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Características demográficas del síndrome de Down en Navarra: Evolución del diagnóstico pre y postnatal durante el periodo 1991-2009
Abstract
This study describes the development of pre and postnatal diagnosis of sindrome de Down (SD) in the Autonomous Community of Navarre from 1991 to 2009 and assesses its preventive impact in the population, as well as to associated socio-demographic changes. In the absence of a prenatal diagnosis for DS, the change in maternal age from 1991 to 2009 would have caused a 50% increase in births with this disorder. However, the antenatal rate detection of DS increased from 15.8% in 1991-4 to 64.3% in 2006-9, giving rise to a decreasing incidence trend, not statistically significant, during the study period and to a higher mean age of mothers of live births with DS (32.75± 5,02 and 34.8±4,82 years during the first and second periods of the study, respectively). The proportion of young mothers (<35 years) of live births with DS was 66% in 1991-4 and 45% in 2006-9. Close to one fifth of the total population of pregnant women, however, did not want to go through a maternal screening test or amniocentesis. Seventeen per cent of all live births with DS had a positive screening test, but mothers decided to continue pregnancy. These results suggest that, despite the application of new and more sensitive prenatal screening tests, the incidence of DS may still be relatively high in our population, an important factor to be considered for future antenatal preventive programs and adequate postnatal care.
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The risk of having a child with Down's syndrome increases with maternal age. However, uptake of screening has never been analyzed according to age. Different studies have shown different screening uptake rates, some low and some high, but it is not clear which age categories are responsible for these trends.
To demonstrate if any age cohorts are responsible for the noted decline in uptake of serum screening.
A large teaching hospital in Hull and East Yorkshire, which has offered second trimester serum screening for Down's syndrome for over 16 years using the same test (triple test).
Uptake of serum screening for Down's syndrome in each 5-year age cohort per year, over 4 years. A secondary outcome measure was the uptake according to parity.
We accessed our hospital records covering a 5-year period for all women booking and delivering in a large North of England teaching hospital. The women were categorized into 5-year age cohorts for analysis of the data.
Down's syndrome screening uptake rates indicate a decline from 63.2 and 65.1% in 2003 to 38.6 and 39% in 2006, respectively, in the age groups 25-29.9 and 30-34.9 years who constitute at least 50% of all pregnant women. There was no evidence of the effect of parity on serum screening.
It is apparent that the noted overall decline in the trends of serum screening uptake are due to the reduced uptake by the 25-35 years age group.
To describe trends in the numbers of Down's syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008. Design and setting The National Down Syndrome Cytogenetic Register holds details of 26488 antenatal and postnatal diagnoses of Down's syndrome made by all cytogenetic laboratories in England and Wales since 1989.
Antenatal screening, diagnosis, and subsequent termination of Down's syndrome pregnancies.
The number of live births with Down's syndrome.
Despite the number of births in 1989/90 being similar to that in 2007/8, antenatal and postnatal diagnoses of Down's syndrome increased by 71% (from 1075 in 1989/90 to 1843 in 2007/8). However, numbers of live births with Down's syndrome fell by 1% (752 to 743; 1.10 to 1.08 per 1000 births) because of antenatal screening and subsequent terminations. In the absence of such screening, numbers of live births with Down's syndrome would have increased by 48% (from 959 to 1422), since couples are starting families at an older age. Among mothers aged 37 years and older, a consistent 70% of affected pregnancies were diagnosed antenatally. In younger mothers, the proportions of pregnancies diagnosed antenatally increased from 3% to 43% owing to improvements in the availability and sensitivity of screening tests.
Since 1989, expansion of and improvements in antenatal screening have offset an increase in Down's syndrome resulting from rising maternal age. The proportion of antenatal diagnoses has increased most strikingly in younger women, whereas that in older women has stayed relatively constant. This trend suggests that, even with future improvements in screening, a large number of births with Down's syndrome are still likely, and that monitoring of the numbers of babies born with Down's syndrome is essential to ensure adequate provision for their needs.
