Screening for fetal aneuploidy Rink, Britton D., MD, MS; Norton, Mary E., MD
Seminars in perinatology,
02/2016, Letnik:
40, Številka:
1
Journal Article
Recenzirano
Abstract Screening is currently recommended in pregnancy for a number of genetic disorders, chromosomal aneuploidy, and structural birth defects in the fetus regardless of maternal age or family ...history. There is an overwhelming array of sonographic and maternal serum-based options available for carrying out aneuploidy risk assessment in the first and/or second trimester. As with any screening test, the patient should be made aware that a “negative” test or “normal” ultrasound does not guarantee a healthy baby and a “positive” test does not mean the fetus has the condition. The woman should have both pre- and post-test counseling to discuss the benefits, limitations, and options for additional testing. Rapid advancements of genetic technologies have made it possible to screen for the common aneuploidies traditionally associated with advanced maternal age with improved levels of accuracy beyond serum and ultrasound based testing. Prenatal screening for fetal genetic disorders with cell-free DNA has transformed prenatal care with yet unanswered questions related to the financial, ethical, and appropriate application in the provision of prenatal risk assessment.
Background Sequential and cell-free DNA (cfDNA) screening are both tests for the common aneuploidies. Although cfDNA has a greater detection rate (DR) for trisomy 21, sequential screening also can ...identify risk for other aneuploidies. The comparative DR for all chromosomal abnormalities is unknown. Objective To compare sequential and cfDNA screening for detection of fetal chromosomal abnormalities in a general prenatal cohort. Study Design The performance of sequential screening for the detection of chromosome abnormalities in a cohort of patients screened through the California Prenatal Screening Program with estimated due dates between August 2009 and December 2012 was compared with the estimated DRs and false-positive rates (FPRs) of cfDNA screening if used as primary screening in this same cohort. DR and FPR for cfDNA screening were abstracted from the published literature, as were the rates of “no results” in euploid and aneuploid cases. Chromosome abnormalities in the entire cohort were categorized as detectable (trisomies 13, 18, and 21, and sex chromosome aneuploidy), or not detectable (other chromosome abnormalities) by cfDNA screening. DR and FPR were compared for individual and all chromosome abnormalities. DR and FPR for the cohort were compared if “no results” cases were considered “screen negative” or “screen positive” for aneuploidy. DR and FPR rates were compared by use of the Fisher exact test. RESULTS Of 452,901 women who underwent sequential screening during the time period of the study, 2575 (0.57%) had a fetal chromosomal abnormality; 2101 were detected for a DR of 81.6%, and 19,929 euploid fetuses had positive sequential screening for an FPR rate of 4.5%. If no results cases were presumed normal, cfDNA screening would have detected 1820 chromosome abnormalities (70.7%) with an FPR of 0.7%. If no results cases were considered screen positive, 1985 (77.1%) cases would be detected at a total screen positive rate of 3.7%. In either case, the detection rate of sequential screening for all aneuploidies in the cohort was greater than cfDNA ( P <.0001). Conclusion For primary population screening, cfDNA provides lower DR than sequential screening if considering detection of all chromosomal abnormalities. Assuming that no results cfDNA cases are high-risk improves cfDNA detection but with a greater FPR. cfDNA should not be adopted as primary screening without further evaluation of the implications for detection of all chromosomal abnormalities and how to best evaluate no results cases.
The management of pregnant women who are themselves affected with genetic diseases is an increasingly relevant and important issue. Improvements in early diagnosis and management of genetic disease, ...as well as advances in assisted reproductive technology have impacted pregnancy rates in a cohort of women who may not have otherwise been able to conceive. A multidisciplinary approach is key to the management of pregnant women with complex health conditions, including genetic diseases. Pertinent issues should be addressed in the preconception, antepartum, intrapartum and postpartum periods to optimize maternal and fetal health. Additionally, counseling regarding risk of inheritance in offspring and options for prenatal diagnosis should be reviewed if available. This reviews aims to help provide background and insight into the management strategies for various commonly encountered and complex genetic conditions in the setting of pregnancy
Women should decide which conditions matter Norton, Mary E., MD; Kuppermann, Miriam, PhD
American journal of obstetrics and gynecology,
11/2016, Letnik:
215, Številka:
5
Journal Article
Recenzirano
Providing reliable prenatal screening performance estimates is critical for patient counseling and policy-making. Women who choose prenatal screening for aneuploidy are likely to be concerned not ...only with the common aneuploidies but with all causes of intellectual disability and serious birth defects. Sequential prenatal screening (combined serum and ultrasound testing) for aneuploidy detection commonly is offered as a primary screening test. Among women identified as screen positive, cell-free (cf)DNA has been added recently as a secondary, noninvasive screening option, before the consideration of invasive diagnostic testing (eg, amniocentesis and karyotype). With the anticipation of lower costs in the future, cfDNA might be an alternative to sequential screening in the general population. Sequential and cfDNA tests are both noninvasive, and both identify common aneuploidies. Screening via cfDNA detects more common chromosome abnormalities (eg, trisomy 21, sex trisomies). Sequential screening can identify other aneuploidies (eg, triploidy), as well as chromosome abnormalities associated with fetal structural abnormalities. When the advantages and disadvantages of routine sequential screening with routine cfDNA screening are compared, one important measure is the proportion and severity of chromosome abnormalities identified. When reporting these detection rates, authors need to carefully consider the impact of multiple well-described biases. For women to make informed choices in situations of this type, determining reliable comparative performance estimates is crucial.
