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Objective: To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy., Methods: A randomized, double-blind intention-to-treat study comprising 427 healthy pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n = 105), 40 mg (n = 108), 60 mg (n = 106), and 80 mg (n = 108) from 18 weeks of gestation. Iron status markers [hemoglobin (Hb), serum ferritin, and serum soluble transferrin receptor (sTfR)] were measured at 18 weeks (inclusion), 32 weeks, and 39 weeks of gestation and 8 weeks postpartum. Side effects of iron supplements were recorded. Iron deficiency was defined as serum ferritin <13 microg/l and iron deficiency anemia as serum ferritin <13 microg/l and Hb <5th percentile in iron replete pregnant women., Results: There were no significant differences between variables in the four groups at inclusion. At 32 and 39 weeks of gestation, group 20 mg had significantly lower median serum ferritin (13 and 16 microg/l) than group 40 mg (17 and 21 microg/l), group 60 mg (18 and 23 microg/l), and group 80 mg (21 and 24 microg/l) (p < 0.0001). At 32 and 39 weeks of gestation, group 20 mg had a significantly higher prevalence of iron deficiency (50 and 29%) than group 40 mg (26 and 11%), group 60 mg (17 and 10%), and group 80 mg (13 and 9%) (p < 0.001). The prevalence of iron deficiency anemia at 39 weeks of gestation was significantly higher in group 20 mg (10%) than in group 40 mg (4.5%), group 60 mg (0%), and group 80 mg (1.5%) (p = 0.02). At 32 weeks of gestation, mean Hb in group 20 mg was lower than in group 80 mg (p = 0.06). There were no significant differences in iron status (ferritin, sTfR, and Hb) between group 40, 60, and 80 mg. Postpartum, group 20 mg had significantly lower median serum ferritin than group 40, 60, and 80 mg (p < 0.01). The prevalence of postpartum iron deficiency anemia was low and similar in the four groups. The frequency of gastrointestinal symptoms was not significantly different in the four iron supplement groups and thus not related to the iron dose., Conclusion: In Danish women, a supplement of 40 mg ferrous iron/day from 18 weeks of gestation appears adequate to prevent iron deficiency in 90% of the women and iron deficiency anemia in at least 95% of the women during pregnancy and postpartum.

Background: The aim was to define reference values for hemoglobin, hematocrit and erythrocyte indices, i.e. erythrocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), in normal pregnancy and after a normal delivery in non-iron-supplemented and iron supplemented women., Methods: Two hundred and six healthy Danish women included at 9-18 weeks of gestation were allocated to treatment with placebo tablets (n=107) or tablets containing 66 mg iron (n=99). Blood samples were obtained at inclusion, every fourth week during gestation, and 8 weeks postpartum., Results: All hematologic indices were significantly lower in placebo-treated than in iron-treated women. In placebo-treated women, the 5th percentile for hemoglobin was 110 g/L in the 1st trimester; in the 2nd trimester it was 105 g/L in the first and the second, and 103 g/L in the last third; in the 3rd trimester, it was 102 g/L in the first, 100 g/L in the second, and 101 g/L in the last third; postpartum it was 113 g/L. In iron-treated women, the 5th percentile for hemoglobin was 111 g/L in the 1st trimester; in the 2nd trimester it was 109 g/L in the first, 106 g/L in the second, and 103 g/L in the last third; in the 3rd trimester, it was 105 g/L in the first and second, and 110 g/L in the last third; postpartum it was 123 g/L., Conclusions: Hematologic reference values should be derived from iron replete women. We suggest that the lowest critical hemoglobin value in iron-treated pregnant women should be 110 g/l (6.8 mmol/L) in the 1st trimester, and 105 g/L (6.5 mmol/L) in the 2nd and 3rd trimester.

Background: Iron supplementation in pregnancy is a controversial issue. The aim of this review was to summarize the results of relevant papers on this subject., Methods: Placebo-controlled studies on iron treatment in pregnancy were identified from the Cochrane database., Results: Among fertile women, 20% have iron reserves of >500 mg, which is the required minimum during pregnancy; 40% have iron stores of 100-500 mg, and 40% have virtually no iron stores. The demand for absorbed iron increases from 0.8 mg/day in early pregnancy to 7.5 mg/day in late pregnancy. Dietary iron intake in fertile women is median 9 mg/day, i.e. the majority of women have an intake below the estimated allowance of 12 18 mg/day. Iron absorption increases in pregnancy, but not enough to prevent iron deficiency anemia in 20%, of women not taking supplementary iron. Iron-treated pregnant women have greater iron reserves, higher hemoglobin levels, and a lower prevalence of iron deficiency anemia than placebo-treated women both in pregnancy as well as postpartum. Furthermore, children born to iron-treated mothers have higher serum ferritin levels than those born to placebo-treated mothers. An iron supplement of 65 mg/day from 20 weeks of gestation is adequate to prevent iron deficiency anemia., Conclusions: In order to avoid iron deficiency in pregnancy, prophylactic iron supplement should be considered. Iron supplements may be administered on a general or selective basis. The selective approach implies screening with serum ferritin in early pregnancy, in order to identify women who can manage without prophylactic iron.

