Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (6)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by van den Broek, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van den Broek, N.
Related Collections
Right arrow Haematology
Right arrow Nutrition
Right arrow Obstetrics and Gynaecology
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

British Medical Bulletin 67:149-160 (2003)
© 2003 Oxford University Press

Anaemia and micronutrient deficiencies

Reducing maternal death and disability during pregnancy

Nynke van den Broek

Liverpool School of Tropical Medicine, Liverpool, UK

Correspondence to: Dr N van den Broek, Senior Lecturer Reproductive Health, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. E-mail: vdbroek{at}liv.ac.uk


   Abstract
Top
 Abstract
Definitions
 Screening
 Prevalence
 Anaemia and maternal mortality...
 Micronutrients and pregnancy
 Micronutrient deficiency and...
 Key points
 References
 
Anaemia in pregnancy is a common and worldwide problem that deserves more attention. For many developing countries, prevalence rates of up to 75% are reported. Anaemia is frequently severe in these situations and can be expected to contribute significantly to maternal mortality and morbidity. After a discussion of definitions, screening for anaemia and prevalence, the relationship between anaemia and maternal mortality and morbidity will be reviewed. Micronutrient deficiency and especially iron deficiency is believed to be the main underlying cause for anaemia. More recently the role of vitamin A deficiency as a contributing factor to anaemia has also been examined. The difficulties of assessment of micronutrient sufficiency or deficiency in pregnancy are described, as is the interaction between infection and micronutrient deficiency states.


   Definitions
Top
 Abstract
 Definitions
Screening
 Prevalence
 Anaemia and maternal mortality...
 Micronutrients and pregnancy
 Micronutrient deficiency and...
 Key points
 References
 
As a result of the normal physiological changes in pregnancy, plasma volume expands by 46–55%, whereas red-cell volume expands by 18–25%1,Go2Go. The resulting haemodilution has, perhaps wrongly, been termed ‘physiological anaemia of pregnancy’. There are in fact insufficient data to give accurate physiological limits for the expected haemodilution. In most published studies, the mean minimum normal haemoglobin in healthy pregnant women living at sea level is 11.0–12.0 g/dl. The mean minimum by WHO criteria is taken to be 11.0 g/dl in the first half of pregnancy and 10.5 g/dl in the second half of pregnancy3,Go4Go. In the only well-conducted longitudinal study that could be found of the ‘hydraemia’ of pregnancy in iron-replete healthy pregnant women, 10.4 g/dl was the lowest recorded value5Go.

Anaemia in pregnancy is further divided into mild anaemia ([Hb] 10.0–10.9 g/dl), moderate anaemia ([Hb] 7.0–9.9 g/dl) and severe anaemia ([Hb]<7.0 g/dl)4Go. The definition of severe anaemia in the published literature, however, varies and this may also be defined as [Hb]<8.0 g/dl. There is discussion in the literature about the relevance of the various cut-off points, whether different cut-off points should be used for different populations5–Go8Go and the need to adjust for populations living at high altitude9Go.


   Screening
Top
 Abstract
 Definitions
 Screening
Prevalence
 Anaemia and maternal mortality...
 Micronutrients and pregnancy
 Micronutrient deficiency and...
 Key points
 References
 
An accepted standard of practice is that all women have at least one haemoglobin measurement during the course of pregnancy. This is usually carried out by electronic (automated) counter. In many developing countries, these methods are not available at Health Centre level and may not be available even at tertiary level. Either screening for anaemia may not be carried out at all or assessment of whether a pregnant woman is anaemic or not may be limited to inspection of the conjunctiva by the nurse or midwife for the presence of pallor during antenatal visits.

There are few published papers reporting on the accuracy of screening for anaemia using clinical inspection of conjunctiva in pregnant women. In a large study conducted in women attending a rural antenatal clinic, sensitivity was 33.2% and 39.7% for haemoglobin values of ≤ 11.0 and ≤ 10.0 g/dl, respectively. Values obtained were better for the lower range of haemoglobin values but did not exceed 62.1%10Go. A study from Mozambique reported a sensitivity of 31.5%, with anaemia defined as a packed cell volume ≤ 3011Go. In a smaller study from Kenya, examination of the conjunctiva was reported to have 62–69% sensitivity for detecting severe anaemia ([Hb] < 7.0 g/dl) in a study population with a high incidence of severe anaemia (16%)12Go. Substantial interobserver variability has also been reported13,Go14Go. Even when used in combination with a conjunctival—or anaemia—recognition card, sensitivity remains low except when anaemia is severe15,Go16Go.