Abstract Prenatal diagnostic testing is available for a growing number of disorders. The goal of prenatal diagnosis was initially focused on the identification of Down syndrome in women aged 35 years ...and older, but invasive prenatal genetic techniques can now detect a far broader array of conditions. The risks of invasive procedures have also decreased over time. Advances in genomic medicine allow testing for smaller but significant chromosomal abnormalities known as copy number variants, in addition to major aneuploidies and structural rearrangements. Molecular DNA techniques can detect many single-gene conditions. In the future, it is likely that whole-exome and whole-genome sequencing will be applied to prenatal genetic testing to allow identification of yet more genetic disorders. With advances in technology, the indications for testing have likewise evolved far beyond recommendations based solely on maternal age to include a more patient-centered view of the goals of prenatal testing.
Abstract Quality measurement is a critical tool for improving palliative care and hospice, but significant research is needed to improve the application of quality indicators. We defined ...methodological priorities for advancing the science of quality measurement in this field based on discussions of the Technical Advisory Panel of the Measuring What Matters consensus project of the American Academy of Hospice and Palliative Medicine and Hospice and Palliative Nurses Association and a subsequent strategy meeting to better clarify research challenges, priorities, and quality measurement implementation strategies. In this article, we describe three key priorities: 1) defining the denominator(s) (or the population of interest) for palliative care quality indicators, 2) developing methods to measure quality from different data sources, and 3) conducting research to advance the development of patient/family-reported indicators. We then apply these concepts to the key quality domain of advance care planning and address relevance to implementation of indicators in improving care. Developing the science of quality measurement in these key areas of palliative care and hospice will facilitate improved quality measurement across all populations with serious illness and care for patients and families.
Objective The purpose of this study was to compare the performance of first-trimester nuchal translucency (NT) cutoff of ≥3.5 mm with NT percentiles that were calculated for crown-rump length to ...identify fetuses with critical congenital heart defects (CCHDs). Study Design This was a population-level study of singleton pregnancies in California with NT measurements performed between 11 and 14 weeks of gestation. Eligible cases were those that resulted in live births from 2009-2010 and had information about the presence or absence of CCHDs available in the hospital discharge records through age 1 year (n = 76,089). Logistic binomial regression methods were used to compare the rate of CCHDs by an NT percentile for crown-rump length and millimeter cutpoints. Results Compared with fetuses with an NT measurement of <90th percentile, fetuses with an NT of ≥99th percentile were >5 times as likely to have a CCHD (1.3% vs 0.2%; relative risk, 5.66; 95% confidence interval, 3.19–10.04) and fetuses with an NT measurement ≥3.5 mm were >12 times as likely to have a CCHD (2.8% vs 0.2%; relative risk, 12.28; 95% confidence interval, 5.11–29.51). NT ≥99th percentile had a sensitivity of 5.8% and a specificity of 98.9% for the detection of CCHDs compared with 2.6% and 99.8% for NT ≥3.5 mm. Conclusion Results show that NT measurements of ≥99th percentile and ≥3.5 mm are not equivalent and that substantial risk for CCHD extends to the less restrictive ≥99th percentile cutpoint. Data suggest that the use of this cutpoint compared with the current standard could double the number of CCHDs that are identified based on NT risk.
Abstract Sonographic soft markers of fetal Down syndrome were first reported in the 1980s. With improvements in aneuploidy screening, detection rates of 90% and higher are possible, and such ...screening is offered to women of all ages. The utility of sonographic detection and reporting of soft markers, particularly to women at low risk of fetal aneuploidy, is controversial. Some soft markers have no additional significance beyond an association with aneuploidy, while some potentially indicate other pathology, and therefore require sonographic follow-up or other evaluation. The definitions of soft markers vary among reported series, and any practice using such markers to adjust the risk of aneuploidy should carefully determine the most appropriate definitions as well as likelihood ratios and how to apply these in practice.
Does length of labor vary by maternal age? Greenberg, Mara B., MD; Cheng, Yvonne W., MD, MPH; Sullivan, Margaret, MPH ...
American journal of obstetrics and gynecology,
10/2007, Letnik:
197, Številka:
4
Journal Article
Recenzirano
Objective The purpose of this study was to examine lengths of first and second stages of labor across maternal age groups to determine whether different norms should be established. Study Design We ...conducted a retrospective cohort study of all laboring, term, singleton, and cephalic deliveries at a single institution between 1980-2001. Median lengths of labor were compared among 6 maternal age groups. Statistical comparisons were made using Kruskal–Wallis and Wilcoxon rank sum tests. Multivariable linear and logistic regression models were performed. Results Among 31,976 births, length of labor differed significantly by maternal age for both nulliparous and multiparous women. Younger nulliparous women (age, <20 yrs) had a shorter median second stage by up to 97 minutes ( P < .001) than older nulliparous women (age, >39 yrs). After we controlled for potential confounders, we found that older women had a persistently higher likelihood of experiencing longer labor and prolonged labor than younger women. Conclusion Length of labor and prolonged labor increases with increasing maternal age.
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