THE EFFECTS OF FOOD SHORTAGE ON HUMAN REPRODUCTION

The first dramatic effect of food shortage is on fertility. During the second world war when many German men were away from home in their armed forces fertility fell only slightly, but when the war ended and the soldiers returned there was a steep decline in fertility. There were no doubt many reasons for this decline in fertility illustrated for the German City of Dresden in Figure 1^1,2. One reason was a sudden fall in food supplies when the German Armies were defeated and German cities were occupied by the Allies. During the war Germany was reasonably well fed with help from occupied territories, but when the sealed trains bringing food from these territories ceased to run there was a food shortage.

Of course the unwillingness of men and women to reproduce in difficult Decline in birth rate in Dresden at end of war times was part of the explanation of the decline in fertility, but fecundity was also affected. There were epidemics of low birthweight, miscarriage and congenital malformations. The epidemic of low birthweight in Leipzig immediately after the war is illustrated in Figure 2, based on 57,000 births³. There were similar epidemics in all the European cities affected by food shortage. Thus in Vienna epidemics of low birthweight were recorded during and after both the first and second world wars^4,8. The mean birthweight of babies delivered at the University Women's Clinic in July 1944 was 3,452g which fell to 2,858g in July 1945⁸. This decline in mean birthweight was accompanied by a substantial increase in preeclampsia.

These epidemics showed that low birthweight can be the consequence of environmental factors acting over quite a short period of time of a few weeks or months. Thus the percentage of low birthweight in Athens, defined as less than 2,500g, more than doubled from 8 to 16.5 per cent in 1941-2 in 12 months after occupation by the German Army⁹. Non-environmental, hereditary, genetic factors have little power to explain these epidemics of low birthweight. The contemporary medical literature attributed the epidemics to food shortage. There were however epidemics of infectious disease which began and ended with the food shortage, and contemporary views that these diseases mediated or aggravated the effects of the food shortage on reproduction will never be shown to have been wrong. These epidemics of low birthweight are a part of European history and their occurrence should have ended the superstition that low birthweight is a gift from the Fates unconnected with the mothers' nutrition.

Epidemics of miscarriage contributed to the decline in fertility wherever there was a food shortage. The sudden increase in miscarriage in Frankfurt at the end of the war is illustrated in Figure 3 from the records of Frankfurt University Women's Clinic¹⁰. This record, nearly half a century old, prompts many questions for today when many countries are suffering food shortages. What causes the miscarriages? Does food restriction or faulty nutrition cause miscarriage in normal times even in the absence of food shortage?

THE EFFECTS OF FOOD SHORTAGE ON HORMONE STATUS

The immediate cause of miscarriage is generally hormonal inadequacy, particularly depressed levels of the hormone progesterone. The progesterone levels of women who suffered from habitual miscarriage and of normal women are contrasted in Figure 4 using data from the Hospital de GinecoObstetricia in Mexico City, published in 1977¹¹. It is seen that the progesterone level of the women who miscarried was substantially lower than that of the women with normal menstruation, through the luteal phase between ovulation and the end of the cycle. This depression of progesterone levels is characteristic of luteal phase deficiency (LPD).

The Max Planck Institute of Psychiatry in Munich has studied the effects of dietary restriction on progesterone levels using healthy women volunteers¹². A slimming diet, reducing food intake from about 2,000 to 1,000 kcal a day, is seen in Figure 5 to reduce progesterone levels already in the first week with further falls thereafter to very low levels. In this particular experiment illustrated in Figure 5 the effect of food restriction on all six women progesterone range for 15 women with normal menses and fertility progesterone mean b1 sem for 10 women who habitually miscarried volunteers was to stop menstruation altogether so that there was no luteal phase at all or cyclical surge in progesterone production, as found during the luteal phase of a normal cycle. All six women became temporarily infertile.

The endocrine system not only of women but of all mammals reacts quite quickly to a food shortage to stop reproduction. This must have had survival value for the human and other species, selecting the well-fed only for reproduction. Women's menstrual cycle is controlled by the hypothalamus at the interface of the brain and endocrine system, and the hypothalamus stops the cycle if nutrition is defective and indeed for other reasons such as exposure to some toxins. There is, however, a marginal stage, sometimes called penumbral, between complete infertility on the one hand and normal reproduction on the other. In this marginal state of nutrition diet is inadequate but not severely inadequate. Hormone levels are depressed but only moderately depressed. Menstruation does not stop, but cycles may be longer and irregular, and the luteal phase may be shorter, characteristic of luteal phase deficiency, already mentioned as associated with miscarriage. Defective ova are produced in this marginal state of nutritional and hormonal adequacy. The conceptuses rejected during early miscarriage have been shown to be defective in the great majority of cases so miscarriage may be regarded as another selection mechanism ~ But all defective conceptuses are not rejected.

