Maternal age in the epidemiology of common autosomal trisomies

Abstract

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.

Maternal MTHFR 677C>T, 1298A>C gene polymorphisms and risk of offspring aneuploidy

“…Our findings also highlighted the maternal 677T allele as a risk factor for offspring aneuploidy in younger women (≤35 years at conception), with 3‐6‐fold higher risk under recessive, homozygous and allele contrast models, suggesting that chromosomal nondisjunction in young women may be the result of complex gene‐environmental interactions involving the lifestyle and genotypes of mother and maternal grandmother, as shown in previous studies on maternal meiosis I and II 4,14 . A stronger association with other chromosome aneuploidies (PHP ≥80% for dominant, recessive and allele contrast models), than with trisomy 21 (PHP trends 59.8% for recessive and 66.3% for allele contrast models), in our study is consistent with recent reports on significantly higher prevalence of sex chromosome aneuploidies in younger women 6,7 . Our data do not support the 677T allele as a risk for trisomy 21 in women older than 35 years, but an increased risk has been observed for other offspring aneuploidies in presence of maternal TT homozygote (recessive model, PHP ≥80%).…”

“…4,14 A stronger association with other chromosome aneuploidies (PHP ≥80% for dominant, recessive and allele contrast models), than with trisomy 21 (PHP trends 59.8% for recessive and 66.3% for allele contrast models), in our study is consistent with recent reports on significantly higher prevalence of sex chromosome aneuploidies in younger women. 6,7 Our data do not support the 677T allele as a risk for trisomy 21 in women older than 35 years, but an increased risk has been observed for other offspring aneuploidies in presence of maternal TT homozygote (recessive model, PHP ≥80%).…”

“…Despite detrimental clinical consequences and extensive research, the cellular and molecular mechanisms involved in chromosome non‐disjunction are still poorly understood. Advanced maternal age at conception is the most convincing clinical factor for autosomal trisomies, although the underlying mechanisms of the aging effects on chromosomal malsegregation are still not clear enough 5,6 . Moreover, a significant number of aneuploidies, particularly of sex chromosomes, are more common among younger women, 7 requiring the search for other risk factors that predispose to aneuploidy in young women.…”

Horse Clinical Cytogenetics: Recurrent Themes and Novel Findings

“…It is well-established that the risk for autosomal trisomies in humans increases with advancing maternal age [98]. No such statistics is available for the horse, mainly because of the small number of reported cases.…”

The origins of aneuploidy research consortium

“…It has long been recognized from epidemiologic data, that the prevalence of trisomies 21, 18 and 13 at birth are strongly maternal age dependent. Cuckle and Morris review the various best‐fit models for maternal age relationships and studies on fetal loss 22 . Although recent data has suggested a U‐shaped curve for relationship between aneuploidy and age in maternal oocytes, 23 Cuckle and Morris note no association with young age for trisomy 21 at birth and a flattening of the curve at the most advanced ages.…”