Efficacy and tolerability of low-dose iron supplements during pregnancy: a randomized controlled trial.

Randomized, placebo-controlled trial in pregnant women in Adelaide, South Australia, including singleton and twin pregnancies. Women were not anemic at enrollment and had no conditions or treatments that would confound iron status; 216 were randomized to the iron arm and 214 to placebo.

Pregnant participants in the active arm received ferrous sulfate tablets providing 20 mg elemental iron orally once daily between meals from 20 weeks of gestation until delivery. If anemia was detected at the routine 28-week assessment or by clinician judgment, additional high-dose iron was advised until the end of pregnancy.

Low-dose iron supplementation was effective and well tolerated. At the end of pregnancy, iron-deficiency anemia was lower in the iron group than in placebo, 6/198 (3%) versus 20/185 (11%), RR 0.28; 95% CI 0.12, 0.68, and iron deficiency was also lower, 65/186 (35%) versus 102/176 (58%), RR 0.60; 95% CI 0.48, 0.76. Hemoglobin and ferritin were higher with iron at delivery, with no significant worsening of gastrointestinal symptoms, serum zinc, SF-36 health concepts, or infant birth outcomes. Benefits persisted postpartum for iron deficiency, with 31/190 versus 51/177 at 6 months postpartum, RR 0.57; 95% CI 0.38, 0.84.

Some biomarker and tolerability analyses were based on subsets with missing data, which reduces precision. The trial was single-center and conducted in Adelaide, so generalizability may be limited. Follow-up extended only to 6 months postpartum, and rescue high-dose iron in women who became anemic could have attenuated between-group differences.