Long-term trends for socio-economic differences in prenatal diagnosis of Down syndrome: diffusion of services or persistence of disparities?

Objective  To assess long-term trends in disparities for prenatal diagnosis of Down syndrome in relation to policy changes.
Design  Population-based observational study.
Setting  Paris.
Population  Residents of Paris who gave birth or had a termination of pregnancy in Paris during 1983–2003 (approximately 23 000 births per year).
Methods  Using population-based data from the Paris Registry of Congenital Malformations on 1934 cases of Down syndrome, we assessed differences in prenatal diagnosis proportions by maternal profession and geographical origin for the years 1983–2003. Analyses included locally weighted scatter plot smoother curves and binomial regression.
Main outcome measure  Trends in proportion of Down syndrome cases diagnosed prior to birth for different maternal occupation groups and women of different geographical origins.
Results  The proportion of prenatally diagnosed cases increased substantially, reaching to about 85–90% of cases in 2003 for most socio-economic groups. This increase was accompanied by a significant decrease in disparities in prenatal diagnosis. Nonetheless, the proportion of prenatally diagnosed cases remained 12% lower for women without a profession compared with those in the highest occupational category (maternal age-adjusted risk difference −12.0%, 95% CI −17.1 to −6.9).
Conclusions  Together with the implementation of policies aimed at providing access to prenatal screening for all women, socio-economic differences in prenatal diagnosis of Down syndrome decreased over time. These trends need to be monitored, particularly in light of technical advances and alternative strategies for prenatal testing. However, while monitoring the proportion of cases with prenatal diagnosis is important, the ideal evaluation of prenatal testing programmes should also include measures of informed choice.     

Are there any changes in Down Syndrome prevalence in France following the implementation of the measurement of nuchal translucency and maternal serum screening?

OBJECTIVE: To evaluate the impact of prenatal screening for Down Syndrome in France in relation to the important changes in the French prenatal screening policy during the years 1996-1997: measurement of nuchal translucency and maternal serum screening, for all women. PATIENTS AND METHOD: Data are those published from three congenital anomalies registries implanted in Centre-Est, Paris and Bas-Rhin areas, from 1990 to 2001. RESULTS: The livebirth prevalence of Down Syndrome decreased from 1/950 in 1990 to 1/1500 in 2000-2001. This decrease was observed from 1994 onwards but has proved stronger since 1996, in spite of the observed increase in the total prevalence partly explained by changes in the maternal age distribution. Extrapolated to all births in France, the calculated annual number of Down Syndrome births would decrease from 800-900 in 1990 to 500-600 in 2001. Consequently, the proportion of induced terminations following prenatal diagnosis increased from 38.6% in 1990 to 75.5% in 2001. In addition, the mean gestational age of the induced terminations is decreasing. CONCLUSION: It seems reasonable to assume that the observed trends followed the changes in the French national policy for prenatal screening: a mass screening for all women, whatever the maternal age.     

Maternal age-specific fetal loss rates in Down syndrome pregnancies

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

The relationship between utilization of prenatal care and Down syndrome live births.

OBJECTIVE: This study evaluated whether utilization of prenatal care, as measured by the Kessner index, affects the number of Down syndrome live births. METHODS: A retrospective analysis of birth certificate data of Down syndrome live births comparing 1989 to 2001 by year, maternal age, gestational age at first prenatal visit, and adequacy of prenatal care according to Kessner categories of adequacy of prenatal care. RESULTS: Down syndrome live births were inversely correlated with adequacy of prenatal care. Reductions in Down syndrome live births were seen in all categories of prenatal care in all age groups. In 2001 a minimum 30% reduction was seen in any category rising to a 58% reduction in women > or =35 years with adequate prenatal care. The largest reductions were seen in women > or =35 years of age. CONCLUSIONS: Reductions in Down syndrome live births occurred in all age groups between 1989 and 2001. Utilization of prenatal care as measured by the Kessner index was associated with reductions in Down syndrome live births, with a greater reduction in women > or =35 years of age.     