FOOD SHORTAGE INCREASES RISK OF NEURAL TUBE DEFECTS AND OTHER CONGENITAL MALFORMATIONS

Epidemics of congenital malformations were recorded after the end of the war in Europe as illustrated for Berlin in Figure 6. Similar epidemics of malformations were recorded in Bonn, Celle and Gottingen¹⁶, in Dresden^1,2, Chemnitz¹⁷, Erlangen¹⁸, Leipzig^3,16,19,20, Munich²¹, Wurzburg²² and other German cities. Epidemics of malformations were also recorded in Hungary in Baja²³ and Debrecen²⁴, in Italy²⁵ and in the Netherlands²⁶. Most of the recorded malformations were anencephalus and spina bifida notably when recorded at birth as in the Berlin record in Figure 6. Neural tube defects are generally easy to diagnose. When records of congenital malformation as a cause of death during the first year, as, for example, in a record for the Netherlands, about 60 per cent were neural tube malformations and 40 per cent other types²⁶. This 60:40 ratio was much the same before, during and after the epidemics. The incidence of some congenital malformations was, however, quite unaffected by the food shortages. For example the incidence of cleft lip or palate continued at the same rate in Berlin right through the war and its aftermath as before the war.

Like miscarriage neural tube defects and some other congenital malformations were a product of the marginal or penumbral state. The women who bore these babies were not so badly fed that they were infertile and not well enough fed to have normal babies. Many conceptuses lost during early miscarriage also have these types of malformation which are associated with depression of the levels of reproductive hormones.

Low birthweight, early miscarriage and congenital malformations are associated with depressed levels of another hormone oestradiol²⁷. If the level of this hormone is too low, but not so low as to cause infertility, the maturation of the ovum is slowed down, ovulation is delayed and the follicle may be smaller in size at ovulation than normal. This slow-down in ovulatory maturation and delay in ovulation is associated with an increased risk of subsequent fetal growth retardation and congenital malformation^28,29. It is this slow-down that also shortens the luteal phase causing luteal phase deficiency (LPD) and depressed levels of progesterone. The follicle is converted into the corpus luteum which is also too small following slowdown in ovulatory maturation and the hormonal environment of the embryo is depressed. It is seen in Figure 7 that dieting has a rapid effect on women's oestradiol levels. The research results in Figure 7 are from experiments at the Max Planck Institute of Psychiatry

It has been seen that the two most important reproductive hormones, oestradiol and progesterone can be influenced simply by changing diet. This is not, however, the only effect of nutritional deficiencies on follicular development. Thus, deficiencies of the B vitamins pyridoxine and folate have been shown in animals to act directly on ovulatory maturation within the follicle independently of hormone levels³⁰. Women's nutritional status before conception is therefore doubly important to prevention.

THE LONG-TERM CONSEQUENCES OF POOR MATERNAL NUTRITION

Two of the staff of the women's clinic of Berlin University at the Charity Hospital published on congenital malformations and pathological embryos seen at their clinic and concluded³¹:

"We must be concerned in future with the optimal and in every sense adequate nutrition of women during the first weeks of pregnancy and not as hitherto only with the last weeks of pregnancy" (translation).

The exposure of women and their babies to food shortage causes serious casualties both early and late in pregnancy. Exposure during the latter half of pregnancy resulted in large increases in subsequent infant mortality at least partly attributable to reduced resistance to infections as illustrated in Figure 8 for the Dutch hunger winter. This particular food shortage came to an end abruptly in a very few weeks when relief arrived from the Allies in May 1945 and .therefore illustrates the effects of a food shortage of well-defined duration.

Food shortage seems nearly always to be accompanied by epidemics of infectious diseases affecting particularly the digestive tract and the lungs. Subsequent studies of the Dutch hunger winter have failed to identify any long term consequences of this exposure of women and their babies late in pregnancy or after childbirth²⁶. The study of the consequences is, however, very difficult more particularly because the infertility and mortality caused by food shortage are socially and physiologically highly selective. For example the families with close relations who were farmers or market gardeners, or who could afford the very high prices on the black market, were able to avoid the worst consequences of the food shortages.

In contrast, exposure of women to food shortage around the time of conception was associated with congenital malformations, thought at the time to be limited to exposure "during the first weeks of pregnancy" or organogenesis. The susceptible period extends, as we now know, to include the later stages of ovulatory maturation and ovulation. In real-life terms this only adds emphasis to the importance of women's nutritional status before conception and during early pregnancy before a woman knows she is pregnant.

The increased incidence of congenital malformations as recorded following a food shortage is only the tip of an iceberg. A 200 page thesis entitled "Obstetric performance of women after in utero exposure to the Dutch famine (1944-45)", was submitted by L.H. Lumey to the Graduate School of Columbia University in 1988³². The next generation was shown to be prejudiced if the mother was in utero during the first trimester of pregnancy when her mother was exposed to food shortage. British research led by David Barker of the Medical Research Council has shown that low birthweight increases the risk many years later of cardiovascular and lung disease³³. There is no doubt that all body systems can be damaged by maternal food shortage before and after the time of conception.

Of course all congenital malformations are not caused by inadequate or faulty nutrition. However, animal experiments have shown, for example, using thalidomide, that nutrient deficiencies can greatly enhance the potency of teratogens and may indeed be necessary to make some substances teratogenic at all. Tests of teratogenicity on well fed animals have only limited value34.

We learn from experience, and it is important for mankind that the effects of food shortage should not be forgotten when many people in the world are suffering or threatened by shortage. Human tragedy has lessons too for individuals. The women of the developed communities of the west are not starving but there are minorities in that marginal, penumbral state that is dangerous to reproduction.

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Address by Arthur Wynn to the Annual General Meeting of the McCarrison Society, London, 12th December 1992