Maternal age specific risk rate estimates for Down syndrome among live births in whites and other races from Ohio and metropolitan Atlanta, 1970-1989.

Our primary objective was to estimate, by one year and five year intervals, maternal age specific risk rates for Down syndrome among whites and among other races from two different populations, metropolitan Atlanta and south west Ohio, using live birth and prenatally diagnosed cases ascertained during 1970-1989. The five year estimates were also calculated separately for each of the five four year periods during these 20 years. Additionally, we compared two different methods of estimating these risk rates by using a third population of whites, and compared two different statistical methods of smoothing the risk rates. The results indicate good agreement between the metropolitan Atlanta and south west Ohio estimates within races, but show a statistically significant difference between the two race categories. Because 86% of live births in the "other races" category in the combined population are to blacks, these data may be seen as the first estimates of maternal age specific risk rates for Down syndrome among blacks calculated by one year intervals. We found excellent agreement in the risk rate estimates among the five four year time periods, between the estimates obtained by using the two different methods of estimation, and between the estimates obtained using the two different methods of statistical smoothing. Our estimated risk rates for white women in their 20s strongly reinforce those from previous studies currently being used for genetic counselling purposes. While we did find somewhat higher rates for women under 20, and increasingly higher rates for those over 30 years of age, these differences are not substantial. Thus, this study in general supports the risk rates estimated from data collected mostly during the 1960s and 1970s.

Epidemiologic study of Down syndrome in a racially diverse California population, 1989-1991.

The prevalence of Down syndrome was studied among all live births occurring between 1989 and 1991 in the California counties monitored by the California Birth Defects Monitoring Program. Objectives of this study were: 1) to calculate adjusted prevalence rates and quinquennial maternal age-specific risk rates of Down syndrome after adjusting for elective abortion of prenatally diagnosed fetuses; 2) to estimate the impact of prenatal diagnosis and subsequent elective abortion of affected fetuses on the observed prevalence of Down syndrome; and 3) to examine sex ratios among liveborn infants and fetuses with Down syndrome. The racial/ethnic diversity and large size of the population allowed the data to be stratified into five racial categories-Hispanics, whites, Asians, blacks, and others. For the period 1989-1991, the observed prevalence of Down syndrome was 1.13 per 1,000 live births, and the adjusted total prevalence, which took into account the termination of affected pregnancies following prenatal diagnosis, was 1.53 per 1,000 live births. In a comparison of quinquennial maternal age-specific risk rates of Down syndrome by race, Hispanics and whites were the only groups with rates that differed significantly from each other, with Hispanics exhibiting higher rates at maternal ages under 40 years. The overall reduction in live births with Down syndrome in 1989-1991 that could be attributed to prenatal diagnosis and elective abortion of affected fetuses was 25.8%, with a 49.1% reduction being observed at maternal ages > or = 35 years. In 1990-1991, Hispanics had the lowest overall reduction (10.0%), while whites had the highest reduction (46.3%). The male: female ratios among liveborns with Down syndrome were significantly higher than those among all live births, and race had a significant association with sex ratios in both cases and controls. These findings indicate that prenatal diagnosis and elective termination of affected pregnancies has had a substantial impact in reducing the number of liveborns with Down syndrome in the monitored California counties. The effect was greatest for whites and least for Hispanics, with results indicating considerable variation in the use of prenatal diagnostic services among racial/ethnic groups. Estimates of adjusted total prevalence and reduction in live births with Down syndrome in this study should be considered minimal because of some underascertainment of prenatally diagnosed cases.

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.

Impact of prenatal diagnosis on revised livebirth prevalence estimates of Down syndrome in the Lothian region of Scotland, 1978-1992.

