How much iron do pregnant women need?
Design: Randomized, double-blind intervention trial.
Participants: 427 healthy pregnant Danish women.
Study Medication and Dosage: Ferrous fumarate was provided at varying dosages: either 20 mg of iron (Fe) (n=105), 40 mg Fe (n=108), 60 mg Fe (n=106), or 80 mg Fe (n=108) from week 18 of pregnancy through to term.
Outcome Measures: Maternal hemoglobin (Hgb) and ferritin were measured at baseline (week 18 of pregnancy), and again at weeks 32 and 39 of pregnancy, and finally at 8 weeks postpartum, with Fe deficiency being defined as ferritin <13 mcg/L and Fe deficiency anemia as ferritin <13 mcg/L plus Hgb below the 5th percentile of iron-replete pregnant women.
Key Findings: At the 40 mg Fe/day level of intake, Fe deficiency was prevented in 90% and Fe deficiency anemia in 95% of participants. At the 20 mg/d level, mean ferritin levels at weeks 32 and 39 fell into the predetermined range of deficiency (13 and 16 mcg/l), especially when compared with those given the 40 mg dose (which produced mean ferritin levels at weeks 32 and 39 of 17 and 21 mcg/l). Differences were quite small between ferritin levels at weeks 32 and 39 in the group receiving 60 mg/d Fe versus those receiving 40 mg/d (1 and 2 mcg/L higher, respectively). Ferritin levels were, as expected, the highest in the group receiving the most (80 mg/d) Fe, (21 mcg/l at week 32 and 24 mcg/L at week 39). The difference between the effects of the 20 mg dosage and the combined other dosages was highly statistically significant (p=0.001). Similarly, postpartum ferritin levels were significantly lower in the 20 mg group compared with the other groups (p<0.01). Most differences between the effects of those in the 40 mg/d dosage and those in groups receiving higher doses did not achieve statistical significance.
The percentages of subjects with Fe deficiency at 32 and 39 weeks respectively were 50% and 29% in the 20 mg Fe group, 26% and 11% in the 40 mg Fe group, 17% and 10% in the 60 mg Fe group, and 13% and 9% in the 80 mg Fe group. The difference between the percentages of subjects with deficiency in the 20 mg dosage and the combined other dosages was highly statistically significant (p=0.0001)
The percentage of subjects with Fe deficiency anemia at 39 weeks were 10% (20 mg Fe group), 4.5% (40 mg Fe group), 0% (60 mg Fe group), and 1.5% (80 mg Fe group). Again, only the difference between the 20 mg group versus other groups was statistically significant (p=0.02).
Practice Implications: Apgar scores, newborn cord blood Hgb, and ferritin did not differ in the offspring. Thus most of our focus goes to the effects that differing levels of Fe supplementation have on the pregnant women themselves. That said, however, in accord with some older research, as maternal ferritin levels increased (at week 39, though not before), birth weights decreased ([R.sub.s]=0.21, p=0.0007).
Concerns about Fe deficiency during pregnancy focus partly on the effects of hemodilution, though whether or not some of the expected resulting drop in serum ferritin is “healthy and normal” or “normal but not optimal” remains unresolved. The fact that mean ferritin levels, even in the group receiving the “acceptable” dose of 40 mg/d were lower than non-pregnant norms should probably be balanced against the “normal” physiological hemodilution during pregnancy. That may explain why the definition of Fe deficiency was so narrow as to include only women with ferritin levels below 13 mcg/L. The other concern about Fe deficiency during pregnancy–potential blood loss at birth–is universally accepted. As a result, doctors involved with obstetrics carefully monitor Fe status.
Postpartum data were of less consequence than data accumulated earlier because Fe status improved significantly in all groups at 8-weeks postpartum such that all were above baseline data.
Though the punch line is that most pregnant women can get by on a supplemental dose of 40 mg of Fe/day, practitioners need to view these data through their own eyes. If you have significant concerns about the possible negative effects of unnecessary Fe supplementation on the newborn or on the mother, or if their pregnant patient is complaining of constipation or other GI side effects, then the 40 mg/d dose may well appear adequate. The authors themselves say that “iron doses should be kept as low as possible,” their concern being formation of free radicals in the intestinal mucosa and interference with absorption of other essential divalent cations.
However, for clinicians who do not share these concerns (particularly because Fe supplementation will probably not be continued long term and because, by definition, these subjects are young and most are probably healthy) then the slightly better results reported at doses higher than 40 mg may be appealing, particularly in pregnant patients who do not suffer significant side effects at such doses–which brings us to one final observation of these researchers that appears to violate our common sense. Ironically, the incidence of GI side effects in the current trial was not significantly different between the four doses! Perhaps our common belief that side effects of Fe supplementation increase in a dose-dependent fashion may derive from the fact that many practitioners currently use 100 mg/day to treat deficiency–a dosage higher than any used in the current trial.
Milman N, Bergholt T, Eriksen L, et al. “Iron prophylaxis during pregnancy–How much iron is needed? A randomized dose-response study of 20-80 mg ferrous iron daily in pregnant women.” Acta Obstet Gynecol Scand, 2005; 84:238-47.
By Steve Austin, ND
COPYRIGHT 2005 Original Internist, Inc.
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