This retrospective observational study of registered pregnancies in Gloucestershire between 1 April 1993 and 31 March 1999 compares the impact of different Down syndrome antenatal screening policies on detection and amniocentesis rates. The screening policies in East and West Gloucestershire are based on early second-trimester maternal serum and maternal age screening, respectively. Maternal serum screening can identify a greater proportion of pregnancies affected by Down syndrome than a programme founded on age-based amniocentesis and 20 weeks' ultrasound. In addition, maternal serum screening of women older than 34 approximately halves the number of amniocenteses performed to detect one affected fetus. However, the proportion of pregnant women who have amniocentesis is nearly doubled by offering serum screening to women aged over 24 years. These findings of the impact of established second-trimester screening policies in low-risk populations provides an useful benchmark to compare the performance of screening procedures that will be introduced in the United Kingdom over the next 3 years.
Despite the wide availability of prenatal screening and diagnosis, a number of studies have reported no decrease in the rate of babies born with Down syndrome. The objective of this study was to investigate the geodemographic characteristics of women who have prenatal diagnosis in Victoria, Australia, by applying a novel consumer behaviour modelling technique in the analysis of health data.
A descriptive analysis of data on all prenatal diagnostic tests, births (1998 and 2002) and births of babies with Down syndrome (1998 to 2002) was undertaken using a Geographic Information System and socioeconomic lifestyle segmentation classifications.
Most metropolitan women in Victoria have average or above State average levels of uptake of prenatal diagnosis. Inner city women residing in high socioeconomic lifestyle segments who have high rates of prenatal diagnosis spend 20% more on specialist physician's fees when compared to those whose rates are average. Rates of prenatal diagnosis are generally low amongst women in rural Victoria, with the lowest rates observed in farming districts. Reasons for this are likely to be a combination of lack of access to services (remoteness) and individual opportunity (lack of transportation, low levels of support and income). However, there are additional reasons for low uptake rates in farming areas that could not be explained by the behaviour modelling. These may relate to women's attitudes and choices.
A lack of statewide geodemographic consistency in uptake of prenatal diagnosis implies that there is a need to target health professionals and pregnant women in specific areas to ensure there is increased equity of access to services and that all pregnant women can make informed choices that are best for them. Equally as important is appropriate health service provision for families of children with Down syndrome. Our findings show that these potential interventions are particularly relevant in rural areas. Classifying data to lifestyle segments allowed for practical comparisons of the geodemographic characteristics of women having prenatal diagnosis in Australia at a population level. This methodology may in future be a feasible and cost-effective tool for service planners and policy developers.
To document trends in serum screening for Down's syndrome.
Trends in the uptake of serum screening for Down syndrome have not been documented in a UK population.
A retrospective review of the rate of uptake in a unit that has offered serum screening for Down syndrome to all pregnant women.
A large north of England hospital that has offered universal Down syndrome screening using the 'triple test' since 1992.
A total of 47,998 women who booked for antenatal care.
Uptake of serum screening for Down syndrome.
The results of the screening programme were contemporaneously recorded on a computer database, and the study team accessed the data.
There was a significant reduction in the uptake of serum screening for Down syndrome from a maximum of 82.6% in 1993 to 41.4% in 2005. There was a significant but small trend upwards in the age of women accepting screening and also a significant trend in the increase in the screen-positive rates.
The reduction in uptake of Down syndrome screening over the past 13 years must be taken into account when planning a screening programme. Other units should be encouraged to review their rate of uptake to determine if our data are representative of a wider trend.
EUROCAT is a network of population-based registries for the epidemiologic surveillance of congenital anomalies covering approximately one quarter of births in the European Union. Down syndrome constitutes approximately 8% of cases of registered congenital anomaly in Europe, with over 7000 affected pregnancies in the 15 current member states of the European Union each year. In this paper, we aim to examine trends in the live birth prevalence of Down syndrome in Europe in the light of trends in maternal age and in prenatal diagnosis.
Descriptive analysis of data from 24 EUROCAT registries, covering 8.3 million births 1980-99. Cases include live births, stillbirths and terminations of pregnancy following prenatal diagnosis.