In a randomized, double-blind, placebo controlled study of the effect of iron supplementation during pregnancy, iron status (hemoglobin (Hb), serum (S-)transferrin saturation, S-ferritin) and S-erythropoietin (EPO) were assessed in 120 healthy pregnant women at 14-16 weeks of gestation, and just before delivery; 63 women were treated with 66 mg iron daily, and 57 with placebo. There were no differences in baseline values in the two groups. At term, the iron treated group had significantly higher Hb, transferrin saturation, S-ferritin (median 22 micrograms/l vs. 14 micrograms/l, (p < 0.0001) and lower S-EPO compared to the placebo treated group. In the iron group, 30.2% had exhausted iron stores (i.e. S-ferritin < 20 micrograms/l), 6.3% latent iron deficiency (S-ferritin < 20 micrograms/l and transferrin saturation < 15%), and no patients had iron deficiency anemia (S-ferritin < 20 micrograms/l and transferrin saturation < 15% and HB < 110 g/l). In the placebo group, 93.0% had exhausted iron stores, 54.4% latent iron deficiency, and 17.5% iron deficiency anemia; S-EPO was inversely correlated to iron status markers: Hb, rs = -0.51, p < 0.001; transferrin saturation, rs = -0.65, p < 0.0001; S-ferritin, rs = -0.31, p < 0.01, suggesting that the elevation in S-EPO was secondary to iron deficient erythropoiesis. Newborns to iron treated mothers had higher cord S-ferritin, median 155 micrograms/l, than newborns to placebo treated mothers, median 118 micrograms/l (p < 0.02); there were no differences in birth weight, transferrin saturation, or S-EPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Iron status was assessed by serum (S-) ferritin and hemoglobin (Hb) in a population survey comprising 883 non-gravid Danish women in age cohorts of 35, 45, 55, and 65 years. Premenopausal women (n = 676) had lower S-ferritin, median 42 micrograms/l, than postmenopausal women (n = 207), median 80 micrograms/l (p < 0.0001). Of premenopausal women, 12.1% had S-ferritin < or = 20 micrograms/l (i.e. depleted iron stores), and 35.6% S-ferritin of 21-40 micrograms/l (i.e. small iron stores). Corresponding figures in postmenopausal women were 0.5% and 13.2%. Premenopausal blood donors (n = 88) had lower S-ferritin than non-donors (p < 0.001). In premenopausal women, S-ferritin levels were strongly dependent on the duration of menstrual bleeding (p < 0.0001), which in turn was related to the method of contraception. Women (n = 64) using hormonal contraceptives (the pill) had menstrual bleeding of shorter duration than those (n = 511) not using pills or intrauterine devices (IUD), who in turn had bleeding of shorter duration than those (n = 101) using IUD. Median S-ferritin in pill users was 62 micrograms/l, in those not using pills or IUD 42 micrograms/l, and in IUD users 36 micrograms/l. S-ferritin values < 40 micrograms/l (i.e. small and depleted iron stores) were seen in 25% of pill users, in 48% of those not using pills or IUD, and in 61% of IUD users.(ABSTRACT TRUNCATED AT 250 WORDS)

Iron status, including hemoglobin, S-ferritin, S-iron, S-transferrin, transferrin saturation and the erythrocyte zinc protoporphyrin/hemoglobin (ZPP:Hb) ratio, was evaluated in 85 healthy iron-supplemented mothers at parturition and in 74 of their term newborn infants. Of the mothers, 17% had a S-ferritin level less than 15 micrograms/l (i.e. depleted iron stores), 9.9% had S-ferritin less than 15 micrograms/l and transferrin saturation less than 15% (i.e. latent iron deficiency), and 2.4% had S-ferritin less than 15 micrograms/l, transferrin saturation less than 15% and Hb less than 120 g/l (i.e. iron deficiency anemia). Newborn infants had higher S-ferritin than mothers: median 128 micrograms/l versus 21 micrograms/l (p less than 0.0001), higher transferrin saturation: 48% vs. 21% (p less than 0.0001), and higher ZPP:Hb ratio: 74 mumol/mol Hb vs. 41 mumol/mol Hb (p less than 0.0001). During the first 5 post-natal days, median S-ferritin rose from 128 to 236 micrograms/l (p less than 0.0001). S-ferritin appeared to be the best single indicator of maternal iron status. Ferritin levels in newborn infants were correlated to levels in mothers (rs = 0.36, p less than 0.01), indicating that fetal iron reserves are dependent on maternal iron stores.