In the JournalsPerspective

Intermittent iron supplementation appears effective for pregnant women

Twice-weekly supplementation with iron tablets appears as effective for pregnant women as daily supplementation, according to study results.

Researchers observed no significant differences in mean birth weight or growth outcomes of infants born to women included in the study. In addition, twice-weekly antenatal iron–folic acid was associated with significant improvements in cognitive outcomes in infants at age 6 months.

Iron deficiency anemia is a global public health problem, particularly in low- and middle-income countries. Anemia in pregnancy is associated with poor outcomes, including increased maternal mortality and morbidity, higher rates of low birth weight and pre-term birth, and reduced infant survival, according to background information in the study.

Daily iron–folic acid supplementation starting early in pregnancy has been the standard approach to treat and prevent anemia, but the cost and side effects pose challenges.

Intermittent antenatal iron supplementation could be a beneficial alternative, but the impact of that strategy on infants has not been determined.

Researchers conducted a cluster randomized trial to compare the effect of intermittent antenatal iron supplementation with daily iron supplementation on maternal and infant outcomes in rural Vietnam.

The investigators assigned 1,258 pregnant women at less than 16 weeks gestation to either daily iron–folic acid, twice-weekly iron–folic acid or twice-weekly multiple micronutrient supplementation.

Infant birth weight served as the primary outcome measure.

Researchers observed no differences in infant birth weight among women assigned twice-weekly iron–folic acid vs. daily iron–folic acid (mean difference: 28 g; 95% CI, -22 to 78), or twice-weekly multiple micronutrient vs. daily iron–folic acid (mean difference: -36.8 g; 95% CI, 82 to 8.2).

Women assigned daily iron–folic acid had higher levels of maternal ferritin at 32 weeks gestation compared with those assigned twice-weekly iron-folic acid (geometric mean ratio: 0.73; 95% CI, 0.67-0.80). Lower levels of ferritin also were observed among women assigned a twice-weekly multiple micronutrient vs. those assigned daily iron–folic acid (geometric mean ratio: 0.62; 95% CI, 0.57-0.68). No differences were observed in hemoglobin levels among any groups.

Conversely, twice-weekly iron–folic acid was associated with higher cognitive scores at age 6 months when compared with infants of mothers assigned daily iron–folic acid (MD: 1.89; 95% CI, 0.23-3.56).

Researchers also reported a significantly higher adherence rate in the twice-weekly iron–folic acid group compared with the daily supplementation group.

“Twice weekly antenatal iron–folic acid or multiple micronutrient did not produce a clinically important difference in birth weight, when compared to daily iron–folic acid supplementation,” the researchers wrote. “The significant improvement in infant cognitive outcomes at 6 months of age following twice-weekly antenatal iron–folic acid requires further exploration, and provides additional support for the use of intermittent, rather than daily, antenatal iron–folic acid in populations with low rates of iron deficiency.”

Disclosure: This study was funded by a grant from the National Health and Medical Research Council of Australia.

Twice-weekly supplementation with iron tablets appears as effective for pregnant women as daily supplementation, according to study results.

Researchers observed no significant differences in mean birth weight or growth outcomes of infants born to women included in the study. In addition, twice-weekly antenatal iron–folic acid was associated with significant improvements in cognitive outcomes in infants at age 6 months.

Iron deficiency anemia is a global public health problem, particularly in low- and middle-income countries. Anemia in pregnancy is associated with poor outcomes, including increased maternal mortality and morbidity, higher rates of low birth weight and pre-term birth, and reduced infant survival, according to background information in the study.

Daily iron–folic acid supplementation starting early in pregnancy has been the standard approach to treat and prevent anemia, but the cost and side effects pose challenges.

Intermittent antenatal iron supplementation could be a beneficial alternative, but the impact of that strategy on infants has not been determined.

Researchers conducted a cluster randomized trial to compare the effect of intermittent antenatal iron supplementation with daily iron supplementation on maternal and infant outcomes in rural Vietnam.

The investigators assigned 1,258 pregnant women at less than 16 weeks gestation to either daily iron–folic acid, twice-weekly iron–folic acid or twice-weekly multiple micronutrient supplementation.

Infant birth weight served as the primary outcome measure.

Researchers observed no differences in infant birth weight among women assigned twice-weekly iron–folic acid vs. daily iron–folic acid (mean difference: 28 g; 95% CI, -22 to 78), or twice-weekly multiple micronutrient vs. daily iron–folic acid (mean difference: -36.8 g; 95% CI, 82 to 8.2).

Women assigned daily iron–folic acid had higher levels of maternal ferritin at 32 weeks gestation compared with those assigned twice-weekly iron-folic acid (geometric mean ratio: 0.73; 95% CI, 0.67-0.80). Lower levels of ferritin also were observed among women assigned a twice-weekly multiple micronutrient vs. those assigned daily iron–folic acid (geometric mean ratio: 0.62; 95% CI, 0.57-0.68). No differences were observed in hemoglobin levels among any groups.

Conversely, twice-weekly iron–folic acid was associated with higher cognitive scores at age 6 months when compared with infants of mothers assigned daily iron–folic acid (MD: 1.89; 95% CI, 0.23-3.56).

Researchers also reported a significantly higher adherence rate in the twice-weekly iron–folic acid group compared with the daily supplementation group.

“Twice weekly antenatal iron–folic acid or multiple micronutrient did not produce a clinically important difference in birth weight, when compared to daily iron–folic acid supplementation,” the researchers wrote. “The significant improvement in infant cognitive outcomes at 6 months of age following twice-weekly antenatal iron–folic acid requires further exploration, and provides additional support for the use of intermittent, rather than daily, antenatal iron–folic acid in populations with low rates of iron deficiency.”

Disclosure: This study was funded by a grant from the National Health and Medical Research Council of Australia.

    Perspective
    Ralph Green, MD, PhD

    Ralph Green, MD, PhD

    It has long been known that iron deficiency during pregnancy is undesirable, being associated with negative outcomes for both mother and child. In this large population study designed to evaluate the efficacy of twice-weekly compared with daily supplements of iron and folic acid given to pregnant women, some interesting and unexpected observations emerged. There was no difference in infant birth weight between the two regimens, but cognitive outcomes at 6 months of age were better in the infants whose mothers received the intermittent supplement regimen. This raises some important questions about the potential deleterious effects of excessive amounts or too frequent administration of maternal iron supplements. As with other nutrients, the Goldilocks mantra applies to iron supply during pregnancy. Iron supply should not be too little and not be too much. It needs to be "just right."

    • Ralph Green, MD, PhD
    • HemOnc Today Editorial Board member

    Disclosures: Green reports no relevant financial disclosures.