Ramsay et al. [(1991) Biomed Pharmacother 45:267-272] reported on the livebirth prevalence of Down syndrome in the Lothian region of Scotland during 1978-1989. Their results suggested a temporal association between the events of Chernobyl in April 1986 and a significant-excess of cases in 1987. In the current study the data were extended for 3 years and reanalyzed, a major objective being to correct for the differential loss of fetuses with Down syndrome which occurs between prenatal diagnosis and birth. Other objectives were to estimate the prevalence reduction due to prenatal diagnosis, quinquennial maternal age-specific risk rates, and the level of ascertainment of cases. The reanalysis found a 12-year prevalence rate of 1.29 vs. the previous rate of 1.34, and a shift of the annual prevalence peak to 1988, with a reduced prevalence in 1987 compared to that found in the earlier study. The new results are less consistent in showing an association of Down syndrome clustering with the Chernobyl accident. For the 15-year study period, a 23% overall reduction in prevalence occurred due to prenatal diagnosis and elective abortion of affected fetuses, with a 50% reduction to women > or = 35 years of age. For 1988-1992, these reductions were 33% and 60%, which are among the highest reported in the literature for these time periods. The estimated quinquennial maternal risk rates were very similar to others already reported, and the data are consistent with a high level of case ascertainment. Since these women are approaching the upper limits of fetal detection through advanced maternal age alone, continued reduction in prevalence rates for Down syndrome through prenatal diagnosis and elective abortion will come mostly from increased use of other (chemical) screening techniques now available.

Evaluating false positives in two hospital discharge data sets of the Birth Defects Monitoring Program.

The principal goal in this study was to quantify false positives in the hospital discharge data of the Birth Defects Monitoring Program conducted by the Centers of Disease Control and Prevention. The two hospital data processing agencies which contribute data to the Birth Defects Monitoring Program, the Commission on Professional and Hospital Activities and the McDonnell Douglas Health Information Systems, had respective levels of false positives of 13.2 percent and 8.5 percent, levels which were statistically different from each other. These false positive levels should be considered minimal because these data bases do not include information on sick babies who may be transferred into or out of member hospitals, and who may have their initial diagnoses significantly modified. Potential correlates of false positives were evaluated, including hospital size, diagnostic certainty, race, sex, and insurance source. Two-thirds of all false positives were due to the miscoding of correctly diagnosed anomalies, and another quarter were clearly contradicted in notes easily available before the patients were discharged. The authors hope that this study of false positives will enhance the interpretation of the Birth Defects Monitoring Program data and lead to improved understanding of data collection and processing.

Evaluating a new algorithm for linking maternal and newborn medical records.

Linking material and newborn medical records is a valuable tool for assessing the relationship between maternal variables and fetal outcome. This study evaluated the Center for Disease Control's newly developed maternal and newborn medical record linkage system, a computer program that uses weighted variables to determine the most likely maternal and newborn pairs. Any newborn record not achieving a set minimum score with a maternal record remains nonmatched. The objectives of the study were to estimate the program's matching accuracy, determine causes of incorrect matches and nonmatches, develop suggestions for program revisions, and evaluate the effects of the revisions. The study sample included 521 matched and 247 nonmatched maternal and newborn medical records from seven Ohio hospitals. Of all available newborn records (10,068), 574 (5.7%) did not match with maternal records; for those in which a match occurred, the authors ascertained a 98% matching accuracy and determined explanations for nonmatched and incorrectly matched records. The authors noted a greater prevalence of birth defects and prematurity among newborns with nonmatched records than among those with matched records. Program revisions, therefore, focused on reducing the prevalence of nonmatched records. The revised program reduced the prevalence of nonmatched records from 5.7% to 3% but reduced matching accuracy.

Comparative epidemiology of Down syndrome in two United States population, 1970-1989.

