Sex chromosome trisomies in Europe: prevalence, prenatal detection and outcome of pregnancy

This study aims to assess prevalence and pregnancy outcome for sex chromosome trisomies (SCTs) diagnosed prenatally or in the first year of life. Data held by the European Surveillance of Congenital Anomalies (EUROCAT) database on SCT cases delivered 2000–2005 from 19 population-based registries in 11 European countries covering 2.5 million births were analysed. Cases included were livebirths diagnosed to 1 year of age, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly (TOPFA). In all, 465 cases of SCT were diagnosed between 2000 and 2005, a prevalence of 1.88 per 10,000 births (95% CI 1.71–2.06). Prevalence of XXX, XXY and XYY were 0.54 (95% CI 0.46–0.64), 1.04 (95% CI 0.92–1.17) and 0.30 (95% CI 0.24–0.38), respectively. In all, 415 (89%) were prenatally diagnosed and 151 (36%) of these resulted in TOPFA. There was wide country variation in prevalence (0.19–5.36 per 1000), proportion prenatally diagnosed (50–100%) and proportion of prenatally diagnosed resulting in TOPFA (13–67%). Prevalence of prenatally diagnosed cases was higher in countries with high prenatal detection rates of Down syndrome. The EUROCAT prevalence rate for SCTs diagnosed prenatally or up to 1 year of age represents 12% of the prevalence expected from cytogenetic studies of newborn babies, as the majority of cases are never diagnosed or are diagnosed later in life. There is a wide variation between European countries in prevalence, prenatal detection and TOPFA proportions, related to differences in screening policies as well as organizational and cultural factors.     

Trisomy 13 and 18—Prevalence and mortality—A multi‐registry population based analysis

The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty‐four population‐ and hospital‐based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data‐reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3–2.06), and for T18 was 4.08 (95% CI 3.01–5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38–0.72), and for T18 was 1.07 (95% CI 0.77–1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1‐year follow‐up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions.     

Increased nuchal translucency in trisomy 13 fetuses at 10–14 weeks of gestation

In a multicenter screening study for trisomy 21 involving ultrasonographic measurement of fetal nuchal translucency thickness (NT) at 10–14 weeks of gestation, 100,311 singleton pregnancies with a live fetus were examined. There were 46 cases of trisomy 13, and in 33 (72%) of these, the NT was above the 95th centile. The estimated risk for trisomy 21, based on maternal age-related risk for this chromosomal abnormality and fetal NT, was above 1 in 300 in 37 (80.1%) of the trisomy 13 fetuses. The fetal crown-rump length was significantly reduced, but the fetal heart rate was increased, being above the 95th centile in 64% of cases. Additionally, 24% of trisomy 13 fetuses had holoprosencephaly and 10% had exomphalos. This study has demonstrated that at 10–14 weeks of gestation, about 80% of fetuses with trisomy 13 can be identified in a screening program for trisomy 21, based on a combination of maternal age and fetal NT. Am. J. Med. Genet. 86:205–207, 1999. © 1999 Wiley-Liss, Inc.     

Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management

Noninvasive prenatal testing by massive parallel sequencing of maternal plasma DNA has rapidly been adopted as a mainstream method for detection of fetal trisomy 21, 18 and 13. Despite the relative high accuracy of current NIPT testing, a substantial number of false-positive and false-negative test results remain. Here, we present an analysis pipeline, which addresses some of the technical as well as the biologically derived causes of error. Most importantly, it differentiates high z-scores due to fetal trisomies from those due to local maternal CNVs causing false positives. This pipeline was retrospectively validated for trisomy 18 and 21 detection on 296 samples demonstrating a sensitivity and specificity of 100%, and applied prospectively to 1350 pregnant women in the clinical diagnostic setting with a result reported in 99.9% of cases. In addition, values indicative for trisomy were observed two times for chromosome 7 and once each for chromosomes 15 and 16, and once for a segmental trisomy 18. Two of the trisomies were confirmed to be mosaic, one of which contained a uniparental disomy cell line. As placental trisomies pose a risk for low-grade fetal mosaicism as well as uniparental disomy, genome-wide noninvasive aneuploidy detection is improving prenatal management.     

Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population-based congenital anomaly registers in Europe

The aim of this study is to quantify the prevalence and types of rare chromosome abnormalities (RCAs) in Europe for 2000-2006 inclusive, and to describe prenatal diagnosis rates and pregnancy outcome. Data held by the European Surveillance of Congenital Anomalies database were analysed on all the cases from 16 population-based registries in 11 European countries diagnosed prenatally or before 1 year of age, and delivered between 2000 and 2006. Cases were all unbalanced chromosome abnormalities and included live births, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. There were 10,323 cases with a chromosome abnormality, giving a total birth prevalence rate of 43.8/10,000 births. Of these, 7335 cases had trisomy 21,18 or 13, giving individual prevalence rates of 23.0, 5.9 and 2.3/10,000 births, respectively (53, 13 and 5% of all reported chromosome errors, respectively). In all, 473 cases (5%) had a sex chromosome trisomy, and 778 (8%) had 45,X, giving prevalence rates of 2.0 and 3.3/10,000 births, respectively. There were 1,737 RCA cases (17%), giving a prevalence of 7.4/10,000 births. These included triploidy, other trisomies, marker chromosomes, unbalanced translocations, deletions and duplications. There was a wide variation between the registers in both the overall prenatal diagnosis rate of RCA, an average of 65% (range 5-92%) and the prevalence of RCA (range 2.4-12.9/10,000 births). In all, 49% were liveborn. The data provide the prevalence of families currently requiring specialised genetic counselling services in the perinatal period for these conditions and, for some, long-term care.     

Prevalence,prenatal diagnosis and clinical features of oculo-auriculo-vertebral spectrum: a registry-based study in Europe

Oculo-auriculo-vertebral spectrum is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. We present the largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990–2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths. In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies. There was a high rate (69.5%) of associated anomalies of other organs/systems. The most common were congenital heart defects present in 27.8% of patients. The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ear anomalies and at least one major characteristic anomaly, was 3.8 per 100 000 births. Twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes were confirmed as risk factors. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.     

Maternal age in trisomy

By comparison with a more general theory, data on trisomy in live births, amniocenteses, and spontaneous abortions by year of maternal age are shown to fit a logistic augmented by a proportion independent of maternal age. The frequency of trisomy increases monotonically, with no discrepancy at extremely low or high maternal age. Trisomy 16 is exceptional in that all cases appear to be age-dependent. For groups A, B, and C most trisomies arise by a process independent of maternal age. A small proportion of these trisomies and about half of trisomies for smaller chromosomes (excluding trisomies 16 and perhaps 22) originate by some process dependent on maternal (but not paternal) age and therefore presumably independent of crossingover, which in the female takes place before birth.     

Meckel–Gruber Syndrome: a population-based study on prevalence,prenatal diagnosis,clinical features,and survival in Europe

Meckel–Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11–36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.     

Investigation of maternal blood enriched for fetal cells: Role in screening and diagnosis of fetal trisomies

Prenatal diagnosis of chromosomal abnormalities relies on assessment of risk followed by invasive testing in the group with highest risk. Assessment of risk by a combination of maternal age and fetal nuchal translucency and invasive testing in the 5% of the population with the highest risk would identify about 80% of trisomy 21 pregnancies. Preliminary reports suggest that chromosomal abnormalities can also be diagnosed by fluorescent in situ hybridization (FISH) in maternal blood enriched for fetal cells. This study examines the potential role of this method on the prenatal diagnosis of fetal trisomies. Maternal blood was obtained before invasive testing in 230 pregnancies at 10–14 weeks of gestation. After enrichment for fetal cells, by triple density centrifugation and anti-CD71 magnetic cell sorting, FISH was performed and the proportion of cells with positive signals in the chromosomally normal and abnormal groups was determined. Fetal karyotype was normal in 150 cases and abnormal in 80 cases, including 36 with trisomy 21. Using a 21 chromosome-specific probe, three-signal nuclei were present in at least 5% of the enriched cells from 61% of the trisomy 21 pregnancies and in none of the normal pregnancies. For a cut-off of 3% of three-signal nuclei the sensitivity for trisomy 21 was 97% for a false positive rate of 13%. Similar values were obtained in trisomies 18 and 13 using the appropriate chromosome-specific probe. Examination of fetal cells from maternal blood may provide a noninvasive prenatal diagnostic test for trisomy 21 with the potential of identifying about 60% of affected pregnancies. Alternatively, this technique can be combined with maternal age and fetal nuchal translucency as a method of selecting the high-risk group for invasive testing. Potentially, 80% of trisomy 21 pregnancies could be identified after invasive testing in less than 1% of the pregnant population. Am. J. Med. Genet. 85:66–75, 1999. © 1999 Wiley-Liss, Inc.     

