Annals of Hematology

, Volume 85, Issue 9, pp 567–573

Body iron and individual iron prophylaxis in pregnancy—should the iron dose be adjusted according to serum ferritin?

Authors

    • Department of Obstetrics, Gentofte HospitalUniversity of Copenhagen
    • Department of Medicine B 2142Rigshospitalet
  • Keld-Erik Byg
    • Department of Obstetrics, Gentofte HospitalUniversity of Copenhagen
  • Thomas Bergholt
    • Department of Obstetrics, Gentofte HospitalUniversity of Copenhagen
  • Lisbeth Eriksen
    • Department of Obstetrics, Gentofte HospitalUniversity of Copenhagen
  • Anne-Mette Hvas
    • Department of Clinical Biochemistry, Skejby HospitalAarhus University Hospital
Original Article

DOI: 10.1007/s00277-006-0141-1

Cite this article as:
Milman, N., Byg, K., Bergholt, T. et al. Ann Hematol (2006) 85: 567. doi:10.1007/s00277-006-0141-1

Abstract

This study aims to evaluate iron prophylaxis in pregnant women from the individual aspect, i.e. according to serum ferritin levels at the beginning of pregnancy, and to assess which dose of iron would be adequate to prevent iron deficiency (ID) and iron deficiency anaemia (IDA) during pregnancy and postpartum. A randomised, double-blind study comprising 301 healthy Danish pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n=74), 40 mg (n=76), 60 mg (n=77) and 80 mg (n=75) from 18 weeks gestation (inclusion) to 8 weeks postpartum. Iron status markers [serum ferritin, serum soluble transferrin receptor (sTfR), haemoglobin] were recorded at 18, 32 and 39 weeks gestation and 8 weeks postpartum. Body iron was calculated using the serum sTfR/serum ferritin ratio. ID was defined by serum ferritin <12 μg/l in pregnancy and <15 μg/l postpartum; IDA as serum ferritin <12 μg/l and haemoglobin <5th percentile in iron-replete pregnant women. Women in the iron supplement groups were stratified according to serum ferritin levels at inclusion; 50.7% had ferritin ≤30 μg/l, 37.7% ferritin 30–70 μg/l and 11.6% ferritin >70 μg/l. At 32 weeks, women with ferritin ≤30 μg/l had an ID frequency of: 20-mg group 54.1%, 40 mg 29.7%, 60 mg 24.4%, 80 mg 20.6% (p<0.001); women with ferritin >30 μg/l had an ID frequency of: 20-mg group 20.0%, 40 mg 13.9%, 60 mg 5.7%, 80 mg 5.1% (p<0.001). Women with ferritin >70 μg/l had no ID. Postpartum, ID was found in 4.7% in 20-mg group, 2.9% in group 40 mg and 0% in group 60 and 80 mg. IDA: At 32 weeks, women with ferritin ≤30 μg/l had an IDA frequency of: 20-mg group 2.7%, 40 mg 2.7%, 60 and 80 mg 0%; none of the women with ferritin >30 μg/l displayed IDA. Body iron at 18 weeks was 10.4 mg/kg, similar in the four iron groups. Later in pregnancy body iron declined significantly, being lower the 20 mg group, and similar in the 40, 60 and 80-mg groups. Postpartum body iron rose to inclusion levels being 9.3 mg/kg in the 20-mg group and 10.5 mg/kg in the 40-, 60- and 80-mg groups. This study gives an estimate of iron dosage in individual iron prophylaxis adjusted to serum ferritin levels in early pregnancy. In the prevention of ID, we suggest 80–100 mg ferrous iron/day to women having ferritin ≤30 μg/l and 40 mg ferrous iron/day to women having ferritin 31–70 μg/l. In the prevention of IDA, we suggest 40 mg ferrous iron/day to women having ferritin ≤70 μg/l. Women with ferritin >70 μg/l have no need for iron supplement.

Keywords

AnemiaIron deficiencyDeliveryFerritinHemoglobinsIronPregnancyPuerperiumSupplementFood

Introduction

Pregnant women have an increased demand for iron to expand their erythrocyte mass and generate the iron supply to the growing foetus [1, 2]. When discussing iron prophylaxis in pregnancy, it is important to discriminate between the situation in undeveloped countries where severe iron deficiency with anaemia is frequent among pregnant women [3], and the affluent Western societies, where the prevalence of clinically significant iron deficiency is low [4]. However, women in the Nordic countries have a dietary iron intake that does not fulfil the demands in pregnancy [5]. The low dietary iron intake is predominantly due to a low energy intake, being a consequence of the sedentary lifestyle. The Nordic Nutrition Recommendations conclude that normal pregnancy poses demands on iron supplies that cannot be fulfilled by dietary iron intake and refrain from giving specific figures for recommended dietary iron intake [5].

