Cytogenetic evidence for enhanced selective miscarriage of trisomy 21 pregnancies with advancing maternal age

Abstract

The effect of advancing maternal age on the risk of death of fetuses with certain chromosome abnormalities has been tested by comparing their frequency at the time of chorionic villus sampling (CVS) with that at amniocentesis. The frequency of chromosome abnormalities among women whose sole risk factor for a chromosome abnormality was advanced maternal age (> or = 35 years old) was determined in a pooled group of 15,147 CVS cases, of whom > 1/3 were from the initial 7,500 CVS cases at the University of California, San Francisco, and compared with a pooled group of 74,851 amniocentesis cases collected from the literature. The frequency of trisomy 21 not only increased with advancing maternal age as expected, but the slope of the increase was about 25% greater in the CVS group than in the amniocentesis group (P = 0.08 for the difference in slopes by a logistic statistical model and P = 0.04 by a normit model). Similar patterns were seen for trisomies 18 and 13, but the P values for the differences in slopes were much higher. These results suggest that the miscarriage rate of trisomy 21 during the gestational interval studied is selectively greater with advancing maternal age. The basis for the enhanced selective loss of trisomy 21 with maternal age may be a reduced ability of the ageing "maternal compartment" to compensate for abnormal conceptuses.

Estimating the spontaneous loss of Down syndrome fetuses between the times of chorionic villus sampling, amniocentesis and livebirth

“…The estimated odds ratios (ORs) relating to these groups were interpreted as RRs to enable estimation of spontaneous loss between the corresponding times of gestation. Halliday et al (1995) estimate an overall loss of Down syndrome fetuses of 31 per cent between CVS and livebirth, a 17 per cent loss between CVS and amniocentesis, which is similar to previous studies (Hook et al, 1988;Kratzer et al, 1992), and an 18 per cent loss between amniocentesis and livebirth, which is lower than other published estimates. For example, Hook (1983) estimates the loss to be 30 per cent and Hook et al (1989) present an estimate of 29 per cent.…”

“…Although these gestational ages were not identical to those given in some other studies (such as Snijders et al, 1995), a sensitivity analysis showed that the results were robust to small changes in the maternal age adjustment. Macintosh et al (1995) pool maternal agespecific rates of Down syndrome at CVS obtained from the Danish cytogenetic register with CVS data from Snijders et al (1994) and three other published studies (Hook et al, 1988;Leschot et al, 1989;Kratzer et al, 1992). The pooled rates were checked and corrected from the original sources and combined by adding cases and the total number of women undergoing karyotyping at each maternal age.…”

“…These data resulted from combining several surveys published in the literature (Ferguson-Smith and Yates, 1984;Hook et al, 1984Hook et al, , 1988Kratzer et al, 1992) with their own CVS and amniocentesis data. Observed rates amongst livebirths, published by Cuckle et al (1987), were used to calculate relative risks (RRs) and estimate spontaneous losses of Down syndrome fetuses after times of CVS and amniocentesis, respectively.…”

The proform of eosinophil major basic protein: a new maternal serum marker for Down syndrome

“…However, very early screening may identify many DS cases that would have spontaneously aborted. Based on data available from weeks 9-14, it can safely be assumed that more than 50 per cent of the DS pregnancies diagnosed prior to week 10 will miscarry (Macintosh et al, 1995;Hook et al, 1988;Kratzer et al, 1992;Snidjers et al, 1994). The DS cases used in this study were identified either at CVS/ amniocentesis or at birth, indicating that the DS cases identified through screening using proMBP will not solely be cases destined for abortion.…”

Expanding non‐invasive prenatal testing beyond chromosomes 21, 18, 13, X and Y

“…Incidence of chromosome abnormalities at CVS in advanced maternal age women. For the autosomal trisomies, sex‐chromosome abnormalities, structural abnormalities and triploidy, the data is based on 16,855 CVS in women aged 35 or older with testing prior to the widespread use of chromosome microarrays . Because these studies may have used various criteria for defining mosaic cases, the results for mosaic other autosomal trisomies was extracted from a separate study involving 45,867 cases.…”