Pregnancy and diabetes before the discovery of insulin

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A full historical review of fertility and of the outcome of pregnancy in different parts of the world is beyond the scope of this chapter, but there are a number of aspects that are of particular relevance to the story of diabetes. Medical history, in particular, is constrained by publication bias, and there is much more available data regarding Europe and North America than in other parts of the world. The geographical and ethnic differences in the distribution, development and management of diabetes in different places at different times would be of great interest to review, but as the data are patchy and both diabetic and obstetric treatments often poorly defined, it may be that: 'History followed different courses for different peoples, because of differences among peoples' environments, not because of biological differences among peoples themselves.'7 There are certainly both environmental and genetic reasons for the differing prevalence and incidence of diabetes in different countries, as much as for the different outcomes of pregnancy, but the international historical study of these factors is still in its infancy.

The collection of vital statistics first became available at varying times in the developed Western countries. The Scandinavian countries were first (Sweden 1749, Denmark 1801), England and Wales followed (1838) and then Russia (1867); although the process was initiated in the USA in 1880 it was not complete until 1933.8 Fertility rates have varied as much as death rates and migration in different countries, so that population dynamics will have a considerable effect on reported statistics for a single condition such as diabetes in pregnancy. The classical Malthusian checks on death rate - disease, famine and war - and the effects of celibacy and restraint on birth rate, will have more effect on the overall outcome statistics of pregnancy in diabetic mothers than the diabetes itself. The general fertility rate for England and Wales was about 130 live births per 1000 women between the ages of 15 and 44 in 1840, but is now only half that rate. At present the total fertility rate (average number of children born per woman) varies from 2.1 in western Europe to 6.7 in West Africa.9 However, there is no doubt that untreated diabetes must have been virtually incompatible with successful pregnancy before about 1850. In 1856 Blott in Paris wrote that 'True diabetes was inconsistent with conception,' and certainly the then short life expectancy of a young woman with what we now call Type 1 diabetes before the discovery of insulin would support that statement. Recent speculation on the possible nutritional causes of the present-day epidemic of Type 2 diabetes in older patients means that any data on diabetes successfully treated by diet only (which was probably Type 2, rather than Type 1) is of considerable theoretical interest, but it is perhaps important that these cases were not often reported in the literature and may well have been missed due to not even testing the urine for sugar.

In the pre-insulin days, and for some time after, death of the mother during or soon after pregnancy from uncontrolled diabetes was the major risk. But maternal mortality was high for many reasons unrelated to diabetes, and retrospective analysis of data from England and Wales between 1850 and 1937 shows that poor interventional obstetric care with increased risk of puerperal sepsis was more important than social or economic deprivation.10 The maternal mortality rates for Scandinavian countries were much lower, and it is now clear that this was due to better overall obstetric management in the prevention of sepsis; in the USA maternal mortality between 1921 and 1924 was 6.8 per 1000 births, in England and Wales 3.9 per 1000 births and in the Netherlands only 2.5 per 1000 births.8 These differences at national level have been widely discussed, but must be borne in mind when considering the isolated effect of maternal diabetes over those years.

Overall perinatal mortality (death of the fetus after 28 weeks or within 7 days of delivery) has shown a more consistent fall over the same period of time in all Western countries. Most of the decline was in postneonatal mortality related to rising standards of living and nutrition, but also to improved public health measures - broadly speaking, the predominant form of infant mortality in Western countries was postneonatal in the nineteenth century and neonatal in the twentieth. There was no close link between neonatal and maternal mortality, but there were very considerable differences in each of these measures between countries at the time of discovery of insulin (Table 1.1). The overall infant mortality

Table 1.1 Overall maternal mortality and infant and neonatal mortality for selected countries at the time of discovery of insulin (from Loudon8)

Country

Maternal deaths, 1921-1924, per 1000 births

Infant deaths, 1924, per 1000 births

Neonatal deaths, 1924, per 1000 births

The Netherlands

2.5

67.3

18.6

Japan

3.3

166.4

67.5

England/Wales

3.9

75.1

33.1

Australia

4.5

57.1

29.8

USA

6.8

70.8

38.6

rates in Scandinavian countries were persistently lower than in England and Wales, or Belgium, between 1920 and 1965, although all countries show a steady exponential decline.8 As perinatal mortality is now used as a main comparator for the outcome of diabetic pregnancy, it is important to bear these long-standing historical trends in mind.

Congenital malformations are also an important comparator for obstetric results but the recognition of a possible link with maternal diabetes is much more recent: anecdotal accounts in small series in the 1940s were not supported until the report by the UK Medical Research Council in 195511 and the larger series from Copenhagen in 1964.12 Historical records on the frequency of congenital malformations are very incomplete and it was not until the International Clearinghouse for Birth Defects began to operate after 1974 that any baseline data on the prevalence of congenital malformations became possi-ble.13 It is still difficult to compare results for specifically identified diabetic pregnancies with overall national malformation rates where the collection of cases is much less detailed.14 Other obstetric complications such as pre-eclampsia appear today to be more common in diabetic pregnancy but it is difficult to trace this possible inter-relationship back to the days before organized antenatal care. Some of the cases where maternal death occurred in a diabetic pregnancy may have been due to eclampsia rather than diabetic coma.

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