Health authorities in the European Union advocate the use of iron supplements to women who have pre-pregnancy iron reserves of <500 mg [5, 6]. General iron prophylaxis is advocated by most National Health Authorities, as no European country performs routine screening of iron status in pregnant women. Pregnant Danish women who do not take iron supplements have a frequency of iron deficiency of 50% and a frequency of iron deficiency anaemia of 21% [7, 8].

Women having mobilizable body iron reserves of 500 mg or more can go through pregnancy without iron supplements [5, 6]. However, among fertile Danish women 40% have small or absent body iron reserves, i.e. serum ferritin <30 μg/l. Less than 20% have iron reserves of >500 mg, i.e. serum ferritin >70 μg/l being adequate for pregnancy [4, 9].

Should prophylactic iron supplement to pregnant women be given as a general prophylaxis or as individually dosage-adjusted prophylaxis? [10, 11]. In a previous study on pregnant women, we found that an adequate general iron prophylaxis could be obtained by a daily supplement of 40 mg ferrous iron [12].

The aims of the present study were: first, to assess calculated body iron using the serum-soluble transferrin receptor (sTfR)/serum ferritin ratio [13]; second, to evaluate iron prophylaxis in pregnant woman from the individual point of view, i.e. knowing serum ferritin at the beginning of pregnancy, to estimate which dose of iron may be adequate to prevent iron deficiency during the remaining period of pregnancy and postpartum.

Materials and methods

Women

The investigation was a double-blind, dose-response, parallel-study examining the effect of four different doses of ferrous iron taken from 18 weeks gestation, in which the details have been described in our previous paper [12].

The participants were healthy Danish, Caucasian women, residents in Copenhagen County. Previous pregnancies were uncomplicated. Women treated with iron tablets or having anaemia (haemoglobin <6.4 mmol/l=103 g/l) were not included. The initial visit at the maternity clinic was at 17–18 weeks gestation.

Approximately 30% of the women took vitamin–mineral supplements containing iron, which were discontinued at inclusion. Non-fasting venous blood samples were taken at inclusion, at 32 and 39 weeks gestation and 8 weeks postpartum. Haemoglobin (Hb) was measured on Cell-Dyn 3500 (Abbott Laboratories, Chicago, Illinois, USA); to convert from Hb in mmol/l to Hb in g/l, multiply by 16.115. Serum ferritin was measured by a microparticle enzyme immunoassay (Abbott AxSYM Ferritin assay, Abbott Laboratories, Chicago, IL, USA). Between-assay variation is 5.4% at a serum ferritin concentration of 20 μg/l, and results are given without decimal. The kit is calibrated closely to the World Health Organization (WHO) International Human Liver Ferritin Standard 80/602 [14]. AxSYM ferritin values were transformed into WHO International Human Liver Ferritin Standard values using the proportionality: Ferritin AxSYM=1.057 × Ferritin WHO [14]. Serum sTfR was measured by ELISA (Orion Diagnostica, Turku, Finland).

A serum ferritin value of <12 μg/l was chosen to indicate absent iron reserves and iron deficiency during pregnancy [7, 15], while a ferritin value of <15 μg/l was chosen as an indicator of depleted iron reserves postpartum [16, 17]. Iron deficiency anaemia was defined as serum ferritin <12 μg/l and haemoglobin below the 5th percentile in iron replete women (having serum ferritin >30 μg/l) in the specific period of pregnancy and postpartum; at 18 weeks: <6.6 mmol/l (106 g/l); at 32 weeks: <6.5 mmol/l (105 g/l); at 39 weeks: <7.2 mmol/l (115 g/l); at 8 weeks postpartum: <7.6 mmol/l (123 g/l) [8].

Body iron was calculated according to the formula reported by Cook et al. [13] using the serum sTfR/serum ferritin ratio: body iron (mg/kg)=−[log(sTfR/ferritin)-2.8229]/0.1207.

