Article

The risk of fetal loss following a prenatal diagnosis of trisomy 13 or trisomy 18

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Abstract

The objective of this study is to determine the risk of fetal loss (spontaneous abortion or stillbirth) following a prenatal diagnosis of trisomy 13 (T13; Patau syndrome) or trisomy 18 (T18; Edwards syndrome). Five regional congenital anomaly registers in England and Wales provided details on the outcomes of 198 pregnancies prenatally diagnosed with T13 and 538 prenatally diagnosed with T18. For each pregnancy the time from prenatal diagnosis until birth, miscarriage or termination occurred was calculated and these times were analyzed using Kaplan-Meier survival functions. Our results showed that between 12 weeks gestation and term an estimated 49% (95% CI: 29-73%) of pregnancies diagnosed with T13 and 72% (61-81%) of pregnancies diagnosed with T18 ended in a miscarriage or stillbirth. Between 18 weeks and term the proportions were 42% (18-72%) for T13 and 65% (57-79%) for T18 and between 24 weeks and term the proportions were 35% (5-70%) for T13 and 59% (49-77%) for T18. Male fetuses with T18 appeared to be more likely to be lost than female fetuses. These are the most precise estimates currently available for the risk of loss in a general population. These estimates should be useful in counseling women who are carrying an affected fetus and knowing the risk of fetal loss is essential to compare the performance of prenatal screening programs occurring in the first and second trimester.

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... To allow for fetal losses, rates were applied according to trisomy, gestation and gender, which had been derived in another BINOCAR study discussed below. 39 Logistic regression was carried out on the observed age-specific prevalences. Based on the regression curves the overall prevalence was for Edwards syndrome 1/8 of that for Down syndrome based on the NDSCR regression curve 10 and for Patau syndrome the overall prevalence was 1/13 of Down syndrome. ...
... More reliable loss rates are provided by a study from five members of BINOCAR, which included 475 Edwards and 175 Patau syndrome cases diagnosed prenatally and followedup. 39 Actuarial survival analysis estimated that for Edwards syndrome the loss rates from 12 and 18 weeks were 72% and 65%; ...
... Early small studies reported that the Edwards syndrome fetal loss rate was higher in males than females. 22 This was confirmed by the large BINOCAR study with loss rates from 12 weeks of 79% and 67%, and from amniocentesis, 85% and 64%, respectively, 39 and by the NDSCR study. 46 However, none of these gender effects was statistically significant. ...
Article
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The birth prevalence rate of each common autosomal trisomy generally increases with advancing maternal age and there is a substantial fetal loss rate between late first trimester and term. The literature is reviewed in order to provide the best estimates of these rates, taking account where possible of biases due to prenatal diagnosis and selective termination of pregnancy. There is an almost exponential increase in Down syndrome birth prevalence between ages 15 and 45 but at older ages the curve flattens. There is no evidence of the claimed relatively high birth prevalence at extremely low ages. Gestation-specific intra-uterine fetal loss rates are estimated by follow-up of women declining termination of pregnancy after prenatal diagnosis, comparison of observed rates with those expected from birth prevalence and comparison of age-specific curves developed for prenatal diagnosis and birth. Down syndrome fetal loss rates reduce with gestation and increase with maternal age. Edwards and Patau syndrome birth prevalence is approximately 1/8 and 1/13 that of Down syndrome overall, although the ratio differs according to maternal age, particularly for Patau syndrome where it reduces steadily from 1/9 to 1/19. Fetal loss rates are higher for Edwards and Patau syndromes than for Down syndrome.
... The substantial multiple major malformations these patients develop can explain the reported high mortality rate. Major causes of death include central apnea, respiratory insufficiency, aspiration, and heart failure due to structural malformations [3,11]. Our patient had a recent episode of aspiration pneumonia along with several in the past requiring hospitalizations; however, it was successfully managed, and the patient remained clinically stable throughout her entire hospital course. ...
... Structural cardiac defects represent a major comorbidity in these patients as well. In a case series of 174 fetuses with trisomy 18, more than 70% had abnormal cardiac findings, including VSD, patent ductus arteriosus (PDA), tetralogy of Fallot, and atrioventricular defects [7,11,12]. Our patient has a well-functioning heart and no major malformations other than a small VSD, which potentially could have helped in the patient's long-term survival. ...
... Some more recent studies have shown more favorable outcomes in patients with trisomy 18 and cardiac defect surgery in select populations with significant defects [12]. In addition to cardiac defects, a large percentage of these patients are found to have renal abnormalities, including horseshoe kidney, hydronephrosis, and polycystic kidney disease, as well as central nervous system abnormalities such as Dandy-Walker syndrome [11,13,14]. Almost all patients with trisomies, including trisomy 18, have been found to have developmental delay, as seen in our patient [3,11]. ...
Article
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Background: Trisomy 18, also known as Edwards syndrome, was first described in the 1960s and is now defined as the second most common trisomy. While this genetic disease has been attributed to nondisjunction during meiosis, the exact mechanism remains unknown. Trisomy 18 is associated with a significantly increased mortality rate of about 5-10% of patients surviving until 1 year of age. We present a case of a 26-year-old female diagnosed with trisomy 18, well outliving her life expectancy, maintaining a stable state of health. Case presentation: A 26-year-old female with non-mosaic Edwards syndrome presented to the clinic for follow up after recent hospitalization for aspiration pneumonia. The definitive diagnosis of trisomy 18 was made prenatally utilizing chromosomal analysis and G-banding and fluorescence in situ hybridization (FISH) on cells obtained via amniocentesis. Her past medical history is characterized by severe growth and intellectual limitations; recurrent history of infections, especially respiratory system infections; and a ventricular septal defect (VSD) that was never surgically repaired. She remains in good, stable health and is under close follow-up and monitoring. Conclusions: Despite the fact that Edwards syndrome carries a significantly high mortality rate due to several comorbidities, recent literature including this case report has identified patients surviving into adulthood. Advancements in early detection and parent education have likely allowed for these findings. We aim to present a case of an adult with trisomy 18, living in stable condition, with an importance on medical follow-up.
... There are several reports in recent years that have addressed prenatal diagnosis, what families choose, and the natural history of obstetrical outcomes should parents choose expectant management that are important for prenatal consultation. [32][33][34][35][36][37] Ethical counseling requires knowing outcome data as opposed to generalizations of myths (see Table 2 ). All too often, expectant parents are presented with misinformation from their obstetrician, pediatrician, or perhaps even a neonatologist and maternal-fetal medicine physicians, about when and how these infants die. ...
... a Pregnancy decisions vary depending on maternal age, detection in the first versus second trimester, insurance status, state abortion laws, and presence of other anomalies b Rates of stillbirth and IUFD are combined in some studies. From references 29,32,33,34. c Only 1 study has examined differences in outcomes depending on the level of maternal-fetal monitoring. d Outcome after receipt of interventions may depend on individual patient factors such as birth weight, gender, coexisting type, and severity of anomalies . ...
Article
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Background: Families with a prenatal diagnosis of trisomy 13 or 18 are told many things, some true and some myths. They present with differing choices on how to proceed that may or may not be completely informed. Purpose: To provide the prenatal counselor with a review of the pertinent obstetrical and neonatal outcome data and ethical discussion to help them in supporting families with the correct information for counseling. Methods/search strategy: This article provides a review of the literature on facts and myths and provides reasonable outcome data to help families in decision making. Findings/results: These disorders comprise a heterogeneous group regarding presentation, outcomes, and parental goals. The authors maintain that there needs to be balanced decision-making between parents and providers for the appropriate care for the woman and her infant. Implications for practice: Awareness of this literature can help ensure that prenatal and palliative care consultation incorporates the appropriate facts and parental values and in the end supports differing choices that can support the infant's interests.
... Our microsimulation allows each woman to be followed in the model on a weekly cycle's basis during pregnancy up to birth in order to well take into account the risks of spontaneous losses and voluntary induced abortion. Indeed, clinical evidence have shown that the risk of spontaneous pregnancy loss is higher in the first trimester than in the second and in third trimester [27][28][29][30][31]. In addition, in Quebec, the proportion of voluntary induced abortion are high ranging between 20 and 25% of all pregnancies. ...
... A virtual population of 15-49 years old singleton pregnant women was generated and calibrated using Quebec statistics data [33,34]. This population is followed weekly by taking into account the risks of spontaneous losses and voluntary pregnancy termination [27][28][29][30][31] as well as the age-specific risk of DS [25,26]. Input data used are based on the Prenatal Screening Program of Quebec for trisomy 21 data [9] and on published sources. ...
Article
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Background Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma is a high accurate test for prenatal screening for Down syndrome. Although it has been reported to be cost effective as a contingent test, evidence about its budget impact is lacking. Objective To evaluate, using computer simulations, the budget impact of implementing NIPT as a contingent test in the Quebec Program of screening for Trisomy 21. Methods A semi-Markov analytic model built to simulate the budget impact of implementing NIPT into the current Quebec Trisomy 21 public Prenatal Screening, Serum Integrated prenatal screening (SIPS). Comparisons were made for a virtual population similar to that of expected Quebec pregnant women in 2015 in terms of size and age. Data input parameters were retrieved from a thorough literature search and in government databases, especially data from Quebec Program of screening for Trisomy 21. The 2015–2016 fiscal year budget impact was estimated from the Quebec healthcare system perspective and was expressed as the difference in the overall costs between the two alternatives (SIPS minus SPS + NIPT). Results Our study found that, at a baseline cost for NIPT of CAD$ 795, NIPT as a second-tier test offered to high-risk women identified by current screening program (SIPS + NIPT) may be affordable for Quebec health care system. Compared to the current screening program, it would be implemented at a neutral cost, considering a modest annual savings of $ 80,432 (95% CI $ 79, $ 874–$ 81,462). Results were sensitive to the NIPT costs and the uptake-rate of invasive diagnostic tests. Conclusion Introducing NIPT as a contingent test in the Quebec Trisomy 21 screening program is an affordable strategy compared to the current practice. Further research is needed to confirm if our results can be reproduced in other healthcare jurisdictions.
