Vitamin A Deficiency and Increased Mortality in Children Lessons From Denmark

From 1909 to 1920, the Danish ophthalmologist Olaf Blegvad (1888-1961) documented cases of xerophthalmia, or clinical vitamin A deficiency, among children in Denmark (48). From 1911 to 1917, there was a strong, gradual increase in the number of cases of keratomalacia, the most severe eye lesion of vitamin A deficiency, followed by a decline in 1918 and 1919 and then an increase in 1920. During the same period in neighboring Sweden, there was no epidemic of xerophthalmia. Blegvad showed that the export of butter and cheese from Denmark and increased consumption of margarine within the country were linked with the increase in vitamin A deficiency. The manufacture of margarine ceased in 1917 after a German submarine blockade halted importation of raw materials, and butter, which was produced in Denmark at an expensive price, was then rationed at a more affordable cost for the poor after December 21, 1917. On May 1, 1919, butter rationing ceased (Fig. 1) (48). The mortality rate observed among 434 children with xerophthalmia was about 21%, with the highest mortality noted among younger infants. The high mortality of children was attributed to infections and the lack of vitamin A, and it resembled the infections and mortality found in animals experimentally raised on a vitamin A-deficient diet (48). Blegvad concluded that efficacious treatment with whole milk or cod-liver oil containing vitamin A reduced the mortality of children with xerophthalmia (49).

Carl Bloch (1872-1952), a pediatrician in Copenhagen, also dealt with the epidemic of xerophthalmia and provided important descriptions of the epidemiology and treatment of vitamin A deficiency (50). Bloch observed that the number of cases of children admitted with xerophthalmia at the State Hospital in Copenhagen rose from 1912 to 1917 and then dropped dramatically in 1918 (Fig. 2) (51). The abrupt decline in cases of xerophthalmia in 1918 coincides with butter rationing for the poor in 1918 (Fig. 1). Bloch noted that xerophthalmia was associated with lack of milk and green vegetables in the diet and that children with xerophthalmia had retarded growth. He concluded that vitamin A deficiency was characterized by a decline in immunity, increased severity of infections, and a higher risk of death. Child mortality was reduced by providing foods containing vitamin A. Bloch advocated the provision of milk, cream, butter, and cod-liver oil to treat eye disease, promote growth and development, and to reduce infectious diseases of children (50,52). Bloch noted that "the death rate among children is considerable after recovery from xerophthalmia; hardly two thirds of these children reach the age of 8 years" (52).

The concerns about vitamin A deficiency clearly extended beyond children who had xerophthalmia, or clinical vitamin A deficiency. The concept of subclinical vitamin A deficiency was widely discussed in major medical journals in the 1920s. Based on the observations in Denmark and animal studies, Erik Widmark (1889-1945), Professor of Medical and Physiological Chemistry at the University of Lund, concluded in The Lancet "...there must be in a population in which xerophthalmia occurs a much larger number of cases in which the deficiency in vitamin A, without producing the eye disease, is the

Denmark Nutrition

Fig. 1. Relative amount of butter used each year (oblique lines), substitutes made from animal fats (white spaces), and vegetable fat substitutes (black spaces). From December 1917 to May 1919 butter was rationed so that even the poor could afford it. (Reprinted from ref. 48, with permission from Elsevier.)

Fig. 1. Relative amount of butter used each year (oblique lines), substitutes made from animal fats (white spaces), and vegetable fat substitutes (black spaces). From December 1917 to May 1919 butter was rationed so that even the poor could afford it. (Reprinted from ref. 48, with permission from Elsevier.)

cause of a diminished resistance to infections, of general debility, and of malnutrition" (54). A state of subclinical vitamin A deficiency was acknowledged as "the borderline between health and disease" where a child would appear healthy, but in the face of an infection would do less well because of an underlying vitamin deficiency (55). The emphasis shifted from targeting children with xerophthalmia to ensuring adequate vitamin A status of children in populations.

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