ORIGINAL ARTICLE

Iron supplementation during pregnancy INGERS. GULDHOLT,BIRGITTAG. TROLLE and LONEE. HVIDMAN

From the Department of Gynecology and Obstetrics, Horsens Hospital, Denmark

Acta Obstet Gynecol Scand 1991; 70: 9-12

192 pregnant women were consecutively randomized to either a vitamin-mineral pill or a vitamin mineral pill with a high iron content in a prospective, open, randomized investigation. The participants were advised about iron-rich foodstuffs twice during pregnancy. Iron status of the mother proved to be without any significance for the outcome of pregnancy. A serum ferritin level of 80 pmoM in mid-pregnancy followed by a control in the last trimester was suggested as a guide in deciding of whether or not to prescribe supplementary iron during pregnancy. Key words: iron supplementation, serum ferritin, pregnancy Submitted June 8, 1990 Accepted October 22, 1990

The diagnosis of an iron deficiency anemia during pregnancy is a difficult diagnostic challenge. During pregnancy, blood volume expands by about 50% and red cell mass by 20% (1). The resulting hemodilution will inevitably cause a fall in hemoglobin concentration, which is often mistaken for anemia. The purpose of the present study was to evaluate whether the prescription of iron supplementation to all pregnant women is necessary,and alternatively to define the category of pregnant women for whom iron supplementation is advisable. The study was designed as a double-blind, controlled clinical trial. As expansion in blood volume is known to be greater in multiparas than in primiparas we dealt with the two separately. Serum ferritin was evaluated as a predictor for the need of iron treatment during pregnancy, as serum femtin has been found by Addison and others (2, 3, 4) to closely reflect the size of iron stores.

Material and methods The investigation was performed at the Department of Gynecology and Obstetrics, Horsens Hospital, Denmark during the period November 1, 1985 to June 30, 1986 and included all healthy, Danish-

speaking women with singleton pregnancies. Women having a hemoglobin concentration less than 7.0mrnoVI at the first visit were excluded as this is the lower limit of normal values at our laboratory. The participants were interviewed by a nutritionist in the 20th and 28th weeks of pregnancy. They were also advised how to compose their meals, especially with regard to iron absorption. At the first visit in the 20th week, the participants were consecutively randomized to either a vitaminmineral pill containing 15 mg ferro-iron (Multitabs ") or one containing 100 mg ferro-iron (Duroferonvitamin "). The pills were generously supplied by N S Ferrosan and N S Hassle. Venous blood samples were taken in the 20th, 28th and 36th weeks of gestation and were analysed with regard to hemoglobin concentration, serum iron, serum transfemn, serum ferritin, mean cell volume (MCV), and mean corpuscular hemoglobin concentration (MCHC). Blood samples were drawn from the umbilical cord at delivery to determinate the hemoglobin concentration and serum femtin. The participants gave informed consent and the study was approved by the Medical Ethics Committee. The statistical analysis was generally performed with a Mann-Whitney test. If any other analytic staAda Obstet Gynecol Scand 70 (1991)

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I. S. Guldholt et al.

Table I. Hemoglobin, serum iron, serum transferrin, serum ferritin, MCV, and MCHC in 2Oth, 28th. and 36th weeks of gestation in relation to high and low iron supplementation Serum iron (pmol/ I)

Serum transferrin

Serum ferritin

( W O W

(PmOW

7.65 0.4 7.0-8.9

21.8 6.4 11-40

45.8 5.6 36-61

64.0

Low iron

7.56 0.4 7.0-9.0

24.1 11.1 5-80

46.9 8.1 29-77

70.0 58-82

P

NS

NS

NS

Valid cases I92

Hernoglobin (mmoWI)

MCV

(fl)

MCHC (mmol/ I)

