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At least 19 recordsLinked to original sources
PubMed1978

Down syndrome, paternal age, maternal age and birth order.

Recent cytogenetic evidence has shown that trisomy 21 can arise, perphaps even in substantial proportion, from paternal nondisjunction. The statistical association between Down syndrome incidence and maternal age, paternal age and birth order has been studied in a sample of over 4000 cases. The size of this sample made it possible to control for the effect of maternal age by single years of age during the search for a paternal age effect and vice versa, and the importance of such stringent control is emphasized. The maternal age association was confirmed with an extremely high degree of statistical significance while no independent effect of paternal age was found; indeed, the rates at paternal ages over 45 years appear to be nearly constant. After adjusting for the effects of parental age, a significant inverse association of birth order with incidence was noted. It also appears that the incidence among very young mothers may be high: for maternal ages 15 years and less the rates seem to be equivalent to those found at 30 or 35 years. In order to help answer the question of whether the maternal age association is the result of increasing rates of nondisjunction or of some other mechanism (for example, an age related defect in a spontaneous abortion screening mechanism), the proportion of cases due to maternal and paternal nondisjunction at different parental ages must be determined.

Adolescent↗
PubMed1977

Down syndrome and maternal age in Japan, 1950-1973.

The mean maternal age and the percentage age distribution of 2,650 mothers of children with Down syndrome were calculated for 1950-1973, from hospital records. Mean maternal age had dropped both for controls (28.55 leads to 27.37) and Down syndrome (31.26 leads to 29.59). The observed maternal age distributions were very similar to those expected in corresponding periods, from the age specific incidences of Collmann & Stoller (1962). It is conceivable that the fall in maternal age in Down syndrome in recent years has resulted from the general trend to decreasing maternal age. There has been no change in the age-specific incidences of Down syndrome. The incidence of Down syndrome seems to be falling in Japan.

Adult↗
PubMed1976

Down syndrome in British Columbia, 1952-73: incidence and mean maternal age.

Records of children with Down syndrome (DS) at the BC Health Surveillance Registry were linked to their Birth Registrations to derive maternal ages. Incidence and maternal-age specific rates were calculated for 1952-73. Mean maternal age has declined both for normal and DS children, the latter to a marked degree, so that in 1972-73 80% were born to women under 35 years. Using maternal age of 40 and over as an indication for amniocentesis would only detect 10% of DS children. The crude incidence rate (mean 1.28/1000 livebirths) has not changed appreciably over the study period except for 1969 in which a statistically significant peak occurred. The standarized rate showed an increasing trend but it is not clear whether this was a true biological increase or resulted from better ascertainment.

Adult↗
PubMed2026

Genomic risk profiling in advanced maternal age: a Tamil Nadu prenatal study.

BACKGROUND: Advanced maternal age (AMA; > = 35 years) is associated with increased fetal chromosomal risk and is an important indication for invasive prenatal diagnosis. This study evaluates karyotyping and chromosomal microarray analysis (CMA) findings among AMA pregnancies in Tamil Nadu, India. METHODS: In this prospective observational study, 2,200 pregnant women aged ≥35 years who underwent amniocentesis between July 2020 and June 2021 were enrolled. Conventional karyotyping was performed in all cases. CMA was performed as a reflex or complementary test when predefined clinical or cytogenetic criteria were present, including ultrasound abnormalities, high-risk screening/NIPT results, abnormal or uncertain karyotype findings, prior adverse pregnancy history suggestive of genetic etiology, parental chromosomal abnormalities, or patient request after counseling. RESULTS: Numerical chromosomal abnormalities were detected in 76/2200 cases (3.5%), and structural abnormalities were detected in 9/2200 cases (0.4%). The total abnormal cytogenetic yield was therefore 85/2200 cases (3.9%) when numerical and structural abnormalities were considered together. Age-stratified analysis showed an increasing trend in chromosomal abnormalities with advancing maternal age, reaching 10.4% in women aged > = 43 years. Cases with additional clinical indications showed higher abnormality rates than simple AMA. CMA was performed in selected cases and contributed to characterization of clinically relevant genomic abnormalities, supporting its role in indicated high-risk AMA pregnancies. CONCLUSION: The Tamil Nadu cohort provides regional evidence on age-stratified cytogenetic risk in AMA pregnancies and supports the use of clearly defined criteria for integrating CMA with conventional karyotyping in prenatal diagnosis.

