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Iron and folic acid supplementation became part of the standard antenatal care to prevent anemia and other complications in pregnant women and their offspring.1 The supplement during pregnancy has also been associated with reduced child mortality especially in countries with low- and middle-income countries.2

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A recently published cluster randomized trial included 1,258 pregnant women, (<16 weeks gestation) and looked into the differences in maternal and infant outcomes between daily iron–folic acid (IFA), twice weekly IFA, or twice weekly multiple micronutrient (MMN) supplementation. Primary outcome was birth weight. Secondary outcomes were maternal hemoglobin and ferritin at 32 weeks, and infant length-for-age z-scores, hemoglobin, ferritin, and cognitive development at 6 months of age.3

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The authors found no difference in birth weights of infants of women receiving twice weekly IFA compared to daily IFA (mean difference [MD] 28 gram [gm]; 95% Confidence Interval [CI] -22 to 78), or twice weekly MMN compared to daily IFA (MD 236.8 g; 95% CI -82 to 8.2). At 32 week gestation, maternal ferritin was lower in women receiving twice weekly IFA compared to daily IFA (geometric mean ratio 0.73; 95% CI 0.67 to 0.80), and in women receiving twice weekly MMN compared to daily IFA (geometric mean ratio 0.62; 95% CI 0.57 to 0.68). There was no difference in hemoglobin levels among groups. Of interest, using the Bayley Scales of Infant and Toddler Development, 3rd edition (BSID III), infants of mothers who received twice weekly IFA had higher cognitive scores at 6 months of age compared to those who received daily IFA (MD 1.89; 95% CI 0.23 to 3.56).

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Based on these findings, authors concluded that in populations with low rates of iron deficiency, there is no clinical difference between intermittent or daily IFA in except in the significant improvement observed in cognitive outcomes of 6-month-old infants whom their mothers received twice-weekly antenatal IFA. Needless to say, this requires further investigation.

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These findings are interesting in many aspects. Less frequent administration of a drug is certainly a major advantage in improving patient compliance – a problem that hinders optimization of drugs therapy worldwide. In addition, the findings of improved cognitive scores of the infants of those mothers who received the less frequent drug are worth investigating. However, one of the important questions the trial did not address was the incidence of spinal bifida, a major birth defect related to folic acid deficiency, between groups. Perhaps addressing this outcome will provide more validity to these findings.

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1. World Health Organization [WHO]. (2012). Guideline: Intermittent iron and folic acid supplementation in non-anaemic pregnant women (ISBN: 978 92 4 150201 6). Retrieved from: http://www.who.int/nutrition/publications/micronutrients/guidelines/guideline_intermittent_ifa_non_anaemic_pregnancy/en/index.html.
2. Rajaratnam JK, Marcus JR, Flaxman AD, et al. Neonatal, postneonatal, childhood, and under-5 mortality for 187 countries, 1970-2010: a systematic analysis of progress towards Millennium Development Goal 4. Lancet. 2010;375:1988–2008.   [PubMed: 20546887]
3. Hanieh S, Ha T, Simpson JA, et al. The Effect of Intermittent Antenatal Iron Supplementation on Maternal and Infant Outcomes in Rural Vietnam: A Cluster Randomised Trial. PLOS Medicine 2013;10(6):e1001470.

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