Multiple Micronutrients and Docosahexaenoic Acid Supplementation during Pregnancy: A Randomized Controlled Study

Abstract

Maternal dietary intake during pregnancy needs to meet increased nutritional demands to maintain metabolism and to support fetal development. Docosahexaenoic acid (DHA) is essential for fetal neuro-/visual development and in immunomodulation, accumulating rapidly within the developing brain and central nervous system. Levels available to the fetus are governed by the maternal diet. In this multicenter, parallel, randomized controlled trial, we evaluated once-daily supplementation with multiple micronutrients and DHA (i.e., multiple micronutrient supplementation, MMS) on maternal biomarkers and infant anthropometric parameters during the second and third trimesters of pregnancy compared with no supplementation. Primary efficacy endpoint: change in maternal red blood cell (RBC) DHA (wt% total fatty acids) during the study. Secondary variables: other biomarkers of fatty acid and oxidative status, vitamin D, and infant anthropometric parameters at delivery. Supplementation significantly increased RBC DHA levels, the omega-3 index, and vitamin D levels. Subscapular skinfold thickness was significantly greater with MMS in infants. Safety outcomes were comparable between groups. This first randomized controlled trial of supplementation with multiple micronutrients and DHA in pregnant women indicated that MMS significantly improved maternal DHA and vitamin D status in an industrialized setting-an important finding considering the essential roles of DHA and vitamin D.

Keywords: docosahexaenoic acid; long-chain polyunsaturated fatty acids; maternal biomarkers; micronutrients; neurodevelopment; pregnant women; supplementation; vitamin D.

Figure 1

Study design. Visit 1 (V1, screening): pregnant women were screened for study eligibility and blood collection was performed. Visit 2 (V2, baseline): eligible women meeting the inclusion and exclusion criteria were randomized equally to one of the two study groups; nutritional status was assessed using a semi-quantitative FFQ. Visits 3 and 4 (V3 &V4, MMS supplementation or no supplementation): FFQ was administered and blood sampling took place—the red blood cell DHA level measured at Visit 4 was compared with the value measured at Visit 1 to assess the primary endpoint. Visit 5 (V5, delivery): obstetric evaluations were performed in all women and infant anthropometric parameters were measured. Concomitant medications and adverse events were assessed at all Visits. GA, gestational age; DHA, docosahexaenoic acid; FFQ, food frequency questionnaire; MMS, multiple micronutrients and DHA supplementation.

Figure 2

Flow diagram for study participants. DHA, docosahexaenoic acid; MMS, multiple micronutrients and DHA supplementation; RBC, red blood cells; PP, per protocol.

Figure 3

Mean change (± standard deviation) from Visit 1 to Visit 4 in maternal (a) RBC DHA (wt% TFA) (p < 0.0001 in favor of MMS), (b) omega 3 index (p < 0.0001 in favor of MMS), and (c) calcidiol (25-hydroxyvitamin D) (p = 0.0122 in favor of MMS) (per protocol population; LOCF approach). Visit 1: Screening (GA Week 11/14); Visit 3: GA Week 24/26; Visit 4: GA Week 34/36. DHA, docosahexaenoic acid; GA, gestational age; LOCF, last observation carried forward; MMS, multiple micronutrients and DHA supplementation; RBC, red blood cells; SD, standard deviation; TFA, total fatty acids; wt, weight.