Antenatal Multiple Micronutrient Supplementation Compared to Iron-Folic Acid Affects Micronutrient Status but Does Not Eliminate Deficiencies in a Randomized Controlled Trial Among Pregnant Women of Rural Bangladesh

Abstract

Background: Antenatal multiple micronutrient (MM) supplementation improves birth outcomes relative to iron-folic acid (IFA) in developing countries, but limited data exist on its impact on pregnancy micronutrient status.

Objective: We assessed the efficacy of a daily MM (15 nutrients) compared with IFA supplement, each providing approximately 1 RDA of nutrients and given beginning at pregnancy ascertainment, on late pregnancy micronutrient status of women in rural Bangladesh. Secondarily, we explored other contributors to pregnancy micronutrient status.

Methods: Within a double-masked trial (JiVitA-3) among 44,500 pregnant women, micronutrient status indicators were assessed in n = 1526 women, allocated by cluster to receive daily MM (n = 749) or IFA (n = 777), at 10 wk (baseline: before supplementation) and 32 wk (during supplementation) gestation. Efficacy of MM supplementation on micronutrient status indicators at 32 wk was assessed, controlling for baseline status and other covariates (e.g., inflammation and season), in regression models.

Results: Baseline status was comparable by intervention. Prevalence of deficiency among all participants was as follows: anemia, 20.6%; iron by ferritin, 4.0%; iron by transferrin receptor, 4.7%; folate, 2.5%; vitamin B-12, 35.4%; vitamin A, 6.7%; vitamin E, 57.7%; vitamin D, 64.0%; zinc, 13.4%; and iodine, 2.6%. At 32 wk gestation, vitamin B-12, A, and D and zinc status indicators were 3.7-13.7% higher, and ferritin, γ-tocopherol, and thyroglobulin indicators were 8.7-16.6% lower, for the MM group compared with the IFA group, with a 15-38% lower prevalence of deficiencies of vitamins B-12, A, and D and zinc (all P < 0.05). However, indicators typically suggested worsening status during pregnancy, even with supplementation, and baseline status or other covariates were more strongly associated with late pregnancy indicators than was MM supplementation.

Conclusions: Rural Bangladeshi women commonly entered pregnancy deficient in micronutrients other than iron and folic acid. Supplementation with MM improved micronutrient status, although deficiencies persisted. Preconception supplementation or higher nutrient doses may be warranted to support nutritional demands of pregnancy in undernourished populations. This trial was registered at clinicaltrials.gov as NCT00860470.

Keywords: Bangladesh; South Asia; antenatal; micronutrients; minerals; pregnancy; supplementation; trial; vitamins.

FIGURE 1

Consolidated Standards of Reporting Trials diagram for participants in the micronutrient status assessment substudy of the JiVitA-3 trial of antenatal multiple micronutrient (MM) compared with iron–folic acid (IFA) supplementation among women of rural Bangladesh. Pregnancy losses included those due to miscarriage, stillbirth, or elected pregnancy termination. Unmet refers to an inability to locate a woman in time to gain consent for or engage her participation in intended study visits.

FIGURE 2

Percentage (95% CI) difference in micronutrient status indicators at 32 wk gestation in MM compared with IFA recipients (represented by brackets) in the context of pregnancy-associated changes in micronutrient status indicators expressed as percentage change (95% CI) from baseline (bars). Differences in MM versus IFA are derived from adjusted (model 2 from Table 2 using log10-transformed indicators), and percentage change over pregnancy from unadjusted, analyses. For example, there was no significant difference in Hb in late pregnancy between intervention groups (0.4% lower in MM than in IFA), while Hb was ∼6% lower in late compared to early pregnancy in both IFA and MM recipients. Ferritin was 9.0% lower among the MM than IFA recipients, and declined by 47% with IFA and 52% with MM from baseline to 32 wk gestation. Shaded indicators are those for which higher concentrations represent poorer status. Hb, hemoglobin; IFA, iron–folic acid; MM, multiple micronutrients; TfR, transferrin receptor; Tg, thyroglobulin; α-Toco, α-tocopherol; α-Toco:Chol, α-tocopherol:cholesterol ratio; γ-Toco, γ-tocopherol; 25(OH)D, 25-hydroxyvitamin D.

FIGURE 3

Percentage contribution of intervention (MM compared with IFA), baseline micronutrient status indicator concentrations (accounting for season, gestational age, and AGP concentration), and other covariates (including factors that differed at baseline and season, gestational age, and AGP concentration at the time of the 32-wk measurement) to the total variance in late pregnancy micronutrient indicator concentrations among women in rural Bangladesh. Data are from regression model 2 in Table 2. Also shown is the total explained variance (R²), in italics, of 32-wk micronutrient indicator concentrations based on model 2. AGP, α₁-acid glycoprotein; Hb, hemoglobin; IFA, iron–folic acid; MM, multiple micronutrient; TfR, transferrin receptor; Tg, thyroglobulin; α-Toco, α-tocopherol; α-Toco:Chol, α-tocopherol:cholesterol ratio; γ-Toco, γ-tocopherol; 25(OH)D, 25-hydroxyvitamin D.