Ferropenic Anaemias as a Problem of Public Health

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There are several levels of consideration when analysing the problem of the ferropenic anaemias. Firstly there is the overall prevalence in the population, which is quite low in the UK when compared to the developing world (see on). Secondly we need to differentiate between the physiological ferropenic anaemias such as those which occur in pregnancy, those which occur as a result of disease states such as the various forms of malabsorbtion and those which occur through neglect or malnutrition (in the widest possible sense).(Allen, L et al. 2001)

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The physiological anaemias are not a major public health issue as they are almost invariably screened for in the routine ante-natal clinics and when found, are generally treated on an expectant basis. Iron stores may be depleted after pregnancy and during the breast feeding period, but again, one could reasonably expect that these conditions would be detected and treated as a matter of course. (Ramakrishnan, U. 2001)

The same comments generally apply, although with not quite such universal accuracy, in the malabsorbtion states. Such states are generally found as part of another (usually more clinically obvious) pathophysiological process or as part of a post-operative syndrome. (I M 2001)

One would hope that, as such, they would be part of the general management of the overall condition and therefore do not pose a particular public health issue.

Another area where the Public Health is a potential concern is that where the ferropenic anaemias occur as a result of malnutrition, poor diet or neglect.

One way of considering these issues is to analyse the situation in circumstances where the prevalence of ferropenic anaemias is greater than in the UK (where it is comparatively unusual). (Gibson, R. S et al. 2001)

In the developing world, the ferropenic anaemias are a major Public Health issue and some countries have instituted measures to directly combat them.(Yip, R. 1994)

The first issue to address is to consider the notion that the commonly measured index of haemoglobin concentration is actually a good measure of iron stores. The evidence base here is quite clear that in developed countries where the level of nutrition is generally good, there is a reasonable (but not exact) correlation. In countries with less good nutritional values, there is a marked disparity between haemoglobin levels and iron levels.

Haemoglobin distributions of a subset of iron deficient U.S. children (dotted line) and children who are not iron deficient (solid line). The key observation is the substantial overlap

Haemoglobin distributions of Palestinian refugee children (dotted line) and U.S. children (solid line). The key observation is the relatively small overlap.

(after Yip et al. 2002)

Secondly we should note that as a matter of basic pathophysiology, not all anaemia is due to iron deficiency and not all iron deficiency will be reflected in anaemia. Therefore uncritical use of the haemoglobin index as a measure of the ferropenic anaemias is basically flawed. These charts suggest that the linkage between haemoglobin and serum iron is closer in developed countries than in developing ones.

We can point to other indicators of iron status including transferring saturation, serum ferritin, free erythrocyte protoporphryn (FEP) or the more technologically advanced transferrin receptor levels . (Gimferrer E et al. 1997) which can be utilised to give indicators of iron levels either in a specific patient or on a population level. (Lynch, S et al. 2001). There is another consideration here and that these indicators, although probably accurate on an individual level, may not be so helpful on the population level as, particularly in the developing countries, their laboratories may not have a sufficient level of sophistication to perform the assays and also these tests are less accurate in populations where there is a high prevalence of infections

One of the main areas of concern to the Public Health is that of the ferropenic anaemias in children. There is a relative period of “physiological” anaemia in the child which occurs between 6 and 18 months. The word physiological is in parenthesis because it is not strictly accurate. It is physiological insofar as this is the time when the child’s body has its highest levels of iron requirement (almost 10 times higher than in the adult in comparison to body weight) and the comparative depletion is generally rectified by dietary means once the period of high usage is over. (IM 2001). The second factor in this situation is that the typical diet of this age range tends to be low in bio available iron when compared to that of an adult. (O’Donnell, A. M et al. 1997)

In the UK it is rare for a child to develop a ferropenic anaemia because those at risk (underweight and malnourished) are generally picked up by routine Health Visitor screening and also because of the better dietary quality of the average diet which is high in meat with a high iron content. Specifically designated infant food in the UK is commonly fortified with additional iron in any event. (Hall, A et al. 2001). We should not overlook that fact that breast milk has a high content of bio available iron and is a useful source of protection (although not universally effective) against the ferropenic anaemias in the young child

