Prenatal diagnosis, pregnancy terminations and prevalence of Down syndrome in Atlanta

BACKGROUND: The impact of prenatal diagnosis on the live birth prevalence of Down syndrome (trisomy 21) has been described. This study examines the prevalence of Down syndrome before (1990-1993) and after inclusion of prenatally diagnosed cases (1994-1999) in a population-based registry of birth defects in metropolitan Atlanta. METHODS: We identified infants and spontaneous fetal deaths with Down syndrome (n = 387), and pregnancies electively terminated after a prenatal diagnosis of Down syndrome (n = 139) from 1990 to 1999 among residents of metropolitan Atlanta from a population-based registry of birth defects, the Metropolitan Atlanta Congenital Defects Program (MACDP). Only diagnoses of full trisomy 21 were included. Denominator information on live births was derived from State of Georgia birth certificate data. We compared the prevalence of Down syndrome by calendar period (1990-1993, 1994-1999), maternal age (<35 years, 35+ years), and race/ethnicity (White, Black, other), using chi-square and Fisher's exact tests. RESULTS: During the period when case ascertainment was based only on hospitals (1990-1993), the prevalence of Down syndrome was 8.4 per 10,000 live births when pregnancy terminations were excluded and 8.8 per 10,000 when terminations were included. When case ascertainment also included perinatal offices (1994-1999), the prevalence of Down syndrome was 10.1 per 10,000 when terminations were excluded and 15.3 when terminations were included. During 1990-1993, the prevalence of Down syndrome was 24.7 per 10,000 among offspring to women 35+ years of age compared to 6.8 per 10,000 among offspring to women <35 years of age (rate ratio [RR] = 3.65, 95% confidence interval [CI] = 2.53-5.28). During 1994-1999, the prevalence of Down syndrome was 55.3 per 10,000 among offspring to women 35+ years compared to 8.5 per 10,000 among offspring to women <35 years (RR = 6.55, 95% CI = 5.36-7.99). There was no statistically significant variation in the prevalence of Down syndrome by race/ethnicity within maternal age and period of birth strata. During 1994-1999, the proportion of cases that were electively terminated was greater for women 35+ years compared to women <35 years (RR = 5.10, 95% CI = 3.14-8.28), and lower for Blacks compared to Whites among women 35+ years of age (RR = 0.33, 95% CI = 0.16-0.66). CONCLUSIONS: In recent years, perinatal offices have become an important source of cases of Down syndrome for MACDP, contributing at least 34% of cases among pregnancies in women 35+ years of age. Variation in the prevalence of Down syndrome by race/ethnicity, before or after inclusion of cases ascertained from perinatal offices, was not statistically significant. Among Down syndrome pregnancies in mothers 35+ years we found a lower proportion of elective termination among Black women compared to White women. We suggest that future reports on the prevalence of Down syndrome by race/ethnicity take into account possible variations in the frequency of prenatal diagnosis or elective termination by race/ethnicity.     

Epidemiology of Down syndrome (Trisomy 21), Hawaii, 1986-97

BACKGROUND: The live birth prevalence of Down syndrome is approximately 10 per 10,000 live births in the United States. Down syndrome prevalence has been reported to change over time and to vary by selected demographic factors. METHODS: Data from a population-based birth defects registry in Hawaii involving 363 Down syndrome cases delivered during 1986-97 were used to calculate overall prevalence and to investigate secular trends and differences by selected demographic factors. RESULTS: The total (live birth, fetal death, and elective termination) prevalence was 14.74 per 10,000 live births and fetal deaths. The unadjusted live birth prevalence was 8.67 per 10,000 live births. The adjusted live birth (live births and proportion of elective terminations expected to have resulted in live births) prevalence was 12.59 per 10,000 live births. No significant secular trends were observed for either total prevalence (P = 0.688) or adjusted live birth prevalence (P = 0.604). The total Down syndrome prevalence per 10,000 live births was highest for Far East Asians (22.01), followed by whites (17.06), Filipinos (15.94), and Pacific Islanders (9.21). Prevalence per 10,000 births was higher in metropolitan Honolulu (18.57) than in the rest of Hawaii (14.15). After adjusting for maternal age, however, the differences within the demographic groups were not statistically significant. CONCLUSIONS: The live birth prevalence of Down syndrome in Hawaii during 1986-97 was lower than reported in the literature. Prevalence did not change significantly over time. Any differences in prevalence by maternal race/ethnicity and place of residence appeared to result from differences in maternal age distribution.     

Changes in maternal age distribution and their possible impact on demand for prenatal diagnostic services

Between 1977 and 1985 there was a 65% increase in births to women aged 35 or more in England and Wales, but only a 15% increase in all births. Two factors of roughly equal importance were responsible for this differential increase. Firstly, the proportion of older women (35-44) among all women of reproductive age (15-44) increased from 28% in 1977 to 31% in 1985; and, secondly, in the same period the fertility rate for women aged 35-39 increased from 18·2 to 24·1 per 1000 and for women aged 40-44 from 4·1 to 4·6 per 1000.The increased fertility rate among older women is not due to an extension of the reproductive period but to a delay in childbearing. This delay was seen in women married only once and also in those who had remarried.As prenatal diagnosis for the exclusion of chromosome abnormalities is customarily offered to older mothers the increased numbers of women aged 35 or more and their increased fertility rate have important implications for the provision of obstetric and laboratory services. There were 51 859 live births to women aged 35 and over in 1985; the projected figure for 2001 is 85 000. If the use of prenatal diagnosis continues to increase facilities for about 70 000 prenatal cytogenetic analyses will be needed in 2001.     

Trisomies 13 and 18: prenatal diagnosis and epidemiologic studies in Hawaii, 1986-1997

Using a birth defects registry, this study examined the influence of prenatal diagnosis and elective termination of pregnancy on trisomy 13 and trisomy 18 prevalence in Hawaii between 1986 and 1997. The investigation also evaluated the impact of various demographic factors on risk for the aneuploidies. Forty-seven cases of trisomy 13 and 116 cases of trisomy 18 were identified. The total prevalence of trisomy 13 was 1.91 per 10,000 births and of trisomy 18 was 4.71 per 10,000 births. Elective terminations accounted for 38.3% of trisomy 13 cases and 48.3% of trisomy 13 cases. The 1-year mortality rate for trisomy 13 was 89.5% and for trisomy 18 was 74.3%. Rates for both aneuploidies increased during the time period. The racial/ethnic group with the highest prevalence of both anomalies was Far East Asian. The aneuploidies were more common in metropolitan Honolulu than the rest of Hawaii. Demographic factors demonstrated differences in risk for trisomies 13 and 18, although most of these differences appeared to be due, at least in part, to differences in maternal age distribution. For the secular trend, increased prenatal diagnosis of the anomalies also contributed to the observed increase.     

An analysis for temporal variation in Down syndrome births in Ohio, 1970–1979

Our study investigates the epidemiology of Down syndrome (DS) in the state of Ohio during the 1970s. The occurrence of DS births was examined to learn if statistically significant temporal variation was present among these data. Both monthly and annual numbers of DS births, adjusted for changing numbers of live births, were tested for such variation; furthermore, the data were analyzed for cyclic variation by attempting to fit simple trigonometric functions to the data.

Individuals with DS were ascertained using the records of cytogenetics laboratories and birth certificate records. Demographic data such as race, date of birth, and maternal age were collected on these individuals using their birth certificates as the data source. Appropriate parallel live-birth data were obtained from the Ohio Department of Health. The total number of affected individuals ascertained was 1,364, 66.7% of the total estimated population size. The data analysis was restricted to whites only (1,203 individuals) because they represented a more homogeneous sample than the total.

Monthly and annual variation in the numbers of live births was removed by producing single-year maternal-age adjusted numbers of DS births using the total Ohio white live births as the reference population. Analysis of covariance using single-year maternal ages ≤ 16 and ≥ 45 as the covariate was used to analyze the adjusted numbers of DS births for temporal variation.

No significant differences were detected among the annual adjusted numbers of DS births (P = .24), nor were there differences among the monthly adjusted numbers of DS (P = .37). The modes of ascertainment were tested to learn if there were annual or monthly differences in the method of ascertainment. No significant differences were detected for these data (P = .82 and P = .85, respectively). Furthermore, the data were separated into the maternal-age categories < 35 and ≥ 35, and annual and monthly adjusted DS births to these two maternal-age categories were examined for temporal variation. No significant differences were found among these data, P > .10 for all four of the tests. No simple cyclic functions were found to fit either the annual or monthly data.

The Ohio study reported here showed that through the use of a large sample, controlling for variation in the numbers of live births, and the use of detailed statistical tests, no significant temporal variation in the occurrence of DS births existed during the 1970s.