Trisomies 13 and 18: population prevalences, characteristics, and prenatal diagnosis, metropolitan Atlanta, 1994-2003

In recent years, prenatal diagnosis and elective pregnancy termination have affected the reported birth prevalence of trisomies 13 and 18. We examined the prevalence and characteristics of these conditions using 1994-2003 data from a population-based surveillance system, the Metropolitan Atlanta Congenital Defects Program. Including fetal deaths and elective terminations increased the number of affected pregnancies by 58.7% for trisomy 13 and 72.2% for trisomy 18. Prenatal cytogenetic testing was reported in 70.8% of trisomy 13 cases and 76.1% of trisomy 18 cases. Among those with prenatal cytogenetic tests, 60.8% of trisomy 13 and 59.7% of trisomy 18 cases were electively terminated. Compared with non-Hispanic whites, non-Hispanic black race was associated with a decreased frequency of prenatal cytogenetic testing for both trisomy 13 and trisomy 18 (OR 0.24, 95% CI: 0.08-0.78 and OR 0.32, 95% CI: 0.14-0.69, respectively). The reported rates of prenatal cytogenetic testing remained stable throughout the period. As expected, maternal age > or =35 years was a risk factor for both conditions. However, while 67.1% (n = 55) of the trisomy 18 case mothers were > or =35 years, only 46.9% (n = 15) of the trisomy 13 case mothers were > or =35 years. Among live-born infants, the sex ratio among trisomy 18 infants showed an increased proportion of females: 60.4% female versus 39.6% male. However, the proportion was 48.3% female and 51.7% male among fetuses that were electively terminated in the second trimester. Inclusion of pregnancies that are prenatally diagnosed is critical for accurate surveillance and population-based analyses of these conditions.     

Sex ratios in fetuses and liveborn infants with autosomal aneuploidy

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.     

Autosomal trisomy and maternal use of multivitamin supplements

Recent reports suggest that women carrying certain polymorphisms of folate genes associated with suboptimal folate status might be at increased risk for having a child with Down syndrome or other autosomal trisomies, and hypothesized that maternal use of multivitamin supplements might reduce such risk. To evaluate this hypothesis, we examined data from a population-based case-control study, and contrasted cases of Down syndrome, trisomy 18, and trisomy 13, with unaffected controls. Periconceptional multivitamin use, compared to no such use, was associated with an odds ratio (OR) of 0.9 (95% confidence interval [CI], 0.6-1.3) for having a pregnancy affected by an autosomal trisomy. The OR was 0.8 (95% CI, 0.5-1.3) for Down syndrome and 1.4 (95% CI, 0.5-3.6) for trisomies 13 and 18, with little variation by maternal race or age. Periconceptional multivitamin use was not associated with a major reduction in the risk for common autosomal trisomies.     

Performance of prenatal screening by non-invasive cell-free fetal DNA testing for women with various indicationsCSCD

Objective: To assess the performance of non-invasive prenatal testing (NIPT) based on massive parallel sequencing. Methods: A total of 10 275 maternal blood samples were collected. Fetal chromosomal aneuploides were subjected to low coverage whole genome sequencing. Patients with high risks received further prenatal diagnosis. The outcome of all patients were followed up. Results: High-throughput sequencing detected 72 pregnancies with fetal autosomal chromosomal aneuploidy, including 57 cases of trisomy 21, 14 cases of trisomy 18, and 1 case of trisomy 13. The positive predictive value for trisomies 21 and 18 were 98.25% and 91.67%, respectively. Comparing its performance in intermediate or high risk pregnancies, advanced maternal age pregnancies and volunteering to test pregnancies, the positive predictive value were 100%, 95%, 90% and 50%, respectively. The follow up result was only 1 case of 21 trisomy false negative with high risk. For the 56 cases of trisomy 21, the high risk group accounted for 55%, advanced maternal age accounted for 29%, the intermediate risk referred to 14%, the volunteering to test group accounted for 2%. Conclusion: The performance of NIPT for trisomies 21, 18 and 13 was satisfactory. The method can be used for women with advanced gestational age. NIPT has offered an ideal secondary screening method for those with an intermediate or high risk, and can reduce the rate of birth defects. © 2018 West China University of Medical Sciences. All rights reserved.     