Since 1980, the proportion of births to mothers of 35 years of age and over has risen quite dramatically from 8 to 14% for the European Union as a whole, with steeper rises in some regions. By 1995-1999, the proportion of "older" mothers varied between regions from 10% to 25%, and the total prevalence (including terminations of pregnancy) of Down syndrome varied from 1 to 3 per 1000 births. Some European regions have shown a more than twofold increase in total prevalence of Down syndrome since 1980. The proportion of cases of Down syndrome which were prenatally diagnosed followed by termination of pregnancy in 1995-1999 varied from 0% in the three regions of Ireland and Malta where termination of pregnancy is illegal, to less than 50% in 14 further regions, to 77% in Paris. The extent to which terminations of pregnancy were concen trated among older mothers varied between regions. The live birth prevalence has since 1980 increasingly diverged from the rising total prevalence, in some areas remaining approximately stable, in others decreasing over time.
The rise in average maternal age in Europe has brought with it an increase in the number of pregnancies affected by Down syndrome. The widespread practice of prenatal screening and termination of pregnancy has in most of the regions covered by EUROCAT counteracted the effect of maternal age in its effect on live birth prevalence. Under the joint influences of maternal age and prenatal screening the pattern of geographic inequalities in Down syndrome live birth prevalence in Europe has also been changed.
The aim of this study was to examine trends of Down syndrome (DS) in relation to maternal age and termination of pregnancies (ToP) in 20 registries of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR).
Trends of births with DS (live-born and stillborn), ToP with DS, and maternal age (percentage of mothers older than 35 years) were examined by year over a 12-year period (1993-2004). The total mean number of births covered was 1550,000 annually.
The mean percentage of mothers older than 35 years of age increased from 10.9% in 1993 to 18.8% in 2004. However, a variation among the different registers from 4-8% to 20-25% of mothers >35 years of age was found. The total mean prevalence of DS (still births, live births, and ToP) increased from 13.1 to 18.2/10,000 births between 1993 and 2004. The total mean prevalence of DS births remained stable at 8.3/10,000 births, balanced by a great increase of ToP. In the registers from France, Italy, and the Czech Republic, a decrease of DS births and a great increase of ToP was observed. The number of DS births remained high or even increased in Canada Alberta, and Norway during the study period.
Although an increase in older mothers was observed in most registers, the prevalence of DS births remained stable in most registers as a result of increasing use of prenatal diagnostic procedures and ToP with DS.
Current indications for cytogenetic evaluation leave the majority of Down syndrome fetuses undetected. Using advanced maternal age and low maternal serum alpha-fetoprotein (AFP) levels as criteria, only 40% of fetuses with Down syndrome (trisomy 21) are identified (positive predictive value, 0.4% to 1%). We evaluate the sonographically detectable physical features of second trimester fetuses to determine whether these features are more sensitive and specific than maternal age for detecting fetuses with abnormal karyotypes. From March 1, 1990, to September 1, 1991, more than 5,000 fetuses between 14 and 20 weeks of development were referred for genetic amniocentesis because of advanced maternal age or abnormal AFP levels. Forty-three of these 5,000 fetuses were later found to have autosomal trisomies by karyotype (32 with trisomy 21, nine with trisomy 18, and two with trisomy 13). A sample of 588 consecutive normal fetuses from the total of more than 5,000 amniocenteses performed during this period of time was used as our control group for statistical analysis. The sonographic features of these 588 normal second trimester fetuses and the 43 trisomic fetuses recorded prospectively prior to knowledge of the karyotype were evaluated statistically. The femur and humerus lengths, nuchal fold, renal pelvic dimension, and major structural defects were compared in the normal and trisomic fetuses. On the basis of our results, a weighted sonographic score was developed to optimize the detection of fetuses at risk for aneuploidy. Using our previously published formulas and criteria for a short femur and humerus, 17/32 (53%) fetuses with Down syndrome and 23/588 (3.9%) of the normal fetuses were identified. Twenty two of 32 Down syndrome fetuses (69%) and 2/588 (0.34%) of normals had a nuchal fold > or = 6 mm, and 11 of 32 Down syndrome fetuses and all those with trisomies 18 and 13 had a major anomaly detected sonographically. The following scoring system was developed for the detection of aneuploidy: nuchal fold = 2, major structural defect = 2, and short femur, short humerus, and pyelectasis = 1 each. Selecting fetuses with a score of > or = 2 would identify 26/32 (81%) Down syndrome fetuses, and 9/9 (100%) and 2/2 (100%) fetuses with trisomies 18 and 13 respectively, but only 26/588 (4.4%) of the normal fetuses. Using the sonographic score of 2 results in a positive predictive value for a 1/250 risk group of 6.87% for identifying Down syndrome fetuses and 7.25% for all three trisomies.(ABSTRACT TRUNCATED AT 400 WORDS)