In the absence of a functioning automated (Coulter) counter, several alternative methods for measurement of haemoglobin concentration are available17Go. A relatively expensive but simple to use portable haemoglobin meter (HemoCue) has been evaluated and found to have a sensitivity of between 80% and 97% and a specificity of between 79% and 99% depending on the cut-off points for haemoglobin concentration used10,Go18–Go20Go. Another method which has been studied in antenatal clinic settings is the copper sulphate method21–Go24Go. This method relies on the preparation and availability of a solution of copper sulphate of known specific gravity. There is a fixed range of haemoglobin values for which a blood sample can be tested, e.g. [Hb] < 8.0 g/dl or < 10.0 g/dl.

In response to the need for a simple, cheap and accurate method for the estimation of haemoglobin concentration, a new Colour Scale was recently developed by the WHO25Go which is similar to the Talquist26Go scale and consists of a card with 6 colour standards corresponding to the colour of bloodstains of various haemoglobin concentrations (range 4.0–14.0 g/dl). Assessment in an antenatal population with high prevalence of anaemia by comparison with Coulter counter measurements gave sensitivities of 75.4% and 81.6% for cut-off points of [Hb] < 11.0 and < 10.0 g/dl, respectively. Specificity was 47.2% and 45.3%, respectively, but improved to 76.4% for [Hb] < 8.0 g/dl and 98.5% for [Hb] < 6.0 g/dl. The sensitivity of the WHO Colour Scale as a screening tool to detect anaemia was consistently better than if conjunctival inspection was used for screening10Go.


   Prevalence
Top
 Abstract
 Definitions
 Screening
 Prevalence
Anaemia and maternal mortality...
 Micronutrients and pregnancy
 Micronutrient deficiency and...
 Key points
 References
 
It has been estimated that over half the pregnant women in the world have a haemoglobin level indicative of anaemia. In industrialized countries, anaemia in pregnancy occurs in less than 20% of women. This does, however, still reach the level of public health significance (≥ 10%). Published rates of prevalence for developing countries range from 35% to 72% for Africa, 37–75% for Asia and 37–52% for Latin America27Go. Not only is anaemia common, it is often severe. From the published reports available, it can be estimated that 2–7% of pregnant women have values < 7.0 g/dl, and, probably 15–20% < 8.0 g/dl. Those authors who publish their range of haemoglobin values not infrequently report on patients with values well below 5.0 g/dl28–Go30Go. Up-to-date information from many countries is, however, still scanty; the few published studies often describe small sample sizes and are usually from hospital-based populations. There is a lack of data from rural areas. It has been suggested that the prevalence of anaemia may depend on the season, increasing in relation to malaria transmission in the wet season or in relation to increased food shortage at the end of the dry season, but published prevalence rates rarely reflect measurements performed all year round.

In 1993, the World Bank31Go ranked anaemia as the eighth leading cause of disease in girls and women in developing countries. Although anaemia is assumed to be less common in non-pregnant women, there is a lack of data on the prevalence of anaemia in this population group. Studies are also needed to assess the association between anaemia in pregnancy and pre-pregnancy haemoglobin levels.


   Anaemia and maternal mortality and morbidity
Top
 Abstract
 Definitions
 Screening
 Prevalence
 Anaemia and maternal mortality...
Micronutrients and pregnancy
 Micronutrient deficiency and...
 Key points
 References
 
Each year more than 500,000 women die from pregnancy-related causes, 99% of these in developing countries32Go. Estimates of maternal mortality resulting from anaemia range from 34/100,000 live births in Nigeria to as high as 194/100,000 in Pakistan4,Go27Go. In combination with obstetric haemorrhage, anaemia is estimated to be responsible for 17–46% of cases of maternal death33–Go35Go. A review of symptoms associated with maternal deaths in Bangladesh led researchers to conclude that anaemia had played a secondary role in nearly all cases36Go.

Anaemia is probably a chronic rather than acute condition in many cases. There is a resulting compensatory shift of the oxygen dissociation curve to the right. Thus, women with very low haemoglobin concentrations may be seen in the antenatal period without the expected overt symptoms of cardiac failure. They will, however, easily become tired by any form of physical activity and may decompensate, e.g. as a result of labour. Should any adverse event such as bleeding occur, their risk of death is high.

The available data on the association between anaemia and maternal survival are limited and there are serious methodological flaws in most of the studies, as pointed out by Rush37Go in his excellent review. It must be noted that pregnancy outcome will also be related to the underlying causes of anaemia, e.g. HIV, iron deficiency, recurrent antepartum haemorrhage, etc. Most of the published studies report on outcome for hospital-based patients. In developing countries, this is rarely representative of the population as a whole. In particular, conclusions about association or causality drawn from a single measurement during delivery in hospital must be considered flawed. In many cases, haemoglobin concentration may have been measured only because of, for instance, a prior history of bleeding, fever or suspected malaria, which may be the reason for referral to the hospital in the first place.

