Fuentes de Estrés Laboral

The word ’folate’ is derived from the Latin word ’folia’ meaning ’le a f because it was

first found in spinach. Folates are a light-sensitive family o f water-soluble vitamins found in almost all foods of animal or plant origin. They are heat-labile and are

particularly plentiful in liver, dark green vegetable leaves, yams, sweet potatoes, egg yolk, fish, pulses, nuts and fruits such as plantains, bananas and mangoes (Fleming,

1989). Some of the important staples in developing countries such as rice, cassava,

millet, sorghum and maize are poor sources o f folate (Metz et al., 1970; Fluq et al., 1983).

Although the bioavailability of folates from foods is variable, it is a less important factor than in iron deficiency. The absorption o f folates from poorly bioavailable

foods is up to 30 - 50% (Tamura & Stokstad, 1973). An important factor in the aetiology of folate deficiency particularly in developing countries is prolonged heating or repeated reheating of food (Fleming, 1970; Baynes et al., 1986).

Some studies estimate that the normal folate requirements are of the order of 100-150 pg/day (Moscovitch & Cooper, 1973; Chanarin, 1975), while others have recommended a daily intake of 3 pg/kg (Herbert, 1987), which represents an

approximate daily intake of between 150-200 pg. These calculations are based on a six month study of 40 adult males kept on a strictly controlled diet (Milne et al., 1983), when it was shown that a daily intake of 200 ± 68 pg/day maintained normal

red cell and serum folate levels. The WHO recommend an intake of 400 pg/day for adults (WHO, 1972).

Folate demands rise in pregnancy particularly in the third trimester and the puerperium. Folate requirements are believed to double in pregnancy from about 150

to 300 pg/day, as it has been shown that folate deficiency can be prevented by

supplementing a normal United Kingdom diet (approximate folate content 200 pg/day) with 100 pg/day of folate daily (Chanarin, 1968). There is also evidence that in

women with poor folate stores, subsisting on diets low in folate, folate deficiency can be prevented by giving 300 pg of folate daily (Colman, 1975). Many studies have

demonstrated a steady fall in serum folate levels throughout pregnancy. Hall (1976)

showed that there was a greater fall in women from lower socioeconomic groups, multigravidae, smokers and twin pregnancies.

1.4.1 Increased folate requirements

Folate requirements can be increased by disease processes associated with haemolysis

such as malaria and sickle cell disease. Malaria infection is usually followed by erythroid hyperplasia which markedly increases the requirements for folate (Fleming,

1981). In northern Nigeria, antimalarial prophylaxis alone, without folate supplements, reduced the frequency of megaloblastosis in primigravidae from 56 to

25%. The addition of folic acid supplementation completely abolished the megaloblastosis (Fleming, 1986).

In the absence o f folate supplementation, the frequency o f megaloblastic haemopoiesis is high. In studies in London, Montreal, Johannesburg and Texas (Lowenstein et al., 1966; Turchetti et al., 1966; Scott et al., 1970; Chanarin & Rothman, 1971), about

25% of bone marrow samples were megaloblastic and 30% were megaloblastic in Ireland (Temperly et al., 1968). With the widespread use o f iron-folate supplements in developed countries, the condition is rare except in women not having normal antenatal care. The incidence o f megaloblastic anaemia is higher in the developing

countries where the nutrition is poor and there is the added burden of malaria infection. In a study of aetiology of severe anaemia in Zambia (Fleming, 1989b)

found that 62% of women were folate deficient, but concluded that most of this was associated with malaria.

Megaloblastic erythropoiesis is particularly common in W est Africa (Fleming, 1989a) where it is being diagnosed in up to 75% of severely anaemic pregnant women. This

has been attributed to a combination of nutritional inadequacy, malaria and other infections, frequency of haemoglobinopathies (especially Hb SC) in pregnancy (Harrison, 1982) and the high rate of twinning.

Similar to iron deficiency, folate deficiency may have deleterious effects independent of the effects o f megaloblastic anaemia. Baumslag et al., (1970) reported that in folate

deficient African women, folate added to iron supplementation, increased birth weight and reduced the incidence of prematurity, but had no effect when given to well

nourished Caucasian women. Other studies (Iyengar & Rajalakshmi, 1975; Rolschau

et al., (1979) and Tchernia et al., (1982) have confirmed these findings and in addition have shown that placental weight was also increased suggesting that the beneficial

effect on infant weight was due to improved nutrition. Giles et al., (1971) and Fletcher et al., (1971) have also confirmed Baum slag's findings that folate

supplementation does not appear to improve birth weight in well-nourished populations.

Masawe et al., (1974); Fleming et al., (1969) and Giles (1966) reported an increase

in the incidence o f infections in folate deficiency. Defects in cell mediated immunity have also been reported in poorly nourished pregnant women. However, Iyengar & Rajalakshmi (1975) and Fleming et al., (1968) found no effect on the incidence of infection.

Harrison et al., (1985) reported some limitation o f growth and pelvic development in folate deficient Nigerian pregnant girls below the age o f 16 years. These two factors are important as they could lead to an increase in obstructed labours, instrumental

deliveries and Caesarian sections which are likely to be associated with an increase in maternal and foetal morbidity and mortality. In fact, in Harrison’s study antenatal

supplementation, especially with folic acid, was associated with the stimulation of

growth in primigravidae aged less than 16 years from a mean of 1 cm to a mean of 3 cm. This was also associated with development o f the pelvis and a highly

significant reduction in the number of operative deliveries due to disproportion.

Smithells et al., (1976) have suggested a possible association between neural tube defects in the foetus and folate deficiency based on the finding o f low red cell folate

levels in the first trimester in six women who subsequently gave birth to infants with neural tube defects as compared to the control group. Laurence et al., (1981) and

Smithells et al., (1981) therefore proposed that folate supplements be given to the mother before conception to reduce the frequency of neural tube defects.

Iron deficiency may conceal the presence o f a co-existing megaloblastic process. In Nigeria, a marked increase in the incidence o f anaemia in pregnancy has been noted

between April and September which coincides with the rainy season. This has been

attributed to the scarcity and expense of yams, a good source of folic acid (Fleming, 1970).

1.4.2 Diagnosis of folate deficiency

Folate deficiency usually causes a megaloblastic anaemia, with characteristic changes in the bone marrow aspirates. These changes are often associated with macrocytic red

cells and hypersegmented polymorphs on a thin blood film. In severe anaemia, there is often a mild leucopenia/neutropenia and thrombocytopenia. As iron deficiency is associated with small red cells, a combined iron/folate deficient anaemia may mask the typical changes o f either deficiency (Chanarin et al., 1977), although a double

population o f hypochromic/microcytic and macrocytic cells may be seen in a blood film suggesting a combined deficiency. This is often referred to as a "Dimorphic picture". Folate status can be accurately assessed by measuring the red cell folate concentrations which are a good reflection of the tissue folate depletion. Serum folate

estimates on the other hand are less accurate due to lack of sensitivity.

Bone marrow aspiration is still a very valuable diagnostic tool. The interpretation of bone marrow samples are however subjective and may be associated with poor

reproducibility (Bentley & Williams, 1974). In addition, iron can be immobilized in the reticuloendothelial system by folate deficiency and bone marrow iron may be

present in patients with severe megaloblastic anaemia although the total body iron stores are insufficient to restore the haemoglobin to normal with folic acid treatment

alone (Fleming, 1969; Oluboyede et al., 1977; Fleming, 1982). In areas where

laboratory facilities are limited, the microscopic examination o f bone marrow smears offers the best estimate of iron status and megaloblastic change.