Prenatal diagnosis and elective termination of Down syndrome in a racially mixed population in Hawaii, 1987-1996

The impact of demographic factors on the prenatal diagnosis and elective termination of Down syndrome in Hawaii between 1987 and 1996 were examined. Data were obtained from a population-based birth defects registry and included 306 Down syndrome cases. 131 (43 per cent) of the cases were prenatally diagnosed. Of the prenatally diagnosed cases, 110(84 per cent) were electively terminated. Advanced maternal age or having a maternal serum alpha-fetoprotein screen performed increased the probability of having an affected pregnancy prenatally diagnosed and electively terminated. Far East Asians were substantially more likely to have an affected pregnancy prenatally diagnosed and electively terminated. Pacific Islanders and Filipinos were less likely to have cases prenatally diagnosed and electively terminated. Prenatally diagnosed and electively terminated Down syndrome cases had disproportionately fewer additional birth defects than live births or fetal demises, suggesting that for many of the electively terminated cases additional birth defects may not have been identified. This implies that the elective termination of Down syndrome-affected pregnancies may influence not only the Down syndrome prevalence but also that of other birth defects.     

The relationship between utilization of prenatal care and Down syndrome live births

Objective. This study evaluated whether utilization of prenatal care, as measured by the Kessner index, affects the number of Down syndrome live births.

Methods. A retrospective analysis of birth certificate data of Down syndrome live births comparing 1989 to 2001 by year, maternal age, gestational age at first prenatal visit, and adequacy of prenatal care according to Kessner categories of adequacy of prenatal care.

Results. Down syndrome live births were inversely correlated with adequacy of prenatal care. Reductions in Down syndrome live births were seen in all categories of prenatal care in all age groups. In 2001 a minimum 30% reduction was seen in any category rising to a 58% reduction in women ≥35 years with adequate prenatal care. The largest reductions were seen in women ≥35 years of age.

Conclusions. Reductions in Down syndrome live births occurred in all age groups between 1989 and 2001. Utilization of prenatal care as measured by the Kessner index was associated with reductions in Down syndrome live births, with a greater reduction in women ≥35 years of age.     

Trends in live birth prevalence of down syndrome in the Northern Netherlands 1987-96: the impact of screening and prenatal diagnosis

In the Northern Netherlands, we examined the live birth prevalence of Down syndrome (DS) and the impact of maternal serum screening (MSS) and prenatal cytogenetic diagnosis (PCD) during the period 1987-96. In this period the live birth prevalence, based on the maternal age distribution and the age specific risk of delivering a child with DS was expected to increase from 1.26 in 1987 to 1.62 in 1996. The introduction of MSS in 1991 made PCD available to women of all ages. Nevertheless, the utilization of PCD remained very stable. In 1991, 4.7% of pregnant women underwent a diagnostic test. In 1996 this percentage was 6.4%. As a result of MSS and PCD, the live birth prevalence of DS was 19% lower than expected (p<0.01). Despite utilization of PCD based on opting-in and a discouraging government policy regarding the offer of MSS, the percentage of DS cases detected by PCD increased from of 17% during the period 1987-90 to 27% in the period 1991-96 when MSS was available. The percentages have been corrected for spontaneous pregnancy loss. From a medical and financial point of view, MSS was the most cost-effective indication for PCD. However, the potential of reducing the birth prevalence of DS is limited by the low utilization of MSS and PCD by pregnant women.     

Changes in fetal prevalence and outcome for trisomies 13 and 18: a population-based study over 23 years

Objective.?Changes in prenatal diagnosis and maternal age are likely to have an impact on live born prevalence of trisomies 13 and 18. We investigated trends in diagnosis, prevalence, and survival in these conditions.

Methods.?A population-based study of one UK health region in 1985–2007 using a well-established congenital abnormality register. Individual records were reviewed and live birth and maternal age data obtained.

