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Risk of a Down syndrome live birth in women 45 years of age and older
Abstract
To determine the risk of a Down syndrome (DS) live birth for women 45 years of age and over.
A meta-analysis of data from five published articles, 13 EUROCAT congenital anomaly population registers and two unpublished sources.
Information was available on the number of DS live births occurring amongst 13,745 live births to women 45 years of age and over. Information was also available on DS pregnancies diagnosed prenatally that were subsequently terminated. These pregnancies were adjusted for expected fetal loss to estimate the number of live births that would have occurred in the absence of prenatal diagnoses, when a total of 471 DS live births were estimated to have occurred. The risk of a DS birth did not increase for women 45 years of age and over. The average risk was 34 per 1000 births (95% CI: 31-37).
The risk of a DS live birth for women 45 years of age and over is considerably lower than has often been previously assumed. The most likely explanation is that women of this age are more likely to miscarry DS pregnancies than younger mothers.
... Natural aging may reduce fertility in a patient seeking IVF treatment [16]. Women aged ≥35 years present increased risk of abortion, significantly reduced pregnancy and live birth rates, and increased risk of pregnancy comorbidities and complications [17][18][19][20]. Women aged ≥46 years were excluded from this study because their pregnancy rate tended to be 0% under a natural condition [21], and a recent study suggested that IVF treatment was futile in women aged ≥44 years (CLBR of 3% was never reached irrespective of the number of retrieved oocytes) [11]. ...
... Women who become pregnant at the age of ≥40 years face increased risks of stroke and heart attack later in their life compared with women who become pregnant at a younger age [29]. Increased risk of neonatal birth defects such as Down syndrome and cerebral palsy is associated with increased age during pregnancy [18,30]. ...
Objective:
The use of cumulative live birth rate (CLBR) per ovarian stimulation cycle is proving to be an accurate method to calculate the success of IVF; however, the cycle outcome is closely associated with the number of embryos transferred (ET). Our aim was to report CLBR after IVF according to the number of embryos required to achieve a live birth in women aged ≥35 years, considering age, body mass index (BMI), and ethnicity.
Methods:
We conducted a retrospective cohort study including 1344 patients who underwent IVF between January 2013 and June 2016 at the First Affiliated Hospital of Xinjiang Medical University. The cumulative probability of live birth for each couple was estimated using the Kaplan-Meier method, and survival curves were compared according to age, BMI, and ethnicity using the log-rank test.
Results:
CLBR increased rapidly from 1 to 5 ETs, moderately from 6 to 10 ETs, and slowly thereafter. CLBR was significantly different across 4 categories based on BMI as well as across those based on age; low CLBR was significantly associated with the age of ≥42 years and obesity.
Conclusion:
The association between CLBR and number of ET provides realistic and precise information regarding the success of IVF and can be applied to guide clinicians and patients.
... • Age is an independent risk factor for women's fecun- For women 35 years and older, the risk of spontaneous miscarriage, various pregnancy complications, and neonatal birth defects, as well as the incidence of infertility increase significantly, whereas the pregnancy rate and live birth rate decline significantly with age. [29][30][31][32][33] Advanced age is associated with a decreased fecundity and a higher incidence of female infertility: 6% at age 20-24, 9% at age 25-30, 15% ...
... 37 Women who were conceiving after 40 years old and greater face a higher risk of stroke and heart diseases in the future. 38 Neonates born to women with advanced age are more likely to suffer from certain birth defects such as Down's syndrome, cerebral palsy, etc. 31,39 Recommendation 3 ...
More women postpone childbearing nowadays while female fertility begins to decline with advancing age. Furthermore, with the rolling out of the two‐child policy, there is a huge demand for a second child for Chinese aged women. There are various assisted reproductive technology (ART) strategies applied for age‐related infertility without solid evidence. On behalf of the Society of Reproductive Medicine, Chinese Medical Association, we would like to develop a Chinese guideline of ART strategies for age‐related infertility. This guideline was produced following the recommendations for standard guidelines described in the 2012 WHO Handbook for guideline development. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was also followed. A protocol was formulated and a Guideline Development Group was formed with specialists of reproductive medicine, methodologists from Chinese GRADE working group, and patient representative. Questions regarding the ART strategies for aged infertility were formulated and 8 most important ones were chosen to be structured in PICO format (Population, Intervention, Comparison, Outcomes). Comprehensive search and review of the literature were performed and the quality of the evidence was assessed and rated based on certain criteria and be categorized as high, moderate, low, or very low. Twenty‐five recommendations were formulated among members of the Guidelines Development Group (Delphi method) basing on the overall quality of the evidence, in addition to the balance between benefits and harms, values and preferences, and resource implications. The final recommendations were agreed on by consensus during face‐to‐face meetings. This is the first Chinese practice guideline in reproductive medicine developed following the standard and scientific method.
