High-dose prenatal vitamin D3 linked to better childhood memory, but experts caution results

A new study has found that high-dose vitamin D3 supplementation during pregnancy is positively associated with visual and verbal memory, as well as flexibility among children by the age of 10. 

The authors say the findings strengthen evidence of prenatal vitamin D exposure with childhood cognition.

The study has sparked reactions among experts, claiming it to be a well-conducted trial with detailed follow-up testing, but some cautioned about its interpretation due to the modest difference observed.

“The study provides interesting evidence because it uses a robust experimental design and assesses children’s cognitive development at a relatively late age, 10 years old, which is unusual in this field,” says Lucía Iglesias Vázquez, researcher and lecturer in Nutrition and Public Health at the University of Rovira i Virgili, and the Southern Catalonia Biomedical Research Institute, and the Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition.

She explains that the results suggest that prenatal supplementation with high doses of vitamin D could be associated with certain improvements in specific cognitive functions, particularly verbal and visual memory, although no differences in overall intelligence were observed. 

“The fact that the associations appear in specific domains of memory rather than in more global measures is consistent with recent literature, which suggests more specific and subtle effects of prenatal nutritional status on neurodevelopment.” 

Cautioning interpretation of results

Iglesias Vázquez cautions against the interpretation of the study results. “This is a post hoc analysis, meaning it was not the original primary objective of the trial, and the observed effect sizes are modest. Furthermore, most participants had relatively adequate vitamin D levels at the start of the study, so the results may not be generalizable to populations with more severe deficiency.”

“Overall, the study reinforces the hypothesis that prenatal nutrition may influence child neurodevelopment, but further studies are still needed to determine which levels and timing of supplementation might have the greatest clinical impact.”

The study has been published in Jama Network Open and included 623 Danish mother-child pairs.

The follow-up neurocognitive testing was completed by 498 children.It divided the 623 pregnant women from week 24 to one week postpartum into consuming only the recommended dose of 400 IU vitamin D3, or the daily recommended dose plus 2,400 IU of vitamin D3. To determine adherence, the researchers counted the returned capsules. 

The follow-up neurocognitive testing was completed by 498 children at an average age of 10.3 years. They tested 11 specific cognitive functions across areas: intelligence, processing speed, reaction time, attention, motor function, memory, working memory, and executive functions. 

Cognitive testing

The research team found that after adjusting for factors such as sex, age, and season of birth, the children from mothers who received the high dose of vitamin D3 when pregnant had better visual and verbal memory. 

The same children also showed a positive association with flexibility or set shift — switching attention, thoughts, or behaviors when faced with new tasks or changes. However, it did not show an impact on the remaining areas.

Another expert not involved in the study, Asma Khalil, professor of Obstetrics and Maternal Medicine and Consultant Obstetrician, City St George’s, University of London, UK, comments: “This is a well-conducted follow-up of a randomized trial, with detailed cognitive testing at age 10 years.” 

“The findings are interesting because children whose mothers received higher-dose vitamin D3 supplementation in late pregnancy performed slightly better on some memory measures than those whose mothers received standard-dose supplementation.”

“The association with flexibility and set shifting also did not remain significant after correction for multiple testing.”

Echoing Iglesias Vázquez’s points about the study being a post hoc secondary analysis with modest results, Khalil stresses that the findings should not be interpreted as proof that high-dose vitamin D improves children’s intelligence or overall cognitive ability. 

“The cohort was largely White, Danish, and relatively vitamin D sufficient at baseline, so the findings may not apply directly to more diverse populations or to women with significant vitamin D deficiency,” she concludes.