and duplications down to a 50- to 100-kb level. The purpose of this document is to discuss the technique, advantages, and disadvantages of chromosomal microarray analysis and its indications and limitations. We recommend the following: (1) that chromosomal microarray analysis be offered when genetic analysis is performed in cases with fetal structural anomalies and/or stillbirth and replaces the need for fetal karyotype in these cases (grade 1A); (2) that providers discuss the benefits and limitations of chromosomal microarray analysis and conventional karyotype with patients who are considering amniocentesis and CVS, and that both options should be available to women who choose to undergo diagnostic testing (grade 1B); (3) that pre- and posttest counseling should be performed by trained genetic counselors, geneticists, or other providers with expertise in the complexities of interpreting chromosomal microarray analysis results (Best Practice); (4) that patients be informed that chromosomal microarray analysis does not detect every genetic disease or syndrome and specifically does not detect autosomal-recessive disorders associated with single gene point mutations, as well as that chromosomal microarray analysis can detect consanguinity and nonpaternity in some cases (Best Practice); (5) that patients in whom a fetal variant of uncertain significance is detected by prenatal diagnosis receive counseling from experts who have access to databases that provide updated information concerning genotype-phenotype correlations (Best Practice); and (6) that chromosomal microarray analysis not be used as a first-line test to evaluate first and second trimester pregnancy losses due to limited data (grade 1C).
Cell-free DNA fetal fraction and preterm birth Dugoff, Lorraine, MD; Barberio, Andrea, MD; Whittaker, Paul G., D. Phil ...
American journal of obstetrics and gynecology,
08/2016, Volume:
215, Issue:
2
Journal Article
Peer reviewed
Open access
Abstract Background Cell-free DNA is increasingly being used to screen for fetal aneuploidy. The majority of fetal cell-free DNA in the maternal blood results from release from the ...syncytiotrophoblast as a result of cellular apoptosis and necrosis. Elevated levels of fetal cell-free DNA may be indicative of underlying placental dysfunction which has been associated with preterm birth. Preliminary studies have demonstrated that fetal cell-free DNA is increased in pregnancies complicated by spontaneous preterm birth. There are limited data on the association between fetal cell-free DNA levels and fetal fraction and preterm birth in asymptomatic women in the first and second trimester. Preliminary studies have failed to find an association between first trimester cell-free DNA levels and preterm birth while there is conflicting evidence as to whether elevated second trimester cell-free DNA is associated with a subsequent spontaneous preterm birth clinical event. Objective To evaluate the association between first and second-trimester cell-free DNA fetal fraction and preterm birth. Study Design Retrospective cohort study of women with singleton pregnancies at increased risk for aneuploidy who had cell-free DNA testing at 10-20 weeks gestation between October 2011 and May 2014. The cohort was subdivided by gestational age at the time of cell-free DNA testing (10-14 weeks or 14.1-20 weeks). The primary outcome was preterm birth less than 37 weeks gestation and the secondary outcomes were preterm birth at less than 34 weeks gestation and spontaneous preterm birth at less than 37 and 34 weeks gestation. Results Among 1349 pregnancies meeting inclusion criteria 119 (8.8 %) had a preterm birth prior to 37 weeks with 49 cases (3.6 %) delivering prior to 34 weeks. While there was no significant association between fetal fraction and the preterm birth outcomes for those who underwent cell-free DNA testing at 10-14 weeks gestation, there were significant associations among those screened at 14.1- 20.0 weeks gestation. Fetal fraction greater than or equal to the 95th percentile at 14.1- 20.0 weeks gestation was associated with an increased risk for preterm birth less than 37 and 34 weeks gestation (adjusted OR 4.59; 95% CI 1.39 -15.2; adjusted OR 22.0; 95% CI 5.02-96.9). Conclusion Elevated fetal fraction levels at 14.1-20.0 weeks gestation were significantly associated with an increased incidence of preterm birth. Our findings warrant future exploration including validation in a larger, general population and investigation of the potential mechanisms which may be responsible for the initiation of preterm labor associated with increased fetal cell-free DNA.
Testing cell-free DNA (cfDNA) in maternal blood samples has been shown to have very high sensitivity for the detection of fetal aneuploidy with very low false-positive results in high-risk patients ...who undergo invasive prenatal diagnosis. Recent observation in clinical practice of several cases of positive cfDNA tests for trisomy 18 and trisomy 13, which were not confirmed by cytogenetic testing of the pregnancy, may reflect a limitation of the positive predictive value of this quantitative testing, particularly when it is used to detect rare aneuploidies. Analysis of a larger number of false-positive cases is needed to evaluate whether these observations reflect the positive predictive value that should be expected. Infrequently, mechanisms (such as low percentage mosaicism or confined placental mosaicism) might also lead to positive cfDNA testing that is not concordant with standard prenatal cytogenetic diagnosis. The need to explore these and other possible causes of false-positive cfDNA testing is exemplified by 2 of these cases. Additional evaluation of cfDNA testing in clinical practice and a mechanism for the systematic reporting of false-positive and false-negative cases will be important before this test is offered widely to the general population of low-risk obstetric patients. In the meantime, incorporating information about the positive predictive value in pretest counseling and in clinical laboratory reports is recommended. These experiences reinforce the importance of offering invasive testing to confirm cfDNA results before parental decision-making.