... Plusieurs méthodes de dépistage ont été étudiées et continuent à voir le jour. Le principe du dépistage est basé sur un calcul de risque d'aneuploïdies tenant compte des facteurs de risque [1][2][3] liés à l'âge maternel, aux marqueurs biochimiques et aux marqueurs échographiques. Certains pays ont instauré un plan national pour organiser le dépistage prénatal de ces anomalies et la performance des différentes stratégies a été étudiée. ...
... Dans notre travail, le test combiné s'est avéré plus intéressant dans le sens où son utilisation aurait pu nous éviter 18 prélèvements invasifs. Le premier facteur de risque d'aneuploïdies a été l'âge maternel avec une prévalence, chez les femmes de 45 ans ou plus, de 34 pour 1000 [2]. Ainsi à la fin des années 70, la plupart des pays européens ont déterminé des « âges seuils » à partir desquels un caryotype pouvait être proposé aux patientes et pris en charge par le système de soin. ...
En Tunisie, nous ne disposons pas de plan national de dépistage des aneuploïdies. Nous nous proposons de comparer pour une même population deux méthodes de dépistage des aneuploïdies, et de discuter de l'importance de la qualité des mesures de la clarté nucale lors de l'échographie du premier trimestre. Il s'agit d'une étude prospective réalisée sur une période de 18 mois. Nous avons comparé les résultats du calcul de risque réalisé selon deux méthodes. La première tenant compte uniquement de l'âge maternel et des marqueurs sériques, et la deuxième intégrant en plus la clarté nucale. 19% des 221 parturientes étaient âgées de plus de 38 ans. Le test de dépistage selon la 1ère méthode était sensible pour le seul cas d'aneuploïdie rencontré. La puissance de ce test était de 60%. Le dosage des marqueurs sériques du deuxième trimestre a permis le dépistage des défauts de fermeture du tube neural avec une valeur statistiquement significative en termes de spécificité (98,6%) et de valeur prédictive négative (100%). La médiane des mesures de CN était de 0,75 MoM pour l'âge gestationnel. Uniquement 17,6% des mesures étaient situées dans l'intervalle [0,9 -1,1] MoM. Nous n'avons pas objectivé de différence significative entre les deux méthodes dépistage en matière de puissance. Cependant, en termes de faux positifs le test combiné s'est avéré plus intéressant, son utilisation aurait pu nous éviter 18 prélèvements invasifs. L'avenir immédiat en Tunisie doit se diriger vers un dépistage combiné au premier trimestre. Cette stratégie ne peut se faire qu'après instauration d'un contrôle qualité des mesures à la fois biologiques et échographiques.
... Table 2 shows the observed age-specific prevalence rates for each single year of age between 45 and 49 or more in 10 studies included in the four meta-analyses, in NDSCR and 87 cases from 12 of the congenital malformations registries belonging to the European network EUROCAT. 20 For Australia and Belgium, the studies in the second meta-analysis replacing those in the first metaanalysis were used, except that the 1960-1964 data from Australia was not excluded. The study from Wales did not include data in this maternal age range. ...
The birth prevalence rate of each common autosomal trisomy generally increases with advancing maternal age and there is a substantial fetal loss rate between late first trimester and term. The literature is reviewed in order to provide the best estimates of these rates, taking account where possible of biases due to prenatal diagnosis and selective termination of pregnancy. There is an almost exponential increase in Down syndrome birth prevalence between ages 15 and 45 but at older ages the curve flattens. There is no evidence of the claimed relatively high birth prevalence at extremely low ages. Gestation-specific intra-uterine fetal loss rates are estimated by follow-up of women declining termination of pregnancy after prenatal diagnosis, comparison of observed rates with those expected from birth prevalence and comparison of age-specific curves developed for prenatal diagnosis and birth. Down syndrome fetal loss rates reduce with gestation and increase with maternal age. Edwards and Patau syndrome birth prevalence is approximately 1/8 and 1/13 that of Down syndrome overall, although the ratio differs according to maternal age, particularly for Patau syndrome where it reduces steadily from 1/9 to 1/19. Fetal loss rates are higher for Edwards and Patau syndromes than for Down syndrome.
... The risk of having a baby with DS and risk of pregnancy loss because of invasive diagnostic procedures are approximately same at age 35. Consequently, age 35 has been used as a cut-off value for offering an invasive testing as a result of the study of Morris et al. (2005). ...
... However, the data used to construct the initial curve were collected between 1966 and 1980, when the proportion of older mothers was at its lowest in the relevant populations, and confidence intervals for the oldest groups were consequently very wide. Subsequent studies have included more data points (Ferguson-Smith and Yates 1984;Morris et al. 2002Morris et al. , 2005. We therefore combined the data of Hecht and Hook (1996) and Morris et al. (2002) in order to maximise the number of older mothers included (see ESM 1: Table 1 online resources). ...