It must also be noted that there are currently no agreed international standards or sets of criteria for attributing death to anaemia. It is in fact often difficult to establish accurately the cause of death in situations where clinical information is incomplete and data collection is not standardized. Thus, in many cases, the only two laboratory tests that may have been available to clinicians could be a haemoglobin concentration and a peripheral blood slide for malaria parasitaemia. Death from anaemia may sound better than death from haemorrhage, in that the latter could be perceived as the result of the health facility’s inability to provide adequate care. Finally, level of access to emergency obstetric care and in particular to blood transfusion and the quality and speed of care received are of prime determining importance. Thus, a study from Indonesia38Go illustrated the much higher risk of maternal death in anaemic women from rural areas than from urban areas, possibly as a result of problems with timely access to obstetric care.

Morbidity resulting from anaemia is similarly difficult to establish. Diminished work capacity and physical performance have been reported as a result of anaemia39,Go40Go.

Iron deficiency anaemia leads to abnormalities in host defence and neurological dysfunction41,Go42Go. Increased risks of premature labour43–Go45Go and low birth weight43,Go46,Go47Go have also been reported in association with anaemia in pregnancy. Both are common problems in developing countries and contribute significantly to high perinatal mortality. However, most published work on this comes from industrialized countries where anaemia is much less of a problem and much less severe in nature. Confounding factors such as poverty, poor antenatal clinic attendance and recurrent infection, which can result in low birth weight and prematurity, are seldom examined at the same time. Further research on the effect of anaemia per se on birth weight and prematurity is therefore necessary to establish a clear causal relationship.


   Micronutrients and pregnancy
Top
 Abstract
 Definitions
 Screening
 Prevalence
 Anaemia and maternal mortality...
 Micronutrients and pregnancy
Micronutrient deficiency and...
 Key points
 References
 
Vitamins and minerals are referred to collectively as the ‘micronutrients’. The micronutrient deficiencies which are thought to be of the greatest public health significance globally are iron deficiency, vitamin A deficiency and iodine deficiency. Both iron deficiency and vitamin A deficiency can result in anaemia. Dietary inadequacy is thought to be the major cause for vitamin A and iron deficiency.

Iron deficiency

Iron is obtained in the form of non-haem iron from vegetables and as haem iron from meat. Haem iron is absorbed about two to three times better than non-haem iron. A small amount of haem iron in the diet will improve absorption of non-haem iron and thus the diet composition is an important determinant of the amount of iron actually absorbed. Iron is stored in the reticulo-endothelial system as ferritin and haemosiderin. Iron is a component of haemoglobin and iron deficiency ultimately leads to defective erythropoiesis and anaemia.

Pregnant women are particularly vulnerable to iron deficiency as a result of the increased demand for iron. The requirements for iron during pregnancy have been estimated at a total of about 1000 mg1,Go48Go. In response to pregnancy, iron absorption is increased48,Go49Go.

The marked physiological changes that occur in pregnancy influence the laboratory measurements used to evaluate iron status. The expansion of plasma volume, increase in erythropoiesis and increased demand of the fetoplacental unit for iron occur throughout gestation and can vary markedly between individuals. The resulting changes in serum levels of biochemical markers for iron status make it necessary to re-define cut-off values for the diagnosis of iron deficiency in pregnancy50Go. Serum ferritin is the most frequently used indicator of iron status.

The range of values for serum ferritin found in non-anaemic individuals is 12–300 µg/l. In the presence of anaemia, values of < 20 µg/l are commonly taken as evidence of iron deficiency51Go. However, patients with levels of up to 37 µg/l have been shown to have absent marrow haemosiderin52Go. In pregnancy, serum ferritin is lower and mean values are close to the iron deficient range53Go. More recently, the measurement of serum transferrin receptors and the serum transferrin receptor/ferritin ratio have been proposed as new indices of iron deficiency54,Go55Go. Receptor synthesis is up-regulated in iron deprived tissues. It can be argued that assessment of iron status at the tissue level is of more functional importance when examining the effects of iron depletion on the body than an assessment of stores.