The women were randomised in four groups taking 20, 40, 60 and 80 mg ferrous iron daily as fumarate from inclusion until delivery and further until 8 weeks postpartum. The tablets should be taken at bedtime or between meals.

Four hundred and twenty-seven women fulfilled the inclusion criteria and were randomised. At inclusion, there were no significant differences between key variables in the four groups [12]. In the present analysis, we have focused on the relationship between serum ferritin levels at inclusion and iron deficiency later in pregnancy and postpartum. Consequently, only women (n=302) having at least two ferritin and haemoglobin measurements (at inclusion and later in pregnancy or postpartum) were eligible for the present analysis. Compliance was similar in the four supplement groups.

Statistics

Parametric statistics [Student’s t test for unpaired values, analysis of variance (ANOVA)] were used for variables with a normal distribution. Non-parametric statistics (Kruskal–Wallis test, χ2 test with Yates correction) were used for the comparison of non-normal distributed variables.

Dropouts

Dropouts were evenly distributed between the four supplement groups and there were no significant differences between dropouts and participants concerning baseline key variables, age, body weight, body height, body mass index (BMI), parity, hemoglobin, serum ferritin and serum sTfR [12]. There were 137 dropouts from 18 weeks gestation to 8 weeks postpartum. In eight women, blood samples were missing at 32 weeks gestation; 19 women dropped out between 32 and 39 weeks gestation due to lack of compliance and 23 women had a normal delivery before 39 weeks gestation and had no blood sampling at 39 weeks. It was difficult to motivate the participants for postpartum follow-up, which is the major reason why only 55% of the included women were examined 8 weeks after delivery.

Body iron

Calculated body iron is shown in Fig. 1. At 18 weeks gestation, mean body iron in all women was 10.4 mg/kg body weight with a minimum value of 2.4 mg/kg. At 32 and 39 weeks gestation, there was a significant fall in body iron in all iron supplement groups. The fall was most pronounced in the 20-mg group and identical in the 40- to 80-mg groups. At 39 weeks gestation minimum body iron value was −3.0 mg/kg in the 20-mg group and 0.7 mg/kg in the 40-, 60- and 80-mg groups. Eight weeks postpartum body iron in the 20-mg group was significantly lower than at 18 weeks gestation (p<0.05), whereas the 40-, 60- and 80-mg groups had similar body iron postpartum as at 18 weeks gestation.
https://static-content.springer.com/image/art%3A10.1007%2Fs00277-006-0141-1/MediaObjects/277_2006_141_Fig1_HTML.gif
Fig. 1

Calculated body iron (mean±SEM) [13] during pregnancy and postpartum in women taking four different doses of iron supplement from 18 weeks gestation

Results seen from the aspect of general iron prophylaxis

Serum ferritin

There was no significant difference between serum ferritin or serum sTfR values in the four groups at inclusion (Table 1). However, at 32 and 39 weeks gestation as well as postpartum, the 20-mg group had significantly lower ferritin than the 40-, 60- and 80-mg groups. There were no significant differences between ferritin in the 40-, 60- and 80-mg groups.
Table 1

Serum ferritin and serum soluble transferrin receptor (sTfR) during pregnancy and postpartum (pp) in the four iron supplement groups

Gestation (weeks)

n

Iron supplement (mg/day)

P valueb

20

40

60

80

Serum ferritin (μg/l)a

      

18

302

29 (14–76)

30 (13–68)

29 (12–71)

32 (9–80)

NS

32

294

12 (8–26)

16 (9–34)

17 (9–26)

20 (11–40)

<0.0001*

39

252

15 (9–27)

20 (12–36)

22 (12–43)

23 (14–53)

<0.0001*

8 pp

165

30 (16–79)

52 (24–134)

47 (23–96)

47 (27–88)

<0.01*

Serum sTfR (mg/l)a

      

18

302

1.2 (0.7–1.9)

1.1 (0.6–2.0)

1.3 (0.7–2.3)

1.3 (0.7–2.4)

NS

32

294

2.0 (1.2–2.8)

1.6 (1.0–3.0)

1.7 (0.9–3.0)

1.9 (1.0–3.5)

NS

39

252

2.1 (1.2–3.7)

2.0 (1.0–3.3)

1.9 (1.1–3.3)

1.9 (1.1–3.4)

NS

8 pp

165

1.8 (1.0–3.6)

1.7 (0.9–3.2)