... Trisomy 18 (Edwards syndrome, T18) is the second most common trisomy aneuploidy (1). This chromosomal anomaly is characterized by multiple congenital anomalies frequently involving cardiac, respiratory, neurological, gastrointestinal, genitourinary, and skeletal malformations (2). ...
... Most population-based studies have reported that patients with trisomy 18 do not live beyond the first year of life, and the majority of articles reported a 1-year survival rate of 10% (1,2,10). Because of these poor outcomes, cardiac surgery has not been justified and is performed in a limited number of patients with T18. ...
Article
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Background: There are reports about cardiac surgery in patients with trisomy 18. However, total cardiac repair with bypass is limited in those patients. Objectives: We aimed to evaluate palliative cardiac surgery and compare it to total cardiac repair in patients with trisomy 18. Methods: Retrospectively, 11 patients’ medical records were reviewed. The patients were grouped as palliative surgery (3 patients), total repair followed by palliative surgery (6 patients), and one-stage total repair (2 patients). A total of 17 cardiac surgeries in all patients consisted of nine palliative surgeries and eight total cardiac repairs with bypass. The cumulative survival and post-operative outcomes including complications were investigated. Results: Eleven patients underwent 17 cardiac surgeries in total. Four patients survived, with a median age of 827.5 days. The survivors consisted of two after one-stage total repair and two after total repair followed by palliative surgery. No survivors were found after only palliative surgery. When post-operative outcomes after palliative surgery in nine patients were compared to those after total cardiac repair in eight patients, there were no differences in operative mortality, postoperative intensive care unit stay, and hospital stay. No differences in post-operative complications were found. Conclusions: For post-operative outcomes and survival, palliative surgery in patients with trisomy 18 was not different from total cardiac repair with bypass but involved a difficult postoperative course including various complications similar to those after total repair with bypass.
... Studies from the United Kingdom have estimated spontaneous pregnancy loss rates from 12 weeks to term of 43% (95% confidence interval [CI], 31%-54%) for trisomy 21, 85 72% (95% CI, 61%-81%) for trisomy 18, 86 and 49% (95% CI, 29%-73%) for trisomy 13 86 when estimating live birth prevalence. 84 We used the same spontaneous pregnancy loss rates to estimate the prevalence of trisomies 21, 18, and 13 at 12 weeks' gestation. ...
... Studies from the United Kingdom have estimated spontaneous pregnancy loss rates from 12 weeks to term of 43% (95% confidence interval [CI], 31%-54%) for trisomy 21, 85 72% (95% CI, 61%-81%) for trisomy 18, 86 and 49% (95% CI, 29%-73%) for trisomy 13 86 when estimating live birth prevalence. 84 We used the same spontaneous pregnancy loss rates to estimate the prevalence of trisomies 21, 18, and 13 at 12 weeks' gestation. ...
Article
Background: Pregnant people have a risk of carrying a fetus affected by a chromosomal anomaly. Prenatal screening is offered to pregnant people to assess their risk. Noninvasive prenatal testing (NIPT) has been introduced clinically, which uses the presence of circulating cell-free fetal DNA in the maternal blood to quantify the risk of a chromosomal anomaly. At the time of writing, NIPT is publicly funded in Ontario for pregnancies at high risk of a chromosomal anomaly. Methods: We completed a health technology assessment, which included an evaluation of clinical benefits and harms, value for money, budget impact, and patient preferences related to NIPT. We performed a systematic literature search for studies on NIPT for trisomies 21, 18, and 13, sex chromosome aneuploidies, and microdeletions in the average-risk or general population. We evaluated the cost-effectiveness of traditional prenatal screening, NIPT as a second-tier test (performed after traditional prenatal screening), and NIPT as a first-tier test (performed instead of traditional prenatal screening). We also conducted a budget impact analysis to estimate the additional costs of funding first-tier NIPT. We interviewed people who had lived experience with NIPT and people living with the conditions NIPT screens for, or their families. Results: The pooled clinical sensitivity of NIPT in the average-risk or general population was 99.5% (95% confidence interval [CI] 81.8%-99.9%) for trisomy 21, 93.1% (95% CI 75.9%-98.3%) for trisomy 18, and 92.7% (95% CI 81.6%-99.9%) for trisomy 13. The clinical specificity for any trisomy was 99.9% (95% CI 99.8%-99.9%). Compared with traditional prenatal screening, NIPT was more accurate in detecting trisomies 21, 18, and 13, and decreased the need for diagnostic testing. We found limited evidence on NIPT for sex chromosome aneuploidies or microdeletions in the average-risk or general population. Positive NIPT results should be confirmed by diagnostic testing.Compared with traditional prenatal screening, second-tier NIPT detected more affected fetuses, substantially reduced the number of diagnostic tests performed, and slightly reduced the total cost of prenatal screening. Compared with second-tier NIPT, first-tier NIPT detected more affected cases, but also led to more diagnostic tests and additional budget of $35 million per year for average-risk pregnant people in Ontario.People who had undergone NIPT were largely supportive of the test and the benefits of earlier, more accurate results. However, many discussed the need for improved pre- and post-test counselling and raised concerns about the quality of the information they received from health care providers about the conditions NIPT can screen for. Conclusions: NIPT is an effective and safe prenatal screening method for trisomies 21, 18, and 13 in the average-risk or general population. Compared with traditional prenatal screening, second-tier NIPT improved the overall performance of prenatal screening and slightly decreased costs. Compared with second-tier NIPT, first-tier NIPT detected more chromosomal anomalies, but resulted in a considerable increase in the total budget. Interviewees were generally positive about NIPT, but they raised concerns about the lack of good informed-choice conversations with primary care providers and the quality of the information they received from health care providers about chromosomal anomalies.
... . These analyses suggest that these new regions in chromosome 18 might contribute to the complexity of phenotypes in trisomy 18 patients, including cardiac muscle development, immune response and basic cell division regulation.DISCUSSIONTrisomy 18 pregnancies, characterized by an extra copy of chromosome 18, have a high risk of fetal loss and stillbirth(Won et al. 2005;Morris and Savva 2008). Insightful studies on pathophysiology and genetic causes of trisomy 18 have been sparse, because of the difficulty of sample collection, unavailability of disease models and extremely high mortality rate among neonates(Cavadino and Morris 2017;Xing et al. 2018). ...
Preprint
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Trisomy 18, commonly known as Edward's syndrome, is the second most common autosomal trisomy among live born neonates. Multiple tissues including cardiac, abdominal, and nervous systems are affected by an extra chromosome 18. To delineate the complexity of anomalies of trisomy 18, we analyzed amniotic fluid cells from two normal and three trisomy 18 samples using single-cell transcriptomics. We identified six cell groups, which function in major tissue development such as kidney, vasculature, and smooth muscle, and display significant alterations in gene expression detected by single-cell RNA-sequencing. Moreover, we demonstrated significant gene expression changes in previously proposed trisomy 18 critical regions, and identified three new regions such as 18p11.32, 18q11, 18q21.32, which are likely associated with trisomy 18 phenotypes. Our results indicate complexity of trisomy 18 at the gene expression level and reveal genetic reasoning of diverse phenotypes in trisomy 18 patients.
... Trisomy 18 pregnancies, characterized by an extra copy of chromosome 18, have a high risk of fetal loss and stillbirth (Won et al., 2005;Morris and Savva, 2008). Insightful studies on pathophysiology and genetic causes of trisomy 18 have been sparse, because of the difficulty of sample collection, unavailability of disease models and extremely high mortality rate among neonates (Cavadino and Morris, 2017;Xing et al., 2018). ...
Article
Full-text available
Trisomy 18, commonly known as Edwards syndrome, is the second most common autosomal trisomy among live born neonates. Multiple tissues including cardiac, abdominal, and nervous systems are affected by an extra chromosome 18. To delineate the complexity of anomalies of trisomy 18, we analyzed cultured amniotic fluid cells from two euploid and three trisomy 18 samples using single-cell transcriptomics. We identified 6 cell groups, which function in development of major tissues such as kidney, vasculature and smooth muscle, and display significant alterations in gene expression as detected by single-cell RNA-sequencing. Moreover, we demonstrated significant gene expression changes in previously proposed trisomy 18 critical regions, and identified three new regions such as 18p11.32, 18q11 and 18q21.32, which are likely associated with trisomy 18 phenotypes. Our results indicate complexity of trisomy 18 at the gene expression level and reveal genetic reasoning of diverse phenotypes in trisomy 18 patients.
... Trisomy 18 is the second most common trisomy syndrome after trisomy 21 (5). It is also important in pre-natal diagnosis due to being associated with a high risk of fetal loss and stillbirth (46)(47)(48). The present study indicated that in the context of mid-pregnancy diagnosis, trisomy 18 accounted for 19.0% of the cases, second to trisomy 21. ...