Because of the increase in absorption during pregnancy coupled with the mobilization of iron stores, if women of childbearing age have enough iron stores to cope with the demands of pregnancy this could be sufficient and iron supplements may not be necessary. However, if iron stores are low, supplementation may be necessary or indicated. Provision of routine iron supplementation to pregnant women who do not have evidence of iron deficiency and have Hb levels > 10 g/dl has been shown to have a positive effect on women’s iron status. The prevalence of low pre-delivery haemoglobin and low haemoglobin at 6 weeks post partum is reduced. There is more stainable iron in the bone marrow with higher serum iron and ferritin levels56Go.

Vitamin A deficiency

Vitamin A is a fat soluble vitamin which is obtained from the diet as preformed vitamin A (retinal) and from some of the carotenoid pigments in food that can be cleaved in the body to give retinol. Preformed vitamin A occurs naturally only in animals and the richest dietary sources are liver, fish oils and dairy products. Between 25 and 35% of the dietary vitamin A will come from carotenoids mainly from plant foods such as carrots and dark leafy vegetables. Carotenoids can be converted to vitamin A in the liver where vitamin A is stored. Absorption from plant sources is thought to be low and animal sources may be needed to achieve adequate levels. The digestion and absorption of vitamin A are also closely linked with lipid absorption and therefore low dietary fat intake may interfere with vitamin A absorption.

Vitamin A deficiency is thought to be common in many developing countries. Much of the work on prevalence has been in children and there is comparatively little information about the occurrence in pregnancy. Estimates of the number of people at risk from vitamin A deficiency are often approximations but it is thought that there is a significant problem in most parts of Africa, South and South East Asia and areas of Latin America and the Western Pacific57Go. In case of marginal vitamin A deficiency, the extra demands made by pregnancy could be expected to result in vitamin A deficiency symptoms such as night blindness.

Assessment of vitamin A status in pregnancy is commonly by measurement of serum retinol. However, serum retinol levels are under strict homeostatic control and not a good measure for individual vitamin A status. Dose response tests have recently been developed which assess vitamin A stores in the liver and this is a more accurate method of assessment58,Go59Go. In pregnancy, as a result of the physiological changes described above, serum retinol levels have been shown to drop below non-pregnancy concentrations60Go.

Vitamin A is believed to be essential for normal embryogenesis, haematopoiesis, growth and epithelial differentiation. In pregnancy, extra vitamin A is required for growth and tissue maintenance in the fetus, for providing it with reserves and for maternal metabolism. Basal requirements in pregnancy are 370 µg per day, which increase during lactation to 450 µg per day.

On the other hand, a relationship has been suggested between the incidence of birth defects and high vitamin A intakes during pregnancy with an apparent threshold of 10,000 IU per day61–Go63Go. However daily doses of up to 10,000 IU or weekly doses of 25,000 IU after day 60 of pregnancy are safe, especially in areas where vitamin A deficiency is common61Go.

Vitamin A is essential for haematopoiesis. A diet devoid of vitamin A results in decreased haemoglobin levels64Go. Antenatal supplementation with both iron and vitamin A was shown to reduce anaemia prevalence in a study from Indonesia65Go but other studies conducted in sub-Saharan Africa were not able to obtain the same positive result66Go. The mechanism whereby vitamin A supplementation could improve haemoglobin and iron status has not been fully elucidated but it has been suggested that vitamin A is required for the mobilization and utilization of iron for haemoglobin synthesis67Go. An anti-infective role has also been suggested as infection is known to be associated with decreased serum iron levels, suppressed erythropoiesis and lower haemoglobin concentration68Go. An important and large study from Nepal has recently generated discussion about the role of vitamin A in the possible reduction in maternal mortality69Go. A clear biological explanation could not be given and anaemia was not studied as an outcome in this trial. Further trials are currently under way to address these issues. Currently, WHO recommends routine vitamin A supplementation during pregnancy or at any time during lactation in areas with endemic vitamin A deficiency (where night blindness occurs)61Go.


   Micronutrient deficiency and anaemia
Top
 Abstract
 Definitions
 Screening
 Prevalence
 Anaemia and maternal mortality...
 Micronutrients and pregnancy
 Micronutrient deficiency and...
Key points
 References
 
Relatively few studies have comprehensively assessed the aetiological factors responsible for anaemia in pregnancy and this is especially so for developing countries where anaemia is more prevalent and more severe and likely to have a greater contribution to maternal mortality and morbidity than in industrialized countries. This is probably for three main reasons. (1) The lack of adequate diagnostic facilities in many institutions in developing countries. (2) The frequent complexity of the aetiological pattern, such that, for example, infection and nutritional deficiency coexist. (3) The relative contribution of each aetiological factor can be difficult to assess in pregnancy when maternal physiological changes alter the parameters used to diagnose deficiency or sufficiency.

