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Objectives: To revise the estimates of maternal age specific live birth prevalence of Down's syndrome in the absence of antenatal screening and selective termination using newly available data. Setting and Design: Data were used from the National Down Syndrome Cytogenetic Register (NDSCR), which contains information on nearly all antenatally or postnatally diagnosed cases of Down's syndrome in which a karyotype was confirmed between 1989 and 1998 in England and Wales. It is the largest single series of data on the prevalence of Down's syndrome. Results and conclusion: The prevalence does not continue increasing at an increasing rate with age above age 45 as has been previously assumed. Above this age the rate of increase declines with increasing age. The overall age pattern is sigmoidal. A new logit logistic model is proposed which fits the data well. The risk of a Down's syndrome live birth is given by: risk=1/(1+exp(7.330-4.211/(1+exp(-0.282x(age-37.23))))). [ABSTRACT FROM AUTHOR]

Objectives: The proportion of Down's syndrome pregnancies detected prenatally in England and Wales is lower in younger mothers than in older mothers. This paper examines the reasons for this apparent age inequality. Methods: We used data from the National Down Syndrome Cytogenetic Register (NDSCR) to examine the time trend of the proportion of Down's syndrome pregnancies diagnosed prenatally according to maternal age over the years 1989–2004 in England and Wales. Results: A lower proportion of younger mothers had their Down's syndrome pregnancy detected prenatally than older mothers; however, this gap has been closing over time. For example, for mothers under 25 years of age only 13% of Down's syndrome pregnancies were detected prenatally from 1989 to 1992, with this figure rising to 34% in 2001–2004, compared with proportions of 74% in both periods for mothers over 44 years of age. A lower uptake of screening among younger women could not explain these differences. The differences in detection rates of the screening methods according to maternal age, particularly of the older screening tests, could account for these differences. Conclusions: The closing gap between the proportions of younger and older women having their affected pregnancy prenatally diagnosed is a confirmation of the improvement of screening methods over time. [ABSTRACT FROM AUTHOR]

The article focuses on birth prevalence of Down's syndrome in Wales and England from 1990 t0 1997. In a study on this subject, it is determined that between 1990 and 1997 the birth prevalence of this disease which would have been expected in the absence of selective termination and antenatal screening has increased from 1.44 per 1000 births in 1996. This trend was studied by using the data gathered by the National Down's Syndrome Cytogenetic Register (NDSCR).

This study describes the cytological and epidemiological findings in 985 trisomy 13 and 2512 trisomy 18 compared with 10,255 trisomy 21 diagnoses between 2004 and 2009 included in the National Down Syndrome Cytogenetic Register of England and Wales. The frequency of occurrence, proportions diagnosed prenatally, sex ratios, mean maternal age, and proportions of mothers with recurrences were analyzed. Ninety-seven, 98%, and 92% were free karyotypes for trisomy 21, 18, and 13, respectively; 3% of 21, 1% of 18, and 8% of trisomy 13 were translocations; and under 1% of trisomies 21 and 18 were double or triple aneuploids. Overall 1% of each trisomy had mosaicism, but 48% of the trisomy 21 double aneuploids, and 10% of trisomy 18 multiple aneuploids had mosaicism. The proportion of livebirths was 40% of trisomy 21, 11% of 18, and 13% of 13, respectively. Free trisomies 21 and 13 had an excess of males, and 18 had an excess of females, as did mosaic free trisomies 21 and 18. Mean maternal ages were 35.9 years in trisomy 21, 36.4 years in 18, and 34.6 years in 13. During the 6 years of data collection 1% of the mothers had recurrences, most recurrent trisomy 21 or 18 were identical translocations, but hetero-trisomic recurrences included 21 and 18, and 21 and 13. There are significant differences between the trisomic karyotypes and attributes, possibly related to their variable origins. Notable are the relative excess of trisomy 13 translocations, mosaicism in cases with multiple aneuploidy, and the types of homo- and hetero-recurrences., (Copyright © 2012 Wiley Periodicals, Inc.)

This study describes the characteristics of karyotypes leading to phenotypic Down syndrome (trisomy 21) in 29,256 cases diagnosed between 1989 and 2009 in England and Wales included in the National Down Syndrome Cytogenetic Register (NDSCR). The frequency of occurrence of the different karyotypes, proportions diagnosed prenatally, sex ratios, mean maternal age, and proportions of mothers with recurrences were analyzed. Nearly 97% of all cases were free trisomy 21; 2.9% contributory trisomy 21, 0.3% double or triple aneuploidies; 1% of all were mosaics. Mean maternal age of free trisomy 21 cases was 35 years, 54% were male, and 1% of mothers had recurrences. Free trisomy 21 mosaics had a lower mean maternal age (33 years), a lower proportion of males (39.5%), and 2.5% of mothers had recurrences. The majority of contributory translocations were Robertsonian or rea (21;21). Their mothers were younger, particularly those of Robertsonian translocations (28 years). Of the Robertsonian der (14;21) translocations of known parental origin, 54% were de novo, 41% maternal and 5% paternal and 15.8% of mothers of those of maternal origin had recurrences. Multiple aneuploidies have the highest proportion of males (67%), highest proportion of mosaics (40%), a mean maternal age of 37 years, and no mothers had a recurrence. The size of this national register allowed the frequency of occurrence of the rarer karyotypes of Down syndrome to be estimated and their epidemiology described., (Copyright © 2012 Wiley Periodicals, Inc.)