Article
Quantitative fluorescence polymerase chain reaction (QF-PCR) may be used as a mid-pregnancy test to confirm the diagnosis of common fetal aneuploidies, but its use is controversial. The present study aimed to determine the value of QF-PCR for diagnostic confirmation of karyotyping and the impact of parental origin and meiosis stage on the detected aneuploidy. The present prospective cohort study included pregnant women (age, 21-45 years; gestational age, 17-25 weeks) who consulted between May 2015 and December 2016. Women were screened and only consecutive high-risk individuals were included (n=428). QF-PCR analysis of amniocytes was performed. Karyotype analysis was considered the gold standard. Parental karyotyping was performed if the embryo exhibited any aneuploidy. GeneMapper 3.2 was used for data analysis. There were no false-negative or false-positive QF-PCR results, with 100% concordance with the karyotype. The aneuploidy distribution (n=105) was 68.6% for trisomy 21, 19.0% for trisomy 18, 7.6% for sex chromosome aneuploidy, 3.8% for trisomy 13 and 1.0% for 48,XXX,+18. Regarding trisomy 21, most cases (86.1%) were of maternal origin, 8.3% paternal and 6.5% undefined. Trisomy 18 was 88.2% maternal and 11.8% paternal. Maternal meiosis stage errors in trisomy 21 mainly occurred in meiosis I, while the origin of trisomy 18 exhibited similar proportions between meiosis I and II. The combination of non-invasive pre-natal testing and QF-PCR may become a rapid and effective method for fetal aneuploidy detection. QF-PCR may provide more genetic information for clinical diagnosis and treatment than karyotyping alone.
... Down syndrome occurs in 1 in 800 live births, whereas about 1 in 10,000 newborns is estimated to carry trisomy 13, and the incidence of trisomy 18 is about 1 out of every 6,000 live births [6,7]. Due to Down syndrome and Patau syndrome, as well as Edwards syndrome with high rates of spontaneous loss, live-born infants are less likely to survive beyond the early stage [8]. Only 5-10% of live-born infants with the three aneuploidies can survive more than one year [9,10]. ...
Article
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Background: Molecular size determination of circulating free fetal DNA in maternal plasma is an important detection method for noninvasive prenatal testing (NIPT). The fetal DNA molecule is the primary factor determining the overall performance of NIPT and its clinical interpretation. The proportion of cell-free fetal DNA molecules is expressed as the fetal DNA fraction in the plasma of pregnant women. Methods: We proposed an effective method to deduce fetal chromosomal aneuploidy based on the proportion of a certain range of DNA fragment lengths from maternal plasma. We gradually narrowed the range of the upper and lower boundary via a traversing algorithm. Results: We explored the optimal range of the upper and lower boundary by using size-based DNA fragment length. Using this range, the accuracy of the sensitivity and specificity could be improved by up to 100% for detecting the three most common autosomal aneuploidies, namely trisomy 13, trisomy 18, trisomy 21 in the sample set. Conclusions: Numerical experiments demonstrate that our method is effective and efficient. The program is available upon request.
... Approximately half of pregnancies with trisomy 13 result in miscarriage or stillbirth between 12 weeks' gestation and term. 5 Physical findings in live-born infants with trisomy 13 include holoprosencephaly, microphthalmia, cleft lip/palate, microcephaly, scalp defects, polydactyly, capillary hemangiomas, colobomas of the iris, and umbilical hernias. 6 Most infants born with trisomy 13 die during the perinatal period. ...
Chapter
Trisomy 13 (Patau syndrome) is the third most common autosomal trisomy in newborns. It results from an extra chromosome 13 secondary to nondisjunction or translocation. In the United States, most cases of trisomy 13 are detected prenatally, either by genetic screening or ultrasound. Greater than 90% of fetuses with trisomy 13 have findings detected on prenatal ultrasound. The most common abnormalities visualized are cardiac abnormalities, holoprosencephaly, omphalocele, and cleft lip/palate. Fetuses with trisomy 13 have a 50% risk of intrauterine fetal demise after 12 weeks of gestation. Of live-born infants, most will not survive the immediate newborn period. Those that survive have severe physical and neurocognitive deficits.
... Survival beyond the first year of life is unusual and exceptional beyond the first decade, with only a small number of cases experiencing pubertal age. Mortality in Patau is attributed to cardiopulmonary failure, congenital heart defects and pneumonia [1,2]. ...
Article
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Patau syndrome is the third most frequent chromosomal trisomy, with an estimated mortality rate that is about 50 times higher than the general neonatal mortality rate. Trisomy 13 mosaicism is a subtype that may result in a milder form of the disease, potentially leading to a longer life expectancy in these patients, allowing them to reach puberty. In this report, we discuss the case of a young boy who was evaluated for delayed puberty and karyotyping revealed mosaicism for trisomy 13. A detailed history, physical examination and appropriate laboratory studies and imaging were performed that showed a picture of suggestive of hypogonadotropic hypogonadism and an abnormal male karyotype with mosaicism for trisomy 13. To date, there is no clear explanation to the association between trisomy 13 and gonadal axis, specifically with normal imaging of pituitary. We postulate that delayed puberty could be a clinical feature of mosaic trisomy 13.
... One study examining outcomes for 538 fetuses prenatally-diagnosed with trisomy 13 or 18 found that between 12 weeks gestation and term many ended in spontaneous abortion or stillbirth (49% and 72%, respectively). (150) In the case of CA surveillance and research, natural fetal loss (including both spontaneous abortion and stillbirth) and elective medical abortions are crucial to our understanding of the true occurrence of these outcomes. ...
Thesis
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The field of prenatal screening and diagnosis has developed rapidly over the past halfcentury, enabling possibilities for detecting anomalies in reproduction that were never before contemplated. A simple blood sample can aid in the identification of several conditions in the fetus early in the pregnancy. If a fetus is found to be affected by Down syndrome, anencephalus, spina bifida, or Edward's syndrome, a decision must then be made whether to continue or terminate the pregnancy. As prenatal screening becomes increasingly commonplace and part of routine maternal care, researchers are faced with the challenge of understanding its effects at the level of the population and monitoring trends over time. Greater uptake of prenatal screening, when followed by prenatal diagnosis and termination, has important implications for both congenital anomaly surveillance and infant and fetal mortality indicators. Research in Canada suggests that this practice has led to reductions in the congenital-anomaly specific infant mortality rate and increases in the stillbirth rate.(1, 2) The current study is a population-based, epidemiological exploration of demographic predictors of maternal serum screening (MSS) and amniocentesis uptake, with special attention to variations in birth outcomes resulting from different patterns of use. To accomplish our objectives, multiple data sources (vital statistics, hospital and physician services, cytogenetic and MSS laboratory information) were compiled to create a comprehensive maternal-fetal-infant dataset. Data spanned a six-year period (2000-2005) and involved 93,171 pregnancies. A binary logistic regression analysis found that First Nations status, rural-urban health region of residence, maternal age group, and year of test all significantly predicted MSS use. Uptake was lower in women living in a rural health region, First Nations women, and those under 30 years of age. The study dataset identified ninety-four terminations of pregnancy following detection of a fetal anomaly (TOPFA), which led to a lower live birth prevalence of infants with Down syndrome, Trisomy 18, and anencephalus. While a significant increasing trend was observed for the overall infant mortality rate in Saskatchewan between 2001-2005, a clear trend in one direction or the other could not be seen in regards to infant deaths due to congenital anomaly. First Nations status and maternal age were important predictors of both MSS and amniocentesis testing, and appeared to influence the decision to continue or terminate an affected pregnancy. The fact that First Nations women were less likely to screen (9.6% vs. 28.4%) and to have diagnostic follow-up testing (18.5% vs. 33.5%), meant that they were less likely to obtain a prenatal diagnosis when the fetus had a chromosomal anomaly compared to other women (8.3% vs. 27.0%). This resulted in a lower TOPFA rate compare to the rest of the population (0.64 vs.1.34, per 1,000 pregnancies, respectively) and a smaller difference between the live birth prevalence and incidence of Down syndrome and Trisomy 18 for First Nations women. Women under 30 years of age were much less likely to receive a prenatal diagnosis when a chromosomal anomaly was present (18.4% vs. 31.8%). While risk for a chromosomal anomaly is considerably lower for younger mothers, 53.5% of all pregnancies with chromosomal anomalies and 40.7% of DS pregnancies belonged to this group. Consistent with other studies pregnancy termination rates following a prenatal congenital anomaly diagnosis are high (eg. 74.1% of prenatally diagnosed Down syndrome or Trisomy 18 cases), but these rates may be misleading in that they are based on women who chose to proceed to prenatal diagnosis. The fact that two-thirds (67.3%) of Saskatchewan women who received an increased-risk result declined amniocentesis, helps to put this finding into context. Strong surveillance systems and reasonable access to research datasets will be an ongoing challenge for the province of Saskatchewan and should be viewed as a priority. Pregnancies and congenital anomalies are two particularly challenging outcomes to study in the absence of perinatal and congenital anomaly surveillance systems. Still pregnancies that never reach term must be accounted for, in order to describe the true state of maternal-fetal-infant health and to study its determinants. While our study was able to identify some interesting trends and patterns, it is only a snapshot in time. Key to the production of useful surveillance and evaluation is timely information. The current system is not timely, nor is it user-friendly for researchers, health regions or governments. Data compilation for the current study was a gruelling and cumbersome process taking more than five years to complete. A provincial overhaul is warranted in both the mechanism by which researchers access data and in the handling of data. The Better Outcomes Registry & Network (BORN) in Ontario is an innovative perinatal and congenital anomaly surveillance system worthy of modelling.(3) Academic papers in non-ethics' journals typically focus on the technical or programmatic aspects of screening and do not effectively alert the reader to the complex and profound moral dilemmas raised by the practice. A discussion of ethics was felt necessary to ensure a wellrounded portrayal of the issue, putting findings into context and helping to ensure their moral relevance did not remain hidden behind the scientific complexities. Here I lay out the themes of the major arguments in a descriptive manner, recognizing that volumes have been written on the ethics of both screening and abortion. A major ethical tension arising within the context of population based prenatal screening is the tension between community morality and the principle of respect for personal autonomy. Prenatal screening and selective termination have been framed as a purely private or medical matter, thereby deemphasizing the social context in which the practice has materialized and the importance of community values. I consider how a broader sociological perspective, one that takes into account the relevance of community values and limitations of the clinical encounter, could inform key practice and policy issues involving prenatal screening. It is my position that the community's voice must be invited to the conversation and public engagement processes should occur prior to any additional expansion in programming. I end with a look at how the community’s voice might be better heard on key issues, even those issues that at first glance seem to be the problems of individuals. As Rayna Rapp (2000) (4) poignantly observed, women today are 'moral pioneers' not by choice, but by necessity. By elucidating the effects of prenatal screening and the extent of the practice of selective termination in the province, the true occurrence of important categories of congenital anomalies in our province can be observed. Without this knowledge it is very difficult to identify real increases or decreases in fetal and infant mortality over time as the etiologies are complex. Evidence suggests a large and increasing impact of TOPFA on population-based birth and mortality statistics nationally, whereas in Saskatchewan the effect appears to be less pronounced. Appreciation of the intervening effect of new reproductive technologies will be increasingly important to accurate surveillance, research, and evaluation as this field continues to expand.