This study compared the epidemiology of Down syndrome over a 20-year period, 1970-1989, in two populations in which livebirths with Down syndrome were believed to be highly ascertained. One population was a 10-county region in southwest Ohio; the second was a five-county region in metropolitan Atlanta, Georgia. The major objectives were to 1) compare observed incidences of Down syndrome over the entire study period; 2) calculate expected incidences of Down syndrome for each population and compare these with observed incidences; 3) determine incidence trends throughout the period; and 4) examine the impact of prenatal diagnosis on the observed incidence of Down syndrome in each population. Excluding aborted fetuses with Down syndrome diagnosed prenatally, the observed incidence of Down syndrome, 0.98, was significantly lower than that expected, 1.27, within the Atlanta white data set. Once the observed data were adjusted to include aborted fetuses with Down syndrome (total incidence = 1.17), no statistically significant differences remained. No differences were found between observed and expected incidences of Down syndrome for whites in southwest Ohio or for other races in either population. Although uncorrected observed incidences were significantly different between the two populations of whites for the entire 20-year period, the differences again disappeared after the data were corrected to include aborted fetuses. No significant effect of prenatal diagnosis on those of other races was found in either population. Expected Down syndrome incidences rose from the late 1970s throughout the 1980s for both racial groups in Ohio and Atlanta, Georgia; however, because the termination of fetuses with Down syndrome increased over the decade, the observed incidence among whites in southwest Ohio remained at earlier levels and actually fell among whites in Atlanta. These results indicate the increasing importance of prenatal diagnosis and selective abortion in the epidemiology of Down syndrome and of correcting for it when comparing incidences between populations, even within the same time period. These data from 2 decades show that differences in both observed and expected incidences of Down syndrome exist between both populations and races, principally because of differences in demographic age structure and maternal age fertility rates and because of differential use of prenatal diagnosis and selective abortion.

Revised estimates and projections of Down syndrome births in the United States, and the effects of prenatal diagnosis utilization, 1970-2002.

The objectives of this study were to: calculate revised estimates and projections of United States annual Down syndrome (DS) births for 1970-2002, and estimate the effects of amniocentesis on these baseline DS birth projections. Three models of amniocentesis utilization among 30-34 and greater than or equal to 35-year-old women were considered. The recently revised Census Bureau birth projections, and new single year maternal age DS risk rates estimated from a 1970-1983 Ohio data set, were used. Data from all three Census Bureau projection series were analysed; series II was considered in depth since it is consistent with recent fertility levels. Assuming no use of amniocentesis, total estimated DS births dropped from about 4770 in 1970 to 4120 in 1980 (a 14 per cent decline), but are projected to a plateau of about 5100 by the year 1990 (a 24 per cent increase). DS births to women greater than or equal to 35 would increase dramatically from about 1050 in 1980 to 1900 in 2000 (an 81 per cent increase). Assuming 1983 Ohio prenatal diagnosis ratios for women aged 30-34 (1.7 per cent) and greater than or equal to 35 (23.4 per cent) are used nationally, an annual reduction of about 7 per cent of DS births in 1986 and 9 per cent in 2002 would result. Fifty and 70 per cent utilization among women 30-34 and greater than or equal to 35, respectively, would reduce DS births by about 33 per cent in 1986 and 38 per cent in 2002. Therefore, if the projected increase in DS births is to be averted, utilization of prenatal diagnosis by greater than or equal to 30-year-old women must increase substantially.

Temporal changes in Ohio amniocentesis utilization during the first twelve years (1972-1983), and frequency of chromosome abnormalities observed.

The history of amniocentesis utilization in the seventh largest state of the United States is documented from its inception in 1972 through the first half of 1984. Amniocentesis utilization ratios for Ohio residents aged greater than or equal to 35 have increased from 0.21 per cent (19/9091) in 1972 to 23.4 per cent (1655/7531) in 1983, representing an average annual growth rate of 43.1 per cent. Of the amniocenteses performed from January 1, 1978-July 1, 1984, 71 per cent were referred for advanced maternal age (greater than or equal to 35), 15 per cent for maternal anxiety (30-34), 10 per cent for family history or previous child with a genetic defect, and 4 per cent for other reasons. Between 1978-1983 utilization by women 45 years of age was only 20 per cent higher than women 35 even though their risk of giving birth to a Down syndrome child was bout one order of magnitude higher. In addition, various factors were tested as to whether they affected utilization of amniocentesis by women greater than or equal to 35 during 1978-1983. A strong correlation of +0.89 existed between county population size and utilization ratios. No difference in utilization was found between whites and nonwhites, regardless of county population size. When utilization ratios were compared separately between Protestants, Catholics and other religions in Ohio's most populated county, no statistical differences were found. From 1978-July 1, 1984, the frequency of all cytogenetically abnormal chromosome results observed in Ohio amniocenteses to women greater than or equal to 35 was 2.48 per cent (187/7536). Of these, 2.15 per cent (162/7536) had unbalanced karyotypes. Future maximum amniocentesis utilization for women greater than or equal to 35 is estimated at 60-70 per cent.