Negative results are also interesting and important

CIH/CISMAC researcher Ingrid Kvestad, Tor Strand and colleagues recently published in Pediatrics the results of a long-term study in Northern India that has shown limited long-term benefits in terms of cognitive development to vitamin B12 and folate supplements.

While long-term studies are logistically challenging and costly, their results are important and can have important impacts on health policy, as well as our understanding of health.

Their paper also merited a commentary article in Pediatrics.

Article:

Vitamin B12, Folate, and Cognition in 6- to 9-Year-Olds: A Randomized Controlled Trial

By Ingrid Kvestad, Sunita Taneja, Ravi P. Upadhyay, Mari Hysing, Nita Bhandari and Tor A. Strand

“BACKGROUND AND OBJECTIVES: Vitamin B₁₂ and folate are important for normal brain development. Our objective for this study was to measure the effects of 6-month supplementation of vitamin B₁₂ and/or folic acid in early childhood on cognition when the children were 6 to 9 years old.

METHODS: The study is a follow-up of a factorial randomized, double-blind, placebo-controlled trial in 1000 North Indian children. Children 6 to 30 months of age were randomly assigned to receive a placebo or 1.8 µg of vitamin B₁₂, 150 mg of folic acid, or both daily for 6 months. After 6 years, we re-enrolled 791 of these children for cognitive assessments. We compared the scores of the main outcomes (the Wechsler Intelligence Scale for Children, Fourth Edition [India], the Crichton Verbal Scale, and subtests of the NEPSY-II) between the study groups. We also measured the associations between markers of the B vitamins (plasma cobalamin, folate, and total homocysteine concentrations) in early childhood and the cognitive outcomes.

RESULTS: There were no differences between the intervention groups and the placebo group on the cognitive outcomes. Plasma cobalamin, folate, and total homocysteine concentrations in early childhood were associated with the cognitive outcomes at follow-up in the unadjusted models. These associations disappeared in models adjusted for relevant confounders.

CONCLUSIONS: Our findings, from both an observational and a randomized design suggest that vitamin B₁₂ and folate in children 6 to 36 months have limited public health relevance for long-term cognition.”

Comment:

Importance of Follow-up Studies to Examine Sustained Effects of Early Nutrition Interventions

by Leila M. Larson and Beverley-Ann Biggs

“With 43% of children <5 years of age worldwide at risk for poor mental development,¹ interventions aimed at sustained improvement of cognition are urgently needed. Nutrition has proven to be an important predictor of neurodevelopment, and interventions to address malnutrition in many low- and middle-income countries have improved children’s short-term development.² The expectation is that the early life neurobehavioral benefits, when the brain is developing rapidly and is most sensitive to interventions, extend beyond childhood. Yet little is known about the consequences of improving cognition in early life on school-aged and adult outcomes, such as school achievement, economic productivity, and overall well-being. Only a handful of nutrition interventions in children <5 years old follow up with the same participants to examine long-term benefits. Consequently, the follow-up study by Kvestad et al³ titled “Vitamin B₁₂, Folate, and Cognition in 6- to 9-Year-Olds: A Randomized Controlled Trial” makes an important contribution to our understanding of the sustainability of early benefits.”