... The prevalence at birth is higher in females compared to males (F: M %, 60.4), but this difference is not present among electively terminated fetuses (F:M % 48:51.) [4] The studies have shown that the fetal death is higher for males compared to females [12,13]. ...
Conference Paper
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The Trisomy 18 Syndrome (Edwards Syndrome) occurs due presence of an extra chromosome 18 (full or mosaic trisomy) or partial trisomy 18q and it is the second most common autosomal trisomy after trisomy 21. The aim of this study was to determine the incidence of Edwards Syndrome in the population of fetuses whose mothers underwent diagnostic amniocentesis for fetal karyotyping and display characteristics of individual cases. We performed a retrospective analysis of data on 5421 pregnant women who made amniocentesis over 11 years. The incidence of fetuses with trisomy 18 estimated as 1: 493 in pregnancies that were followed by amniocentesis (0.2%). It is noted significantly more (P<0.5) male fetuses with Edwards Syndrome compared to female (72.7% vs. 27.3%). These findings are inconsistent with the clinical reports that showed higher prevalence at birth in female.
... Rates for pregnancy losses have been reported and shown to differ with stage of gestation and the condition (Morris and Savva 2008;Morris and Wald 1999). In MGDb, we use rates for foetal deaths i.e. from 20 weeks of pregnancy onwards. ...
Article
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Chromosomal disorders, of which Down syndrome is the most common, can cause multi-domain disability. In addition, compared to the general population, there is a higher frequency of death before the age of five. In many settings, large gaps in data availability have hampered policy-making, programme priorities and resource allocation for these important conditions. We have developed methods, which overcome this lack of data and allow estimation of the burden of affected pregnancies and their outcomes in different settings worldwide. For example, the methods include a simple equation relating the percentage of mothers 35 and over to Down syndrome birth prevalence. The results obtained provide a starting point for consideration of services that can be implemented for the care and prevention of these disorders.
... Rates for pregnancy losses have been reported and shown to differ with stage of gestation and the condition (Morris and Savva 2008;Morris and Wald 1999). In MGDb, we use rates for foetal deaths i.e. from 20 weeks of pregnancy onwards. ...
Article
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Chromosomal disorders, of which Down syndrome is the most common, can cause multi-domain disability. In addition, compared to the general population, there is a higher frequency of death before the age of five. In many settings, large gaps in data availability have hampered policy-making, programme priorities and resource allocation for these important conditions. We have developed methods, which overcome this lack of data and allow estimation of the burden of affected pregnancies and their outcomes in different settings worldwide. For example, the methods include a simple equation relating the percentage of mothers 35 and over to Down syndrome birth prevalence. The results obtained provide a starting point for consideration of services that can be implemented for the care and prevention of these disorders. Electronic supplementary material The online version of this article (10.1007/s12687-017-0336-2) contains supplementary material, which is available to authorized users.
... The sex ratio at birth is slightly skewed towards female presumably because of decreased survival among male. A significant number of cases that are trisomy for chromosome 13 end in spontaneous abortion, fetal demise, or stillbirth [5]. In our case the foetus was a male who died in utero. ...
Article
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Patau syndrome is a congenital disorder associated with trisomy 13. The extra chromosome 13 causes numerous fetal structural defects specially of the central nervous system, cardiovascular system and urogenital system. Major structural anomalies are occasionally identified in the late first or early second trimester. Other anomalies will be visible on ultrasound done around 20 weeks. Any discovery of multiple structural anomalies in a foetus increases the chances of chromosomal anomalies and women should be offered amniocentesis or other invasive tests to establish the foetal karyotype. Following a confirmed prenatal diagnosis of Patau syndrome, the decision to be made is either to terminate the pregnancy or to manage it conservatively. Most pregnancies will result in miscarriage or death in utero but some survive the first few weeks of life. Here we present a case of Patau syndrome which was diagnosed prenatally due to the presence of omphalocele and congenital cardiac abnormalities. This was followed by amniocentesis which confirmed the diagnosis. Pregnancy termination was offered to her but declined. Ultimately the foetus died in utero and delivered later without any complications.
... In pregnancies with Edwards' syndrome there is a high risk of fetal loss and stillbirth [3,7] but nowadays most cases are prenatal diagnosed based on first-trimester combined screening and amniocentesis followed by pregnancy termination in a significant percentage of cases [3,8]. ...
Article
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Edwards' syndrome, also known as trisomy 18, is a genetic disease caused by an extra copy of chromosome 18 in some or in all of the body cells [1, 2]. It is the second most common autosomal trisomy after trisomy 21(with an incidence of 1 in 8000 births) [3] but it is also more serious. Almost half of trisomy 18 infants die within the first week of life, and the majority of the remaining ones die in the next 12 months because of central apnea, upper airway obstruction, respiratory insufficiency, aspiration, cardiac failure, or a combination of these and other factors [1, 4]. Currently most cases of trisomy 18 are prenatally diagnosed, based on screening by maternal age, maternal serum marker screening, or detection of sonographic abnormalities e.g increased nuchal translucency thickness, growth retardation, choroid plexus cyst, overlapping of fingers, and congenital heart defects [3].Ultrasound scan for fetal anomalies is the most effective screening test for trisomy 18. A policy of conservative management for women with positive second-trimester biochemical screening or first-trimester combined screening for trisomy 18 is reasonable in the absence of ultrasound fetal abnormalities according to some authors. Unnecessary invasive tests can be avoided [5]. However, when can we decide on a conservative management and when do we need to check by amniocentesis and fetal DNA analyzing? It is a question without a clear answer despite numerous studies and articles on the subject. In our case the diagnosis was suggested by an ultrasound marker considered minor (choroid plexus cyst) and it would have been missed or found much later if we ignore this marker and we rely on the normal result of first-trimester screening with the nuchal translucency and biochemical markers in normal range.
... Notably, trisomic cells, including stem and progenitor cells, have an impaired proliferation rate (Hibaoui et al., 2014;Liu et al., 2015), which might partially be associated with miscarriage in early pregnancy. About 50% of fetuses with trisomy 21 and up to 72% of those with trisomy 18 cases are miscarried (Morris and Savva, 2008;Witters et al., 2011). ...
Article
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Human trisomies have recently been investigated using transcriptomics approaches to identify the gene expression (GE) signatures characteristic of each of these specific aneuploidy conditions. We hypothesized that the viability of cells with gross genomic imbalances might be associated with the activation of resilience mechanisms that are common to different trisomies and that are reflected by specific shared GE patterns. We report in this article our microarray GE analyses of amniocytes from fetuses with viable trisomy conditions, trisomy 21 or trisomy 18, to detect such common expression signatures. Comparative analysis of significantly differentially expressed genes in trisomies 18 and 21 revealed six dysregulated genes common to both: OTUD5, ADAMTSL1, TADA2A, PPID, PIAS2, and MAPRE2. These genes are involved in ubiquitination, protein folding, cell proliferation, and apoptosis. Pathway-based enrichment analyses demonstrated that both trisomies showed dysregulation of the PI3K/AKT pathway, cell cycle G2/M DNA damage checkpoint regulation, and cell death and survival, as well as inhibition of the upstream regulator TP53. Our data collectively suggest that trisomies 18 and 21 share common functional GE signatures, implying that common mechanisms of resilience might be activated in aneuploid cells to resist large genomic imbalances. To the best of our knowledge, this is the first study to use global GE profiling data to identify potential common mechanisms in fetal trisomies. Studies of other trisomies using transcriptomics and multiomics approaches might further clarify mechanisms activated in trisomy syndromes.
... The rates of termination of pregnancy may be above 78% for T13 and T18 (Lakovschek et al., 2011). The natural history of these trisomies is characterized by a high risk of spontaneous fetal loss, with pregnancy loss rates ranging from 49-66% for pregnancies with T13 and between 72-87% for T18 (Morris and Savva, 2008;Lakovschek et al., 2011;Houlihan and O'Donoghue, 2013). Less than 10% of the live births of T13 and T18 have a 1-year overall survival (Lin et al., 2006;Vendola et al., 2010;Houlihan and O'Donoghue, 2013). ...