We should note however, that in studies that have compared breast fed children, with “normal” diet children and compared them also against those with a fortified diet (defined by being primarily fed on artificial milk) there was virtually no significant incidence of ferropenic anaemias in those children who were given the fortified diet suggesting that those countries who still utilise the fortified milk system as a Public Health measure are spending their money in a cost effective way. (Walter T et al. 2001)

Because of the substantial evidence base that supplementation of iron in the diet of the young child is both cost effective and demonstrably workable, (Bothwell T H et al. 1999)

One should really also to consider the additional question as to whether there is a case for supplementing other micronutrients as well as iron. This is a question that is outside the strict parameters of the essay title set here so we will not consider it further except to observe that there is a substantial evidence base to support this as well. (Solomons N W et al. 1993)

If we now expand the arguments to women of reproductive age, we note that the risk of developing a ferropenic anaemia during pregnancy is greater than during virtually any other stage of life. In approximate values, a pregnant woman can expect her circulating blood volume to expand by about 35% during pregnancy. She would expect to have a total pregnancy requirement of about 590 mg of elemental iron for the foetus and physiological RBC turn over. Routine prophylaxis in the UK supplies about 750 mg during a pregnancy which leaves about 160 mg for erythropoesis. Studies have suggested that the typical woman needs about 1100 mg of elemental iron throughout her pregnancy to avoid a “natural ferropenic anaemia “. (Viteri F E 1999)

There is considerable evidence that a pre-pregnancy ferropenic anaemia increases the risk of developing further anaemia during a first (and progressively greater in subsequent) pregnancies as it suggests that the iron stores in the body are already depleted.

There is evidence to suggest that, in women in the reproductive years in the developed world, ferropenic anaemia is more likely to be associated with increased blood loss (menorrhagia or polymenorrhoea) than it is to be associated with poor diet.

Lennartsson, (J et al. 1999) made a substantial study of ferropenic anaemias in women and identified a “substantial sub-set” whose menstrual loss was such that a normal diet could not keep up with their iron requirements.

In the context of our essay we can state that iron deficits that are due to menstrual loss appear to have the greatest effect on women in the developing world as they tend to have diets which are already comparatively poor in both overall iron content and bioavailability. Paradoxically, women in the developed world who do develop ferropenic anaemias due to excessive blood loss, are more likely to suffer from multiple micronutrient dietary deficiencies as well, most notably zinc, copper, calcium and vitamin A, (Hall, A et al. 2001). It is also the case that in the developing world, intercurrent infections such as helminthic infestations and malaria may also result in increased levels of blood loss and therefore the underlying causes will also need to be addressed as well as simply correcting the iron deficiency.

The nutritional iron requirements of the pregnant woman are typically twice that of the non-pregnant woman, who, in turn, has approximately twice the requirement of the same aged man (corrected for appropriate energy expenditure). Recent studies have shown that 50% of women in developed countries do not have sufficient iron stores for pregnancy requirements. (Kim, I et al. 1998). This fact is essentially the rationale behind the fairly routine prescription of iron tablets to pregnant women in the UK

Iron requirements in relation to energy intake for infants, men, women and pregnant women. (After IM 2001)

We note that different countries adopt different strategies taking account of costs and available resources. Many, including the UK and the USA, adopt a fortification strategy as a Public Health measure as not only women but men and children will also benefit. Some countries chose to adopt periodic supplementation under supervision such as in a school or the workplace. (Viteri, F. E. 1999)

Many countries, including the UK, choose to fortify basic food ingredients such as wheat flour which is currently fortified to levels of 60 µg/g. Basic calculations based on an annual intake of 20 kg/yr (which is fairly low by UK standards) would suggest that this measure alone equates to 3 mg of elemental iron per day or about 25% of the recommended daily requirement. (Viteri, F.E. 1997)

In terms of Public Heath costs a recent estimate suggests that it costs about 70p ($1.30) to fortify one ton of wheat flour with six micronutrients, including iron. (Lofti, M 1998). If we revert back to the 20 kg per year estimate of minimal intake, the cost is only a few pence per year ($0.025). Some sources have suggested a programme of plant development and breeding to develop strains of staples such as rice and wheat that have a intrinsically higher micronutrient content. (Gibson, R. S et al. 2001). These measures are certainly within the technological capabilities of the majority of countries and therefore make such measures a viable option.