India↗
PubMed1977

An unexpected high frequency of trisomic fetuses in 229 pregnancies monitored for advanced maternal age.

In 229 pregnancies monitored because of advance maternal age, 16 (7%) abnormal fetal karyotypes were detected. We found 13 cases of trisomy 21, twice a trisomy 18, and once an additional marker chromosome. The frequency of abnormal fetal karyotypes in different maternal age groups was found to increase from 1:20 at 38--40 years, to 1:16 at 41--43 years, and finally to 1:4.5 in women of 44--46 years. The overall incidence of chromosomal aberrations and specifically of trisomy 21 is considerably higher than that described in retrospective studies.

Adult↗
PubMed2026

Maternal age as a driver of genome instability: mechanisms linking aneuploidy, mutagenesis and mitochondrial dysfunction.

Advanced maternal age is a well-established risk factor for adverse reproductive outcomes due to increased rates of aneuploidy. However, emerging evidence indicates that the genetic consequences of maternal aging extend well beyond chromosome mis-segregation. Aging oocytes acquire a broad spectrum of genetic abnormalities, including maternally derived nuclear de novo mutations (DNMs) and mitochondrial DNA mutations, together with epigenetic dysregulation of DNA methylation and post-translational modification levels. These changes reflect the unique biology of the female germline in which oocytes remain arrested in meiotic prophase I for decades. Age-related deterioration of key processes, such as erosion of cohesion complexes, altered meiotic recombination, and weakened spindle assembly checkpoint surveillance collectively destabilize meiotic chromosome architecture, directly driving chromosome mis-segregation. At the same time, accumulation of endogenous DNA damage and declining DNA damage and repair processes increase the chances of transmitting lesions that can be converted into sequence-level mutations during the earliest embryonic divisions, when genome maintenance relies exclusively on maternal factors. High-resolution sequencing studies further demonstrate that maternal aging is associated with increased DNMs burden in both nuclear and mitochondrial DNA. Together, these findings support a model in which maternal aging is a driver of genome-wide instability that links aneuploidy and mutagenesis through shared defects in meiotic surveillance, declining DNA repair efficiency, and mitochondrial function. This framework positions delayed childbearing as a multifaceted genetic risk factor that extend beyond aneuploidy to include mutations and other genomic alterations that can impact intergenerational genetic risk.

Aneuploidy↗
PubMed1978

Maternal age and Down syndrome: age-specific incidence rates by single-year intervals.

Maternal age-specific risks of giving birth to a child with the Down syndrome (DS) are given by single-year age intervals. Such data are of value for more precise genetic counseling and in cost-benefit analyses of prenatal diagnosis programs. The data were obtained by linking records of children with DS at the British Columbia Health Surveillance Registry ( BCHSR ) to the appropriate birth registrations to derive maternal ages. The data related to 519 affected children out of a total of 354,880 live births in British Columbia between 1961 and 1970. The results, which are based on a high level of ascertainment, are compared to those reported in the only other published study relating to risks by single-year maternal age groupings, where completeness of ascertainment was estimated to be only 38%.

Adolescent↗
PubMed1978

Frequency of Down syndrome in livebirths by single-year maternal age interval: results of a Massachusetts study.

An analysis of rates of intra-state Down syndrome livebirths to Massachusetts residents by single-year maternal age interval in 1958-1965 inclusive was carried out. A gradual increase of rate of the Down syndrome occurred from age 20 to about age 31, and a steeper increase thereafter. Different regression equations were derived in the 20-31 and the 33-45 age group. The regression equations were ln y = 0.04515 x -1.45759 for those age 20-31 and ln y = 0.24302x-7.57870, for those age 33-45, where y = rate per 1,000 and x = maternal age. The regression-derived rates are slightly lower than those reported in similar analyses of data from Sweden and New York State, but they are not markedly discrepant.