Chemical measurements of iron status are influenced by inflammation, and there is a lack of clearly defined and validated cut-off points for the diagnosis of deficiency in these circumstances70Go. Evaluation of suitably stained bone marrow aspirates may then be necessary to provide meaningful results71Go.

Despite the lack of stringent criteria and definitional problems, pregnancy anaemia in sub-Saharan Africa is most often believed to be the result of nutritional deficiencies, especially iron deficiency72,Go73Go. Folate deficiency has been described in West Africa74Go. Studies from Indonesia indicate that vitamin A deficiency may contribute to anaemia in pregnancy65Go. Vitamin B12 deficiency was found to be an unrecognized but important cause of anaemia in Zimbabwe75Go. It must be noted that micronutrient deficiencies are often studied in isolation but in actual fact are very likely to occur together and in many cases there is a multiple micronutrient deficiency state.

In many developing countries, it is difficult to meet daily nutrient requirements with diet alone especially for pregnant women. Animal products and fats are often relatively expensive and in addition, there may be food taboos which influence dietary intake in pregnancy. The benefit of multiple micronutrient supplements is therefore being considered76Go.

Although the contribution of malaria is generally acknowledged, the role of other chronic infections has been discussed77Go but not extensively studied in pregnant women. In the last decade, HIV infection has become more prevalent and it must now be considered a possible aetiological factor30,Go78Go. A recent study from Malawi illustrates the complex interaction between multi-micronutrient deficiency and infection71Go.

Thus, possible aetiological factors responsible for anaemia are multiple and their relative contributions can be expected to vary by geographical area, as well as by season. Knowledge of the relative importance of different causes should form the basis for intervention strategies.


   Key points
Top
 Abstract
 Definitions
 Screening
 Prevalence
 Anaemia and maternal mortality...
 Micronutrients and pregnancy
 Micronutrient deficiency and...
 Key points
References
 

  • In many areas of the world, as many as 75% of women are anaemic during pregnancy by WHO standards ([Hb] < 11.0 g/dl). Many have severe anaemia ([Hb] < 7.0 g/dl or < 8.0 g/dl). It is not known whether most women enter pregnancy already anaemic or whether anaemia develops primarily during pregnancy. Detection of anaemia often relies solely on conjunctival inspection, which is probably insufficient. The introduction of cheap but accurate screening tools should be encouraged.
  • There is a lack of studies measuring haemoglobin levels prospectively before and during pregnancy with assessment of maternal mortality and morbidity. Thus, it is not possible to indicate which level of haemoglobin is particularly associated with adverse outcome. However, on the basis of the available evidence, it seems reasonable to assume that the risk of maternal mortality in developing countries is increased, especially with severe anaemia.
  • In many pregnant women, anaemia is probably caused by a combination of disease including both micronutrient deficiency and infection. The complex pattern of interaction between the two requires further study. Haemoglobin concentration should perhaps be regarded as a ‘marker of morbidity’ in these situations.


   References
Top
 Abstract
 Definitions
 Screening
 Prevalence
 Anaemia and maternal mortality...
 Micronutrients and pregnancy
 Micronutrient deficiency and...
 Key points
 References
 

