Long-Term Effects of Multiple-Micronutrient Supplementation During Pregnancy, Lactation, and Early Childhood on the Cognitive Development of Children Aged 4-14 Years: A Systematic Review of Randomized Controlled Trials.

Ten studies met inclusion criteria for long-term cognitive effects of MMN or MNP supplementation on children aged 4-14 years in LMICs.

• Six studies examined maternal supplementation, three examined early childhood interventions, and one combined both approaches.
• Most studies were conducted in Asia, with one in Tanzania and one in Peru.
• Studies were identified from six databases and gray literature, screened using PRISMA guidelines (PROSPERO CRD42023459846).
• Eligible interventions occurred during pregnancy, lactation, or early childhood, with cognitive, motor, or socio-emotional outcomes assessed.

Two large UNIMMAP-based trials indicated modest long-term improvements in procedural memory and intelligence following maternal MMN supplementation.

• These were described as 'large UNIMMAP-based trials', referring to the United Nations International Multiple Micronutrient Antenatal Preparation formulation.
• The improvements were characterized as 'modest' and limited to specific cognitive domains: procedural memory and intelligence.
• Most findings across the ten included studies were not statistically significant.
• These trials were among the six studies focused on maternal supplementation.

One early childhood point-of-use MNP trial suggested enhanced pre-academic skills.

• This finding was from one of three studies examining early childhood interventions.
• The intervention involved point-of-use micronutrient powder (MNP) supplementation.
• Pre-academic skills were among the cognitive outcomes assessed in children aged 4-14 years.
• The result was noted as a suggestion rather than a definitive finding, consistent with the overall limited evidence base.

Micronutrient deficiencies during pregnancy and early life are prevalent in low- and middle-income countries and may impair cognitive outcomes.

• Inadequate nutrition, poor health care, and limited stimulation were identified as factors constraining early childhood development and cognitive potential.
• Maternal MMN and point-of-use MNP supplements are known to improve birth outcomes and iron status.
• The long-term cognitive impact of these supplements remained unclear prior to this review.
• The review focused specifically on LMICs where micronutrient deficiencies are most prevalent.

Evidence on the long-term effects of MMN and point-of-use MNPs on cognitive development remains limited, highlighting the necessity for further research.

• Most findings across included studies were not statistically significant.
• Only ten studies met inclusion criteria despite searches across six databases and gray literature updated through July 2025.
• The review covered a broad age range (4-14 years) and multiple supplementation windows (pregnancy, lactation, early childhood).
• Data were synthesized using Review Manager following PRISMA guidelines.