Chromosomal disorders, of which Down syndrome is the most common, can cause multi-domain disability. In addition, compared to the general population, there is a higher frequency of death before the age of five. In many settings, large gaps in data availability have hampered policy-making, programme priorities and resource allocation for these important conditions. We have developed methods, which overcome this lack of data and allow estimation of the burden of affected pregnancies and their outcomes in different settings worldwide. For example, the methods include a simple equation relating the percentage of mothers 35 and over to Down syndrome birth prevalence. The results obtained provide a starting point for consideration of services that can be implemented for the care and prevention of these disorders.
... However, the data used to construct the initial curve were collected between 1966 and 1980, when the proportion of older mothers was at its lowest in the relevant populations, and confidence intervals for the oldest groups were consequently very wide. Subsequent studies have included more data points (Ferguson-Smith and Yates 1984;Morris et al. 2002Morris et al. , 2005. We therefore combined the data of Hecht and Hook (1996) and Morris et al. (2002) in order to maximise the number of older mothers included (see ESM 1: Table 1 online resources). ...
Chromosomal disorders, of which Down syndrome is the most common, can cause multi-domain disability. In addition, compared to the general population, there is a higher frequency of death before the age of five. In many settings, large gaps in data availability have hampered policy-making, programme priorities and resource allocation for these important conditions. We have developed methods, which overcome this lack of data and allow estimation of the burden of affected pregnancies and their outcomes in different settings worldwide. For example, the methods include a simple equation relating the percentage of mothers 35 and over to Down syndrome birth prevalence. The results obtained provide a starting point for consideration of services that can be implemented for the care and prevention of these disorders.
Electronic supplementary material
The online version of this article (10.1007/s12687-017-0336-2) contains supplementary material, which is available to authorized users.
... Both models seemed to fit very well from the ages of 34 to 41, but at and after the age 42 the rates predicted by logistic regression increased steadily, to much higher levels than in the chosen regression model with 2 parameters, for both the T21 rate and the rates of common autosomal trisomies (S1 and S2 Tables, S1 and S2 Figs). As the T21 rate at the age of more than 45 was observed to stop increasing, presumably due to very early spontaneous abortion [16], the continual increment of the rate in the logistic regression model was thus contradictory. These findings may well be the result of the lower numbers of cases (N <1,000) in the 42-and-higher age groups (Table 1). ...
To provide maternal age-specific rates for trisomy 21 (T21) and common autosomal triso-mies (including trisomies 21, 18 and 13) in fetuses. We retrospectively reviewed prenatal cytogenetic results obtained between 1990 and 2009 in Songklanagarind Hospital, a university teaching hospital, in southern Thailand. Maternal age-specific rates of T21 and common autosomal trisomies were established using different regression models, from which only the fittest models were used for the study. A total of 17,819 records were included in the statistical analysis. The fittest models for predicting rates of T21 and common autoso-mal trisomies were regression models with 2 parameters (Age and Age 2). The rate of T21 ranged between 2.67 per 1,000 fetuses at the age of 34 and 71.06 per 1,000 at the age of 48. The rate of common autosomal trisomies ranged between 4.54 per 1,000 and 99.65 per 1,000 at the same ages. This report provides the first maternal age-specific rates for T21 and common autosomal trisomies fetuses in a Southeast Asian population and the largest case number of fetuses have ever been reported in Asians.
... The risk of having a baby with DS and risk of pregnancy loss because of invasive diagnostic procedures are approximately same at age 35. Consequently, age 35 has been used as a cut-off value for offering an invasive testing as a result of the study of Morris et al. (2005). ...
The aim of this paper is to demonstrate the prenatal screening variables and risk factors of pregnancies with Down syndrome (DS) babies, and to explicate invasive prenatal testing strategies.This study consist of 21 " trisomy-21 " fetuses, diagnosed prenatally within the framework of prenatal screening and diagnosis programs at the Division of Perinatology, Hacettepe University. It also consist of a review of the prenatal screening variables and gestational risk factors for invasive prenatal testings. Researchers observed that advanced maternal age is the main risk factor for having an invasive prenatal testing. The other important factor associated with DS is ultrasonografic findings. Increased " double/combined test " risk (n=12), and increased " triple test " risk (n=3) were noted in 21DS cases. Among all the DS cases; 18 of them were terminated, the rest rejected the termination option. Prenatal diagnosis of DS is important in clinical practice, but physicians often come under the pressure of social and legal issues.
... The frequency of any chromosomal abnormality at birth for mothers at age 40 years is 1.5% and at age 45 4.8% in the absence of prenatal screening (Heffner, 2004). A meta-analysis of five published articles and 13 EUROCAT registries reported that trisomy 21 aneuploidy rose from 0.26% of births at age 35 to 0.94% at age 40 and 3.4% at age 45 (Morris et al., 2005). ...
BACKGROUND
The majority of women 40–49 years of age need an effective method of contraception because the decline in fertility with age is an insufficient protection against unwanted pregnancy. Although pregnancy is less likely after the age of 40 years, the clinical and social consequences of an unexpected pregnancy are potentially detrimental. No contraceptive method is contraindicated by advanced reproductive age alone; thus there is a need to discuss the effectiveness, risks and non-contraceptive benefits of all family planning methods for women in this age group.