  1. Letsky EA. The haematological system. In: Hytten F, Chamberlain G, Broughton Pipkin F (eds) Clinical Physiology in Obstetrics. Oxford: Blackwell Scientific Publications, 1998; 71–110
  2. Letsky EA. Blood volume, haematinics, anaemia. In: de Swiet M (ed) Medical Disorders in Obstetric Practice, 3rd edn. Oxford: Blackwell Science, 1995; 33–70
  3. World Health Organization. Nutritional Anaemias. Technical report series no. 503. Geneva: WHO; 1972
  4. World Health Organization. Prevention and Management of Severe Anaemia in Pregnancy. Geneva: WHO; 1993
  5. Leeuw NKM, de, Lowenstein L, Hsieh YS. Iron deficiency anaemia and hydraemia in normal pregnancy. Medicine Baltimore 1966; 45: 291–315[Medline]
  6. Johnson-Spear MA, Yip R. Hemoglobin difference between black and white women with comparable iron status: justification for race-specific anaemia criteria. Am J Clin Nutr 1994; 60: 117–21[Abstract/Free Full Text]
  7. Dallman PR, Barr GD, Allen AM. Hemoglobin concentration in white, black and oriental children: is there a need for separate criteria in screening for anemia. Am J Clin Nutr 1978; 31: 377–80[Abstract/Free Full Text]
  8. Berti P, Leonard WR. The merits of race-specific standards. Am J Clin Nutr 1994; 60: 616
  9. Berger J, Aguayo VM, San Miguel JL, Lujan C, Tellez W, Traissac MS. Definition and prevalence of anemia in Bolivian women of childbearing age living at high altitudes: the effect of iron-folate supplementation. Nutr Rev 1997; 55: 247–56[Web of Science][Medline]
  10. van den Broek NR, Ntonya C, Mhango E, White SA. Diagnosing anaemia in pregnancy in rural clinics: assessing the potential of the Haemoglobin Colour Scale. Bull World Health Organ 1999; 77: 15–21[Web of Science][Medline]
  11. Liljestrand J, Bergstrom S. The value of conjunctival pallor in the diagnosis of pregnancy anaemia in Mozambique. J Obstet Gynaecol East Centr Afr 1992; 10: 45–6[Medline]
  12. Shulman CE, Levene M, Morison L, Dorman E, Peshu N, Marsh K. Screening for severe anaemia in pregnancy in Kenya, using pallor examination and self-reported morbidity. Trans R Soc Trop Med Hyg 2001; 95: 250–5[CrossRef][Web of Science][Medline]
  13. Gjorup T, Bugge PM, Hendriksen C, Jensen AM. A critical evaluation of the clinical diagnosis of anemia. Am J Epidemiol 1986; 124: 657–65[Abstract/Free Full Text]
  14. Sanchez-Carrillo CI. Bias due to conjunctiva hue and the clinical assessment of anemia. J Clin Epidemiol 1989; 42: 751–4[CrossRef][Web of Science][Medline]
  15. Sanchez-Carillo CI, de Jesus Ramirez-Sanchez T, Zambrana-Castenada M, Selwyn BJ. Test of a non-invasive instrument for measuring haemoglobin concentration. Int J Technol Assess Health Care 1989; 5: 659–67[Medline]
  16. Ghosh S, Mohan M. Screening for anaemia. Lancet 1978; 1: 823[Web of Science][Medline]
  17. United States Agency for International Development. PATH—Program for Appropriate Technology in Health. Anemia Detection in Health Services. Guidelines for Program Managers. Washington, DC: USAID; 1996
  18. van den Broek NR, Kayira E, White SA, Medina A, Neilson JP, Molyneux ME. The accuracy of measuring haemoglobin concentration using a HemoCue haemoglobinometer: comparison with an automated method; In press
  19. Neville RG. Evaluation of portable hemoglobinometer in general practice. BMJ (Clin Res Edn) 1987; 294: 1263–5
  20. Hudson-Thomas M, Bingham KC, Simmons WK. An evaluation of the HemoCue for measuring haemoglobin in field studies in Jamaica. Bull World Health Organ 1994; 72: 423–6[Web of Science][Medline]
  21. Politzer WM, Myburgh WM, van der Merwe JF. Haemoglobin estimation—reliability of the copper sulphate specific gravity v. the cyanhaemoglobin colorimetric method. S Afr Med J 1988; 73: 111–2[Web of Science][Medline]
  22. Pistorius LR, Funk M, Pattinson RC, Howarth GR. Screening for anaemia in pregnancy with copper sulfate densitometry. Int J Gynaecol Obstet 1996; 52: 3–36[CrossRef][Medline]
  23. Kegels G, Cornelis G, Mangelschots E, Van Brabant R, van Lerberghe W. Haemoglobin and packed cell volume measurement: the reliability of some simple techniques for use in surveys or rural hospitals. Ann Soc Belg Med Trop 1984; 64: 413–9[Web of Science][Medline]
  24. Wilkinson D, Sach ME. Cost-effective on-site screening for anaemia in pregnancy in primary clinics. S Afr Med J 1997; 87: 463–5[Web of Science][Medline]