1.7 (1.0–3.2)

1.7 (1.0–2.9)

NS

*Significant difference between 20 mg vs 40, 60 and 80 mg. No significant difference between 40, 60 and 80 mg

aMedian (10–90 percentile)

bKruskal–Wallis test

Iron deficiency and iron-deficiency anemia

At inclusion, there was no significant difference in iron status between the four iron supplement groups (Table 2). At 32 and 39 weeks gestation, the 20-mg group had a significantly higher frequency of iron deficiency than the other groups. At 39 weeks gestation, the frequency of iron-deficiency anemia was significantly higher in the 20-mg group than in the other groups. The frequency of iron deficiency and iron-deficiency anemia in the 40-, 60- and 80-mg groups was not significantly different either at 32 or 39 weeks gestation. Postpartum, the prevalence of iron deficiency and iron-deficiency anemia was not significantly different in the four supplement groups.
Table 2

Frequency of iron deficiency and iron-deficiency anaemia in women during pregnancy and postpartum (pp) according to iron supplement dose

 

Iron deficiencya

Iron-deficiency anaemiab

Gestation (weeks)

18

32

39

8 pp

18

32

39

8 pp

n

302

294

252

165

302

294

252

165

 

(%)

(%)

(%)

(%)

(%)

(%)

(%)

(%)

Iron (mg/day)

        

20

4.1

43.1

22.8

4.7

0

1.4

6.9

0

40

6.6

21.9

9.7

2.9

1.3

1.4

1.3

0

60

6.5

15.8

8.7

0

0

0

0

0

80

10.7

12.3

9.4

0

0

0

0

0

P value***

NS

<0.0001

0.004

NS

NS

NS

0.04

NS

***χ2 test

aPregnancy: ferritin <12 μg/l; postpartum: ferritin <15 μg/l

bPregnancy: ferritin <12 μg/l and Hb <6.6 mmol/l (18 weeks), <6.5 mmol/l (32 weeks), <7.2 mmol/l (39 weeks); postpartum: ferritin <12 μg/l and Hb <7.6 mmol/l

Results seen from the aspect of individual iron prophylaxis

Iron deficiency

In Table 3, the participants in the iron supplement groups are stratified according to their serum ferritin at inclusion. There was no significant difference in the frequency of iron deficiency in the four groups at inclusion. In the total series (n=302), 28.6 and 50.7% had ferritin of ≤20 μg/l and ≤30 μg/l, respectively, at inclusion.
Table 3

Frequency of iron deficiency in women during pregnancy and postpartum (pp) according to iron supplement dose and serum ferritin at inclusion at 18 weeks gestation

Iron (mg/day)

Gestation (weeks)

32

39

8 pp

Serum ferritin at inclusion (μg/l)

(n)

Iron deficiencya

(n)

(%)

(n)

(%)

(n)

(%)

20

≤30

38

20/37

54.1

8/30

26.7

1/22

4.6

 

31–70

28

6/27

22.2

5/22

22.7

1/15

6.7

 

>70

8

1/8

12.5

0/5

0

0/6

0

40

≤30

40

11/37

29.7

5/32

15.6

0/17

0

 

31–70

29

5/29

17.2

0/24

0

1/13

7.7

 

>70

7

0/7

0

0/6

0

0/4

0

60

≤30

41

10/41

24.4

3/36

8.3

0/25

0

 

31–70

28

2/28

7.1

3/26

11.5

0/17

0

 

>70

8

0/7

0

0/7

0

0/4

0

80

≤30

34

7/34

20.6

5/30

20.0

0/20

0

 

31–70

29

2/28

7.1

1/24

4.2

0/14

0

 

>70

12

0/11

0

0/10

0

0/8

0

 

n=

302

294

252

165

aFor definition, see text and Table 2

Group 20 mg:

At ferritin levels of ≤30 μg/l, the frequency of iron deficiency was 54.1% at 32 weeks, 26.7% at 39 weeks and 4.6% postpartum. At ferritin of >30 μg/l, the frequency of iron deficiency was 20.0% at 32 weeks, 18.5% at 39 weeks and 4.8% postpartum.

Group 40 mg:

At ferritin of ≤30 μg/l, there was a moderate frequency of iron deficiency during pregnancy, but none postpartum. Women having ferritin of >30 μg/l had a low frequency of iron deficiency in pregnancy and postpartum.