Using current demographic projection of maternal age-structure, age-specific fertility rates, and the availability, detection and utilization rates of prenatal diagnosis and subsequent termination rates, predictions are made of the likely numbers of births with Down's syndrome (DS) in England and Wales to be expected up to the year 2000. Further predictions are made of age-specific prevalence of the condition bearing in mind recent trends in survival. These figures show that, despite current screening policies based on maternal age alone, the observed live birth prevalence of DS will rise to levels higher than have been seen for 20 years. Together with consistently increased survival, this will mean that, throughout the next century, the population prevalence of DS will be higher than ever before. Work based in other countries has reached similar conclusions. As the prevention of all births affected by DS is not possible in the forseeable future, and some would argue that it is not desirable, society will need to provide for those affected.
To assess the value of inhibin A as an additional second-trimester maternal serum marker of Down's syndrome we studied 56 affected and 280 unaffected pregnancies matched for gestational age. The median level in the cases was 1.62 multiples of the gestation-specific median (MOM) in the controls, with 95 per cent confidence limits of 1.34-1.96. The distribution of inhibin levels in affected and unaffected pregnancies was approximately log Gaussian, with means about 1 standard deviation apart. This degree of separation was similar to that for human chorionic gonadotropin (hCG), free beta-hCG, and unconjugated oestriol (uE3), but about double that of alpha-fetoprotein (AFP) measured in the same samples. Inhibin was largely uncorrelated with AFP and uE3, whereas the log correlation coefficient with hCG was 0.29 (P = 0.19) for Down's syndrome and 0.41 (P < 0.0001) for unaffected pregnancies; with free beta-hCG, it was 0.18 (P = 0.38) and 0.38 (P < 0.0001), respectively. On the basis of these results and other published studies, we estimate that measuring inhibin A in addition to AFP and hCG or free beta-hCG (with or without uE3) will increase the detection rate for a fixed 5 per cent false-positive rate by about 7 per cent.
In South Belgium (Wallonia), the 'triple test' was introduced in 1990-1991, and is nowadays a widely accepted screening method for assessment of trisomy 21 risk in pregnancy. The 'triple test' is not regulated and can be freely performed by any biomedical lab, making epidemiological data unavailable. By contrast, cytogenetic investigations are limited to a few genetic centres, and accurate statistics can be easily built from their files. During the period 1984-1989, a total of 244 trisomy 21 (1/876 pregnancies) were diagnosed in the Genetic Centres of Liège and Loverval, 42 (17%) of them prenatally. During the period 1993-1998, 294 trisomy 21 (1/704 pregnancies) were observed, 165 (56%) of which prenatally, and more than 90% of affected pregnancies were terminated. Even after correction for late foetal loss of trisomic foetuses, the difference is highly significant, and corresponds to a theoretical shift in the incidence of trisomy 21 at birth from 1/794 to 1/1606. As no remarkable progress occurred in other non-invasive prenatal screening procedures or general health care policies in Belgium, the most reasonable explanation is the use on a large scale of triple test by pregnant women, and the election of termination for most affected pregnancies.
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.
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.
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))))).
To evaluate the impact of policy and practice changes in prenatal screening for Down's syndrome on prenatal diagnosis and live birth prevalence of Down's syndrome.
Population-based observational study.
Greater Paris.
Residents of Greater Paris who gave birth or had a termination of pregnancy in Paris during 1981-2000 (approximately 38,000 births per year).