     

Chromosome abnormalities and spontaneous fetal death following amniocentesis: Further data and associations with maternal age

The pooled results are presented of two North American surveys concerning spontaneous fetal deaths of conceptuses with cytogenetic abnormalities diagnosed prenatally whose mothers had declined elective abortion. The rate of fetal death of those with nonmosaic genotypes associated with Down syndrome was 30.1% (95% confidence interval of 19.0%–42.0%), which is almost identical with the difference of 30% previously estimated between rates observed at amniocentesis and in live births. The fetal death rate for (nonmosaic) 47,+18 was 68.0% (95% confidence interval of 46.5%–85.1%), close to the estimated difference of 75% between rates at amniocentesis and in live births for this genotype. For other nonmosaic genotypes, the rates (and 95% confidence intervals) were: 47,+13, 42.9% (9.9%–81.6%); 47,XXX, 0% (0%–9.0%); 47,XXY, 8.1% (0.8%–11.0%); 47,XYY, 3.0% (.08%–15.8%); for balanced translocations and inversions, 2.8% (0.3%–9.8%); and for markers, variants, and fragments, 0% (0%–12.8%). For 45,X, the rate was 75.0% (42.8%–94.5%), in contrast to the rate for 46,XX/45,X of 10.5% (1.3%–33.1%) and for structural X abnormalities associated with Turner syndrome of 0% (0%–60.2%). The rate for nonmosaic 45,X is significantly different from that for either of the other two categories associated with Turner syndrome. The maternal age of nonmosaic 47,+21 fetuses that survived to live birth was 39.1 ± 6.2, not significantly different from the rate for fetal deaths: 39.5 ± 3.8. The observations provide no support for opposing hypotheses by other groups that maternal age is positively or negatively associated with fetal death of 47,+21 conceptuses. For other chromosome abnormalities, maternal ages of fetal deaths are slightly lower than for live births, but none of the differences are significant. The rates of spontaneous fetal deaths derived here are likely to be pertinent to genetic counseling. Their use in adjusting the rates of abnormalities diagnosed at amniocentesis will enable derivation of predicted contemporary live-birth prevalence rates of abnormalities that would be observed in absence of selective abortion.     

Rates of trisomies 21, 18, 13 and other chromosome abnormalities in about 20 000 prenatal studies compared with estimated rates in live births

Summary Data were analyzed on the results of 19675 prenatal cytogenetic diagnoses reported to two chromosome registries on women aged 35 or over for whom there was no known cytogenetic risk for a chromosome abnormality except parental age. The expected rates at amniocentesis of 47,+21; 47,+18; 47,+13; XXX; XXY; XYY; and other clinically significant cytogenetic defects by maternal age were obtained from a regression analysis on the observed rates, using a first degree exponential model. After an adjustment for maternal age, these rates were compared with previously estimated rates by maternal age in live births. The rates of 47,+21 at amniocentesis and live birth are approximately parallel, with the latter about 80% of the amniocentesis rates. The rates of 47,+18 at amniocentesis and live birth are approximately parallel, with the live birth rates about 30% of the amniocentesis rates, consistent with high fetal mortality of 47,+18 after amniocentesis. The rates of 47,+13 at amniocentesis indicate an increase in maternal age that is not as marked as thar previously estimated in live births. The rates at amniocentesis for XXX and XXY increase with maternal age, with the rates of XXY almost identical to those estimated previously in live births, suggesting no late fetal mortality of XXY. The rates of XYY show a slight decrease with maternal age also consistent with little late fetal mortality of XYY. No consistent trend with age is seen for the pooled group of other clinically significant defects.     

Extremely high prevalence of neural tube defects in a 4-county area in Shanxi Province, China

