Iron prophylaxis during pregnancy -- how much iron is needed? A randomized dose- response study of 20-80 mg ferrous iron daily in pregnant women.
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.


CONCLUSIONS
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.
Milman
Nils
N
Department of Obstetrics, Gentofte Hospital, Copenhagen, Denmark. milman@rh.dk
Bergholt
Thomas
T
Eriksen
Lisbeth
L
Byg
Keld-Erik
KE
Graudal
Niels
N
Pedersen
Palle
P
Hertz
Jens
J
D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000453:epidemiology / Q000517:prevention & control*; D003718:Denmark / Q000453:epidemiology; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005293:Ferritins / Q000097:blood; D005312:Fetal Blood; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D007501:Iron / Q000008:administration & dosage*; D000090463:Iron Deficiencies; D009752:Nutritional Status; D049590:Postpartum Period / Q000097:blood; D011247:Pregnancy / Q000097:blood*; D015995:Prevalence; D011990:Receptors, Transferrin / Q000378:metabolism
D006454:Hemoglobins; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron