Introduction

There has been considerable interest in couples deciding to delay having children for financial or career reasons, with concern about the effects of this on the prevalence of Down’s syndrome. However, the increases in maternal age have generally been compared only since the 1980s.1, 2 This paper aims to examine changes in maternal age and the associated live birth prevalence of Down’s syndrome in England and Wales from 1938 to 2010.

Methods

The numbers of live births in England and Wales between 1938 and 2010 were extracted from Birth Statistics and Characteristics of Birth 2010, where they are stratified into 5-year maternal age groups.3, 4Maternal age is the strongest risk factor for Down’s syndrome and the maternal age-specific risk of having a baby with Down’s syndrome has been accurately estimated using the following equation: risk=1/(1+exp (7.330–4.211/(1+exp (−0.282 × (age −37.23))))).5, 6 The average age-specific risk was calculated for each age group (it was 0.66 per 1000 for under 20 years of age; 0.70 per 1000 for ages 20–24; 0.84 per 1000 for ages 25–29; 1.48 per 1000 for ages 30–34; 4.72 per 1000 for ages 35–39; 15.22 per 1000 for ages 40–44 and 30.71 per 1000 for 45 years and older). For each year of birth the number of live births with Down’s syndrome was estimated by multiplying these risks by the number of live births in that age group and summing across all age groups.

The number of babies born with Down’s syndrome has been reported annually since the National Down Syndrome Cytogenetic Register (NDSCR) started to collect details of antenatal and postnatal diagnoses of Down’s syndrome in England and Wales in 1989,7, 8, 9 and such data were extracted from the 2010 NDSCR annual report.8

A χ2 test was used to examine differences in maternal age distribution at three different time points. Poison regression was conducted to investigate the trend of observed and expected live birth prevalence between 1989 and 2010.

Results

Figure 1 shows how the maternal age distribution has changed since 1940. The maternal age distribution was significantly different between 1940 and 1980 (P=0.0001) and between 1980 and 2010 (P<0.0001), but not different between 1940 and 2010 (P=0.46). In particular, the proportion of mothers who are aged under 25 increased dramatically to 1970 and then decreased to the level in 1940s.

Figure 1
figure 1

Distribution of maternal ages according to year of birth in England and Wales from 1940 to 2010.

Full size image

Figure 2 shows the proportion of mothers 35 years of age or older reached a peak of 19.7% in 1945, declined to 5.5% in 1977 before rising to a new peak of 20.4% in 2007. In the absence of prenatal diagnosis and subsequent terminations the estimated live birth prevalence of Down’s syndrome mirrored these changes, with a peak of 2.27 per 1000 births in 1945 down to 1.22 per 1000 in 1976 and then up to 2.18 per 1000 in 2007.

Figure 2
figure 2

Live birth prevalence of Down’s syndrome and proportion of mothers 35 and older according to year of birth in England and Wales from 1938 to 2010.

Full size image

Figure 3 and Table 1 shows the estimated live birth prevalence of Down’s syndrome in the absence of prenatal diagnosis and subsequent terminations compared with the observed live birth prevalence of Down’s syndrome in England and Wales. The difference between the two curves was due to prenatal diagnosis and subsequent terminations being performed. Poisson regression for data between 1989 and 2010 shows an increase of 2.8% (95% CI: 2.6–3.0%) per annum in the estimated live birth prevalence, but only a very small annual increase of 0.3% (95% CI: 0.1–0.5%) in the observed live birth prevalence. The percentage reduction between the observed and expected live birth prevalence increased since 1989 (Table 1). In 2010, the observed live birth prevalence of Down’s syndrome was 0.99 per 1000 births, 54% lower than expected due to prenatal diagnosis and subsequent terminations being performed.

Figure 3
figure 3

Live birth prevalence of Down’s syndrome estimated in the absence of screening and subsequent termination (1938–2010) and observed in England and Wales (1989–2010).

Full size image
Table 1 Number of all births and births with Down’s syndrome estimated in absence of screening and selective termination and number recorded by the NDSCR in England and Wales: 1938–2010
Full size table

Discussion

Figure 1 demonstrates that the recent proportions of older women having children are in fact similar to the proportions in the 1940s, even though the births to older mothers in the past would have been to women having large families, whereas the births now are likely to be either first or second children to mothers who have delayed having children. Birth order is not associated with the prevalence of Down’s syndrome, it is only the age of the mothers that is important.5, 6 Figure 2 shows how the prevalence of Down’s syndrome is predicted by maternal age. Although the use of infertility treatments using donated eggs is increasing, their use is still too infrequent to make a detectable change in the population prevalence of Down’s syndrome.

Other studies in Europe and the rest of the world have also observed increases in the proportion of mothers aged 35 and over since the 1980s.2, 10, 11, 12, 13 As the changes in the live birth prevalence of Down’s syndrome are also dependant on the proportion of Down’s syndrome cases diagnosed prenatally and the proportion of subsequent terminations being performed, the birth prevalence of Down’s syndrome only increased slightly in the United States,11 stayed stable in Singapore and Europe,2, 12, 13 and decreased in Australia.10 In developing countries, such as China,14 with a lower availability of prenatal diagnosis and subsequent termination, the increase in the proportion of mothers aged 35 and over had a bigger impact on the birth prevalence of Down’s syndrome.

With the increasing availability of more powerful screening tests, such as the combined test, a higher proportion of Down’s syndrome fetuses are being detected prenatally particularly among younger mothers (the proportion of mothers under 35 with Down’s syndrome diagnosed prenatally increased from 10% to nearly 60% in England and Wales from 1989 to 2010, Figure 2 in NDSCR report8). The result of this increased detection rate and subsequent terminations in younger mothers has been to increase the maternal age of mothers with Down’s syndrome births from 30 to 35 years of age (Figure 4 in NDSCR report8). This 5 year increase is important when considering the implications for the long-term care of these children and subsequently adults with Down’s syndrome. The introduction of new techniques, such as sequencing fetal DNA in maternal blood,15, 16 would be expected to increase these trends in increasing detection rates. However, the birth prevalence of Down’s syndrome will continue to be highly influenced by any increases in maternal age and women should be made aware of these increased risks.

One of the weakness of this study is that before 1989 we do not know how many babies are born with Down’s syndrome. Data on the numbers of babies born with Down’s syndrome was collected by the National Congenital Anomaly Service (NCAS), and published annually by the Office for National Statistics from 1971 to 2008.17 However, both the NDSCR and other regional congenital anomaly registers demonstrated that the NCAS system had a significantly lower ascertainment rate.18, 19 Therefore, we have chosen not to use the data from NCAS for 1971–1989. The data on population births is only available in 5 year age bands, which will produce a small amount of inaccuracy.

In conclusion, this paper demonstrates that recent increases in maternal age mirror the decreases that occurred from the 1940s and that the live birth prevalence of babies with Down’s syndrome has remained reasonably constant since the introduction of prenatal diagnosis in the 1980s.