Groups 60 mg and 80 mg:

At ferritin levels of ≤30 μg/l, there was a moderate frequency of iron deficiency during pregnancy, but none postpartum. Women having ferritin of >30 μg/l displayed a low frequency of iron deficiency.

It was a consistent finding in all groups that women having ferritin >70 μg/l displayed no iron deficiency.

Iron-deficiency anaemia

At inclusion, there was no significant difference in the frequency of iron deficiency anaemia between the groups. Table 4 shows the occurrence of iron deficiency anaemia in pregnancy according to ferritin levels at inclusion.
Table 4

Frequency of iron-deficiency anaemia in women during pregnancy and postpartum (pp) according to iron supplement dose and serum ferritin at inclusion

Iron (mg/day)

Gestation (weeks)

32

39

8 pp

Serum ferritin at inclusion (μg/L)

(n)

Iron-deficiency anaemiaa

(n)

(%)

(n)

(%)

(n)

(%)

20

≤30

38

1/37

2.7

3/30

10.0

0/22

0

 

>30

36

0/35

0

2b/26

7.7

0/21

0

40

≤30

40

1/37

2.7

1/32

3.1

0/17

0

 

>30

36

0/36

0

0/30

0

0/17

0

60

≤30

41

0/41

0

0/36

0

0/25

0

 

>30

36

0/35

0

0/33

0

0/21

0

80

≤30

34

0/34

0

0/30

0

0/20

0

 

>30

41

0/39

0

0/34

0

0/22

0

 

n=

302

294

 

251

 

165

 

aFor definition, see text and Table 2

bFerritin at inclusion 37 and 38 μg/l

Group 20 mg:

At ferritin of ≤30 μg/l, the frequency of iron deficiency anaemia was 10% (3/30 women) at 39 weeks gestation. At ferritin >30 μg/l, iron deficiency anaemia was found in 7.7% (2/26 women) having ferritin at inclusion of 37 and 38 μg/l.

Group 40 mg:

At ferritin of ≤30 μg/l, there was a low frequency of iron deficiency anaemia during pregnancy. Women having ferritin of >30 μg/l had no iron deficiency.

Groups 60 mg and 80 mg:

none of the women had iron deficiency anaemia either in the low (≤30 μg/l) or high (>30 μg/l) ferritin group.

In all four groups, women having ferritin >70 μg/l displayed no iron deficiency anaemia.

Discussion

From the nutritional and toxicological points of view, it appears sound to give the lowest dose of iron supplement, which fulfils the criteria for prophylaxis. Iron deficiency may lead to increased absorption of toxic divalent cations, lead and cadmium [18, 19]. On the other hand, iron supplement may have negative influence on the absorption of essential divalent cations (zinc, copper, chromium, molybdenum, manganese, magnesium) [20, 21] and there is a risk of damage to the intestinal epithelium due to the formation of free radicals and an increased oxidative stress [22].

Taylor et al. [23] and Milman et al. [7] reported that 65 mg ferrous iron/day from 20 weeks gestation was adequate to prevent iron deficiency in 90% of the women and iron-deficiency anaemia in all women. In the present study, 60 mg ferrous iron daily from 18 weeks gestation had a similar effect (Table 2). Galan et al. [24] reported the same effect of 40 mg ferrous iron/day to French women. Even 27 mg iron daily has a positive effect on iron status in pregnancy [25].

Iron status during pregnancy and postpartum was significantly lower in women taking 20 mg iron/day than in those taking 40 to 80 mg iron/day. However, there were no significant differences in iron status between women taking 40, 60 or 80 mg iron/day. From the aspect of general iron prophylaxis, a daily dose of 40 mg of ferrous iron taken between meals from 18 weeks gestation appears adequate to prevent iron deficiency and iron-deficiency anaemia [12].

Both serum ferritin and calculated body iron at 39 weeks gestation were low but showed a significant increase at 8 weeks postpartum in all groups, indicating that postpartum iron supplement had a positive influence on the mothers’ iron status. In a placebo-controlled study, 16% of non-iron-treated mothers had iron depletion and 12% had iron deficiency anaemia 8 weeks postpartum [7, 8]. These figures, compared with the present results, indicate that even the 20-mg iron dose has a positive impact on iron status, especially postpartum [26].

