Title: Iron in Pregnancy

Key words: Anaemia, iron supplementation, iron metabolism, Vitamin C, iron stores, haemoglobin

Date: June 1999

Category: 10. Reproduction

Type: Article

Author: Dr van Rhijn

Iron in Pregnancy

The Need for Supplementation

The need for routine iron supplements remains a longstanding controversy¹, partly due to disagreements regarding the definition of anaemia², markers of iron deficiency and aspects of iron metabolism³, despite evidence for an increased iron requirement during pregnancy⁴.

Increase in plasma volume (1250 ml) and red cell mass (240 ml – 400 ml iron dependant) during pregnancy, result in a ‘physiological anaemia’ due to haemodilution⁵. The extra iron needed to meet this demand amounts to 1040 mg, much of it (43%) to increase the mother’s haemoglobin mass during the last trimester. The absorption of iron is unequally distributed. During the first trimester it decreases by 7.6 %, then in the second it increases to 21.1 % and during the last trimester it goes up to 37.4 %, matching the growth of the foetus⁶. These values may be optimistic as iron absorption was enhanced with vitamin C in this study.

Despite this physiological adaptation, the deficit remains approximately 400 – 500 mg of iron which, in most industrialised countries, cannot be obtained by diet alone⁷. One in three British women in a survey had levels below the LRNI⁸. Soluble serum transferrin receptor⁹ and serum ferritin¹⁰ are indicators of storage iron, where a cut-off point of 25 - 30 microg/l indicates low iron stores¹¹.

The development of iron deficiency anaemia during pregnancy (30% prevalence in 3^rd trimester¹²) is dependent upon whether the mother enters pregnancy with adequate iron stores¹³. Infants born to mothers with iron depleted stores have reduced iron accumulation, which will affect the iron status of the infant¹⁴. Of western women, 25 – 30% had no iron stores, 20% had 250mg and only 5% reached 400mg, short of the preferred 500mg before entering pregnancy. Women from developing countries¹⁵, in lower socio-economic groups, teenagers and multiparous women are at the highest risk of iron deficiency, due to their reduced dietary intakes or empty postpartum iron stores.

Maternal iron deficiency (Hb < 10 mg/dl) has been associated with increased rates of prematurity¹⁶, low birth weight and perinatal mortality¹⁷. High concentrations of haemoglobin were also associated with poor pregnancy outcomes, probably due to gestational hypertension in these women¹⁸. Low hematocrit women (37%) had twice the risk of a premature birth¹⁹, but the cause of the hematocrit was not examined. Low maternal haemoglobin, secondary to inadequate iron, was strongly related to high placental/birth weight ratio, and this anaemia may be predictive of long-term cardiovascular disease and hypertension²⁰, but this relationship has yet to be elucidated.

Despite the facts that:

• the major cause of anaemia in pregnancy is iron deficiency (> 80%)
• non-supplemented women have a higher risk of developing anaemia,
• iron absorption is under strict control to prevent overload²¹
• supplementation is clinically effective²²,

there remains a reluctance to introduce regional or national supplementation programmes²³ in the UK. This in contrast to the USA, where the evidence for increased iron demand has been sufficient for the authorities to recommend supplementation with iron of 30 mg/d after 12 weeks of pregnancy²⁴.

1. James, P.T. Long-Term Fetal Programming of Body Composition and Longevity. Nutr. Rev. 1997; Vol. 55, No1. S31 – S43.
2. Long, P.J. Rethinking iron supplementation during pregnancy. J. Nurse Midwifery. 1995; 40:1, 36 – 40.
3. Allen, L.H. Pregnancy and iron deficiency: unresolved issues. Nutr. Rev. 1997; 55:4, 91 – 101.
4. Yip, R. & Dallman, P.R. Iron. In: Ziegler E. & Filer L. Present knowledge in Nutrition. Seventh Edition. ILSI Press. Washington. 1996; Chapter 28 pp 277 - 292.
5. Maternal and Foetal Nutrition: Fact File No 11: 1994; National Dairy Council. London.
6. Whittaker, P.G. et al. Iron absorption during normal human pregnancy: a study using stable isotopes. Br. J. Nutr. 1991; 65, 457 – 463.
7. Hallberg, B. Iron, zinc and other trace elements. In: Garrow, J.S & James, W.P. Human nutrition and Dietetics. Ninth Edition. Churchill Livingstone. 1996; Ch. 12. pp. 174 – 188.
8. Gregory, J. et al. The Dietary and Nutritional Survey of British Adults. London: HMSO. 1990
9. Akesson, A. et al. Serum transferrin receptor: a specific marker of iron deficiency in pregnancy. Am. J. Clin. Nutr. 1998; 68:6, 1241 – 1246.
10. van den Broek NR et al. Iron status in pregnant women: which measurements are valid? Br J Haematol. 1998; 103:3, 817 - 824.
11. Cook, J.D. et al. Iron deficiency and the measurement of iron status. Nutr. Res. 1992; Rev. 5, 189 – 202.
12. Perry, G. et al. Nutritional risk factors among low-income US women. Semin. Perinatol. 1995; 19, 211 – 221.
13. Hytten, F.E. Nutrition. In: Hytten, F. and Chamberlain, G.V.P. (eds). Clinical Physiology in Obstetrics. Second Edition. Oxford: Blackwell Scientific Publications, 1991; pp. 150 - 172.
14. Letsky, E. The haematological system. In: Hytten, F. and Chamberlain, G.V.P. (eds). Clinical Physiology in Obstetrics. Second Edition. Oxford: Blackwell Scientific Publications, 1991; pp. 39 – 82.
15. Yip, R. Iron deficiency: contemporary scientific issues and international programmatic approaches. J. Nutr. 1994; 124, S1479 – S1490.
16. Scholl, T.O. et al. Anemia vs iron deficiency, increased risk of preterm delivery in a prospective study. Am. J. Clin. Nutr. 1992; 55, 985 – 988.
17. Murphy, J.F. et al. Relation of haemoglobin levels in first and second trimesters to outcome of pregnancy. Lancet 1986; I, 992 – 994.
18. Garn, S.M. et al. Maternal haemoglobin levels and pregnancy outcomes. Seminars in Perinatology. 1981; 5, 155 – 162.
19. Lieberman, E. et al. Association of maternal hematocrit with premature labour. Am. J. Obs. & Gyn. 1988; 159, 107 – 114.
20. Godfrey, K.M. et al. The effect of maternal anaemia and iron deficiency on the ratio of foetal weight to placental weight. Br. J. Obst. Gynaecol. 1991; 98, 886 – 891.
21. Hulten, L. et al. Iron absorption from the whole diet. Relation to meal composition, iron requirements and iron stores. Eur. J. Clin. Nutr. 1995; 49, 794 – 808.
22. Singh, K. et al. The role of prophylactic iron supplementation in pregnancy. Int. J. Food Sci. Nutr. 1998; 49:5, 383 – 389.
23. Walker, A.R. The remedying of iron deficiency: what priority should it have? Br. J. Nutr. 1998; 79:3, 227 – 735.
24. Institute of Medicine/Subcommittee on Nutritional Status and Weight Gain During Pregnancy. Nat. Acad. Press. Washington DC. 1990