METHODS
MEDLINE searches were done by topic (epidemiology, age and reproduction, sexual function, delayed childbearing and specific contraceptive methods). The topic summaries were presented to the Workshop Group and omissions or disagreements were resolved by discussion.
RESULTS
The decline in fecundity in the fifth decade is insufficient for contraceptive purposes. Thus a family planning method is needed. Sterilization is by far the most common method in several countries. Copper intrauterine devices and hormone intrauterine systems have similar effectiveness, with fewer than 1% failures in the first year of typical use. Special considerations in this age group include the frequency of menstrual irregularity, sexual problems and the possibility of menopausal symptoms, all of which may respond to hormonal methods of contraception.
CONCLUSIONS
Women should be advised to continue with a contraceptive method until they have reached the menopause with its natural state of sterility.
... Das geringste Risiko, ein Kind mit Down Syndrom zu bekommen, haben junge Mütter um 25 Jahre in 2 pro 1000 Fällen. Bis Anfang dieses Jahres, ging man davon aus, dass dieser Anstieg mit weiter steigendem mütterlichem Alter exponentiell verläuft, dies wurde jedoch durch [Morris et al. 2005] Individuen infolge dessen höhere Plasmawerte für Homocystein (Abbildung 2). d TMP: Desoxythymidin Monophosphat; d UMP: Desoxyuridin Monophosphat Der Polymorphismus ist weit verbreitet. ...
Das Down Syndrom trägt wesentlich zur Morbidität und Mortalität im Kindesalter bei und ist die häufigste Ursache geistiger Behinderung bei Neugeborenen. Überwiegend handelt es sich um Neumutationen mütterlichen Ursprungs. Die hohe Rate an Neumutationen und deren starke Zunahme mit dem mütterlichen Alter sprechen dafür, dass die Chromosomensegregation in der Oogenese ein sehr fehleranfälliger Prozess ist. Im Rahmen dieser Pilotstudie konnte eine deutliche Alterskorrelation zwischen dem Auftreten der Geburt eines Down Syndrom Kindes und dem elterlichen Alter beobachtet werden. Wie in anderen publizierten Studien wurde in der vorliegenden Studie gezeigt, dass das Geschlechterverhältnis bei den Down Syndrom Kindern von 1.37:1 (m:w ) deutlich zugunsten der Jungen verschoben ist. Der Schwerpunkt dieser Arbeit lag auf der molekulargenetischen Analyse der elterlichen Herkunft des zusätzlichen Chromosoms 21, der Verteilung der Cross-over, und der Analyse des MTHFR-Polymorphismus. Betrachtet man die 72 voll informativen maternalen Meiosen, so ergibt sich ein Verhältnis von Meiose I zu Meiose II von 80:20. Dieses Verhältnis korreliert mit anderen Studien zur parentalen Herkunft des zusätzlichen Chromosoms 21. Bemerkenswerter Weise fand sich unter den 93 paternal informativen Meiosen kein paternales Non-disjunction Ereignis. Dieses Ergebnis unterscheidet sich von den bisherigen epidemiologischen Studien zur parentalen Herkunft des zusätzlichen Chromosoms 21, wofür derzeit keine Erklärung existiert. Die Assoziation zwischen mütterlichem Alter und meiotischer Rekombination wurde analog zu der Studie von [Lamb et al. 2005] durchgeführt und bestätigt. Die erhobenen Daten aus dem Oman zeigen, dass das C-Allel mit 87% im Oman deutlich häufiger ist als in den anderen untersuchten Populationen. Dieses Ergebnis spricht für eine große geographische Variabilität des Polymorphismus und dafür, dass möglicherweise besondere Selektionsbedingungen auf der arabischen Halbinsel vorliegen.
... The advanced maternal age (AMA) is the only well known risk factor for giving birth to a child with DS, since birth prevalence increases 100-fold between the maternal ages of 15 and 45 (Penrose, 1933;Hook, 1976;Jones, 2006). The risk of having a live birth baby with DS for women 45 years of age or over is 1:29 and thereafter the risk remains static with increasing age (Ferguson-Smith and Yates, 1984;Morris et al., 2005a). It is, therefore, important to take maternal age into account in comparing outcomes of pregnancies, since the differences in age distribution cause the difference in Tr21 prevalence rates. ...
... Down syndrome (DS) corresponds to the phenotype produced by chromosome 21 trisomy. Its incidence is well-known to increase with strongly accelerating rate when mothers approach menopause (Penrose 1934;Hook 1981; Morris et al. 2002Morris et al. , 2005. Contrary to explanations involving accumulation of defects at recombination during prolonged first meiotic prophase , such dynamics may be anticipated from chromosomal drive (CD) for trisomy 21 (Day and Taylor 1998). ...