Results.?Pregnancies with trisomies 13 and 18 increased from 0.08 to 0.23 per 1000 registered births and 0.20 to 0.65 per 1000 registered births, respectively. Prenatal diagnosis increased and was associated with high termination rates. Live born prevalence with trisomy 13 decreased from 0.05 to 0.03 per 1000 live births and with trisomy 18 from 0.16 to 0.10 per 1000 live births. Postnatal survival remains poor: one baby (3%) with trisomy 13 and four (6%) with trisomy 18 survived the first year. The percentage of mothers over 35 years increased from 6 to 15%.

Conclusions.?Changes in prenatal screening and maternal age have had dramatic effects on the live born prevalence of trisomies 13 and 18. Infant survival remains largely unchanged with the majority dying in the neonatal period.     

An outcomes analysis of five prenatal screening strategies for trisomy 21 in women younger than 35 years

OBJECTIVE: This study was undertaken to examine the cost-effectiveness and procedural-related losses associated with 5 prenatal screening strategies for fetal aneuploidy in women under 35 years old. STUDY DESIGN: Five prenatal screening strategies were compared in a decision analysis model: triple screen: maternal age and midtrimester serum alpha-fetoprotein, human chorionic gonadotropin (hCG), and unconjugated estriol; quad screen: triple screen plus serum dimeric inhibin A; first-trimester screen: maternal age, serum pregnancy-associated plasma protein A and free beta-hCG and fetal nuchal translucency at 10 to 14 weeks' gestation; integrated screen: first-trimester screen plus quad screen, but first-trimester results are withheld until the quad screen is completed when a composite result is provided; sequential screen: first-trimester screen plus quad screen, but the first-trimester screen results are provided immediately and prenatal diagnosis offered if positive; later prenatal diagnosis is available if the quad screen is positive. Model estimates were literature derived, and cost estimates also included local sources. The 5 strategies were compared for cost, the numbers of Down syndrome fetuses detected and live births averted, and the number of procedure-related euploid losses. Sensitivity analyses were performed for parameters with imprecise point estimates. RESULTS: In the baseline analysis, sequential screening was the least expensive strategy ($455 million). It detected the most Down syndrome fetuses (n=1213), averted the most Down syndrome live births (n=678), but led to the highest number of procedure-related euploid losses (n=859). The integrated screen had the fewest euploid losses (n=62) and averted the second most Down syndrome live births (n=520). If fewer than 70% of women diagnosed with fetal Down syndrome elect to abort, the quad screen became the least expensive strategy. CONCLUSION: Although sequential screening was the most cost-effective prenatal screening strategy for fetal trisomy 21, it had the highest procedure-related euploid loss rate. The patient's perspective on detection versus fetal safety may help define the optimal screening strategy.     

Influence of maternal smoking on the birth prevalence of Down syndrome and on second trimester screening performance

OBJECTIVES: To determine the influence of maternal smoking on the birth prevalence of Down syndrome and on second trimester screening performance. METHODS: First, a meta-analysis of cohort and case-control studies was performed to estimate the effect of maternal smoking on the live birth prevalence of Down syndrome. Then, data from 8779 women screened using the quadruple test (alphafetoprotein (AFP), unconjugated estriol (uE(3)), human chorionic gonadotrophin (free beta-hCG), and inhibin-A levels with maternal age) were used to determine the effect of smoking on the serum markers. A Monte Carlo simulation was used to assess the impact of adjusting for smoking status on screening performance. RESULTS: The relative risk of Down syndrome in smokers (versus non-smokers) was 0.95 (95% confidence interval (CI) 0.87 to 1.03). Serum marker levels were determined as multiples of the median for non-smokers of the same gestational age and adjusted for maternal weight (MoM). The MoM values for AFP were 5% higher (95% CI 2-7%), uE(3) 4% lower (95% CI 2-5%), free beta-hCG 20% lower (95% CI 17-23%) and inhibin-A 62% higher (95% CI 57-67%) in smokers compared with non-smokers. Adjusting marker levels for smoking resulted in less than a 1 percentage point increase in the detection rate for a 5% false positive rate with the double, triple or quadruple tests. CONCLUSIONS: There is no evidence of an association between the birth prevalence of Down syndrome and maternal smoking. The case for adjusting screening marker levels for smoking is not compelling. But if smoking data are collected routinely adjustment could be made and this would yield similar detection and false positive rates in smokers and non-smokers.     