Objectives: To determine the recurrence risk of a free trisomy 21 pregnancy., Methods: Data from the National Down Syndrome Cytogenetic Register (NDSCR), which contains information on nearly all cases of Down syndrome between 1989 and 2001 in England and Wales were used. Among 11 281 women with a Down syndrome pregnancy who had had at least one previous pregnancy there were 95 women who had had a previous Down syndrome pregnancy., Results: Women who have had a previous Down syndrome pregnancy have a constant absolute excess risk above their maternal age-related risk of having a subsequent affected pregnancy. This absolute excess risk is determined by the age at which the affected pregnancy occurred and is higher for younger than for older women. For example, after a Down syndrome pregnancy at age 20, this excess is 0.62% (95% CI: 0.24 to 1.15%) at early second trimester, and, after one at age 40, it is 0.04% (95% CI: 0.01 to 0.07%)., Conclusion: More precise risk estimates by single year of maternal age for use in genetic counselling are provided, but they need validation from other studies before they are incorporated in the risk estimation routines used in Down syndrome screening programmes., (Copyright 2005 John Wiley & Sons, Ltd)

Objective: Whether the introduction of antenatal screening for Down syndrome in England and Wales with serum biochemistry or ultrasound has led to improvements in patient outcomes is unknown. The purpose of this study was to relate pregnancy outcomes to the dominant method used for prenatal Down syndrome screening., Study Design: For the years 1989 through 1999, England and Wales were divided into geographically defined areas where specific hospitals, health authorities, and cytogenetic laboratories provided maternity care for well-defined populations. For each year from 1989 through 1999, the dominant Down syndrome screening method that was used in each area was determined. Outcomes for area-years that used serum biochemistry or ultrasound (first or second trimester) were compared with area-years that used advanced maternal age as the dominant screening method. The percent of Down syndrome cases that were diagnosed prenatally (effectiveness) and the number of invasive prenatal tests that were performed to diagnose each Down syndrome case prenatally (efficiency) were compared., Results: There were 5,980,519 births and 335,184 referrals for prenatal karyotyping (amniocentesis and chorionic villus sampling) that occurred in the area-years studied, of which 12,047 pregnancies were diagnosed as Down syndrome; 5393 cases of Down syndrome (45%) were diagnosed prenatally. Invasive testing increased from 4.4% of pregnancies in 1989 to 6.4% in 1997 and declined slightly in 1999 (5.8%). Prenatal diagnosis of Down syndrome cases rose from 28% in 1989 to 53% in 1999, and the number of invasive tests that were performed to diagnose each Down syndrome case fell from 89.7 to 47.7 (P [for trend]<.0001). Areas with serum or ultrasound as the dominant screening method detected 50% more Down syndrome cases in prenatally (52% and 53% vs 36%; P<.0001) and performed fewer invasive procedures to diagnose each Down syndrome case (60.7 and 52.0 vs 88.0; P<.0001) compared with areas in which advanced maternal age screening was dominant, despite serving populations with similar mean/median maternal ages., Conclusion: In clinical practice, screening programs for Down syndrome that were based on maternal serum biochemistry or ultrasound were more effective and efficient than the screening programs that used advanced maternal age alone.

Objectives: To evaluate the completeness of notifications of Down's syndrome live births and terminations to the Office for National Statistics (ONS) using data from the National Down Syndrome Cytogenetic Register (NDSCR). To examine the agreement of observed birth prevalence of Down's syndrome with the expected birth prevalence derived from published maternal age specific rates., Methods: The number of live births (adjusted to allow for the estimated underascertainment) and the number of terminations due to fetal Down's syndrome from NDSCR were compared with those figures reported to the ONS. Subsequently, using the NDSCR figures, the live birth prevalence of Down's syndrome that would have occurred in the absence of antenatal diagnosis and selective termination was calculated in England and Wales in the years 1990-1993. These figures were compared with those derived by applying published age specific prevalences to the maternal age distribution in England and Wales., Results: It is estimated that only 48% and 46% respectively of Down's syndrome live births and terminations of pregnancy were notified to ONS between 1990 and 1993. The annual expected birth prevalences of Down's syndrome obtained by applying maternal age specific prevalences to the maternal age distribution were in close agreement with observed rates from NDSCR., Conclusions: There is considerable underreporting of Down's syndrome births and terminations to ONS. The NDSCR data are more complete and therefore the effects of screening should be monitored using data from this source, or using estimates derived from the age specific rates of Down's syndrome.