References

Allen, L. & Casterline-Sabel, J. (2001)

Prevalence and causes of nutritional anemias. Ramakrishnan, U. eds.

Nutritional Anemias 2001 : 7-22

CRC Press Boca Raton, FL

Bothwell T H, Charlton R W, Cook J D, Finch C F, eds. 1999

Iron metabolism in man.

Oxford, United Kingdom: Blackwell Scientific Publications, 1999 ; 21.

Gibson, R. S. & Hotz, C. (2001)

Dietary diversification/modification strategies to enhance micronutrient content and bioavailability of diets in developing countries.

Br. J. Nutr. 85 (suppl. 2) : S159-SS66.

Gimferrer E, J. Ubeda, M.T. Royo, G.J. Marigó, N. Marco, N. Fernández, A. Oliver, R. Padrós, and I. Gich 1997 Serum Transferrin Receptor Levels in Different Stages of Iron Deficiency Blood, Aug 1997 ; 90 : 1332 – 1333.

Hall, A., Drake, L. & Bundy, D. (2001)

Public measures to control helminth infections. Ramakrishnan, U. eds. Nutritional Anemias 2001 : 215-240

CRC Press Boca Raton, FL.

IM 2001

Institute of Medicine (2001) Dietary Reference Intakes. . Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, Zinc 2001

National Academy of Sciences Washington, DC. . 2001

Kim, I., Hungerford, D. W., Yip, R., Kuester, S. A., Zyrkowski, C. & Trowbridge, F. L. (1998)

Pregnancy nutrition surveillance system—United States, 1979–1990.

CDC Surveillance Summary,

Morb. Mortal. Wkly. 1998 Rep. 7 : 25-41.

Lennartsson, J., Bengtsson, C., Hallberg, L. & Tibblin, E. (1999)

Characteristics of anaemic women. The population study of women in Goteborg 1968–1969.

Scand. J. Haematol. 22 : 17-24

Lofti, M. eds. 1998

Food Fortification to End Micronutrient Malnutrition—State of the Art. Micronutrient Initiative 1998 Ottawa, Canada. .

Lynch, S. & Green, R. (2001)

Assessment of nutritional anemias. Ramakrishnan, U. eds.

Nutritional Anemias 2001 : 23-42

CRC Press Boca Raton, FL.

O’Donnell, A. M., Carmuega, E. S. & Duran, P. (1997)

Preventing iron deficiency in infants and preschool children in Argentina.

Nutr. Rev. 55 : 189-194

Ramakrishnan, U. (2001)

Functional consequences of nutritional anemia during pregnancy and early childhood. Ramakrishnan, U. eds.

Nutritional Anemias 2001 : 43-68

CRC Press Boca Raton, FL. .

Solomons N W, Mazariegos M, Brown K H, Klasing K. 1993

The underprivileged, developing country child: environmental contamination and growth failure revisited.

Nutr Rev 1993 ; 51 : 327–32.

Viteri, F.E. (1997)

Iron supplementation for the control of iron deficiency in populations at risk.

Nutr. Rev. 55 : 195-209.

Viteri, F. E. (1999)

Iron supplementation as a strategy for the control of iron deficiency and ferropenic anemia.

Arch. Latinoam. Nutr. 49 (suppl. 2) : 15S-22S

Walter, T., Olivares, M., Pizarro, F. & Hertrampf, E. (2001)

Fortification. Ramakrishnan, U. eds.

Nutritional Anemias 2001 : 153-184

CRC Press Boca Raton, FL. .

Yip, R. (1994)

Iron deficiency: contemporary scientific issues and international programmatic approaches.

J. Nutr. 124 : 1479S-1490S

Yip R and Usha Ramakrishnan 2002 Experiences and Challenges in Developing Countries J. Nutr., Apr 2002 ; 132 : 827 – 830.