Article
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Trisomy 18 (T18) and trisomy 13 (T13) are polymalformative syndromes associated with a high rate of spontaneous abortions, intrauterine death, and short postnatal life. This study describes the overall outcome in a country where the therapeutic interruption of pregnancy is not available. The medical records of women with prenatal diagnosis of full trisomy of T13 or T18 between October 1994 and October 2017 were analyzed in order to describe their natural outcomes. Thirteen cases of T13 and 29 cases of T18 were included. The miscarriage rate was 9% for T18 and no cases for T13. Intrauterine fetal death occurred in 46% and 52% of cases for T13 and T18, respectively. The rate of live births for T13 was 54%, and the median survival was one day (95% CI -33.55 - 90.40) and 71% died in the first 24 hours of life. The rate of live births for T18 was 37% and the median survival was two days (95% CI -1.89 - 13.17); 90% of the affected babies died within first week of life. For the affected babies reaching the first year of life and for those who lived longer, multiple invasive and expensive procedures were required, without success in prolonging life beyond 180 days. This large series provides information for professionals and women regarding the natural histories of T13 and T18. Results of this study are consistent with those referenced in the literature, emphasizing the need of structured protocols and guidelines aiming early T13 and T18 diagnosis, prenatal care, gestation/parents follow-up, and counseling processes. For those couples with earlier diagnosis, a better follow-up and counseling during the prenatal care lead to the option for a support or palliative management of the newborn. Finally, when the counseling process is appropriate, it becomes easier to take decisions respecting the parent's autonomy and to look for better outcomes for both, the mother and the fetus.
... for pregnancies with T13 and between 72-87% for T18 (Morris and Savva, 2008;Lakovschek et al., 2011;Houlihan and O'Donoghue, 2013). Less than 10% of the live births of T13 and T18 have a 1-year overall survival (Lin et al., 2006;Vendola et al., 2010;Houlihan and O'Donoghue, 2013). ...
... There is a very real challenge for the healthcare professional communicating complex information in such an emotionally charged context. There is no dressing up the harsh reality that 50-70% of pregnancies affected by Edwards' or Patau's syndrome result in miscarriage or stillbirth [7]. Only 11.6% of babies with Edwards' syndrome and 8.1% of babies with Patau's syndrome were born alive in England in 2018 [2] and these babies are likely to have a range of health challenges, some of which can be serious. ...
... The literature review was performed by searching different datab MEDLINE, PUBMED, and the Cochrane Library, according to the PRISM TOR network guidelines [10][11][12][13], and was updated to December 2021, with on the date of publication. This literature review followed the registered P tocol (CRD42022298553) (Figure 1). ...
Article
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Autosomal aneuploidies are the most frequently occurring congenital abnormalities and are related to many metabolic disorders, hormonal dysfunctions, neurotransmitter abnormalities, and intellectual disabilities. Trisomies are generated by an error of chromosomal segregation during cell division. Accumulating evidence has shown that deregulated gene expression resulting from the triplication of chromosomes 13 and 18 is associated with many disturbed cellular processes. Moreover, a disturbed oxidative stress status may be implicated in the occurrence of fetal malformations. Therefore, a literature review was undertaken to provide novel insights into the evaluation of trisomy 13 (T13) and 18 (T18) pathogeneses, with a particular concern on the oxidative stress. Corresponding to the limited literature data focused on factors leading to T13 and T18 phenotype occurrence, the importance of oxidative stress evaluation in T13 and T18 could enable the determination of subsequent disturbed metabolic pathways, highlighting the related role of mitochondrial dysfunction or epigenetics. This review illustrates up-to-date T13 and T18 research and discusses the strengths, limitations, and possible directions for future studies. The progressive unification of trisomy-related research protocols might provide potential medical targets in the future along with the implementation of the foundation of modern prenatal medicine.
... The prevalence of T18 in live births ranges from 1/3600 to 1/10,000, which is still an extremely rare defect [8,9]. As fetuses with T18 are more likely to die during embryonic and fetal life, the prevalence of T18 is expected to be much higher than the live birth prevalence [10][11][12]. Although the etiology of chromosomal anomalies has not been well understood, epidemiological studies have suggested the relationship between environmental exposures and human aneuploidy. ...
Article
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Background: In this paper, we aimed to investigate the potential impacts of a fire accident in a fertilizer warehouse on chromosomal anomalies, including Trisomy 21 (T21) and Trisomy (T18) among pregnancies in Brazos County, Texas. We conducted an observational study in Brazos County, TX, with all patients of T18 and T21 cases in the live births in Brazos County between 2005-2014. The prevalence of T18 and T21 before, during, and after the accident in Brazos County were calculated and compared. The Standardized Morbidity Ratio (SMR) was applied to compare the prevalence of T18 and T21 in Brazos County to the statewide prevalence in Texas after adjusting for maternal race and age. Compared with statewide risk, the risk of T18 during the impacted years in Brazos county was found to be significantly higher (SMR = 5.0, 95% Confidence Interval(CI): 2.19-9.89), while there was no significant difference before (SMR = 0.77, 0.13-2.54) and after the accident (SMR = 0.71, 0.12-2.36). However, the prevalence of T21 during the impacted years was not significantly different from those before or after the accident. This study conclusively suggests that this fertilizer fire may be related to the increased prevalence of T18 in Brazos County, though the findings warrant further investigation.
... Trisomy 13 (T13) and trisomy 18 (T18) are the two most common aneuploidies after trisomy 21, with a reported prevalence of 1.42/10,000 and 3.19/10,000 pregnancies, respectively, in the United States [1,2]. Both syndromes have been considered "universally lethal," with around 70% of first-trimester pregnancies diagnosed with T18 and nearly 50% of those diagnosed with T13 resulting in fetal demise [3,4]. Mortality remains high among live newborns, with a reported survival of 11.5% for T13 and 13.4% for T18 at one year of age [5]. ...
Article
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There has been substantial controversy regarding treatment of congenital heart defects in infants with trisomies 13 and 18. Most reports have focused on surgical outcomes versus expectant treatment, and rarely there has been an effort to consolidate existing evidence into a more coherent way to help clinicians with decision-making and counseling families. An extensive review of the existing literature on cardiac surgery in patients with these trisomies was conducted from 2004 to 2020. The effects of preoperative and perioperative factors on in-hospital and long-term mortality were analyzed, as well as possible predictors for postoperative chronic care needs such as tracheostomy and gastrostomy. Patients with minimal or no preoperative pulmonary hypertension and mechanical ventilation undergoing corrective surgery at a weight greater than 2.5 kg suffer from lower postoperative mortality. Infants with lower-complexity cardiac defects are likely to benefit the most from surgery, although their expected mortality is higher than that of infants without trisomy. Omphalocele confers an increased mortality risk regardless of cardiac surgery. Gastrointestinal comorbidities increased the risk of gastrostomy tube placement, while those with prolonged mechanical ventilation and respiratory comorbidities are more likely to require tracheostomy. Cardiac surgery is feasible in children with trisomies 13 and 18 and can provide improved long-term results. However, this is a clinically complex population, and both physicians and caretakers should be aware of the long-term challenges these patients face following surgery when discussing treatment options.
... For the trisomy simulations, maternal ages were generated using the maternal age distribution reported in the vital statistics birth data (12). Age-specific risk was then used to determine the number of trisomy pregnancies (13)(14)(15)(16). For ONTD, we assumed an incidence of 1 in 1000 (17). ...
Article
Background Biochemical prenatal screening tests are used to determine the risk of fetal aneuploidy based on the concentration of several biomarkers. The concentration of these biomarkers could be affected by preanalytical factors (PAFs) such as sample type (whole blood vs serum), storage time, and storage temperature. The impact of these factors on posttest risk is unknown. Methods Blood samples were collected from 25 pregnant patients. Each sample was divided into 24 aliquots, and each aliquot was subjected to 1 of 24 different treatments (2 sample types × 2 temperatures × 6 storage times). The impact of each PAF on calculated risk was estimated using mixed-effects regression and simulation analysis. Results PAFs were associated with statistically significant changes in concentration for some analytes. Simulation studies showed that PAFs accounted for 6% of the variation in posttest risk, and analytical imprecision accounted for 94% of the variation. We estimated that the background misclassification rate due to analytical imprecision is approximately 1.37% for trisomy 21 and 0.12% for trisomy 18. Preanalytical factors increased the probability of misclassification by 0.46% and 0.06% for trisomies 21 and 18, respectively. Conclusions Relaxing sample specifications for biochemical prenatal serum screening tests to permit analysis of serum samples stored for up to 72 h at room temperature or 4 °C as well as serum obtained from whole blood stored similarly has a small impact in calculated posttest aneuploidy risk.
... The rates of termination of pregnancy may be above 78% for T13 and T18 (Lakovschek et al., 2011). The natural history of these trisomies is characterized by a high risk of spontaneous fetal loss, with pregnancy loss rates ranging from 49-66% for pregnancies with T13 and between 72-87% for T18 (Morris and Savva, 2008;Lakovschek et al., 2011;Houlihan and O'Donoghue, 2013). Less than 10% of the live births of T13 and T18 have a 1-year overall survival (Lin et al., 2006;Vendola et al., 2010;Houlihan and O'Donoghue, 2013). ...
Article
Perinatal palliative care programs seek to support parents expecting a baby diagnosed with a serious medical condition. Clinicians have increasingly recognized the importance of parental perspectives on the medical care mothers and their fetuses and live-born children receive, especially regarding factors influencing individual choices and knowledge of the medical community. We describe, using literature on trisomy 13 and trisomy 18, how information shared between parents and providers can improve perinatal counseling and family support.