Congenital anterior abdominal wall defects in the north of England, 1986-1996: occurrence and outcome.

The aim was to describe trends in prevalence, maternal age-specific prevalence, associated anomalies, clinical outcomes and the sensitivity of antenatal diagnosis of congenital anterior abdominal wall defects (in particular gastroschisis and exomphalos). Data were identified from a population-based register of major congenital abnormalities in the Northern health region of England, the Northern Congenital Abnormality Survey (NorCAS), between 1986 and 1996. 296 cases were notified; there were 133 cases of gastroschisis, 98 exomphalos, 30 limb-body wall defects and 23 other anterior abdominal wall defects. 12 cases could not be classified. In 19 (6 per cent) the initial diagnosis was changed following case review. 30 (30.6 per cent) cases of exomphalos were associated with a chromosomal anomaly compared with 1 (0.8 per cent) case of gastroschisis. The total prevalence for the 11 years was 6.33 (95 per cent CI=5.57-7.08) per 10 000 live births, still births and terminations of pregnancy, and the overall birth prevalence was 4.30 (95 per cent CI=3.68-4.93) per 10 000 live births and still births. For gastroschisis, there was a significant increase over the study period in both the total prevalence (1.48 in 1986 to 5.29 per 10 000 in 1996; chi(2)=8.41, p=0.00433) and the birth prevalence (1.48 in 1986 to 4.72 per 10 000 in 1996; chi(2)=7.42, p=0.00644), but there was no such significant increase for exomphalos (total prevalence chi(2)=2.29, p=0.13055; birth prevalence chi(2)=0.16, p=0.69348). The maternal age-specific prevalence was highest in the 11-19 year age group for gastroschisis but in the 35-39 year age group for exomphalos. Fewer pregnancies with gastroschisis resulted in a termination and a greater proportion of cases were alive at one year compared with exomphalos. The sensitivity of abnormality detection by ultrasonography was 75 per cent and 77.3 per cent for gastroschisis and exomphalos, respectively. Antenatal diagnosis improved from 47.4 per cent during 1986-91 to 80 per cent between 1992-96 for gastroschisis (chi(2)=5.7, p=0.00169), and from 55.6 per cent to 68.8 per cent for isolated exomphalos, although this increase was not significant. Total and birth prevalence of gastroschisis increased in the Northern region between 1986 and 1996. For exomphalos, there was a trend towards an increase in total prevalence and towards a decrease in birth prevalence. This decreasing trend has been accompanied by improvements in antenatal detection and subsequent termination of cases of exomphalos associated with other anomalies.     

Evolution of Down Syndrome Prenatal Screening Clinical Practices in Québec

ObjectivePrenatal screening for Down syndrome (DS) has evolved greatly over the last decades with the improvement of first- and second-trimester serum screening and the introduction of cell-free fetal DNA. This study aimed to estimate the impact of such changes on practices.MethodsThis retrospective cohort study included fetuses and newborns diagnosed with DS between 2005-2007 and 2015-2017 in the single obstetrical care centre in Québec City. Data were collected on the prenatal screening method, diagnosis, and delivery. The median was compared between the study periods.ResultsComplete clinical data were available for only 78 (66%) of 119 cases of DS. Significant changes were observed in screening methods, including an increase in the use of first-trimester serum, ultrasound, and cell-free fetal DNA. No significant changes were noted in terms of gestational age at diagnosis (median [interquartile range; IQR]: 17.0 [16.0–20.9] weeks in 2005-2007 vs. 17.9 [16.3–22.5] weeks in 2015-2017; P = 0.49) and delivery or termination of pregnancy (median 20.9 [IQR 18.0–23.3] weeks in 2005-2007 vs. 21.3 [18.4–23.4] weeks in 2015-2017; P = 0.46). The methods of diagnosis did not change significantly over the decade, with amniocentesis used 85% and 79% of the time, respectively (P = 0.19).ConclusionThe increased use of first-trimester screening and cell-free fetal DNA tests was not associated with earlier diagnosis of DS or earlier delivery or termination of pregnancy. The use of chorionic villus sampling should be encouraged for DS diagnosis when indicated because it could reduce the gestational age at diagnosis and termination if requested.     