################################################################

8.11.06 Word count 2,251 PDG

 

There are several levels of consideration when analysing the problem of the ferropenic anaemias. Firstly there is the overall prevalence in the population, which is quite low in the UK when compared to the developing world (see on). Secondly we need to differentiate between the physiological ferropenic anaemias such as those which occur in pregnancy, those which occur as a result of disease states such as the various forms of malabsorbtion and those which occur through neglect or malnutrition (in the widest possible sense).(Allen, L et al. 2001)

The physiological anaemias are not a major public health issue as they are almost invariably screened for in the routine ante-natal clinics and when found, are generally treated on an expectant basis. Iron stores may be depleted after pregnancy and during the breast feeding period, but again, one could reasonably expect that these conditions would be detected and treated as a matter of course. (Ramakrishnan, U. 2001)

The same comments generally apply, although with not quite such universal accuracy, in the malabsorbtion states. Such states are generally found as part of another (usually more clinically obvious) pathophysiological process or as part of a post-operative syndrome. (I M 2001)

One would hope that, as such, they would be part of the general management of the overall condition and therefore do not pose a particular public health issue.

Another area where the Public Health is a potential concern is that where the ferropenic anaemias occur as a result of malnutrition, poor diet or neglect.

One way of considering these issues is to analyse the situation in circumstances where the prevalence of ferropenic anaemias is greater than in the UK (where it is comparatively unusual). (Gibson, R. S et al. 2001)

In the developing world, the ferropenic anaemias are a major Public Health issue and some countries have instituted measures to directly combat them.(Yip, R. 1994)

The first issue to address is to consider the notion that the commonly measured index of haemoglobin concentration is actually a good measure of iron stores. The evidence base here is quite clear that in developed countries where the level of nutrition is generally good, there is a reasonable (but not exact) correlation. In countries with less good nutritional values, there is a marked disparity between haemoglobin levels and iron levels.

Haemoglobin distributions of a subset of iron deficient U.S. children (dotted line) and children who are not iron deficient (solid line). The key observation is the substantial overlap

Haemoglobin distributions of Palestinian refugee children (dotted line) and U.S. children (solid line). The key observation is the relatively small overlap.

(after Yip et al. 2002)

Secondly we should note that as a matter of basic pathophysiology, not all anaemia is due to iron deficiency and not all iron deficiency will be reflected in anaemia. Therefore uncritical use of the haemoglobin index as a measure of the ferropenic anaemias is basically flawed. These charts suggest that the linkage between haemoglobin and serum iron is closer in developed countries than in developing ones.

We can point to other indicators of iron status including transferring saturation, serum ferritin, free erythrocyte protoporphryn (FEP) or the more technologically advanced transferrin receptor levels . (Gimferrer E et al. 1997) which can be utilised to give indicators of iron levels either in a specific patient or on a population level. (Lynch, S et al. 2001). There is another consideration here and that these indicators, although probably accurate on an individual level, may not be so helpful on the population level as, particularly in the developing countries, their laboratories may not have a sufficient level of sophistication to perform the assays and also these tests are less accurate in populations where there is a high prevalence of infections

One of the main areas of concern to the Public Health is that of the ferropenic anaemias in children. There is a relative period of “physiological” anaemia in the child which occurs between 6 and 18 months. The word physiological is in parenthesis because it is not strictly accurate. It is physiological insofar as this is the time when the child’s body has its highest levels of iron requirement (almost 10 times higher than in the adult in comparison to body weight) and the comparative depletion is generally rectified by dietary means once the period of high usage is over. (IM 2001). The second factor in this situation is that the typical diet of this age range tends to be low in bio available iron when compared to that of an adult. (O’Donnell, A. M et al. 1997)

In the UK it is rare for a child to develop a ferropenic anaemia because those at risk (underweight and malnourished) are generally picked up by routine Health Visitor screening and also because of the better dietary quality of the average diet which is high in meat with a high iron content. Specifically designated infant food in the UK is commonly fortified with additional iron in any event. (Hall, A et al. 2001). We should not overlook that fact that breast milk has a high content of bio available iron and is a useful source of protection (although not universally effective) against the ferropenic anaemias in the young child