Data on 1916 cases of Down's syndrome were obtained from the Paris Registry of Congenital Anomalies. Analyses included binomial and Poisson models of trends in three periods: prior to 1989 (reference period), 1989-1995 (reimbursement of amniocentesis in case of ultrasonographic anomalies) and 1996-2000(widespread use of reimbursed serum screening and measurement of nuchal translucency).
Trends in proportion of Down's syndrome cases diagnosed prior to birth; live birth prevalence of Down's syndrome.
The proportion of Down's syndrome detected prenatally for women <38 years of age increased ninefold; from 9.5% (95% CI 2.7-22.6) in 1981 to 84.9% (95% CI 74.6-92.2) in 2000. For women >38 years of age, the increase was 1.5-fold. The live birth prevalence of Down's syndrome decreased by 3% per year (prevalence ratio [PR] 0.97, 95% CI 0.96-0.99); the age-adjusted decrease was 13%. The analysis by period showed that the decrease in live birth prevalence of Down's syndrome was greater after 1988.
By far, most cases of Down's syndrome are currently detected prenatally in the Parisian population. Consequently, the live birth prevalence of Down's syndrome has decreased despite consistent trends towards delayed childbearing. These positive public health effects have to be balanced against a relatively high rate of amniocentesis and the potentially negative consequences of widespread prenatal testing for individuals born with Down's syndrome.
We investigated the observed and expected Down syndrome livebirths in the US from 1989 to 2001.
Using birth certificate data, we recorded maternal age-specific live births from 1989 to 2001, and stratified them by women 15 to 34 and 35 to 49 years old. We estimated Down syndrome live births from 1989 to 2001, assuming no terminations. We recorded Down syndrome live births by year from 1989 to 2001.
Despite an expected 1.32-fold increase in Down syndrome live birth rates from 1989 to 2001, Down syndrome live births actually declined. In 1989, the rate of Down syndrome cases was 15% lower than expected, decreasing to 51% by 1998. Women 15 to 34 had 45% fewer affected pregnancies in 2001, while women 35 to 49 had 53% fewer in 2001. We estimated that Down syndrome live births decreased from 3962 in 1989 to 3654 in 2001.
Down syndrome live births declined in the US despite an expected increase caused by delayed or extended childbearing.
This study documents the changes in the percentages of advanced maternal age (AMA) pregnancies in the United States and in Washington State, underlying demographic factors, the impact on the predicted incidence of Down syndrome, and its impact on Down syndrome screening. Data on births in the United States from 1933 to 2002 were obtained from publications and the website of the National Center for Health Statistics. Data for Washington State were obtained from the website of the Washington State Department of Health. Information on births at Swedish Medical Center was obtained from hospital records. The percentage of AMA pregnancies in the US was about 14% before World War II, dropped steadily to about 5% in the 1970s and rose since the 1980s to about 14% in 2002. AMA Fractions are greatest among non-Hispanic Caucasians and Asian/Pacific Islanders, women who have college education and beyond, and are married. However, since 1980, the AMA Fractions have increased across all racial/ethnic groups, educational levels, and married and unmarried women. In Washington State in 2001, the overall AMA Fraction was about 14%, but there was considerable variation in the AMA Fraction across counties. In 1980, AMA pregnancies accounted for about 25% of pregnancies with Down syndrome in the United States. In 2002, AMA pregnancies accounted for more than 50% of Down syndrome pregnancies. Given the current AMA Fraction, offering amniocentesis to women of age 35 and above would result in one in seven pregnant women undergoing amniocentesis. Based on likelihood ratios, AMA as a screening strategy for Down syndrome is significantly inferior to combined serum and sonographic screening.
Pregnancies affected by Down syndrome (DS) have a greater risk of spontaneous fetal loss than those that are unaffected. In this article, we investigate the relationship between maternal age and the risk of spontaneous fetal loss in DS pregnancies.
Fetal loss at different maternal ages were estimated by survival analysis using follow-up of 5177 prenatally diagnosed cases. The maternal age effect on loss rate was subsequently confirmed by a re-analysis of published comparisons of the maternal age-specific prevalence of DS at different gestational ages.