90.8 3.4 81-100

21.2 0.6 I %23

9-99

90.7 2.9 84-99

21.2 0.4 20-22

NS

NS

NS

20th week of gestation

High iron

55-75 15-477

28th week of gestation

High iron

7.63 0.5 6.6-8.9

22.3 12.5 8-80

51.9 1.9 24-77

41.7 3949 10-253

91.5 3.3 83- 102

21.2 0.5 20-22

Low iron

7.39 0.5 6.2-8.4

19.7 7.2 6-39

54.4 8.5 35-75

31.2 26-36 11-193

91.7 3.0 83-98

21.2 0.5 20-22

P

0.001

NS

0.03

O.OO0

NS

NS

36th week of gestation

High iron

7.90 0.6 6.3-9.1

22.0 10.4 7-70

56.4 7.8 41-85

49.0 43-54 11-253

92.0 4.1 82-101

21.1 0.6 18-22

Low iron

7.68 0.5 6.3-8.8

19.9 8.2 7-48

61.O 8.0 45-83

25.5 25-29 9-79

92.2 3.4 80-99

21.1 0.4 20-22

P

0.005

NS

0.003

O.OO0

NS

NS

Values given are mean values, followed in the second row by & 1 SD and in the third row by range (except for serum ferritin where the median value is noted), followed by 95% confidence limits. 1 pmolll = 0.451g/l ferritin.

tistic was used, it is specified in the text. Values of p = or less than 0.05 are referred to as significant, two-tailed.

Results A total of 646 pregnant women were invited to join the study, of whom 241 accepted and 405 declined as they did not have time to spare for the interview lasting about one hour. One hundred and ninety-two of the 241 completed the investigation. Wenty-two were excluded because of a hemoglobin less than 7.0 mmol/l, 10 because of side effects, 2 because of taking other pills, and 15 did not attend the second blood sample. Ninety-five pregnant women were randomized to high-iron supplementation (HIS) and 97 had lowArm Obstet Gynecol Scand 70 (1991)

iron supplementation (LIS). A comparison between the two groups revealed no statistically significant difference with regard to social class, age, parity, prepregnancy weight or weight gain during pregnancy. Blood samples were taken in the 20th, 28th and 36th week of gestation. A comparison between the HIS and LIS groups is shown in Table 1. Fig. 1 shows that primiparas and multiparas receiving HIS had identical mean hemoglobin concentrations in the 20th and 28th week, while LIS groups experienced a decline. Regardless of the type of iron supplementation, mean hemoglobin concentration increased for both primi- and multiparas from the 28th to the 36th week, the extent of increase being equal for both HIS and LIS groups. No significant difference was found in serum iron,

Iron supplementation during pregnancy

11

Discussion

mmolll

8.0 - -

7.0.-

7.8.-

7.7--

7.6.-

7.5-

1.4--

Fig. I . Hemoglobin concentration for high iron supplemented and low iron supplemented primiparas and multiparas in 20th. 28th and 36th week of gestation. 0 ,primipara; W. multipara; high iron supplementation; ---,low iron supplementation.

-.

MCV and MCHC between primiparas and multiparas belonging to HIS or LIS groups. Fig. 2 shows changes in serum ferritin. The HIS and LIS primiparas and multiparas both experienced an initial fall from week 20 to week 28 and then a rise from week 28 to week 36. The curves for the LIS groups exhibited a continuous fall in both periods. In the 20th week, a significantly higher serum ferritin level was found in primiparas than in multiparas. In weeks 28 and 36, serum ferritin levels were significantly higher in the HIS groups. No statistically significant difference was found in hemoglobin or serum ferritin Concentration in cord blood, in birth weight, in Apgar score at one, five and ten minutes, in instrumental deliveries, or in complications during pregnancy. With the purpose of finding a serum ferritin concentration in the 20th week that could be used to predict the need of iron treatment during pregnancy, we only included pregnancies with birth of a liveborn child, born between the 38th and the 42th gestational week. Of the 35 women having a serum ferritin concentration greater than 80 pmol/I in the 20th week, only one became iron-depleted in the 28th week (Table 11). This observed binomial rate of 1:35. corresponding to 2.9% has a 95% confidence interval (0.1% -14.9%). In the 36th week, 8 primipara were iron-depleted with a limit of 26 pmoVl, but only 4 if the limit was 20 pmol/l. For multiparas the corresponding numbers were 4 and 2.

Normal median serum ferritin is known to constitute about 75 pmolll, range 20-275pmoVI; a serum ferritin level below 20-26 pmol/I is usually regarded as indicating depleted iron stores (4). But if iron stores can be demonstrated, iron deficiency cannot be the cause of a falling hemoglobin concentration. The sharp fall in serum ferritin from week 20 to week 28 for both LIS and HIS groups (Fig. 2) coincides with the expansion of the red cell mass, but it has to be borne in mind, however, that this fall in ferritin concentration does not represent an iron loss, but rather a shift of iron from stores to the red cell mass and that iron is returned to the stores after delivery except for iron lost due to bleeding. As the deposition of iron in the fetus takes place mostly in the last part of gestation (2) the rise in serum ferritin from the 28th to the 36th week among HIS women is remarkable, indicating that supply outstrips the need. A corresponding figure for serum ferritin during pregnancy was found by others (2, 5 , 6). Koller et al. (7, 8, 9) have shown that a high hemoglobin concentration during pregnancy may have adverse effects upon the outcome of pregnancy. A high hemoglobin concentration has also been correlated with placental infarction (10). Thus, it still remains to be proved that it is completely harmless to prescribe supplementary iron routinely to all pregnant women. As iron is poorly absorbed during early pregnancy and since iron demands are low before the 20th week of gestation, iron supplementation should not be prescribed until mid-pregFarrllln pmolll