  25. Stott GJ, Lewis SM. A simple and reliable method for estimating haemoglobin. Bull World Health Organ 1995; 73: 369–73[Web of Science][Medline]
  26. Tallqvist TW. Méthode protique d’évaluation directe de la quantité d’hémoglobine du sang. Arch Gen Med 1900; 3: 421–5
  27. World Health Organization. The Prevalence of Anaemia in Women: A Tabulation of Available Information. Geneva: WHO, 1992
  28. van den Broek NR, Rogerson SJ, Mhango CG, Kambala B, White SA, Molyneux ME. Anaemia in pregnancy in southern Malawi: prevalence and risk factors. Br J Obstet Gynaecol 2000; 107: 445–51
  29. Bergsjo P, Seha Am, Ole-King’ori N. Haemoglobin concentration in pregnant women. Experience from Moashi—Tanzania. Acta Obstet Gynecol Scand 1996; 75: 241–4[Web of Science][Medline]
  30. Fleming AF. The aetiology of severe anaemia in pregnancy in Ndola, Zambia. Ann Trop Med Parasitol 1989; 83: 37–49[Web of Science][Medline]
  31. World Bank. World Development Report: Investing in Health. New York: Oxford University Press, 1993; 1–329
  32. World Health Organization. Maternal Mortality Ratios and Rates. Geneva: WHO, 1996
  33. World Bank, WHO, UNFPA. Preventing the tragedy of maternal deaths. A report on the International Safe Motherhood Conference Nairobi, Kenya, 1987. Geneva: WHO.
  34. Harrison KA. Maternal mortality. Trans R Soc Trop Med Hyg 1989; 83: 449–53[CrossRef][Web of Science][Medline]
  35. Harrison KA. Severity of anaemia and operative mortality and morbidity. Lancet 1988; June 18: 1392
  36. Alauddin M. Maternal mortality in rural Bangladesh. The Tangail District. Stud Fam Plann 1986; 17: 13–21[CrossRef][Web of Science][Medline]
  37. Rush D. Nutrition and maternal mortality in the developing world. Am J Clin Nutr 2000; 72 (Suppl.): 212–40
  38. Chi I, Agoestina T, Harbin J. Maternal mortality at twelve teaching hospitals in Indonesia: an epidemiologic analysis. Int J Gynaecol Obstet 1992; 39: 87–92[CrossRef][Medline]
  39. Viteri FE, Torun B. Anaemia and physical work capacity. In: Garby L (ed) Clinics in Haematology, vol. 3, WB Saunders, 1974; 609–26
  40. Hallberg L, Scrimshaw NS. Iron Deficiency and Work Performance. International Nutritional Anemia Consultative Group, 1981
  41. Cook JD, Lynch SR. The liabilities of iron deficiency. Blood 1986; 68: 803–9[Abstract/Free Full Text]
  42. Dallman PR. Iron deficiency and the immune response. Am J Clin Nutr 1987; 46: 329–34[Abstract/Free Full Text]
  43. Garn SM, Ridella SA, Petzold AS, Falkner F. Maternal hematologic levels and pregnancy outcomes. Semin Perinatol 1981; 5: 155–62[Web of Science][Medline]
  44. Klebanoff MA, Shiono PH, Selby JV, Trachtenberg AI, Graubard BI. Anemia and spontaneous preterm birth. Am J Obstet Gynecol 1991; 164: 59–63[Web of Science][Medline]
  45. Allen LH. Iron-deficiency anemia increases risk of preterm delivery. Nutr Rev 51; 2: 49–52
  46. Mitchell MC, Lerner E. Maternal hematologic measures and pregnancy outcome. J Am Diet Assoc 1992; 92: 484–6[Web of Science][Medline]
  47. Harrison KA, Ibeziako PA. Maternal anaemia and fetal birth weight. J Obstet Gynaecol Br Cwlth 1973; 80: 798–804[Web of Science][Medline]
  48. Hallberg L. Iron balance in pregnancy and lactation. In: Fomon SJ, Zlotkin S (eds) Nutritional Anemias, Nestle Nutrition Workshop Series, vol. 30, 1992; 13–28
  49. Barrett JFR, Whitaker PG, Williams JG, Lind T. Absorption of non-haem iron in food during normal pregnancy. BMJ 1994; 309: 79–82[Abstract/Free Full Text]
  50. van den Broek NR, Letsky EA, White SA, Shenkin A. Iron status in pregnant women: which parameters are valid? Br J Haematol 1998; 103: 817–24[CrossRef][Web of Science][Medline]
  51. Cook JD. Iron deficiency anaemia. Baillière’s Clin Haematol 1994; 7: 787–804
  52. Lipschitz DA, Cook JD, Finch CA. A clinical evaluation of serum ferritin as an index of iron stores. N Engl J Med 1974; 290: 1213–6[Web of Science][Medline]
  53. Hallberg L. Prevention of iron deficiency. Baillière’s Clin Haematol 1994; 7: 805–14[CrossRef]
  54. Flowers CH, Skikne BS, Covell AM, Cook JD. The clinical measurement of serum transferrin receptor. J Lab Clin Med 1989; 114: 368–77[Web of Science][Medline]
  55. Skikne BS, Flowers CH, Cook JD. Serum transferrin receptor: A quantitative measure of tissue iron deficiency. Blood 1990; 75: 1870–6[Abstract/Free Full Text]