Article
Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13) both have high natural fetal loss rates. The aim of this study was to provide estimates of these fetal loss rates by single gestational week of age using data from the National Down Syndrome Cytogenetic Register. Data from all pregnancies with Edwards or Patau syndrome that were prenatally detected in England and Wales from 2004 to 2014 was analyzed using Kaplan-Meier survival estimates. Pregnancies were entered into the analysis at the time of gestation at diagnosis, and were considered “under observation” until the gestation at outcome. There were 4088 prenatal diagnoses of trisomy 18 and 1471 of trisomy 13 in the analysis. For trisomy 18, 30% (95%CI: 25-34%) of viable fetuses at 12 weeks will result in a live birth and at 39 weeks gestation 67% (60-73%) will result in a live birth. For trisomy 13 the survival is 50% (41-58%) at 12 weeks and 84% (73-90%) at 39 weeks. There was no significant difference in survival between males and females when diagnosed at 12 weeks for trisomy 18 (P-value = 0.27) or trisomy 13 (P-value = 0.47). This paper provides the most precise gestational age-specific estimates currently available for the risk of fetal loss in trisomy 13 and trisomy 18 pregnancies in a general population.
Article
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Background Cell-free DNA (cfDNA) non-invasive prenatal screening for trisomy (T) 21, 18, and 13 has been rapidly adopted into clinical practice. However, prior studies are limited by lack of follow up genetic testing to confirm outcomes and accurately assess test performance, particularly in women at low-risk for aneuploidy. Objective To compare the performance of cfDNA screening for T21, T18 and T13 between women at low and high-risk for aneuploidy in a large, prospective cohort with genetic confirmation of results. Study design A multicenter prospective observational study at 21 centers in 6 countries. Women who had SNP-based cfDNA screening for T21, T18 and T13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. Test performance and test failure (no-call) rates were assessed for the cohort and women with low and high prior risk for aneuploidy were compared. An updated cfDNA algorithm, blinded to pregnancy outcome, was also assessed. Results 20,194 were enrolled at median gestational age of 12.6 weeks (IQR:11.6, 13.9). Genetic outcomes were confirmed in 17,851 (88.4%): 13,043 (73.1%) low-risk and 4,808 (26.9%) high-risk for aneuploidy. Overall, 133 trisomies were diagnosed (100 T21; 18 T18; 15 T13). cfDNA screen positive rate was lower in low- vs. high-risk (0.27% vs. 2.2%, p<0.0001). Sensitivity and specificity were similar between groups. The positive predictive value (PPV) for the low and high-risk groups was 85.7% vs. 97.5%, p=0.058 for T21; 50.0% vs. 81.3%, p=0.283 for T18; and 62.5% vs. 83.3, p=0.58 for T13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. Trisomy rate was higher in the 287 with no-call results than patients with a result on a first draw (2.8% vs. 0.7%, p=0.001). The updated algorithm showed similar sensitivity and specificity to the study algorhitm with a lower no-call rate. Conclusions In women at low-risk for aneuploidy, SNP-based cfDNA has high sensitivity and specificity, PPV of 85.7% for T21 and 74.3% for the three common trisomies. Patients who receive a no-call result are at increased risk of aneuploidy and require additional investigation.
Article
Purpose: To describe the rate and severity of gestational hypertensive disorders (GHD) in pregnancies complicated by trisomy 13 (T13). Materials and methods: Retrospective cohort study of singleton deliveries in California from 2005-2008 using vital statistics and ICD-9 data. We were interested in gestational hypertension (gHTN), preeclampsia with and without severe features (sPREX and PREX), and gestational age at delivery. Pregnancies and maternal complications affected by prenatally diagnosed T13 were compared to unaffected pregnancies. Regression models were used to compute adjusted odds ratios for pregnancy outcomes by T13 status. Results: Of the 2,029,004 deliveries, 142 women had prenatally diagnosed T13. A diagnosis of GHD occurred in 26.8% of the T13 pregnancies versus 6% of the non-T13 pregnancies(p < 0.001). This remained true for gHTN (9.2% vs 3.2%,p = 0.001), PREX (12% vs 2.2%,p < 0.001), and sPREX (8.5% vs 0.9%,p < 0.001). After adjusting for confounders, T13 pregnancies were 6.3-times more likely to be affected by GHD, and 12.5-times more likely to have sPREX. Delivery <37 and <32 weeks in the setting of GHD was 14.1-times and 11.2-times likely among women with T13. Conclusion: Women with T13 pregnancies were significantly more likely to have gHTN, preeclampsia, sPREX, and to deliver <32 weeks.
Article
Background: assessment of embryonic anatomy by ultrasound since early ages leads to the detection of pregnancies at risk for chromosomal abnormalities. Advanced maternal age alone is not enough. Objective: to assess the results of the nuchal translucency measurement at the first trimester ultrasound as a sonographic marker of chromosomal abnormalities.Methods: a sample of 29 334 pregnant women was studied from September 2006 to December 2010. General performance of the sonographic marker was assessed taking into account the years and maternal age. Effectiveness of increased nuchal translucency in the indirect detection of chromosomal abnormalities was determined using the common parameters. Results: the net number of increased nuchal translucencies diminished over the years, as well as the absolute amount of prenatal karyotypes performed; but its proportion increased along with the positive prenatal karyotypes among women with increased nuchal translucency. Among the 71 fetuses with increased translucency, seven cases of chromosomal abnormalities were confirmed by other elements of the prenatal program. The sensitivity of the isolated nuchal translucency was 14.6%; specificity was high (99.8%); positive and negative predictive values were 18.4% and 99.9%, respectively. Rates of false positives were very low. Conclusions: high specificity reaffirms nuchal translucency as a good early marker of risk for chromosomal abnormalities, particularly Down syndrome and Trisomy 18, with a minimum rate of indications for invasive testing and an extra increase in the detection of fetal defects.
Article
Purpose: Describe practice patterns among obstetrician/gynecologists (OB/GYNs) when caring for women with pregnancy complicated by fetal trisomy 13(T13) or 18(T18), and compare these between maternal-fetal-medicine (MFM) and non-MFM providers. Materials and methods: We conducted an electronic survey using the American College of Obstetricians and Gynecologists database. Using simple statistics, we describe demographics and practice patterns among respondents, and compare those of MFM practitioners with non-MFM providers. Results: The survey was sent to 300 individuals, 161 individuals verified email receipt, and 105 had complete response and were included. The median age was 58 (IQR 53,62). sixty per cent were female, 69% were private practice, and 38% were MFM. All providers were more likely to offer than to recommend antenatal and intrapartum interventions. MFMs were more likely to offer growth ultrasounds and neonatal hospice consults (53 vs. 29%, p=0.02; 88 vs. 60%, , p<0.01). During labor, MFMs were more more likely offer no fetal heart rate monitoring, (90 vs. 52%, p<0.01),) sixty per cent of all providers offer breech vaginal delivery; 32% offer Caesarean delivery for fetal distress. Conclusion: Many providers offer antepartum and intrapartum interventions for pregnancies complicated by T13/18. We recommend that providers elicit each woman’s goals for pregnancies complicated by T13/18 and tailor management options to meet these goals.
Article
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.
Article
Objective: To provide prognostic information to help parents to reach an informed decision about termination or continuation of the pregnancy and to shape peripartum policy based on a large European cohort. Method: Thirteen registries from the European Surveillance of Congenital Anomalies (EUROCAT) network contributed data from January 1, 1998 to December 31, 2011. Terminations for fetal anomalies were excluded. Chromosomal anomalies, syndromes and isolated anomaly groups were distinguished according to EUROCAT guidelines. Perinatal mortality, stillbirths, and early and late neonatal mortality rates (NMR)were analyzed by anomaly group and gestational age. Results: Among 73,337 cases, perinatal mortality associated with congenital anomaly was 1.27 per 1,000 births (95% CI 1.23-1.31). Average stillbirth rate was 2.68%, (range 0-51.2%). Early and late NMR were 2.75% (range 0-46.7%) and 0.97% (range 0-17.9%), respectively. Chromosomal anomalies and syndromes, and most isolated anomalies, had significant differences regarding timing of fetal demise compared to the general population. Chromosomal and central nervous system anomalies had higher term stillbirth rates. Conclusions: We found relevant differences between anomalies regarding rates of stillbirth, NMR and timing by gestational age. Our data can help parents to decide about their unborn child with a congenital anomaly and help inform maternal-fetal medicine specialists regarding peripartum management.
Article
Few population‐based studies have analyzed patterns of co‐occurring birth defects among those with trisomy 13. We evaluated the frequency of all possible combinations of any one, two, three, or four additional co‐occurring birth defects among 736 individuals with trisomy 13 using data from the Texas Birth Defects Registry for deliveries during 1999–2014. We calculated the observed‐to‐expected ratio for each combination, adjusting for the known tendency for birth defects to cluster non‐specifically. To address potential ascertainment differences among live births and non‐live births, we repeated analyses specifically among live births. The combination of defects with the largest observed‐to‐expected ratio was microcephalus, reduction deformities of brain (e.g., holoprosencephaly), anomalies of nose, and polydactyly. As expected, most of the highest 30 observed‐to‐expected ratios involved combinations with documented features of trisomy 13, including defects of the scalp (e.g., aplasia cutis) and heart. Results were similar among sensitivity analyses restricted to live births. Our findings may help further delineate the phenotypic spectrum for trisomy 13 and may inform future research related to improving screening and counseling for the condition.