The neonatal incidence rate of Down syndrome (DS) is well-known to accelerate strongly with maternal age. This non-linearity renders mere accumulation of defects at recombination during prolonged first meiotic prophase implausible as an explanation for DS rate increase with maternal age, but might be anticipated from chromosomal drive (CD) for trisomy 21. Alternatively, as there is selection against genetically disadvantaged embryos, the screening system that eliminates embryos with trisomy 21 might decay with maternal age. In this paper, we provide the first evidence for relaxed filtering stringency (RFS) to represent an adaptive maternal response that could explain accelerating DS rates with maternal age. Using historical data, we show that the proportion of aberrant live births decrease with increased family size in older mothers, that inter-birth intervals are longer before affected neonates than before normal ones, and that primiparae exhibit elevated levels of DS incidence at higher age. These findings are predicted by adaptive RFS but cannot be explained by the currently available alternative non-adaptive hypotheses, including CD. The identification of the relaxation control mechanism and therapeutic restoration of a stringent screen may have considerable medical implications.
... While such selective factors may make a contribution, they cannot explain the size of the levelling observed. We estimated that the rates of Down syndrome for women aged 45 and over were 34 per 1000 births (95% CI: 31-37) (Morris et al., 2005), compared with 49 per 1000 predicted by Hook's most recent model (Hecht and Hook, 1996). A difference of this size could not be accounted for even if all the older mothers were of white European origin and the younger mothers of non-European origin. ...
... Studies have shown that 95% of the cases are of meiotic origin (95% in the egg and 5% in the sperm). Maternal age is the major known determinant, although recent research indicates that the risk of having informative offspring with Down syndrome does not increase beyond 45 years of age (Morris et al., 2003; 2005). In a minority of cases (2–4%), the extra chromosome 21 is present in some, but not all, cells of the individual (mosaicism). ...
The aim of the study was to examine the risk of giving birth to a child with Down syndrome associated with residence near landfill sites in England and Wales.
A 2-km zone around 6289 landfill sites processing special (hazardous), non-special and unknown waste type was used to indicate exposure. Postcodes within the 2-km zone were classified as 'exposed' and people living beyond 2 km comprised the reference population. Health outcome data were Down syndrome registrations from a national registry including 21 cytogenetic laboratories in England and Wales, for the years 1989 to 1998. With a Bayesian regression model, we calculated relative risks for the population living within 2 km of landfill sites relative to the reference population, assuming a common relative risk for all landfill sites. Adjustments were made for major confounders.
There were 4640 cases of Down syndrome within 2 km of a landfill site. We found no excess risks of Down syndrome related to landfill sites. Adjustment for socio-economic status (SES) did not influence our estimates. There were no differences in risk between hazardous waste sites and other landfill sites.
We found no excess risk of Down syndrome in populations living near landfill sites.
This study aims to investigate the trends in maternal age distribution and estimate the live birth and population prevalence of Down syndrome in China.
Using population survey data, we demonstrated the change of maternal age over the past three decades and its effect on the live birth prevalence of Down syndrome. We also integrated the live birth prevalence and the survival rate to estimate the population prevalence of Down syndrome. Chi-square test was used to compare the maternal age distributions across survey years.
The results show that the maternal age has been rising over the past 30 years in China at national level. The proportion of mothers aged 35 and over increased from 3.62% in 1985 to 14.40% in 2010. The estimated live birth prevalence of Down syndrome has mirrored the same increase of the maternal age from 1.07 per 1000 live births in 1985 to 2.36 per 1000 live births in 2010. At City level, the change of maternal age and live birth prevalence of Down syndrome were more significant than at Town and County levels. The proportion of mothers aged 35 and over increased from 2.17% in 1995 to about 16% in 2010 at City level, while it increased from 2.03% to 13.65% at County level. The total estimated number of people with Down syndrome who were still alive in 2012 and aged below 27 was 611,053, and the estimated population prevalence is 0.45 per 1000.
To conclude, this study provides a clear message about the rising trend in maternal age in both urban and rural areas in China since 1985 and its effect on the estimated birth prevalence with Down syndrome. The regional differences should be taken into account for planning population policy and allocating medical resources to reduce the burden of family with Down syndrome.
ABSTRACT: Down Syndrome (DS) is the most frequent form of intellectual disability (ID) of genetic origin, whose main features include craniofacial dysmorphisms and cardiovascular defects. In 1959, Lejeune and coll. described an extra copy of chromosome 21 (Hsa21) in children with DS (trisomy 21, or T21). We first review how different biological mechanisms may lead to the gain of genetic material of Hsa21 in the cells, originating from different combinations of genetic conditions, including a free or translocated extra copy of Hsa21, distributed in all cells or only in a part of them (mosaicism), with a complete or partial representation of the Hsa21 long arm (21q). Although it is broadly agreed that the DS phenotype originates from the altered expression of the genes located on Hsa21, its molecular pathogenesis is still unknown. We therefore illustrate how recent genomic science may be useful in the elucidation of the genotype-phenotype relationship in DS.