I BO-

0 \ \

70-

60-

50-

40-

30-

,Ot

Fig.2. Serum ferritin for high and low iron supplemented primiparas and multiparas in 20th. 28th and 36 week of gestation. 0 , primipara; W , multipara; -, high iron supplementation; ---,low iron supplementation. Acta Obster Gynecol Scand 70 (1991)

12

I . S. Guldholt et al.

Table 11. Serum ferritin level in 28th week depending upon serum ferritin level in 20th week for iron low-supplemented primiparas and multiparas. Ferritin in 20th week: lower inclusion limit (pmoVI) ~~

Primipara Multipara Primipara Multipara Primipara Multipara Primipara Multipara Primipara Multipara

n

Median pmoU I

Ferritin in 28th week

95% confidence lilimits

range

iron depleted in YO

32-69 26-56 3M9 30-60 34-74 37-60 34-74 43-61 36-74 44-73

21-113 21-82 23-1 13 21-82 23-113 21-82 23-113 23-82 24-113 37-82

14.8 28.6 11.5 16.7 8.3 11.8 8.3 6.7 4.5 0

~~

60 65 70 75 80

27 21 26 18 24 17 24 15 22 13

42.0 44.0 44.5 49.0 48.5 50.0 48.5 52.8 51.5 53.3

nancy. Bearing in mind that routine iron prescription may not be entirely harmless, we would suggest that a serum ferritin check at mid pregnancy and in the last trimester should guide the decision as to whether or not prescribe iron supplementation in the uncomplicated pregnancy.

Acknowledgements The investigation was granted by Forebyggelsesudvalget i Vejle Amt, Hede-Nielsen Fondet, Horsens and The Danish Medical Research Council (no. 12-7566) who also gave consultant assistance ( no. 5.52.14.94.).

References Liley AW. Clinical and laboratory significance of variations in maternal plasma volume in pregnancy. Int J Gynaecol Obstet 1970;8: 358-62. Puolakka J. Serum ferntin as a measure of iron stores during pregnancy. Acta Obstet Gynecol Scand, 1980; 59 Suppl 95. Addison GM, Beamish MR, Hales CN, Hodgkins M, Jacob C, Llewellin P. An immunoradiometric assay for ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. J Clin Path 1977;25: 326-9.

Acta Obstet Gynecol Scand 70 (1991)

4. Worwood M. Serum ferritin. Critic Rev Clin Lab Sciences 1979;10: 171-204. 5. van Eijk HG, Kroos MJ, Hoogendoorn GA, Wallenburg HCS. Serum ferritin and iron stores during pregnancy. Clin Chim Acta 1978;83: 81-91. 6. Ishikawa K, Narita 0, Saito H. Gestational anemia and serum ferritin. Jpn J Nuclear Med 1984; 21: 305-10. 7. Koller 0,Sagen N. High hemoglobin levels during pregnancy and fetal risk. Int J Gynaecol Obstet 1980; 18: 53-6. 8. Koller 0, Sagen N, Vaula D. Fetal growth retardation associated with inadequate haemodilution in otherwise uncomplicated pregnancy. Acta Obstet Gynecol Scand 1979;58: 9-13. 9. Koller 0.The clinical significance of hemodilution during pregnancy. Obstet Gynecol Survey 1982; 37: 649-52. 10. Naeye RLN. Placental infarction leading to fetal or neonatal death. Obstet Gynecol 1977;50: 583-8. Address for correspondence:

Inger Guldholt Department of Gynecology and Obstetrics Central Hospital of Bornholm DK-3700 R0nne Denmark

Iron supplementation during pregnancy.

192 pregnant women were consecutively randomized to either a vitamin-mineral pill or a vitamin mineral pill with a high iron content in a prospective,...
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