Thesis
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Introduction: In the Province of Quebec, about 110,000 pregnant women are eligible to voluntary prenatal screening for trisomy 21(T21). Conventional screening strategies select about 4% of women for invasive fetal chromosome testing. Noninvasive prenatal testing using maternal blood cell-free DNA (NIPT) is a new highly accurate screening strategy that could reduce these invasive procedures but evidence about its health economic aspects (cost-effectiveness and affordability) is still lacking. Objectives: The objective of this thesis is to evaluate the expected health economic aspects of introducing NIPT into the Quebec trisomy 21 screening program. The first study systematically reviewed the literature of full economic evaluation studies on NIPT. The second study evaluated the expected cost-effectiveness of screening strategies incorporating NIPT, as well as conventional screening strategies. The third study evaluated the expected budget impact of implementing NIPT into the Quebec trisomy 21 screening program. Methodology: A systematic review of literature was performed for the first study. For the second and third studies, semi-Markov decision-analytic models were built to simulate the cost-effectiveness and the budget impact of NIPT for a virtual cohort of pregnant women similar to that of Quebec in terms of age and pregnancy rate by age. The main outcome for the cost-effectiveness analysis was the incremental cost per additional trisomy 21 detected. The main outcome for the budget impact analysis was the difference in the overall costs between the two alternatives: the current screening strategy vs. the most cost-effective strategy incorporating NIPT). Results: The first study included 16 studies. Results show that compared to current screening practice a universal NIPT screening program is not cost-effective. A program that offers NIPT to high risk pregnant women was found to be the most cost-effective option in the majority of studies included. The second study showed that NIPT as a second-tier test for high-risk women is cost-effective compared to screening algorithms not including NIPT. Out of 13 strategies compared, the integrated serum screening strategy followed by NIPT was the most cost-effective strategy. Other strategies can improve the number of T21 cases identified, but with increasing incremental costs per case (from $ 61,623 to $1,553,615). Results were sensitive to NIPT cost and cut-offs considered to determine high risk pregnant women. The third study found that NIPT as a second-tier test offered to high-risk women identified by the current screening program is affordable for the Quebec health care system. Compared to the current screening program, this strategy could be implemented at a neutral cost considering a modest yearly saving of $80,432 (95% CI: $79,874-$81,462). Results were sensitive to the NIPT costs and the uptake-rate of invasive diagnostic test. Conclusion: NIPT as a second-tier test offered to high-risk women identified by the current screening program is cost-effective and affordable for the Quebec health care system. Decision makers should consider its introduction after considerations of others aspects such as ethical issues.
Chapter
Routine maternal serum screening for multiple markers, together with the determination of one or more ultrasound markers, enabled a four‐ to fivefold increase in the proportion of affected pregnancies detected antenatally and a decrease in the extent of invasive testing. This chapter examines the underlying principles and explains the terminology and outlines the relative efficiency of different screening policies. The relationship between the new approach and the established screening modalities is reviewed. A number of developments have changed the simple paradigm of AFP screening: primary prevention has led to a fall in neural tube defect (NTD) prevalence and advances in detailed ultrasound has limited the need for invasive prenatal diagnosis. Health planners now consider both chromosomal abnormalities and NTDs in program design. The chapter provides information on the more common forms of aneuploidy which are sufficiently viable to survive to term in relatively large numbers and are amenable to screening.
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Families that choose to continue a pregnancy with a prenatal diagnosis of Trisomy 13/18 are a minority that present unique challenges for those in charge of their care. This study investigated the extent to which these patients felt supported by their healthcare providers, and any differences in the perceived level of support experienced by those working with a physician versus those working with a genetic counselor. Two online support groups, SOFT and Hope for Trisomy, distributed an online survey to their members. Means, standard deviations and chi-square analysis were calculated to describe their responses. One-hundred fourteen surveys were included in the final analysis. Respondents were more likely to agree that genetic counselors provided unbiased information in a way that they understood, compared to physicians. Review of qualitative responses found that portrayal of Trisomy 13/18 by healthcare providers used directive language when describing the lethality, morbidity and burden of the condition. Language included terms such as “incompatible with life” and comments on burden to other family members. Healthcare providers can assist families that receive a prenatal diagnosis of Trisomy 13 or 18 by providing up-to-date written resources and connecting them with support groups for parents who have received a similar diagnosis. Our study found that involving genetic counselors in the prenatal care of these patients is likely beneficial.
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Aneuploidy is an abnormal copy number of one or more chromosomes and arises from aberrations in cell division. The most common anueploid conditions that can result in live birth are trisomies of the sex chromosomes; trisomies of chromosomes 13, 18, and 21; and monosomy X. Detection of aneuploidy is one of the major objectives of a prenatal screening program. Ultrasound is a helpful screening test to evaluate for aneuploid fetuses; however, invasive testing with chorionic villus sampling or amniocentesis is required for definitive diagnosis.
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Introduction: Edwards’s syndrome is a chromosomal disorder caused due to the presence of an extra chromosome 18. This syndrome was first reported in 1960 by Edward. The prevalence of this disease is approxi­mately 1:6000 live births, and its prevalence increases with maternal age. Most of these fetuses die in the tenth week of pregnancy in the uterus. Case report: In this study, we presented the case of an infant with Edward’s syndrome, which was diagnosed in utero. Ultrasound screening and maternal serum screening were not performed at 12 weeks. Choroid plexus cyst,atrioventricular septal defect (AVSD), and echogenicity with a diameter of 5 mm in the anterior abdominal wall were observed on ultrasound at 19 weeks. After the karyotype of amniotic fluid, Edward’s syndrome was reported. According to gestational age (23 weeks) therapeutic abortion was not possible. After birth, the baby had multiple abnormalities including small oral opening, micrognathia, arch-shaped mouth, nasal bridge with an upward the tip, wide anterior fontanel, strabismus of the left eye, umbilical hernia, developmental disorders, weak cry, short neck, and closed fingers. He died at 5 months of age. Conclusion: Chromosomal abnormalities such as Down’s, Edward’s and Patau’s syndromes are easily detectable during pregnancy and are considered for therapeutic abortion. Therefore, early diagnosis is important during pregnancy.
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Helping expecting parents grapple with the news that their baby has chromosomal abnormalities can be very challenging. Counseling regarding termination or expectant management is complex and may require ongoing discussion throughout the pregnancy. A team approach is key. Preparing the family for the birth as well as accomodating the possible outcomes of the birth for the newborn must be handled with care and compassion.
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Trisomy 18 is a well-documented cause of spontaneous abortions. When live births do occur, median survival time has been estimated between two and fourteen days. This severely shortened life expectancy is attributed to potentially lethal congenital malformations involving the heart, central nervous system, and gastrointestinal system, among others. Infrequently, affected children survive beyond a year and evidence suggests this may become more common due to increased willingness to intervene in the neonatal period and the success of surgical corrections. This case report documents how a six-year-old female with trisomy 18 has challenged provider expectations and gives perspective in an emerging treatment gray-zone.
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Background: A source of error in prenatal screening for trisomies is PCR amplification error associated with guanine-cytosine (GC) content of DNA fragments in maternal plasma. We describe a simple method of allowing for this. Methods: Data from a Reflex DNA screening programme (67 trisomy 18 and 83 unaffected pregnancies) were used to compare the ratio of chromosome 18 DNA fragment counts to chromosome 8 DNA fragment counts (because chromosome 8 has a similar GC content to chromosome 18) with the percentage of chromosome 18 DNA counts using counts from all autosomes in the denominator, with and without an all autosome correction for the GC content of the DNA fragments. Results: A chromosome 18 to 8 ratio of DNA fragment counts was more discriminatory than the percentage of all autosome counts arising from chromosome 18 without, or with an all autosome correction for GC content bias. It achieves a high screening performance, eg. for a 0.25% false-positive rate, a 97% detection rate instead of 49% without a correction for GC content, and 91% with an all autosome correction for GC content. Conclusion: Consideration can be given to using the ratio of chromosome 18 DNA fragment counts to chromosome 8 DNA fragment counts in cell-free DNA prenatal screening for trisomy 18, avoiding the need for more complex methods of making a correction for the GC content currently used.
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Objective: The cost effectiveness of noninvasive prenatal testing (NIPT) has been established for high-risk pregnancies but remains unclear for pregnancies at other risk levels. The aim was to assess the cost effectiveness of NIPT in average-risk pregnancies from the perspective of a provincial public payer in Canada. Methods: A model was developed to compare traditional prenatal screening (TPS), NIPT as a second-tier test (performed only after a positive TPS result), and NIPT as a first-tier test (performed instead of TPS) for trisomies 21, 18, and 13; sex chromosome aneuploidies; and microdeletions in a hypothetical annual population cohort of average-risk pregnancies (142 000 to 148,000) in Ontario, Canada. A probabilistic analysis was conducted with 5000 repetitions. Results: Compared with TPS, NIPT as a second-tier test detected more affected fetuses with trisomies 21, 18, and 13 (188 vs. 158), substantially reduced the number of diagnostic tests (i.e., chorionic villus sampling and amniocentesis) performed (660 vs. 3107), and reduced the cost of prenatal screening ($26.7 million vs. $27.6 million) annually. Compared with second-tier NIPT, first-tier NIPT detected an additional 80 cases of trisomies 21, 18, and 13 at an additional cost of $33 million. The incremental cost per additional affected fetus detected was $412 411. Extending first-tier NIPT to include testing for sex chromosome aneuploidies and 22q11.2 deletion would increase the total screening cost. Conclusions: NIPT as a second-tier test is cost-saving compared with TPS alone. Compared with second-tier NIPT, first-tier NIPT detects more cases of chromosomal anomalies but at a substantially higher cost.