The autosomal trisomies, trisomy 21 (Down syndrome), trisomy 18 and trisomy 13, are among the most common birth defects seen in live-born children. All three conditions are associated with advanced maternal age. Prenatal serum screening programs in conjunction with high-resolution ultrasound detect increasing numbers of affected pregnancies so that families can make informed decisions. The prognosis for trisomies 18 and 13 remain poor for life and mental development. Families of affected children should receive supportive counseling and a realistic appraisal of the likely outcome. In general, cardiac surgery and other invasive procedures are not indicated for most children with these trisomies. In contrast, the outlook for live-born children with Down syndrome has continued to improve, particularly because of early repair of congenital heart disease, which is seen in nearly half these children. Chronologic surveillance of vision, hearing and endocrine function can further reduce morbidity. Children with Down syndrome have high incidences of chronic otitis media, sleep apnea and hypothyroidism, and regular screening is indicated. The risk for acute lympocytic leukemia (ALL) is 10–20% that of control children, accounting for 1–3% of all children with ALL. Problems of later life include obesity and Alzheimer dementia, which is seen in 50–70% of older adults. Despite these complications, the quality of life experienced by most individuals with Down syndrome is reasonably favorable given surveillance for known complications and a supportive environment.
IntroductionIdentification of fetal congenital chromosomal abnormalities is undoubtedly one of the main challenges faced by obstetricians involved in the prenatal diagnosis of congenital anomalies.
Many European countries show no significant decline in human fecundity but their fertility rates are below the replacement level because men and women want fewer children. Economic and social factors appear to be the main explanation for this reduced desire for children. Effective family-planning methods allow couples to choose whether to avoid or postpone childbearing, even though the outcome is likely to be less favorable at older ages. Other lifestyle choices, such as undernutrition in the woman or, more frequently, being overweight and smoking in both partners, may also negatively affect reproduction. Social programs supporting new families appear important for achieving any substantial increase in the number of children per woman. Within Europe, this effect is clearly evident in France and in the Scandinavian countries, although a low fertility seems to be advisable for many overcrowded regions.
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Purpose of review Individuals with Down syndrome have had significant increase in longevity but may experience neurologic compromise and diminished function during their life span. This review provides the clinician with current information to guide their evaluations in terms of medical, neurologic and musculoskeletal disorder, especially cervical spine instability. Recent findings Musculoskeletal disorders that include hip, knee and cervical spine instability are significant factors that influence the individual's activity level and quality of life. Radiographs of the cervical spine of individuals with Down syndrome are difficult to interpret and should not be compared with radiographic standards based on the non-Down population. Summary While medical conditions are well managed in this population, controversy remains in regards to the evaluation and treatment of musculoskeletal disorders. This review alerts the clinician to potential life-long problems that may impact on the welfare and functional status of the individual with Down syndrome. Diminished function requires increasingly complex nursing care as this population ages. Interventions are directed toward early detection of problems and preservation of function.
To estimate the maternal age-specific live birth prevalence (in the absence of prenatal diagnosis and selective termination) of trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) and compare it with that of trisomy 21 (Down syndrome).
Records of prenatal and postnatal diagnoses from seven UK regional congenital anomaly registers and two Australian registers covering 4.5 million births included 975 diagnoses of trisomy 13 and 2254 of trisomy 18. Prevalence at birth in the absence of prenatal diagnosis and selective termination was calculated by adjusting for prenatally diagnosed pregnancies that were terminated according to their likelihood of surviving to term.
The live birth prevalence in the absence of prenatal screening and selective termination in England and Wales from 1997 to 2004 was 1.4 (95% CI: 1.2-1.6) per 10 000 births for trisomy 13 and 2.3 (95% CI: 2.1-2.5) for trisomy 18. It has increased since 1989-1996, by 13% for trisomy 13 and 25% for trisomy 18. These increases are consistent with those predicted due to increases in maternal age.
This study provides the first estimates of maternal age-specific prevalence of trisomies 13 and 18 for women aged 16-45.
Evolution is driven by the propagation of genes, traits and individuals within and between populations. This propagation depends on the survival, fertility and dispersal of individuals at each age or stage during their life history, as well as on population growth and (st)age structure. Demography is therefore central to understanding evolution. Recent demographic research provides new perspectives on fitness, the spread of mutations within populations and the establishment of life histories in a phylogenetic context. New challenges resulting from individual heterogeneity, and instances where survival and reproduction are linked across generations are being recognized. Evolutionary demography is a field of exciting developments through both methodological and empirical advances. Here, we review these developments and outline two emergent research questions.
An increasing number of studies, addressing the linguistic abilities of individuals with Down syndrome (DS) suggest that they exhibit strengths and weaknesses within the linguistic domain. This article critically reviews the literature on the linguistic profile of individuals with DS, with particular emphasis on the expression and reception of vocabulary and grammar, including nonverbal linguistic expression during infant development. In doing so, attention is given to recent comparative studies of the linguistic abilities of individuals with DS, Specific Language Impairment (SLI), and Williams syndrome (WS). The possibility that deficits in one cognitive system may have consequences in another cognitive system, and that these consequences may define the nature of the impairment in each clinical syndrome is further discussed with suggestions for future research.