Prevalence and Premature Mortality Statistics of Autism Spectrum Disorder Among Children in Korea: A Nationwide Population-Based Birth Cohort Study

BackgroundThe aim of this study was to estimate the 8-year prevalence and mortality statistics of autism spectrum disorder (ASD) according to birth year (2002–2012).MethodsWe used the National Health Insurance Service database with 4,989,351 children born from 2002 to 2012 including 35,529 children diagnosed with ASD until 8 years of age. The 8-year cumulative prevalence of ASD was calculated annually (2010–2020) with 8 years of follow-up. The 8-year mortality was estimated using Cox models adjusted for sex, household income, area of residence, and year of birth.ResultsOf the 473,494 children born in 2002, 2,467 (5.2 per 1,000 births) were diagnosed with ASD until 2010. The ASD prevalence was 2.6 times higher among boys (1,839; 7.4 per 1,000 boy births) than girls (628; 2.8 per 1,000 girl births). Of the 467,360 children born in 2012, 4,378 (9.4 per 1,000 births) were diagnosed with ASD until 2020. The ASD prevalence was 2.7 times higher among boys (3,246; 13.5 per 1,000 boy births) than girls (1,132; 5.0 per 1,000 girl births). The risk of all-cause mortality was higher among children with ASD than those without (hazard ratio [HR], 2.340; 95% confidence interval [CI], 2.063–2.654), which is substantially higher among girls (HR, 4.223; 95% CI, 3.472–5.135) than boys (HR, 1.774; 95% CI, 1.505–2.090).ConclusionThe present study demonstrated that national-level prevalence and mortality statistics of ASD can be estimated effectively using claims data comprising newborns born each year and followed up for to the age of interest. Because this information is essential to establish evidence-based policies, health authorities need to consider producing epidemiological information of ASD continuously using the same methodology.     

Increased nuchal translucency in trisomy 13 fetuses at 10-14 weeks of gestation.

In a multicenter screening study for trisomy 21 involving ultrasonographic measurement of fetal nuchal translucency thickness (NT) at 10-14 weeks of gestation, 100,311 singleton pregnancies with a live fetus were examined. There were 46 cases of trisomy 13, and in 33 (72%) of these, the NT was above the 95th centile. The estimated risk for trisomy 21, based on maternal age-related risk for this chromosomal abnormality and fetal NT, was above 1 in 300 in 37 (80.1%) of the trisomy 13 fetuses. The fetal crown-rump length was significantly reduced, but the fetal heart rate was increased, being above the 95th centile in 64% of cases. Additionally, 24% of trisomy 13 fetuses had holoprosencephaly and 10% had exomphalos. This study has demonstrated that at 10-14 weeks of gestation, about 80% of fetuses with trisomy 13 can be identified in a screening program for trisomy 21, based on a combination of maternal age and fetal NT.     

Trends in maternal age distribution and the live birth prevalence of Down's syndrome in England and Wales: 1938–2010

There have been concerns about the effects of increases in maternal age since the 1980s on the prevalence of Down''s syndrome. This study examined changes in the distribution of maternal age in England and Wales from 1938 to 2010. The live birth prevalence of Down''s syndrome in the absence of screening and subsequent termination was estimated using the numbers of babies born in England and Wales according to maternal age and the maternal age-related risk of a birth with Down''s syndrome. The proportion of women age 35 years or older at the time of giving birth reached a peak of 20% in 1945, declined to 5.5% in 1977 and rose to 20% in 2007. In the absence of screening and subsequent termination, the estimated live birth prevalence of Down''s syndrome would have mirrored these changes (2.3 per 1000 births in 1945, 1.2 per 1000 in 1976 and 2.2 per 1000 in 2007). The observed live birth prevalence (recorded by the National Down Syndrome Cytogenetic Register) was1.0 per 1000 from 1989 to 2010, due to screening and subsequent termination. In conclusion since the 1980s there has been an increase in the mean maternal age and in the expected prevalence of Down''s syndrome. When put in a longer historical context the current expected live birth prevalence is similar to that in the 1940s and the observed live birth prevalence is about 54% less than expected, due to screening and subsequent termination, and has remained reasonably constant since 1989 at 1.0 per 1000 births.     