We should note however, that in studies that have compared breast fed children, with “normal” diet children and compared them also against those with a fortified diet (defined by being primarily fed on artificial milk) there was virtually no significant incidence of ferropenic anaemias in those children who were given the fortified diet suggesting that those countries who still utilise the fortified milk system as a Public Health measure are spending their money in a cost effective way. (Walter T et al. 2001)

Because of the substantial evidence base that supplementation of iron in the diet of the young child is both cost effective and demonstrably workable, (Bothwell T H et al. 1999)

One should really also to consider the additional question as to whether there is a case for supplementing other micronutrients as well as iron. This is a question that is outside the strict parameters of the essay title set here so we will not consider it further except to observe that there is a substantial evidence base to support this as well. (Solomons N W et al. 1993)

If we now expand the arguments to women of reproductive age, we note that the risk of developing a ferropenic anaemia during pregnancy is greater than during virtually any other stage of life. In approximate values, a pregnant woman can expect her circulating blood volume to expand by about 35% during pregnancy. She would expect to have a total pregnancy requirement of about 590 mg of elemental iron for the foetus and physiological RBC turn over. Routine prophylaxis in the UK supplies about 750 mg during a pregnancy which leaves about 160 mg for erythropoesis. Studies have suggested that the typical woman needs about 1100 mg of elemental iron throughout her pregnancy to avoid a “natural ferropenic anaemia “. (Viteri F E 1999)

There is considerable evidence that a pre-pregnancy ferropenic anaemia increases the risk of developing further anaemia during a first (and progressively greater in subsequent) pregnancies as it suggests that the iron stores in the body are already depleted.

There is evidence to suggest that, in women in the reproductive years in the developed world, ferropenic anaemia is more likely to be associated with increased blood loss (menorrhagia or polymenorrhoea) than it is to be associated with poor diet.

Lennartsson, (J et al. 1999) made a substantial study of ferropenic anaemias in women and identified a “substantial sub-set” whose menstrual loss was such that a normal diet could not keep up with their iron requirements.

In the context of our essay we can state that iron deficits that are due to menstrual loss appear to have the greatest effect on women in the developing world as they tend to have diets which are already comparatively poor in both overall iron content and bioavailability. Paradoxically, women in the developed world who do develop ferropenic anaemias due to excessive blood loss, are more likely to suffer from multiple micronutrient dietary deficiencies as well, most notably zinc, copper, calcium and vitamin A, (Hall, A et al. 2001). It is also the case that in the developing world, intercurrent infections such as helminthic infestations and malaria may also result in increased levels of blood loss and therefore the underlying causes will also need to be addressed as well as simply correcting the iron deficiency.

The nutritional iron requirements of the pregnant woman are typically twice that of the non-pregnant woman, who, in turn, has approximately twice the requirement of the same aged man (corrected for appropriate energy expenditure). Recent studies have shown that 50% of women in developed countries do not have sufficient iron stores for pregnancy requirements. (Kim, I et al. 1998). This fact is essentially the rationale behind the fairly routine prescription of iron tablets to pregnant women in the UK

Iron requirements in relation to energy intake for infants, men, women and pregnant women. (After IM 2001)

We note that different countries adopt different strategies taking account of costs and available resources. Many, including the UK and the USA, adopt a fortification strategy as a Public Health measure as not only women but men and children will also benefit. Some countries chose to adopt periodic supplementation under supervision such as in a school or the workplace. (Viteri, F. E. 1999)

Many countries, including the UK, choose to fortify basic food ingredients such as wheat flour which is currently fortified to levels of 60 µg/g. Basic calculations based on an annual intake of 20 kg/yr (which is fairly low by UK standards) would suggest that this measure alone equates to 3 mg of elemental iron per day or about 25% of the recommended daily requirement. (Viteri, F.E. 1997)

In terms of Public Heath costs a recent estimate suggests that it costs about 70p ($1.30) to fortify one ton of wheat flour with six micronutrients, including iron. (Lofti, M 1998). If we revert back to the 20 kg per year estimate of minimal intake, the cost is only a few pence per year ($0.025). Some sources have suggested a programme of plant development and breeding to develop strains of staples such as rice and wheat that have a intrinsically higher micronutrient content. (Gibson, R. S et al. 2001). These measures are certainly within the technological capabilities of the majority of countries and therefore make such measures a viable option.