This article, the ninth in the “To the Point” series that is prepared by the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee, discusses the role of ...the “hidden curriculum” in shaping the professional identity of doctors in training. The characteristics that distinguish the formal curriculum and hidden curriculum are defined. Specific examples of hidden curricula in clinical environments and the positive and negative impacts that may result are highlighted. Techniques to evaluate clinical training environments and to identify the hidden curriculum are provided and are followed by methods to promote its positive messages and lessen its negative ones.
This article, from the To the Point series prepared by the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee, provides educators with an overview of ...considerations for obstetrics and gynecology global health experiences for the medical student. Options for integration of obstetrics and gynecology global health into undergraduate medical curricula are discussed. Specific considerations for global health clinical experiences for medical students, including choosing a clinical location, oversight and mentorship, goals and objectives, predeparture preparation, and evaluation, are reviewed.
This article in the To the Point series will focus on best practices regarding faculty development in medical education in the field of obstetrics and gynecology. Faculty development is an essential ...component in achieving teacher and learner satisfaction as well as improving learner outcomes. The Liaison Committee on Medical Education requires medical school faculty to have the capability and longitudinal commitment to be effective teachers. Although many programs have been created to address faculty development, there remains a paucity of literature documenting the impact of these programs on learner outcomes. We reviewed the qualities of an excellent medical educator, expectations regarding medical school teaching faculty, elements of comprehensive faculty development programs, and outcome measures for evaluating the effectiveness of these programs.
Objective To develop and evaluate a method of estimating patient-specific risk for fetal loss by combining maternal characteristics with serum markers. Study Design Data were obtained on 36,014 women ...from the FaSTER trial. Separate likelihood ratios were estimated for significant maternal characteristics and serum markers. Patient-specific risk was calculated by multiplying the incidence of fetal loss by the likelihood ratios for each maternal characteristic and for different serum marker combinations. Results Three hundred eighteen women had fetal loss < 24 weeks (early) and 103 > 24 weeks (late). Clinical characteristics evaluated included maternal age, body mass index, race, parity, threatened abortion, previous preterm delivery, and previous early loss. Serum markers studied as possible predictors of early loss included first-trimester pregnancy-associated plasma protein A and second-trimester alpha-fetoprotein, and unconjugated estriol. A risk assessment for early loss based on all of these factors yielded a 46% detection rate, for a fixed 10% false-positive rate, 39% for 5% and 28% for 1%. The only significant marker for late loss was inhibin A. The detection rate was 27% for a fixed 10% false-positive rate and only increased slightly when clinical characteristics were added to the model. Conclusion Patient-specific risk assessment for early fetal loss using serum markers, with or without maternal characteristics, has a moderately high detection. Patient-specific risk assessment for late fetal loss has low detection rates.
To the point: a primer on medical education research Nuthalapaty, Francis S., MD; Casey, Petra M., MD; Cullimore, Amie J., BSc, Bed, MD, MSC ...
American journal of obstetrics and gynecology,
07/2012, Volume:
207, Issue:
1
Journal Article
Peer reviewed
This article, from the To the Point series prepared by the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee, provides educators with an introduction to ...medical educational research by describing the framework of educational scholarship, discussing the similarities and differences between clinical and educational research, reviewing the key steps in educational research, and providing examples of well-designed studies in the field of obstetrics and gynecology.
The Obstetrics and Gynaecology Resident as Teacher Cullimore, Amie J., BEd, MSc, MD; Dalrymple, John L., MD; Dugoff, Lorraine, MD ...
Journal of obstetrics and gynaecology Canada,
12/2010, Volume:
32, Issue:
12
Journal Article
Peer reviewed
Abstract In this article we discuss the role residents play in the clinical training and evaluation of medical students. A literature search was performed to identify articles dealing with research, ...curriculum, and the evaluation of residents as teachers. We summarize the importance of resident educators and the need to provide appropriate resources for house staff in this role, and we review evidence-based literature in the area of residents as teachers. Specific attention is given to the unique circumstances of the obstetrics and gynaecology resident, who is often faced with teaching in an emotionally charged and stress-filled environment. We present examples of curricula for residents as teachers and describe barriers to their implementation and evaluation.
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