Seasonal Pattern of Preterm Births in Korea for 2000–2012

The aim of this study was to investigate a seasonal pattern of preterm births in Korea. Data were obtained from the national birth registry of the Korean Statistics Office and included all births in Korea during the period 2000–2012 (n = 6,310,800). Delivery dates were grouped by month of the year or by season (winter [December, January, February], spring [March, April, May], summer [June, July, August], and autumn [September, October, November]). The seasonal patterns of prevalence of preterm births were assessed. The rates of preterm births at 37 weeks were highest twice a year (once in winter and again in summer). The rates of preterm births increased by 13.9% in summer and 7.5% in winter, respectively, than in spring (OR, 1.139; 95% CI, 1.127–1.152, and OR, 1.075; 95% 1.064–1.087, respectively) after controlling for age, the educational level of the parents, maternal parity, and neonatal gender. The pattern for spontaneous preterm births < 34 weeks was similar. In Korea, a seasonal pattern of preterm births was observed, with peak prevalence in summer and winter. A seasonal pattern of preterm births may provide new insights for the pathophysiology of preterm births.     

Investigation of maternal blood enriched for fetal cells: role in screening and diagnosis of fetal trisomies.

Prenatal diagnosis of chromosomal abnormalities relies on assessment of risk followed by invasive testing in the group with highest risk. Assessment of risk by a combination of maternal age and fetal nuchal translucency and invasive testing in the 5% of the population with the highest risk would identify about 80% of trisomy 21 pregnancies. Preliminary reports suggest that chromosomal abnormalities can also be diagnosed by fluorescent in situ hybridization (FISH) in maternal blood enriched for fetal cells. This study examines the potential role of this method on the prenatal diagnosis of fetal trisomies. Maternal blood was obtained before invasive testing in 230 pregnancies at 10-14 weeks of gestation. After enrichment for fetal cells, by triple density centrifugation and anti-CD71 magnetic cell sorting, FISH was performed and the proportion of cells with positive signals in the chromosomally normal and abnormal groups was determined. Fetal karyotype was normal in 150 cases and abnormal in 80 cases, including 36 with trisomy 21. Using a 21 chromosome-specific probe, three-signal nuclei were present in at least 5% of the enriched cells from 61% of the trisomy 21 pregnancies and in none of the normal pregnancies. For a cut-off of 3% of three-signal nuclei the sensitivity for trisomy 21 was 97% for a false positive rate of 13%. Similar values were obtained in trisomies 18 and 13 using the appropriate chromosome-specific probe. Examination of fetal cells from maternal blood may provide a noninvasive prenatal diagnostic test for trisomy 21 with the potential of identifying about 60% of affected pregnancies. Alternatively, this technique can be combined with maternal age and fetal nuchal translucency as a method of selecting the high-risk group for invasive testing. Potentially, 80% of trisomy 21 pregnancies could be identified after invasive testing in less than 1% of the pregnant population.     

Natural outcome of trisomy 13, trisomy 18, and triploidy after prenatal diagnosis

Trisomy 13, trisomy 18, and triploidy belong to the chromosomal abnormalities which are compatible with life, but which are also associated with a high rate of spontaneous abortion, intrauterine death, and a short life span. This study was conducted to analyze natural outcome after prenatal diagnosis of these disorders. Between January 1, 1999 and December 31, 2009, we investigated all amniocenteses and chorionic villus biopsies carried out at our department. All cases with fetal diagnosis of triploidy, trisomy 13, and 18 were analyzed, with a focus on cases with natural outcome. Overall, 83 (78%) cases of pregnancy termination and 24 (22%) patients with natural outcome (NO) were identified. The NO group included 15 cases of trisomy 18, six cases of triploidy, and three cases of trisomy 13. No case of triploidy was born alive. The live birth rate was 13% for trisomy 18 and 33% for trisomy 13. The three live-born infants with trisomy 13 and 18 died early after a maximum of 87 hr postpartum. Our data are consistent with the literature concerning outcome of triploidy, with none or only a few live births. Analyzes of trisomy 13 and 18 indicate a very short postnatal life span. Different study designs and diverse treatment strategies greatly affect the fetal and neonatal outcome of fetuses with triploidy, trisomy 13, and 18. More studies analyzing natural outcome after prenatal diagnosis of these chromosomal abnormalities are needed. Non-termination of these pregnancies remains an option, and specialists advising parents need accurate data for counseling.     

The relative risk for standard 21 trisomy has not increased in young mothers in Belgium, 1960–1978

In the present investigation we directly studied the constancy of the relative risks for standard 21 trisomy in Belgium during the period 1960-1978. The relative risk for standard 21 trisomy in different maternal age-groups, as compared to 20-24 years and 40-44 years remained remarkably constant during the period under investigation. The increasing percentage of children with standard 21 trisomy born to younger mothers does not result from an increased risk for mothers of this maternal age-group, but results from the general shift towards a younger maternal age at birth for the total population of births in Belgium.