World Wide Incidence of Down Syndrome
Stephen G. Read
Spreadsheet of worldwide incidence of Down Syndrome2
Learning Disability Research Unit, University of Huddersfield1
Corresponding author: Professor Stephen G. Read, MD, FRCPsych, Learning Disability Research Unit, University of Huddersfield, HD1 3DH, UK
Introduction: Two previous surveys have shown that exposure to the contraceptive pill at/or around the occasion of conception can affect the risk of Down Syndrome. For young mothers this exposure can increase the risk, whereas for older mothers it can decrease the risk. Methods: A review of records of Down Syndrome rates between 1962 and 2002 was made in an attempt to provide evidence for or against this hypothesis. Results: This meta-analysis confirms these findings. In a comparison of a 2 decade block low in oral contraceptive use with the more recent, 2 decade block high in oral contraceptive use, a Worldwide incidence of Down Syndrome is found to differ in the expected manner. In recent years there has been an increased incidence of Down Syndrome born to young mothers, while the overall incidence has gone down. Conclusion: For young mothers, avoidance of the contraceptive pill, and the use of alternative contraceptive methods prior to attempts at conception should obviate or reduce this risk.
Key words: Woldwide incidence, Down Syndrome, Contraceptive pill, Oral contraceptive
In their extensive survey of the relationship between peri-conceptional exposure to oral contraceptives (OCP) and the incidence of Down Syndrome, Martinez-Frias et al.  and the work of Read  conclude that the OCP does change the incidence of Down Syndrome. The rate is increased for younger mothers and decreased for older mothers. The essential epidemiological finding, and therefore prediction in any further study, is that there will be an increased rate of Down Syndrome for maternal age group 20–29, a decreased rate for maternal age group 30–39 and a gross rate which changes little over time.
This paper attempts a review of records of Down Syndrome rates between 1962 and 2002 in an attempt to provide evidence for or against this hypothesis. In comparing the second half of this period of widespread OCP use with the first half, with less extensive OCP use, the prediction is that the gross rate will be much the same, whereas the rate for younger mothers will have increased. To do this it is necessary to adopt a new method.
Techniques need to be developed for establishing and monitoring the worldwide incidence of Down Syndrome. A part of this is producing an acceptable method of weighting incidence rates according to both the size of the survey and the methods used. This paper is an attempt to do that and produces average rates for the two periods 1962–1983 and 1984–2002 with regard to gross incidence rates and also rates for maternal ages 20–24 and 25–29 (Table 1. Calculation of mean gross rate for the
two blocks. Table 2. Calculation of mean rates for ages 20-24 and 25-29 for the two blocks.).
A Medline search was performed for Down Syndrome and incidence or prevalence. papers were selected if the title suggested that a population had been studied. There were 95 papers of which 48 were excluded as not having the fundamental requirement of an ascertained number of Down Syndrome probands and a calculated gross incidence rate and 2 papers were excluded because they had extreme values for Down Syndrome incidence being < 0.5/1000 or > 2.0/1000 [2-49] .
A Number Rating was produced by dividing the number of Down Syndrome probands for each paper into 3 groups: rating of 1 if <100, 2 if 100–500, 3 if >500.
A Method Rating was produced by assigning a score of 1 if a total live birth number was recorded and a further score of 1 if there was a simultaneous recording of the incidence rates for maternal age 20–24 and 25–29. This was added to a cytogenetic rating of 0 if <25%, 1 if 25–75% and 2 if >75%. This in turn was added to a case finding rating of 0 or 2 depending on the use of 3 or more additional contributions to the main register.
An Overall Rating was then produced by multiplying the Number Rating and the Method Rating by the Gross Incidence.
Finally, a Mean Rate was calculated by dividing the Average Overall Rate by the Average Number Rating and the Average Method Rating. A similar calculation was performed to obtain Overall Ratings for maternal age 20–24 and 25–29, and subsequently to obtain Mean Rates for these groups also.
The whole of these calculations were performed for the period 1962 – 1983 and then repeated for the period 1984–2002. Results show a decrease in the Gross Incidence between the two periods and an increase in the 20–24 Incidence and the 25–29 Incidence (Table 3). No probability has been calculated as it would be spurious until such a method as this has gained acceptance.
If it is reasonable to treat the figures in this fashion, an explanation must be sought as to why a search should not be put in place to determine why the mean rates for younger mothers have gone up yet the mean gross rates have gone down.
We are in a position now, with forty or more years investigation into the rates of Down Syndrome, to perform manipulations of this type. Whatever the effects may be of amniocentesis, it is difficult to understand how this alone could affect the incidence of Down Syndrome for younger mothers who only very exceptionally would be offered this procedure.
Read, and subsequently Martinez-Frias , have suggested an explanation for this phenomenon in peri-conceptional exposure to the oral contraceptive pill. Its small androgenic effect is enough in younger mothers to slightly increase the rate. In older mothers, with higher endogenous androgens, this has no effect, and the oestrogenic effect is enough to reduce the rate.
Further research is needed into the methods described in this paper and into the validity of the underlying hypothesis. In the meantime, the suggestion that the incidence of Down Syndrome has increased for younger women must receive serious attention, and the underlying hypothesis of the association with the oral contraceptive pill must receive serious consideration.
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Table 3. Results: Comparison between calculated incidence rates for the 2 block periods.
Mean Rate Mean Rate Mean Rate
Gross Age 20–24 Age 25-29
1962 – 1983 1.67 0.67 0.85
1984 – 2002 1.34 0.96 1.28