During pregnancy, taking an iron supplement less than once a day may provide similar maternal and infant outcomes compared with taking a daily pill, a systematic review showed.
Infant outcomes were similar whether mothers took iron intermittently or daily during pregnancy, according to Juan Pablo Peña-Rosas, MD, PhD, of the World Health Organization in Geneva, and colleagues.
For the mothers, intermittent supplementation was associated with fewer side effects, a similar risk of having anemia at term, and a lower risk of having high hemoglobin during the second or third trimesters, the researchers reported in a Cochrane Review.
“Although the evidence is limited and the quality of the trials was low or very low,” they wrote, “intermittent may be a feasible alternative to daily iron supplementation among those pregnant women who are not anemic and have adequate antenatal care.”
Anemia is common during pregnancy, particularly in developing countries, where women may have insufficient dietary iron intake to meet the needs of both the mother and the fetus. Typically, the problem has been addressed through the use of daily iron supplementation, although side effects, supply problems, and concerns about safety have limited use of the intervention.
A possible solution for some of those issues is intermittent iron supplementation one, two, or three times a week on nonconsecutive days, either alone or with folic acid or other vitamins and minerals.
To explore the harms and benefits of such an approach, Peña-Rosas and colleagues reviewed data from 4,072 women participating in one of 18 randomized or quasi-randomized trials conducted in 13 different countries. The women were either not anemic or had only mild or moderate anemia.
Three studies evaluated an intervention with iron alone; three looked at iron plus multiple vitamins and minerals; and 12 evaluated iron plus folic acid. The weekly iron doses in the intermittent groups ranged from 80 to 200 mg elemental iron. In the trials with folic acid, the doses ranged from 400 to 3,500 µg per week.
For infant outcomes, there were no significant differences in the following when comparing intermittent and daily supplementation:
Low birth weight: 5.6% versus 7%, pooled RR 0.96 (95% CI 0.61 to 1.52)
Birth weight: mean difference -8.62 grams (95% CI -52.76 to +35.52 grams)
Risk of premature birth: pooled RR 1.82 (95% CI 0.75 to 4.40)
None of the studies reported neonatal deaths or congenital anomalies.
For maternal outcomes, women receiving intermittent supplementation were no more likely to have anemia at term (pooled RR 1.22, 95% CI 0.84 to 1.80) but were less likely to have side effects (25.2% versus 35.9%; RR 0.56, 95% CI 0.37 to 0.84).
There were no maternal deaths or cases of severe anemia in pregnancy reported. None of the studies included data on iron deficiency at term or infections during pregnancy.
“Although the statistical nondifference between regimens was a common pattern across most of the outcomes, the confidence on the applicability and generalizability of these findings may be limited by the reduced number of trials reporting on primary outcomes and probably by the small sample size of the trials,” the authors noted. “It seems wise to limit this intervention to women at low risk of developing anemia while the body of evidence builds up.”
The review was supported by the Children’s Hospital and Oakland Research Institute, the Evidence and Program Guidance Unit of the WHO’s Department of Nutrition for Health and Development, the University of Liverpool, and the National Institute for Health Research in the U.K. One of the study authors is supported by the NIHR NHS Cochrane Collaboration Program grant scheme award for NHS-prioritized centrally-managed, pregnancy and childbirth systematic reviews.
The authors reported that they had no affiliations with or involvement in any organization or entity with a direct financial interest in the subject matter of the review (employment, consultancy, stock ownership, honoraria, expert testimony). Peña-Rosas was author of an excluded study on iron and folic acid intermittent supplementation. One of his co-authors was involved in some included studies with intermittent iron supplementation and is involved in a trial awaiting assessment. Neither author was involved in assessing study eligibility.
Primary source: The Cochrane Library
Source reference: Peña-Rosas J, et al “Intermittent oral iron supplementation during pregnancy (review)” Cochrane Database Syst Rev 2012; DOI:10.1002/14651858.CD009997.