BACKGROUND: In the past, northern China's Shanxi Province has reported the highest incidence of neural tube defects (NTDs) in the world. However, little is known about the epidemiology of NTDs in this area in recent years. METHODS: Data were collected from a population-based birth defects surveillance system in 4 counties that captures information on all live births, stillbirths of at least 20 weeks' gestation, and pregnancy terminations at any gestational age resulting from prenatal diagnosis of a birth defect. We also surveyed mothers of NTD case patients to determine their use of folic acid before and during early pregnancy. RESULTS: During 2003, 160 NTD cases were identified among 11,534 births (NTD birth prevalence = 138.7/10,000 births). The rates of anencephaly, spina bifida and encephalocele were 65.9, 58.1, and 14.7 per 10,000, respectively, and a female predominance was observed among anencephaly cases (male-to-female relative risk [RR], 0.49; 95% confidence interval [CI], 0.30-0.79), but not among spina bifida (RR, 0.90; 95% CI, 0.55-1.45) and encephalocele (RR, 1.03; 95% CI, 0.40-2.69) cases. The percentages of pregnancy termination following prenatal diagnosis of anencephaly, spina bifida, and encephalocele were 50%, 41.8%, and 35.3%, respectively. NTD birth prevalence tended to be higher among mothers aged <20 or > or =30 years (P = .06) and was markedly associated with lower levels of maternal education (P < .001). Among 143 NTD mothers, only 6 (4.2%) used folic acid supplements during the periconceptional period. CONCLUSIONS: The NTD birth prevalence rate in the study area is among the highest worldwide. Folic acid deficiency may be one important risk factor.     

Prevalence of down syndrome among children and adolescents in metropolitan Atlanta

BACKGROUND: Down syndrome (DS) prevalence estimates beyond infancy are needed to assess health service needs among those with DS. METHODS: Children with DS born in metropolitan Atlanta from 1979 through 2003 were ascertained from a population-based birth defects registry. Vital status through 2003 was obtained using case records, vital records, and the National Death Index. Prevalence was calculated by dividing the children surviving with DS by the population derived from U.S. Census estimates. Variations in DS prevalence by race, heart defects, age, birth cohort, and time period were examined using Poisson regression. RESULTS: In metropolitan Atlanta in 2003, there were 67 livebirths with DS (13.0 per 10,000 livebirths) and 738 0- to 19-year-olds surviving with DS (8.3 per 10,000 population). Over time, births to mothers 35 years and older and DS birth prevalence increased. Birth prevalence was higher among Whites, did not vary by sex, and was higher for infants without heart defects. DS prevalence among 0- to 14-year-olds increased over time (p < .05). Within each 5 year birth cohort, prevalence decreased with age: this decrease was greater among Blacks than among Whites and among children with heart defects than among children without heart defects. CONCLUSIONS: DS prevalence increased among livebirths and among young children. Further studies are warranted to determine whether health services are meeting the needs of an increasing number of children with DS.     

Parents' age at birth of their offspring and child survival

This study presents some new results on parental age as a risk factor for child survival. The study is based on individual registration forms for live births and infant deaths collected in Hungary from 1984 to 1988. Logistic regression models have been fitted for early neonatal and neonatal mortality on the one hand, and post-neonatal mortality on the other hand. Children of older males and females have significantly higher early neonatal and neonatal mortality rates compared to those of younger males and females. The impact of age of both parents remains, however, slighter than that of other biological characteristics such as previous number of fetal deaths, induced abortions, or live births. The authors discuss possible biological explanations.     

Inherited structural cytogenetic abnormalities detected incidentally in fetuses diagnosed prenatally: frequency, parental-age associations, sex-ratio trends, and comparisons with rates of mutants

Rates of structural chromosome abnormalities were analyzed in 24,951 fetuses studied prenatally in which there were no grounds to suspect an inherited abnormality. In about one in 200 prenatal cytogenetic diagnoses, an unexpected structural abnormality was found. The observed rate was 5.3 per 1,000, of which 1.7 per 1,000 were unbalanced and 3.6 per 1,000 balanced. The rate of inherited abnormalities was 3.1-3.7 per 1,000 (0.4-0.9 per 1,000 for unbalanced abnormalities and 2.6-2.8 per 1,000 for balanced abnormalities). The rate of mutants in this series was, by contrast, 1.6-2.2 per 1,000 (0.8-1.2 per 1,000 for unbalanced abnormalities and 0.8-1.0 per 1,000 for balanced abnormalities). The rate of balanced Robertsonian translocation carriers was 0.6 per 1,000 (about 0.25 per 1,000 for mutants and 0.35 per 1,000 for inherited abnormalities), and for other balanced abnormalities, 3.0 per 1,000 (about 0.6 per 1,000 for mutants and 2.4 per 1,000 for inherited abnormalities). The rates of unbalanced Robertsonian translocations was about 0.1 per 1,000, almost all of which were mutants. For supernumerary rearrangements, the rate was 0.9 per 1,000 (about 0.4 per 1,000 inherited and 0.5 per 1,000 mutant). The rates of all unbalanced (nonmosaic) inherited abnormalities (4.0-5.2 per 10,000) were intermediate between higher rates estimated in all conceptuses (9.1-15.8 per 10,000) and rates observed in newborns (1.5-2.5 per 10,000). This trend is probably attributable to fetal mortality associated with unbalanced rearrangements. The rates of balanced (nonmosaic) inherited abnormalities (26.0-28.0 per 10,000), however, were considerably higher than the rates in all conceptuses (13-16.7 per 10,000) or in all live births (12.2-16.0 per 10,000). The major difference was in the rate of inversions. The use of "banding" methods in the studies of amniocentesis but not in most of the live births or abortus studies probably contributes to at least some of these differences. One trend in parental age among the inherited abnormalities was noteworthy. Paternal age was elevated for inherited balanced reciprocal structural abnormalities of paternal origin but not of maternal origin. With regard to sex ratio, there was a greater proportion of females than males among the unbalanced rearrangements both inherited and mutant. There was no obvious sex difference among the balanced rearrangements.     