The average fetal loss rate between the time of chorionic villus sampling (CVS) and term was 32% (95% CI: 26-38), increasing from 23% (95% CI: 16-31) for women aged 25 to 44% (33-56) for women aged 45. The average fetal loss rate between the time of amniocentesis and term was 25% (21-31), increasing from 19% (14-27) to 33% (26-45) across the same age range.
The fetal loss rate in DS pregnancies increases with maternal age, and this has consequences when estimating the live birth prevalence of DS in the presence of prenatal diagnosis and termination, and when assessing the performance of prenatal screening techniques.
To investigate the differences in costs and outcomes of Down syndrome screening using data from the First and Second Trimester Evaluation of Risk (FASTER) Trial.
Seven possible screening options for Down syndrome were compared: 1) Triple Screen-maternal serum alpha fetoprotein, estriol, and hCG; 2) Quad-maternal serum alpha fetoprotein, estriol, hCG, and Inhibin A; 3) Combined First-nuchal translucency, pregnancy-associated plasma protein A (PAPP-A), free beta-hCG; 4) Integrated-nuchal translucency, PAPP-A, plus Quad; 5) Serum Integrated-PAPP-A, plus Quad; 6) Stepwise Sequential-Combined First plus Quad with results given after each test; and 7) Contingent Sequential-Combined First and only those with risk between 1:30 and 1:1,500 have Quad screen. The detection rates for each option were used given a 5% false-positive rate except for Contingent Sequential with a 4.3% false-positive rate. Outcomes included societal costs of each screening regimen (screening tests, amniocentesis, management of complications, and cost of care of Down syndrome live births), Down syndrome fetuses identified and born, the associated quality-adjusted life years, and the incremental cost-utility ratio.
Based on the screening results derived from the 38,033 women evaluated in the FASTER trial, the Contingent Sequential screen dominated (lower costs with better outcomes) all other screens. For example, the Contingent Sequential cost 32.3 million dollars whereas the other screens ranged from 32.8 to 37.5 million dollars. The Sequential strategy led to the identification of the most Down syndrome fetuses of all of the screens, but at a higher cost per Down syndrome case diagnosed (690,427) as compared with the Contingent Sequential. Because of the lower overall false-positive rate leading to fewer procedure-related miscarriages, the Contingent Sequential resulted in the highest quality-adjusted life years as well. The Contingent Sequential remained the most cost-effective option throughout sensitivity analysis of inputs, including amniocentesis rate after positive screen, rate of therapeutic abortion after Down syndrome diagnosis, and rate of procedure-related miscarriages.
Analysis of this actual data from the FASTER Trial demonstrates that the Contingent Sequential test is the most cost-effective. This information can help shape future policy regarding Down syndrome screening.
To determine the prevalence, neonatal characteristics, and first-year mortality in Down syndrome (DS) among children in The Netherlands.
The number of DS births registered by the Dutch Paediatric Surveillance Unit (DPSU) in 2003 was compared with total live births (reference population) and perinatal registrations.
The prevalence of DS was 16 per 10,000 live births. Compared with the reference population, the 182 children with trisomy 21 had a gestational age of 38 weeks versus 39.1 weeks (P < .001), a birth weight of 3119 g versus 3525 g in males (P < .001) and 2901 g versus 3389 g in females (P < .001), and mothers with a parity of > or = 4.17% versus 5% (P < .001) and a mean age of 33.6 years versus 31 years (P < .001) and 33% (n = 54) > or = 36 years). The mean age of DS diagnosis was 10.2 days in nonhospital deliveries and 1.8 days in hospital deliveries (P < .001). Children with DS were less often breast-fed (P < .05), and 86% (n = 156) were hospitalized after birth. Neonatal and infant mortality were higher in DS, 1.65% versus 0.36% (P < .02) and 4% versus 0.48% (P < 0.001), respectively.
The prevalence of DS in The Netherlands exceeds previously reported levels and is influenced by the mother's age. Neonatal and infant DS mortality have declined, but still exceed those in the reference population.
Frecuencia del síndrome de Down en Asturias y tendencia temporal, 1990-2004
- C Mosquera Tenreiro
- F Ariza Hevia
- C Rodriguez Dehli
- J Fernandez Toral
- E García López
- I Riano Galan