References

Allen, L. & Casterline-Sabel, J. (2001)

Prevalence and causes of nutritional anemias. Ramakrishnan, U. eds.

Nutritional Anemias 2001 : 7-22

CRC Press Boca Raton, FL

Bothwell T H, Charlton R W, Cook J D, Finch C F, eds. 1999

Iron metabolism in man.

Oxford, United Kingdom: Blackwell Scientific Publications, 1999 ; 21.

Gibson, R. S. & Hotz, C. (2001)

Dietary diversification/modification strategies to enhance micronutrient content and bioavailability of diets in developing countries.

Br. J. Nutr. 85 (suppl. 2) : S159-SS66.

Gimferrer E, J. Ubeda, M.T. Royo, G.J. Marigó, N. Marco, N. Fernández, A. Oliver, R. Padrós, and I. Gich 1997 Serum Transferrin Receptor Levels in Different Stages of Iron Deficiency Blood, Aug 1997 ; 90 : 1332 – 1333.

Hall, A., Drake, L. & Bundy, D. (2001)

Public measures to control helminth infections. Ramakrishnan, U. eds. Nutritional Anemias 2001 : 215-240

CRC Press Boca Raton, FL.

IM 2001

Institute of Medicine (2001) Dietary Reference Intakes. . Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, Zinc 2001

National Academy of Sciences Washington, DC. . 2001

Kim, I., Hungerford, D. W., Yip, R., Kuester, S. A., Zyrkowski, C. & Trowbridge, F. L. (1998)

Pregnancy nutrition surveillance system—United States, 1979–1990.

CDC Surveillance Summary,

Morb. Mortal. Wkly. 1998 Rep. 7 : 25-41.

Lennartsson, J., Bengtsson, C., Hallberg, L. & Tibblin, E. (1999)

Characteristics of anaemic women. The population study of women in Goteborg 1968–1969.

Scand. J. Haematol. 22 : 17-24

Lofti, M. eds. 1998

Food Fortification to End Micronutrient Malnutrition—State of the Art. Micronutrient Initiative 1998 Ottawa, Canada. .

Lynch, S. & Green, R. (2001)

Assessment of nutritional anemias. Ramakrishnan, U. eds.

Nutritional Anemias 2001 : 23-42

CRC Press Boca Raton, FL.

O’Donnell, A. M., Carmuega, E. S. & Duran, P. (1997)

Preventing iron deficiency in infants and preschool children in Argentina.

Nutr. Rev. 55 : 189-194

Ramakrishnan, U. (2001)

Functional consequences of nutritional anemia during pregnancy and early childhood. Ramakrishnan, U. eds.

Nutritional Anemias 2001 : 43-68

CRC Press Boca Raton, FL. .

Solomons N W, Mazariegos M, Brown K H, Klasing K. 1993

The underprivileged, developing country child: environmental contamination and growth failure revisited.

Nutr Rev 1993 ; 51 : 327–32.

Viteri, F.E. (1997)

Iron supplementation for the control of iron deficiency in populations at risk.

Nutr. Rev. 55 : 195-209.

Viteri, F. E. (1999)

Iron supplementation as a strategy for the control of iron deficiency and ferropenic anemia.

Arch. Latinoam. Nutr. 49 (suppl. 2) : 15S-22S

Walter, T., Olivares, M., Pizarro, F. & Hertrampf, E. (2001)

Fortification. Ramakrishnan, U. eds.

Nutritional Anemias 2001 : 153-184

CRC Press Boca Raton, FL. .

Yip, R. (1994)

Iron deficiency: contemporary scientific issues and international programmatic approaches.

J. Nutr. 124 : 1479S-1490S

Yip R and Usha Ramakrishnan 2002 Experiences and Challenges in Developing Countries J. Nutr., Apr 2002 ; 132 : 827 – 830.

################################################################

8.11.06 Word count 2,251 PDG

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