Adolescent↗
PubMed1979

Down's syndrome and maternal age in British Columbia, 1972--75.

The occurrence of Down's syndrome in British Columbia during the period 1972-75 is analyzed with respect to maternal age distribution. This period is compared with previously studied periods. No marked trends are evident in the various age group-specific rates studied. The significance of these findings is discussed in connection with a possible role of environmental nutagens in induction of Down's syndrome and the maternal age effect.

Adult↗
PubMed1978

Chromosomal anomalies of preimplantation rabbit blastocysts and human artificial abortuses in relation to maternal age.

It is well established that in man there is a higher frequency of chromosomally and phenotypically abnormal offspring and a decline in fertility as maternal age increases. This paper describes preliminary work on some chromosomal aspects of 5- and 6-day old preimplantation rabbit embryos, with attention to maternal age dependence of chromosome anomalies. Chromosome preparations were made by a modification of the method of Shaver and Carr (1967). Two trisomic blastocysts were observed among 50 embryos examined from 10 does of 40 to 52 months of age, that is, 45XY with an extra submetacentric chromosome and 45XX with an extra acrocentric chromosome. In man, three trisomies (47XX, G+, 47XX, D+, and 47XY, G+), one monosomy (45X or 45XX, C-) and one double trisomy (48XY, C+, E+ or 48XXY, E+) were karyotyped out of 32 early induced abortuses from women older than 40. Among the 22, induced abortuses analyzed from women between 35 and 39, one trisomic embryo of 47XY, G+ was observed.

Abortion, Induced↗
PubMed1978

[Prenatal diagnosis in pregnancies at advanced maternal age (author's transl)].

Among 113 prenatal diagnoses in pregnancies at advanced maternal age (mothers older than 37 years) 7 aberrant fetal karyotypes were found (6.2%). Detailed reports of one case of trisomy 21, 18 and 13 each, as well as of XXY-, XYY- and XXX gonosomal constitution respectively are presented in the following. The frequency and severity of chromosome aberrations occurring in fetuses from elder women are discussed with respect to data from the literature. It seems that this group bears a higher risk for chromosomally abnormal offspring than has been suggested before.

Abnormalities, Multiple↗
PubMed1975

Ribosomal RNA, maternal age, and Down's syndrome.

A selective loss (or a blocking) of rRNA genes in ageing oocytes, and its compensation through the retention of an acrocentric nucleolar organizer chromosome, is proposed as a possible mechanism responsible for the increased frequency of Down's syndrome with maternal age.

Animals↗
PubMed1979

Maternal age patterns and the incidence of Down's syndrome.

The incidence of Down's syndrome in three counties in southwestern Ontario from 1960 to 1974 was monitored in this retrospective descriptive study. Of 229, 754 live births including 292 Down's syndrome births, there was an incidence of 1.27/1,000 live births. The age-adjusted incidence for 288 cases where mother's age was known was 1.25/1,000. Data from Statistics Canada demonstrated a decrease in proportions of births to women over 35 years and a decrease in mean maternal age. The anticipated decrease in incidence of Down's syndrome because of these factors was not found; a real biological increase to women under 35 years cannot be ruled out.

Birth Rate↗
PubMed1979

An analysis of the influences of maternal age, gestational age, contraceptive method, and the mode of primary treatment of patients with hydatidiform moles on the incidence of subsequent chemotherapy.

In relation to the total number of births in the United Kingdom there was an excess of hydatidiform moles arising in women over 34 years of age and possibly also under 15. The incidence of trophoblastic tumour requiring chemotherapy after hydatidiform mole was greatest in the 30 to 34 years age group and it was also high in the 20 to 24 years age group. This distribution appears to be influenced by the morphology of the moles, the mode of their removal and the use of oestrogens and progestogens in the post-evacuation period. The need for chemotherapy for trophoblastic tumour after evacuation of a hydatidiform mole was found to be two- to three-fold greater in patients who had undergone a medical induction, hysterectomy or hysterotomy compared with those whose hydatidiform moles had been evacuated by vacuum or surgical curettage, or who had aborted spontaneously. The increased risk of chemotherapy was most marked in the earlier weeks of gestation.

Adolescent↗