Epidemiological trends in multiple births in the United States, 1971-1998.

The astounding rise in multiple births in the United States continues. We analyzed live birth files from the U.S. National Center for Health Statistics. Twin, triplet, quadruplet, and quintuplet+ rates were calculated for the period 1971-1977 and for each year between 1990 and 1998. Triplet rates were also computed within categories of mother's education and age. The twin rate increased from 1.8% in 1971-77 to 2.8% in 1998. The rate of triplets increased 5.9-fold, quadruplets 11.9-fold, and quintuplets+ 5.3-fold between 1971-77 and 1998. Increases in triplet rates were much more marked among births to university-educated women and women 30 years and older. Among women 45 years and older, the triplet rate was approximately fifty times higher in 1998 than in 1971-77. This group of older women (> or = 45 years) had the highest multiple birth rate in 1998.     

Perinatal mortality and adverse pregnancy outcomes in a low‐income rural population of women who smoke

We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low‐income, rural mothers who participated in two randomized smoking cessation trials. In the Baby BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women's pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women who had a live infant after November 2004 were recruited again into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population and perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than 20 weeks' gestation, 23% were premature births, and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1000 births (BB study) compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births (United States). The postneonatal infant mortality rate was 13.4 per 1000 live births (BBK) compared with 2.1 per 1000 live births (United States). The health disparity in this population of impoverished, rural, pregnant women who smoke, particularly in regard to perinatal and infant deaths, warrants attention. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.     

Prevalence of esophageal atresia among 18 international birth defects surveillance programs

BACKGROUND: The prevalence of esophageal atresia (EA) has been shown to vary across different geographical settings. Investigation of geographical differences may provide an insight into the underlying etiology of EA. METHODS: The study population comprised infants diagnosed with EA during 1998 to 2007 from 18 of the 46 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research. Total prevalence per 10,000 births for EA was defined as the total number of cases in live births, stillbirths, and elective termination of pregnancy for fetal anomaly (ETOPFA) divided by the total number of all births in the population. RESULTS: Among the participating programs, a total of 2943 cases of EA were diagnosed with an average prevalence of 2.44 (95% confidence interval [CI], 2.35–2.53) per 10,000 births, ranging between 1.77 and 3.68 per 10,000 births. Of all infants diagnosed with EA, 2761 (93.8%) were live births, 82 (2.8%) stillbirths, 89 (3.0%) ETOPFA, and 11 (0.4%) had unknown outcomes. The majority of cases (2020, 68.6%), had a reported EA with fistula, 749 (25.5%) were without fistula, and 174 (5.9%) were registered with an unspecified code. CONCLUSIONS: On average, EA affected 1 in 4099 births (95% CI, 1 in 3954–4251 births) with prevalence varying across different geographical settings, but relatively consistent over time and comparable between surveillance programs. Findings suggest that differences in the prevalence observed among programs are likely to be attributable to variability in population ethnic compositions or issues in reporting or registration procedures of EA, rather than a real risk occurrence difference. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.     

Perinatal mortality and adverse pregnancy outcomes in a low-income rural population of women who smoke

We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low-income, rural mothers who participated in two randomized smoking cessation trials. In the Baby BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women's pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women who had a live infant after November 2004 were recruited again into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population and perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than 20 weeks' gestation, 23% were premature births, and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1000 births (BB study) compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births (United States). The postneonatal infant mortality rate was 13.4 per 1000 live births (BBK) compared with 2.1 per 1000 live births (United States). The health disparity in this population of impoverished, rural, pregnant women who smoke, particularly in regard to perinatal and infant deaths, warrants attention.