Preconception micronutrient supplementation positively affects offspring perceptual reasoning at 10-11 years of age: follow-up of a randomized controlled trial in Vietnam

BACKGROUND: Maternal periconceptional nutrition is important for birth outcomes, but few studies examine long‐term effects on offspring growth and development. OBJECTIVES: We assessed the impact of weekly preconception multiple micronutrients (MM) or iron and folic acid (IFA) supplements compared to folic acid (FA) alone, on cognitive function and nutritional status at 10‐11 y. We also examined associations with early‐life biological and socioenvironmental factors. METHODS: We conducted a follow‐up study of 1599 children from a preconception randomized trial in Vietnam, in which females received weekly FA, IFA, or MM before conception and daily IFA during pregnancy. We assessed cognitive function, academic achievement, and nutritional status at ages 10‐11 y. Early biological factors included maternal nutritional status, birth characteristics, and postnatal linear growth; socioenvironmental variables were maternal schooling, ethnicity, depression, infant feeding, socioeconomic status (SES), and home environment. Analyses used intention‐to‐treat and per protocol comparisons with inverse‐probability‐of‐censoring weights to account for loss to follow‐up. RESULTS: Offspring in the MM and IFA groups had higher perceptual reasoning scores than the FA group {mean difference [95% confidence interval (CI): MM: 1.68 (0.01, 3.35); IFA: 2.04 (0.33, 3.74)]}. The IFA groups also had higher reading scores [0.78 (0.11, 1.44)] and lower anemia prevalence [‐4.26 (‐7.60, ‐0.91)]. No differences were observed in full‐scale intelligence quotient (FSIQ) or anthropometric measures. Maternal underweight was negatively associated with FSIQ [β (95% CI): ‐1.62 (‐3.06, ‐0.18)] and reading scores [‐0.59 (‐1.12, ‐0.06)] whereas postnatal linear growth was positively associated with FSIQ [1.67 (0.91, 2.43)], mathematics [0.36 (0.12, 0.61)], and reading scores [0.47 (0.21, 0.74)]. Maternal schooling, home environment, SES, were also linked to improved cognitive and academic outcomes [β range: 0.64 (0.01, 1.27) to 8.89 (5.20, 12.58)], and exclusive breastfeeding was linked with higher mathematics scores [0.73 (0.27, 1.19)]. CONCLUSIONS: Preconception MM and IFA supplementation improved certain aspects of cognitive functioning at 10‐11 y compared with FA alone, whereas early‐life biological and socioenvironmental factors were positively associated with cognitive and academic outcomes. This study was registered at clinicaltrials.gov as NCT01665378 (https://clinicaltrials.gov/ct2/show/NCT01665378).