Impact of Preconception Micronutrient Supplementation on Anemia and Iron Status during Pregnancy and Postpartum: A Randomized Controlled Trial in Rural Vietnam

Abstract

Objective: Preconception micronutrient interventions may be a promising approach to reduce anemia and iron deficiency during pregnancy, but currently we have limited data to inform policies. We evaluated whether providing additional pre-pregnancy weekly iron-folic acid (IFA) or multiple micronutrient (MM) supplements compared to only folic acid (FA) improves iron status and anemia during pregnancy and early postpartum.

Methods: We conducted a double blind randomized controlled trial in which 5011 Vietnamese women were provided with weekly supplements containing either only 2800 μg FA (control group), IFA (60 mg Fe and 2800 μg FA) or MM (15 micronutrients with similar amounts of IFA). All women who became pregnant (n = 1813) in each of the 3 groups received daily IFA (60 mg Fe and 400 μg FA) through delivery. Hematological indicators were assessed at baseline (pre-pregnancy), during pregnancy, 3 months post-partum, and in cord blood. Adjusted generalized linear models were applied to examine the impact of preconception supplementation on anemia and iron stores, using both intention to treat and per protocol analyses (women consumed supplements ≥ 26 weeks before conception).

Results: At baseline, 20% of women were anemic, but only 14% had low iron stores (ferritin <30 μg/L) and 3% had iron deficiency (ferritin <12 μg/L). The groups were balanced for baseline characteristics. Anemia prevalence increased during pregnancy and post-partum but was similar among intervention groups. In intention to treat analyses, prenatal ferritin was significantly higher among women receiving MM (geometric mean (μg/L) [95% CI]: 93.6 [89.3-98.2]) and IFA (91.9 [87.6-96.3]) compared to control (85.3 [81.5-89.2]). In per protocol analyses, women receiving MM or IFA had higher ferritin 3 months postpartum (MM 118.2 [109.3-127.8]), IFA 117.8 [108.7-127.7] vs control 101.5 [94.0-109.7]) and gave birth to infants with greater iron stores (MM 184.3 [176.1-192.9]), IFA 189.9 [181.6-198.3] vs control 175.1 [167.9-182.6]).

Conclusion: Preconception supplementation with MM or IFA resulted in modest increases in maternal and infant iron stores but did not impact anemia. Further research is needed to characterize the etiology of anemia in this population and identify effective interventions for reducing prenatal anemia.

Trial registration: ClinicalTrials.Gov NCT01665378.

Conflict of interest statement

PHN, MY, IGC, HP, HN, TVT, SN, RM and UR have no conflicts of interest. KBH and GAR are employed by the institutions that funded the research. They participated in study design, but were not directly involved in the implementation of the study both during data collection and analysis. Their contributions to this manuscript include interpretation of findings and review of the final manuscripts.

Figures

Fig 1. Flow diagram of participant progress throughout the study.

FA- Folic Acid, IFA- Iron and Folic Acid, MM- Multiple Micronutrient.

Fig 2. Ferritin at first prenatal visit, by iron status at baseline and treatment group.

a Significant difference (P = 0.003) between MM group and FA group, b Significant difference (P = 0.03) between IFA group and FA group. Difference among treatment groups were tested using generalized linear regression, adjusting for gestational age, duration of supplements and inflammation. FA- Folic Acid, IFA- Iron and Folic Acid, MM- Multiple Micronutrient.