Maternal serum hyperglycosylated human chorionic gonadotrophin (HhCG) in the first trimester of pregnancies affected by Down syndrome,using a sialic acid-specific lectin immunoassay

In a series of 54 cases of pregnancies complicated by Down syndrome and 224 unaffected pregnancies we examined maternal serum levels of hyperglycosylated human chorionic gonadotrophin (HhCG) in samples collected in the first trimester (11-13 weeks) using a sialic acid-specific lectin immunoassay. We compared these levels with those of other potential first trimester serum markers [free beta-hCG, pregnancy-associated plasma protein A (PAPP-A) and total hCG (ThCG)] and modeled detection rates and false-positive rates of various biochemical markers in conjunction with fetal nuchal translucency (NT) and maternal age using an maternal age standardized population. Maternal serum HhCG in cases of Down syndrome were significantly elevated (median MoM 1.97) with 24/54 (44%) of cases above the 95th centile for unaffected pregnancies. Free beta-hCG was also elevated (median MoM 2.09) with 33% of cases above the 95th centile. PAPP-A levels were reduced (median MoM 0.47) with 38% below the 5th centile. ThCG levels, whilst elevated (median MoM 1.34), had only 20% of cases above the 95th centile. Maternal serum HhCG levels were not correlated with fetal NT but showed significant correlation with ThCG and free beta-hCG and with PAPP-A in the Down syndrome group (r=0.536). Maternal serum HhCG levels in cases with Down syndrome had a significant correlation with gestational age, increasing as the gestation increased. When HhCG was combined together with fetal NT, PAPP-A and maternal age, at a 5% false-positive rate the modeled detection rate was 83%, some 6% lower than when free beta-hCG was used and some 4% better than when ThCG was used. Maternal serum HhCG is unlikely to be of additional value when screening for Down syndrome in the first trimester.     

Maternal education modifies the age-related increase in the birth prevalence of Down syndrome

OBJECTIVE: To test the hypothesis that the age-related increase in the birth prevalence of Down syndrome is less for women with higher levels of education due to their more frequent use of prenatal diagnosis. METHODS: We compared the effects of maternal age on the odds of Down syndrome at birth, and on amniocentesis use, in women with <12 years of education with those who had >or=12 years of education. We used a national data set and analyzed the effects of education separately for African Americans (N = 1643054), and non-Hispanic whites (N = 6676885) in the US birth cohorts of 1989-1991. Analyses included Mantel-Haenszel and logistic regression models with the likelihood ratio test to assess interactions between education and age effects. RESULTS: For both African Americans and non-Hispanic whites, the age-related increase in the odds of Down syndrome was substantially less for women with higher levels of education (p < 0.001). For both ethnic groups, women with higher levels of education were more likely to use amniocentesis (p < 0.001). CONCLUSIONS: Our results suggest that women with higher levels of education are more likely to use prenatal diagnosis. Moreover, this effect of education on prenatal diagnosis use, translates into a lower rate of age-related increase in the birth prevalence of Down syndrome.     