OBJECTIVE: Our purpose was to describe the maternal and fetal outcomes of pregnancies in women ≥45 years old at delivery. STUDY DESIGN: A retrospective review of in-hospital deliveries after 20 weeks of gestation was performed in four Utah tertiary care hospitals for the 10-year period between 1985 and 1994. RESULTS: Seventy-nine cases were identified among 126,500 births, with an incidence of 0.63 per 1000 births. Maternal ages were 45 (n = 44), 46 (n = 21), and ≥47 (n = 14) years. Three of the conceptions were assisted, including both twin gestations. Thirty-seven (46.8%) had obstetric complications during pregnancy; the most frequent complications were gestational diabetes (12.7%) and preeclampsia (10.1%). Median (range) gestational age at delivery was 39 (22.9 to 41.7) weeks; 12 (15.2%) deliveries occurred before 37 weeks. Eight (9.9%) karyotype abnormalities were diagnosed. The cesarean section rate was 31.7%; the most frequent indications were abnormal lie (n = 9), fetal distress (n = 5), and previous cesarean delivery (n = 5). There were no maternal deaths. Median (range) birth weight was 3466 (397 to 5085) gm; 14 (17.3%) were <2500 gm and 16 (19.8%) were >4000 gm. Twelve (14.8%) infants were admitted to the neonatal intensive care unit. The corrected perinatal mortality rate was 1.3% (1/78). CONCLUSIONS: In women >45 years old at delivery maternal and fetal outcomes were generally good, but there was a high incidence of pregestational (chronic hypertension, hypothyroidism) and gestational (karyotype abnormalities, gestational diabetes, cesarean section, macrosomia) complications. This information may be helpful for counseling women between 45 and 50 years old who are considering pregnancy. (Am J Obstet Gynecol 1996;175:668-74.)
In this paper we present an analysis of nine data sets in which ascertainment and maternal age risk of Down syndrome are estimated jointly using maximum likelihood. We include data on 4825 Down syndrome cases from nine previously published data sets. These include data from studies carried out before the introduction of prenatal screening and from recent studies involving women who had not received prenatal testing. Our results show that, allowing for under-ascertainment, there is a good degree of consistency between the different data sets. We compare the three- and five-parameter constant plus exponential model with a three-parameter logistic model for maternal age-specific risk. We show that the three-parameter logistic model provides a good fit to the data and compare rates from this model with those derived from published studies of uncertain completeness (Cuckle et al., 1987) and those from data sets believed to be complete (Halliday et al., 1995; Hecht and Hook, 1994, 1996). In general, our results agree closely with those of the latter, but achieve greater precision because of the inclusion of additional data. Our derived rates are considerably higher than those of Cuckle et al. (1987), which are embedded in many computer systems for generating risks. © 1998 John Wiley & Sons, Ltd.
Maternal age specific rates for all major chromosome aberrations have been determined in 52 965 pregnancies in mothers 35 years of age and over at the time of amniocentesis. Rates increase exponentially with advancing maternal age for trisomies 21, 18 and 13, and for the XXX and XXY syndromes, but in the autosomal trisomies this rise appears to be followed by a levelling off at the upper end of the age range. A significant inverse relationship with maternal age is found for 45,X cases. It is postulated that these various patterns are the result of the interaction of three principal factors: a maternal age effect acting particularly on first meiotic nondisjunction: a higher spontaneous abortion rate with advancing maternal age for aneuploid as compared to euploid conceptions; and an increased probability of spontaneous abortion before the time of amniocentesis for conceptions with more extensive chromosome imbalance. A stepwise logistic regression analysis of 13 299 pregnancies in which both parental ages are known shows that the father's age does not influence these maternal age specific rates, with the possible exception of the 47,XXY syndrome.
We examined the proportions (or so called "rates") of fetuses with 47,+21, 47,+18, or 47,+13 diagnosed prenatally in women at the upper extremes of age. Our analysis was prompted by results from a large scale European study of amniocentesis which indicated that after increasing exponentially from age 35 years, the proportions of the autosomal trisomies reached a peak at a specific age and then leveled off or declined at the upper end of the age range. We analyzed North American data on 56,075 fetuses studied because of no known cytogenetic risk factor (aside from maternal age). This is the largest series to date. For 47,+21, the data from amniocentesis studies provide no evidence for any drop in the rate of change of proportion with maternal age up to 49 years. There is, if anything, a trend in our data to a steepening in the exponential rate of change at the upper extreme of age (above 46 years). Data from livebirths on the Down syndrome phenotype are at least consistent with an exponential rate of increase in proportion affected up to age 49 years. For 47,+18 our data from prenatal diagnoses are more consistent with an exponential increase up to age 43 years and a level proportion (or "rate") after that. For 47,+13 no cases were observed above age 42 years, consistent with the drop in proportion affected above this age observed in the European series. We emphasize the possible effect of sampling fluctuation and reporting error upon these apparent trends.