Data from the National Down Syndrome Cytogenetic Register is used to describe the cytogenetics and epidemiology of registered cases. The register comprises notifications from cytogenetics laboratories in England and Wales. This report is of 5737 cases registered between 1989 and 1993: 2169 prenatal and 3436 postnatal diagnoses, and 132 spontaneous abortions. Eighty eight registrations were from multiple pregnancies. Ninety five percent had regular trisomy 21. In 4% there was a translocation, mostly Robertsonian t(14;21) or t(21;21). One percent were mosaics with one normal cell line. Mean maternal age was raised in free trisomy 21, but not in translocations. Where families had been investigated, about a third of translocations were inherited, six to seven times more often from the mother than the father. Associations between free trisomy 21 and structural chromosomal defects in the births were no more common than expected from newborn series. The overall sex ratio was raised (male to female: 1.23 to 1), and there was an excess of associated male sex chromosomal aneuploidy. However, in mosaics with one normal cell line the male to female ratio was 0.8 to 1, and in twins discordant for trisomy 21 there was also a female excess.

Objective: To investigate changes in the numbers of Down's syndrome births and terminations of pregnancies from 1989 to 1993., Design: Data from a national register of cytogenetic diagnoses of karyotypes associated with Down's syndrome were analysed to obtain observed numbers of births and terminations of pregnancies known to be affected. Allowance was made for those cases diagnosed prenatally for whom the eventual outcome of the pregnancies had not yet been ascertained., Results: There has been an increase over the study years in the number of cytogenetic diagnoses of Down's syndrome from 1063 in 1989 to 1137 in 1993, despite an overall fall in births in England and Wales. This is largely due to the increase in antenatal screening and diagnosis, but in part also due to the rise in numbers of pregnancies at increased maternal ages. The rise in prenatally diagnosed cases, of which 92% end in termination, has been accompanied by a fall in both the estimated numbers of affected live births, from 764 in 1989 to 615 in 1993, and the rate per 1000 total live births in the same years from 1.1 to 0.9., Conclusions: Better and speedier information on the outcome of prenatally diagnosed cases of congenital anomalies such as Down's syndrome would improve the quality of information available for those auditing genetic services or those planning for the care of survivors.

The national register of chromosomal anomalies that lead to Down's syndrome has enabled the monitoring of change in prenatal diagnosis for this condition, and the factors which affect the change. The proportion of cases of cytogenetically diagnosed Down's syndrome in England and Wales detected prenatally rose to 46% in 1991-2 from 31% in 1988-9, a 1.5-fold increase (95% confidence interval 1.3 to 1.7). The increase was confined to mothers under 40 years and was due to the introduction of screening by maternal serum analysis and ultrasound. Over a quarter of affected pregnancies in women aged 25-29 were detected prenatally in 1991-2 compared with less than 10% in 1988-9. Analysis of the data showed regional differences in prenatal diagnosis rates, and in the length of time elapsing between the diagnostic test and termination of an affected pregnancy. An inexplicable finding was that this period varied with the sex of the fetus, being on average a day longer for females than for males.

Objective: To examine the feasibility of a national register of Down's syndrome and its effectiveness in evaluating prenatal screening for the syndrome., Design: Information for the register was obtained from all eligible cytogenetic laboratories on relevant cytogenetic diagnoses, including date and place of birth or termination, maternal age, indication for karyotyping, and type of diagnostic test used., Setting: Cytogenetic laboratories in England and Wales., Subjects: All fetuses with trisomy 21 diagnosed prenatally and live births with Down's syndrome diagnosed at birth., Main Outcome Measures: Number of prenatal and postnatal diagnoses of Down's syndrome. National and maternal age specific prevalence of Down's syndrome., Results: For 1989 there were 1060 registrations--323 prenatal diagnoses and 737 postnatal diagnoses--after exclusion of postnatally diagnosed miscarriages and stillbirths. The estimated national rate of affected births for mothers resident in England and Wales was 1.4/1000 live births, assuming no terminations of affected pregnancies and after correction for natural losses which would have occurred in the absence of termination. The corrected maternal age specific rates were close to those found in previous population based studies. The proportion of affected pregnancies diagnosed prenatally in mothers aged 35 to 39 was 44%, and for those aged 40 or more it was 71%. Abnormal findings on ultrasonography played an unexpectedly important part in initiating cytogenetic investigation (13% of the prenatal diagnoses)., Conclusions: The findings establish the feasibility of a national Down's syndrome register and its use in evaluating prenatal screening services. Together with information held by the Office of Population Censuses and Surveys on congenital malformations, data from the register will permit studies of environmental variables affecting the prevalence of the syndrome.