Antenatal detection and impact on outcome of congenital diaphragmatic hernia: a 12-year experience in Auvergne, France

OBJECTIVE: To evaluate the detection rate of prenatal diagnosis and its impact on outcome in congenital diaphragmatic hernia (CDH). STUDY DESIGN: We retrospectively studied 51 cases of CDH registered in the Auvergne area from January 1992 to December 2003 (Birth Defect Registry of Auvergne, Institut Européen des Génomutations). Our main outcome measurements were the detection rate of prenatal diagnosis, the incidence and types of associated anomalies and outcome (termination of pregnancy, in utero fetal demise, neonatal death, survival at the time of registration). RESULTS: Twenty-nine cases of isolated CDH were identified of which 13 were detected prenatally (45%) at a mean gestational age of 26.1 weeks and 22 cases of CDH with associated anomalies with prenatal diagnosis of CDH or any associated anomaly in 16 (73%; p=0.03) at a mean gestational age of 23.9 weeks. In the prenatally detected group (29 cases), there was 1 (3%) in utero fetal death (IUFD), 17 (59%) terminations of pregnancy (TOP) and 11 (38%) live births with early neonatal death in 7 (24%) cases despite delivery in a tertiary care centre in 10/11 cases (four survivors=14%). Most of the undetected cases were isolated CDH (16/22=73%) of which 1 (5%) was a stillborn and 21 (95%) live births with 17 survivors (77%) although 15/21 (71%) were not born at the tertiary care centre (p=0.001). The overall survival rate was 41% with a large variability depending on associated anomalies and prenatal diagnosis (p<0.0001) (prenatally detected cases: 3/13 (23%) isolated CDH and 1/16 (6%) CDH with associated anomalies; undetected cases: 13/16 (81%) isolated CDH and 4/6 (67%) CDH with associated anomalies). CONCLUSION: Prenatal diagnosis of CDH leads to the delivery of affected babies in tertiary care centres but it remains a challenge in particular for isolated CDH cases and it is associated with a lower survival rate. Associated anomalies contribute to prenatal detection, are related to a higher TOP rate but do not facilitate the detection of diaphragmatic defect per se.     

Preference assessment of prenatal diagnosis for Down syndrome: is 35 years a rational cutoff?

OBJECTIVE: To compare the perceptions of miscarriage and birth of a child with Down syndrome among pregnant women and to evaluate the implications of these preferences for the traditional 35-year old maternal age risk boundary. METHODS: An interviewer-administered survey was given to 186 pregnant women receiving antepartum care at a university hospital. Preferences, as reflected by utilities, for birth of a child with Down syndrome and pregnancy miscarriage, stratified by patient characteristics, were assessed. RESULTS: The utility for the birth of a child with Down syndrome decreased (p < 0.001) as clinical severity increased from mild (0.78) to severe (0.65). Miscarriage of a pregnancy had a mean utility of 0.76 +/- 0.31. Women who desired prenatal diagnosis had a utility value for miscarriage (0.79 +/- 0.28) that was significantly higher than for the birth of a child with Down syndrome of unknown severity (0.73 +/- 0.27). In multivariable logistic regression, desire for prenatal diagnosis was the only factor associated with a preference of miscarriage over birth of an affected child (odds ratio 2.26, 95% confidence interval 1.03, 4.96). CONCLUSION: Women who desire prenatal diagnosis do not perceive the birth of a child with Down syndrome and a pregnancy miscarriage to be equivalent health states. This finding calls into question the rationale of the 35-year-old maternal age criterion and suggests that actual patient preferences should be better incorporated into the decision to offer definitive prenatal diagnosis.     

Investigation of the epidemiology and prenatal diagnosis of holoprosencephaly in the North of England

OBJECTIVE: This study was undertaken to provide epidemiologic data on the prevalence of holoprosencephaly and to assess the sensitivity of routine ultrasonographic screening in a low-risk population. STUDY DESIGN: A population-based register of congenital abnormalities was used to identify reported cases of holoprosencephaly between 1985 and 1998. Sources included fetal losses, termination for fetal anomaly, stillbirths, and live births. Prenatal diagnoses and pregnancy outcomes were determined. RESULTS: Sixty-eight cases of holoprosencephaly were found among 531,686 births. The total prevalence (including pregnancy terminations) was 1.2 cases/10,000 registered births, and the birth prevalence (affected live births and stillbirths at >24 weeks' gestation) was 0.49 cases/10,000 births. Prenatal diagnosis was achieved in 71% of cases, rising to 86% during the second half of the study period; the mean gestational age at diagnosis was 19.8 weeks' gestation. Chromosomal abnormalities (75% of which were trisomy 13) were present in 38% of cases in which a karyotype was established. All those with aneuploidy (80% diagnosed prenatally) had other nonfacial anomalies; additional anomalies were also common in the euploid group (61% diagnosed prenatally), with 90% having facial abnormalities and 70% having other abnormalities. CONCLUSION: The prevalence of holoprosencephaly in second-trimester pregnancies was about 1 in 8000. Prenatal detection reached 86% with a routine anomaly scanning program. The etiology could usually be determined, which has important implications for recurrence risks.     