Despite physiological changes in the serum ferritin concentration during pregnancy [7], studies have shown that serum ferritin is the most reliable marker of iron status we have [2729]. However, the cut-off value used for the definition of iron deficiency can be debated. We have chosen a cut-off value of <12 μg/l to define iron deficiency.

Serum sTfR yields information about iron deficiency on the cellular level, whereas serum ferritin gives information about body iron reserves. Serum sTfR levels in iron replete women, pregnant as well as non-pregnant, are similar and independent of the magnitude of body iron reserves [30]. It is only when the supply of iron to the erythroblasts fails due to exhausted iron reserves that serum sTfR rises. Serum sTfR can therefore identify women with low-serum ferritin, who in addition have pronounced iron deficiency [30, 31]. In the present study, there was no significant difference in serum sTfR between the 20-mg group and the 40- to 80-mg groups, indicating that marked iron deficiency was infrequent among women in the 20-mg group.

Fluctuations in serum ferritin may be circumvented by combining measurements of serum ferritin and serum sTfR in the calculation of body iron using the sTfR/ferritin ratio [13]. There was a significant fall in body iron from 18 to 32 weeks gestation whereafter body iron remained stable until the term. Postpartum, body iron increased to levels similar to those in early pregnancy. However, as the method of calculation [13] has not been validated in pregnant women, these results should be interpreted with caution.

The goals concerning iron deficiency during pregnancy should be defined according to iron status in the background population of non-pregnant women. Danish women have a prevalence of depleted iron reserves (serum ferritin <15 μg/l) of 9.7% and a prevalence of iron-deficiency anaemia of 3.4% [32]. The aims of an individual iron prophylaxis should ensure that the frequency of iron deficiency at least do not increase during pregnancy. We suggest that the goal of iron prophylaxis should be to ensure a frequency of iron deficiency of <15% and a frequency of iron-deficiency anaemia of <5% during pregnancy and postpartum.

Prevention of iron deficiency: If iron status at 32 or 39 weeks gestation is chosen as an indicator for iron supplement, and the aim is <15% iron deficiency, then 80–100 mg ferrous iron/day should be given to women having an initial serum ferritin of <30 μg/l and 40 mg ferrous iron/day to women having a ferritin of 31–70 μg/l (Table 3). The Institute of Medicine Report from 1993 has likewise recommended 30 μg/l as discriminatory value for an individual iron supplement in pregnancy [10].

Prevention of iron deficiency anaemia: If the aim is <5% iron-deficiency anaemia, women having an initial serum ferritin of <70 μg/l can obtain this goal by taking 40 mg ferrous iron daily (Table 3). In general, women having ferritin >70 μg/l in early pregnancy have no need for iron supplement.

When should prophylactic iron supplement be started? As iron absorption increases, especially from 20 weeks gestation [2], this is often recommended as the starting point [33]. However, detailed analysis of the absorption studies shows that the increase in iron absorption is mainly elicited by iron deficiency [34]. However, in the foetus iron plays a crucial role in the development of the central nervous system, iron-containing enzymes being involved in the metabolic processes of the brain [35, 36]. Iron deficiency in foetal life may exert a negative influence on brain development and function and on the development of intelligence and behaviour [37]. Therefore, from the foetus’ point of view, iron supplement should probably be started shortly after conception to ensure easy access to iron supplies.

From a physiologic point of view, an individual instead of a general iron prophylaxis should be preferred [2, 10, 11]. Women at risk for iron deficiency may be identified by analysis of serum ferritin or from calculated body iron before pregnancy, or in early pregnancy. Using an individual approach, women with adequate iron reserves avoid unnecessary iron supplement, which may impair the absorption of vital divalent metal ions, increase the oxidative stress of the body, and have negative implications in women with C282Y hereditary haemochromatosis [38].

In conclusion, this dose response study shows that an adequate general prophylaxis of iron deficiency in pregnant Danish women can be achieved by a dose of 40 mg ferrous iron/day from 18 weeks gestation. The analysis also gives an estimate of dosage regimens for individual iron prophylaxis according to serum ferritin levels in early pregnancy.

Acknowledgements

The study was supported by grants from Apotekerfonden and Den Lægevidenskabelige Forskningsfond ved Region 3. The authors appreciate the great help of the midwives at the Department of Obstetrics during the study and the enthusiasm of Chief Physician Robert Jordal† and the laboratory technicians at the Department of Clinical Biochemistry, Gentofte Hospital.

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© Springer-Verlag 2006