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Trisomy 18, sometimes called Edwards syndrome, occurs in about 1/6000 live births and causes multiple birth defects in affected infants. The extra copy of chromosome 18 causes the altered expression of many genes and leads to severe skeletal, cardiovascular, and neurological systems malformations as well as other medical problems. Due to the low rate of survival and the massive genetic imbalance, little research has been aimed at understanding the molecular consequences of trisomy 18 or considering potential therapeutic approaches. Our research is the first study to characterize whole-genome expression in fibroblasts cells obtained from two patients with trisomy 18 and two matched controls, with follow-up expression confirmation studies on 6 independent controls. We show a detailed analysis of the most highly dysregulated genes on chromosome 18 and those genome-wide. The identified effector genes and the dysregulated downstream pathways provide hints of possible genotype-phenotype relationships to some of the most common symptoms observed in trisomy 18. We also provide a possible explanation for the sex-specific differences in survival, a unique characteristic of trisomy 18. Our analysis of genome-wide expression data moves us closer to understanding the molecular consequences of the second most common human autosomal trisomy of infants who survive to term. These insights might also translate to the understanding of the etiology of associated birth defects and medical conditions among those with trisomy 18.
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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.
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Ten data sources were used substantially to increase the available data for estimating fetal and livebirth sex ratios for Patau (trisomy 13), Edwards (trisomy 18), and Down (trisomy 21) syndromes and controls. The fetal sex ratio estimate was 0.88 (N = 584) for trisomy 13, 0.90 (N = 1702) for trisomy 18, and 1.16 (N = 3154) for trisomy 21. All were significantly different from prenatal controls (1.07). The estimated ratios in prenatal controls were 1.28 (N = 1409) for CVSs and 1.06 (N = 49427) for amniocenteses, indicating a clear differential selection against males, mostly during the first half of fetal development. By contrast, there were no sex ratio differences for any of the trisomies when comparing gestational ages <16 and >16 weeks. The livebirth sex ratio estimate was 0.90 (N = 293) for trisomy 13, 0.63 (N = 497) for trisomy 18, and 1.15 (N = 6424) for trisomy 21, the latter two being statistically different than controls (1.05) (N = 3660707). These ratios for trisomies 13 and 18 were also statistically different than the ratio for trisomy 21. Only in trisomy 18 did the sex ratios in fetuses and livebirths differ, indicating a prenatal selection against males >16 weeks. No effects of maternal age or race were found on these estimates for any of the fetal or livebirth trisomies. Sex ratios for translocations and mosaics were also estimated for these aneuploids. Compared to previous estimates, these results are less extreme, most likely because of larger sample sizes and less sample bias. They support the hypothesis that these trisomy sex ratios are skewed at conception, or become so during embryonic development through differential intrauterine selection. The estimate for Down syndrome livebirths is also consistent with the hypothesis that its higher sex ratio is associated with paternal nondisjunction. © 1996 Wiley-Liss, Inc.
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The first congenital anomaly register in the British Isles was established in 1949, with a national system for England and Wales introduced in 1969 in the wake of the thalidomide epidemic. There are now 14 regional congenital anomaly registers and three disease-specific registers. These registers involve an extensive local network of notifiers, use multiple sources of case ascertainment, consistent coding, and include cases resulting in termination of pregnancy for fetal anomaly following prenatal diagnosis. They have optimised the coverage, completeness and ascertainment of congenital anomalies within their population, and are therefore able to provide better quality data than the national system. There are notable variations in the prevalence of congenital anomaly subtypes within these regions that cannot be accounted for in terms of differences in case ascertainment or registration practices. This underlying variation in prevalence should be recognised and taken into consideration in the design of epidemiological studies that are investigating the contribution of environmental influences to congenital anomaly risk, to ensure correct interpretation of the findings. Local congenital anomaly register data has been used to investigate congenital anomaly risk in populations within the British Isles living close to landfill sites and incinerators, and to possible contaminants in drinking water. Whilst the inclusion of high quality data from established congenital anomaly registers enhances the quality of outcome data, such studies are currently limited by the lack of detailed information on exposure. Causal pathways will only be determined if future studies combine high quality congenital anomaly data with increased information on exposure assessment.
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We report the results of an ongoing survey of rates of spontaneous death of fetuses with chromosome abnormalities detected at second-trimester amniocentesis in which the mother did not elect abortion. Estimated excess risks (and conservative 90% confidence intervals) of spontaneous fetal death for various cytogenetic abnormalities are as follows: 47,+21, 25.6% (18.0%-34.0%); 47,+18, 63.8% (49.3%-79.8%); 47,+13, 36.5% (11%-69.7%); 45,X, 65.3% (41.0%-84.2%); and mosaic 45,X/46,XX, 10.8% (1.0%-26.8%). There is little evidence for an excess risk of fetal death, at least following amniocentesis, for 47,XXX, 47,XXY, or 47,XYY. The excess risks of fetal death were adjusted for the likelihood that a fetus of normal karyotype would undergo spontaneous fetal death in a population of older maternal age similar to that in which prenatal cytogenetic diagnosis is undertaken. The absolute fetal death rates when this factor is ignored are about 3.5% higher (i.e., may be derived by adding 3.5% to the values given). The excess risks are those which are most appropriate for use in estimating the contribution of chromosome abnormalities to spontaneous fetal death.
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This study provides data on the incidence of fetal trisomies 21, 18, and 13 at 9-14 weeks' gestation in women aged 35-45 years and estimates of maternal age-specific risks in women aged 20-45 years. Our data from 5814 singleton pregnancies undergoing first-trimester karyotyping for the sole indication of maternal age > or = 35 years were combined with those from two previous reports and the incidence of the trisomies was calculated from a total of 15,793 pregnancies. Comparison of incidences at 9-14 weeks' gestation with published data at 15-20 weeks' gestation and in livebirths demonstrated that at birth the maternal age-specific incidence of trisomy 21 is 33 per cent lower than at 15-20 weeks' gestation and 54 per cent lower than at 9-14 weeks' gestation. Furthermore, the relative frequency of trisomies 18 and 13 decreases from 30 per cent at 9-14 weeks to 22 per cent at 15-20 weeks and 14 per cent at birth.
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It is recognized that pregnancies with Down syndrome are liable to end in spontaneous fetal loss. It is important to determine the magnitude of this effect so that it can be taken into account when assessing the results of antenatal screening programmes for Down syndrome. Failure to do so will tend to overestimate the detection rate in intervention studies in which the screening results are used to identify women for a diagnostic test and the offer of a termination of pregnancy if indicated. We present new data on the spontaneous fetal loss in Down syndrome pregnancies from the National Down Syndrome Cytogenetic Register (1989-1996). We compare our results with published results of other studies on the subject to obtain a summary estimate. We exclude one study from the meta analysis due to incorrect methodology resulting in an overestimate of fetal loss. Based on the combined data (i) between the time of chorionic villus sampling and term an estimated 43 per cent (95 per cent CI: 31-54 per cent) of pregnancies ended in a miscarriage or still birth, (ii) between the time of amniocentesis and term an estimated 23 per cent (95 per cent CI: 19 28 per cent) of pregnancies ended in a miscarriage or still birth, and (iii) 12 per cent (95 per cent CI: 2-23 per cent) of births were stillborn or resulted in a neonatal death.
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Women with chromosomally abnormal fetuses often choose to continue their pregnancy. However, though they may search for specific details whether their fetus will survive, not much information is available. We sought to determine if there was a pattern for timing of demise and to determine if demise was more likely to occur before viability in fetuses with amniocentesis confirmed trisomy 18 or 21. From the California Expanded AFP screening program, 1813 women were identified to have a fetus with trisomy 18 or 21. Of these, 392 women with trisomy 21 and 106 with trisomy 18 continued the pregnancy. Pregnancies ending in fetal demise were analyzed for gestational age at demise. Of the trisomy 21 fetuses, 40 (10.2%) demised and of the trisomy 18 fetuses, 34 (32.1%) demised. The mean gestational age at time of fetal demise was 28.9+/-1.3 weeks SE for trisomy 21 and 32.1+/-1.2 weeks SE for trisomy 18 (p=0.09). There was no clustering of losses as losses were uniformly distributed throughout gestation after 24 weeks. A slightly larger proportion of T-21 (37.1%) losses occurred before viability (24 weeks) compared to those with T-18 (14.8%) (p=0.05). It appears that after 24 weeks' gestation, there is no specific time for fetal demise in fetuses affected by trisomy 21 or 18. There may be an association between trisomy 21 and stillbirth prior to viability. This information may be helpful in counseling those patients found to have a chromosomally abnormal fetus who choose to continue their pregnancy.
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To investigate the pregnancy outcome of fetuses affected with trisomy 18, we analyzed 63 cases diagnosed at our hospital from January 1993 to December 2004. Twenty-nine were males and 34 were females. Fifty-eight were prenatally diagnosed, and in 16 (27.6%) of them intrauterine fetal death (IUFD) occurred between 28 weeks and 41 weeks gestation (34.6 +/- 3.9 weeks, Mean +/- SD). Ten (17.2%) fetuses died during labor and their age ranged from 30 weeks to 40 weeks of gestation. The total number of cases ending in fetal demise was 26 (44.8%) and the mean gestational age at the time of fetal demise was 35.0 +/- 3.6 weeks (Mean +/- SD). All liveborn infants (n = 36) were born after 31 weeks gestation. In our study the preterm birth ratio for trisomy 18 is 34.8%, which is much higher than the ratio for the general population. Females are more likely than males to be long-term survivors. These data are helpful in the counseling of parents faced with the difficult decision of whether or not to continue a pregnancy with a fetus affected with trisomy 18.
Article
Trisomy 18: changes in sex ratio during intrauterine life Niedrist, D; Riegel, M; Achermann, J; Rousson, V; Schinzel, A Niedrist, D; Riegel, M; Achermann, J; Rousson, V; Schinzel, A (2006). Trisomy 18: changes in sex ratio during intrauterine life.