Down's syndrome in the Czech Republic 1961-1997

During the period from 1961-1997 the prevalence of Down's syndrome (DS) was followed up on the territory of the Czech Republic. From a consecutive series of 5,319,002 births in the CR during 1961-1997 4,933 cases of DS were diagnosed, incl. 4,410 in born infants and 523 were diagnosed prenatally and these pregnancies were terminated. The mean incidence of DS in born children during the investigation period was 7.91 per 10,000 liveborn infants. When the results of prenatal diagnosis of DS are added the mean incidence was 9.47 per 10,000 liveborn children. The prenatal diagnosis of DS in the CR was also investigated. The success rate of prenatal diagnosis of DS in the CR increased during the period from 1980-1997 to as much as 60% of detected cases. In 37.31% of all cases of Down's syndrome another inborn defect was found, most frequently inborn heart disease, defects of the central nervous system, gastrointestinal and urogenital tract. The age distribution of DS indicates a significantly increased risk for mothers already from the age of 34 years.     

Prenatal screening for Down syndrome with maternal serum human chorionic gonadotropin levels

Human chorionic gonadotropin levels in midtrimester pregnancies may be predictive of Down syndrome. A commercially available enzyme immunoassay kit was used to measure the beta-subunit of human chorionic gonadotropin in maternal sera from 38 Down syndrome pregnancies and 114 gestational age matched controls. The human chorionic gonadotropin levels were also assayed in 236 normal sera and plasma samples to determine normative values and appropriate individual corrections. Serum and plasma human chorionic gonadotropin levels are closely correlated and are stable at room temperature, during refrigeration, and throughout freeze-thaw cycles. There is no correlation between the human chorionic gonadotropin level and maternal age, weight, or race. However, the human chorionic gonadotropin level decreases with each week of gestation from 15 to 19 weeks. Medians for each week of gestation were established to account for this variable. Up to 63% of the Down syndrome pregnancies were detected with a cutoff of 2.0 multiples of the normal median. A computational combination of human chorionic gonadotropin and maternal serum alpha-fetoprotein testing will detect additional Down syndrome pregnancies and decrease the false-positive rate. The measurement of human chorionic gonadotropin appears to be a valuable addition to maternal serum alpha-fetoprotein screening programs that can significantly increase the proportion of Down syndrome cases diagnosed.     

Birth prevalence of Down's syndrome in England and Wales.

The natural birth prevalence of Down's syndrome for England and Wales in 1974-1987 (i.e., the birth prevalence in the absence of prenatal diagnosis and the induced abortion of affected pregnancies) was estimated by applying the maternal age-specific birth prevalence derived from epidemiological studies to the number of births in single-year age groups tabulated by the Office of Population Censuses and Surveys (OPCS). On average, the natural birth prevalence was 12.6 per 10,000 births and increased slightly from 12.2 to 13.2 per 10,000 births over the 14-year period. Using data on induced abortions carried out on account of Down's syndrome reported to OPCS under the statutory abortion notification scheme, 14 per cent of affected births were avoided by the induced abortion of affected pregnancies, so that the actual birth prevalence of Down's syndrome was estimated at 10.8 per 10,000 births. Using data on Down's syndrome births reported to OPCS under the voluntary congenital malformation notification scheme, the prevalence was 7.2 per 10,000 births, so only 67 per cent of the estimated number of affected births were, in fact, notified to the scheme.