  56. Mahomed K. Iron supplementation in pregnancy (Cochrane Review). In: The Cochrane Library, Issue 4, 2002. Oxford: Update Software
  57. WHO. Global Prevalence of Vitamin A Deficiency. Micronutrient Deficiency Information System. WHO/NUT/95. Geneva: WHO, 1995
  58. WHO. Indicators for Assessing Vitamin A Deficiency and Their Application in Monitoring and Evaluating Intervention Programs. WHO/NUT/94.1 Geneva: WHO, 1994
  59. Tanumidhardjo SA, Suharno D, Parmaesih D et al. Application of the modified relative dose response test to pregnant women for assessing Vitamin A status. Eur J Clin Nutr 1992; 49: 897–903
  60. Hytten FE. Nutrition. In: Hytten FE, Chamberlain G (eds) Clinical Physiology in Obstetrics. Oxford: Blackwell Publications, 1991: 163–93
  61. WHO. Safe Vitamin A Dosage During Pregnancy and Lactation. Recommendations and a Report of a Consultation. WHO/NUT/98. Geneva: WHO, 1998
  62. Mills JL, Simpson JL, Cunningham GC, Comley MA, Rhoads GG. Vitamin A and birth defects. Am J Obstet Gynecol 1997; 177: 31–6[CrossRef][Web of Science][Medline]
  63. Rothman KJ, Moore LL, Singer MR, Nguyen UDT, Mannino S, Milunsky A. Teratogenicity of high Vitamin A intake. N Engl J Med 1995; 333: 1367–73[Free Full Text]
  64. Hodges RE, Sauberlich HE, Canham JE et al. Hematopoietic studies in Vitamin A deficiency. Am J Clin Nutr 1978; 31: 876–85[Abstract/Free Full Text]
  65. Suharno D, West CE, Muhilal, Karyadi D, Hautvast GAJ. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet 1993; 342: 1325–8[CrossRef][Web of Science][Medline]
  66. van den Broek NR, Kulier R, Gulmezoglu AM, Villar J. Vitamin A supplementation during pregnancy (Cochrane Review). In: The Cochrane Library, Issue 5, 2003. Oxford: Update Software
  67. Bloem MW, Wedel M, van Agtmaal EJ, Speek AJ, Soawakontha S, Schreurs WHP. Vitamin A intervention: short term effects of a single oral massive dose on iron metabolism. Am J Clin Nutr 1990; 51: 76–9[Abstract/Free Full Text]
  68. Thurnham DI. Vitamin A and haematopoiesis. Lancet 1993; 342: 1312–3[CrossRef][Web of Science][Medline]
  69. West KP, Kratz J, Khatry SK et al. Double blind randomised trial of low dose supplements with Vitamin A or beta carotene on mortality related to pregnancy in Nepal. The NNIPS-Study Group. BMJ 1999; 318: 570–5[Abstract/Free Full Text]
  70. Cook JD, Baynes RD, Skikne BS. Iron deficiency and the measurement of iron status. Nutr Res Rev 1992; 5: 189–202[CrossRef]
  71. van den Broek NR. The aetiology of anaemia in pregnancy in West Africa. Trop Doct 1996; 26: 5–7[Web of Science][Medline]
  72. Baker SJ, DeMaeyer EM. Nutritional anemia: its understanding and control with special reference to the work of the World Health Organization. Am J Clin Nutr 1979; 32: 368–417[Abstract/Free Full Text]
  73. DeMaeyer EM, Adiels-Tegman M. The prevalence of anaemia in the world. World Health Stat Q 1985; 38: 302–16[Medline]
  74. Fleming AF. A Study of Anaemia in Pregnancy in Ibadan, Western Nigeria with Special Reference to Folic Acid Deficiency. Thesis: Cambridge: Cambridge University, 1968
  75. Savage D, Gangaidzo I, Lindenbaum J, Kiire C, Mukiibi JM, Moyo A et al. Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe. Br J Haematol 1994; 86: 844–50[Web of Science][Medline]
  76. Huffman Sl, Baker J, Shumann MA, Zehner ER. The Case for Promoting Multiple Vitamin/Mineral Supplements for Women of Reproductive Age in Developing Countries. The Linkages Project. Washington, DC: Population Services International, 1998
  77. Yip R, Dallman PR. The roles of inflammation and iron deficiency as causes of anemia. Am J Clin Nutr 1988; 48: 1295–300[Abstract/Free Full Text]
  78. van den Broek NR, White SA, Neilson JP. The association between asymptomatic human immunodeficiency virus infection and the prevalence and severity of anemia in pregnant Malawian women. Am J Trop Med Hyg 1998; 59: 1004–7[Abstract]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (6)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by van den Broek, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van den Broek, N.
Related Collections
Right arrow Haematology
Right arrow Nutrition
Right arrow Obstetrics and Gynaecology
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?