Our purpose was to describe the maternal and fetal outcomes of pregnancies in women > or = 45 years old at delivery.
A retrospective review of in-hospital deliveries after 20 weeks of gestation was performed in four Utah tertiary care hospitals for the 10-year period between 1985 and 1994.
Seventy-nine cases were identified among 126,500 births, with an incidence of 0.63 per 1000 births. Maternal ages were 45 (n = 44), 46 (n = 21), and > or = 47 (n = 14) years. Three of the conceptions were assisted, including both twin gestations. Thirty-seven (46.8%) had obstetric complications during pregnancy; the most frequent complications were gestational diabetes (12.7%) and preeclampsia (10.1%). Median (range) gestational age at delivery was 39 (22.9 to 41.7) weeks; 12 (15.2%) deliveries occurred before 37 weeks. Eight (9.9%) karyotype abnormalities were diagnosed. The cesarean section rate was 31.7%; the most frequent indications were abnormal lie (n = 9), fetal distress (n = 5), and previous cesarean delivery (n = 5). There were no maternal deaths. Median (range) birth weight was 3466 (397 to 5085) gm; 14 (17.3%) were < 2500 gm and 16 (19.8%) were > 4000 gm. Twelve (14.8%) infants were admitted to the neonatal intensive care unit. The corrected perinatal mortality rate was 1.3% (1/78).
In women > 45 years old at delivery maternal and fetal outcomes were generally good, but there was a high incidence of pregestational (chronic hypertension, hypothyroidism) and gestational (karyotype abnormalities, gestational diabetes, cesarean section, macrosomia) complications. This information may be helpful for counseling women between 45 and 50 years old who are considering pregnancy.
In this paper we present an analysis of nine data sets in which ascertainment and maternal age risk of Down syndrome are estimated jointly using maximum likelihood. We include data on 4825 Down syndrome cases from nine previously published data sets. These include data from studies carried out before the introduction of prenatal screening and from recent studies involving women who had not received prenatal testing. Our results show that, allowing for under-ascertainment, there is a good degree of consistency between the different data sets. We compare the three- and five-parameter constant plus exponential model with a three-parameter logistic model for maternal age-specific risk. We show that the three-parameter logistic model provides a good fit to the data and compare rates from this model with those derived from published studies of uncertain completeness (Cuckle et al., 1987) and those from data sets believed to be complete (Halliday et al., 1995; Hecht and Hook, 1994, 1996). In general, our results agree closely with those of the latter, but achieve greater precision because of the inclusion of additional data. Our derived rates are considerably higher than those of Cuckle et al. (1987), which are embedded in many computer systems for generating risks.
It is recognized that pregnancies with Down syndrome are liable to end in spontaneous fetal loss. It is important to determine the magnitude of this effect so that it can be taken into account when assessing the results of antenatal screening programmes for Down syndrome. Failure to do so will tend to overestimate the detection rate in intervention studies in which the screening results are used to identify women for a diagnostic test and the offer of a termination of pregnancy if indicated. We present new data on the spontaneous fetal loss in Down syndrome pregnancies from the National Down Syndrome Cytogenetic Register (1989-1996). We compare our results with published results of other studies on the subject to obtain a summary estimate. We exclude one study from the meta analysis due to incorrect methodology resulting in an overestimate of fetal loss. Based on the combined data (i) between the time of chorionic villus sampling and term an estimated 43 per cent (95 per cent CI: 31-54 per cent) of pregnancies ended in a miscarriage or still birth, (ii) between the time of amniocentesis and term an estimated 23 per cent (95 per cent CI: 19 28 per cent) of pregnancies ended in a miscarriage or still birth, and (iii) 12 per cent (95 per cent CI: 2-23 per cent) of births were stillborn or resulted in a neonatal death.
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 display and compare the different published formulae that specify the association between maternal age and the risk of a Down syndrome live birth.
Papers published since 1987 on the prevalence of Down syndrome live births in relation to maternal age were located using MEDLINE and the references given in other papers. The data series and the models fitted to them were plotted to obtain a visual idea of their similarities and differences.
The observed and modelled age-specific rates for Down syndrome births were remarkably similar in all published series of data for women up to the age of 35, were reasonably similar for women aged 35 to 45, but differed for women older than 45.
In practice, the overall small differences in age-related risk between the different studies did not materially affect the performance of antenatal screening for Down syndrome. If a choice is to be made, the analysis based on the National Down Syndrome Cytogenetic Register (NDSCR) has marginal advantages since it is based on the largest data set and the corresponding model fits the data well. More data is needed to clarify the pattern of risk with maternal age among women over 45 years of age.
Surveillance of Congenital Anomalies in Europe
- Eurocat
- Group
EUROCAT Working Group. 2002. Surveillance of Congenital Anomalies in Europe, 1980-1999. EUROCAT Report 8. University of Ulster: Ulster.