May 18, 2026

expert reaction to a post hoc secondary analysis of an RCT on high-dose vitamin D3 supplementation during pregnancy and test-based cognitive performance at age 10 years

A follow-up of an RCT published in JAMA Network Open looks at vitamin D3 supplementation during pregnancy and cognitive performance of children at age 10 years. 

Prof Asma Khalil, Professor of Obstetrics and Maternal Medicine and Consultant Obstetrician, City St George’s, University of London (CSGUL), said:

“This is a well-conducted follow-up of a randomised 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.

“However, this was a post hoc secondary analysis, not the trial’s primary outcome, and many cognitive outcomes were assessed. The observed differences were modest, and most domains, including estimated intelligence, attention, processing speed, and working memory, did not differ significantly between groups. The association with flexibility/set shifting also did not remain significant after correction for multiple testing.

£The results, therefore, support the possibility that antenatal vitamin D status may influence aspects of later neurodevelopment, but they 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.

In real-world terms, this study adds to the evidence that vitamin D during pregnancy is important, but it does not, by itself, justify changing clinical recommendations. Pregnant women should continue to follow national guidance on vitamin D supplementation, and any higher-dose supplementation should be considered in the context of individual risk factors and clinical advice.

“Overall, this study suggests that children whose mothers took higher-dose vitamin D supplements during pregnancy performed slightly better on some memory tests at age 10 years. However, the differences were small, and the study did not show improvements in overall intelligence or most other areas of cognitive function. The findings are interesting and add to growing evidence that vitamin D is important in pregnancy, but they do not mean that taking very high doses of vitamin D will make children ‘smarter’. Pregnant women should continue to follow existing medical advice on vitamin D supplementation and speak with their healthcare professional before taking higher doses.”  

Prof Andrew Shennan, Professor of Obstetrics, Department of Women and Children’s Health, King’s College London, said:

“This was a well performed analysis of strong randomised data and implies that vitamin D3 may improve brain function after 10 years in the offspring of children from mothers who receive it in pregnancy. The data is supported by finding in animal studies. Given how cheap and safe vitamin D is in these doses, it could have significant public health benefit in the future if the findings are real. As it was an ad hoc analysis and wasn’t pre-defined, this maybe a chance finding from multiple looks at the same data and it would be important to confirm this in other data sets before making recommendations. The benefit could however be even greater in less nourished populations. These findings only were apparent after 10 years so this should encourage others to look at this with this timeframe in mind.”

Comments from our friends at SMC Spain:

Lucía Iglesias Vázquez, a researcher and lecturer in nutrition and public health at the Universitat Rovira i Virgili (URV) and the Institut de Recerca Biomèdica Catalunya Sud (IRBCatSud), CIBERobn, said:

“The study provides interesting evidence because it uses a robust experimental design (randomised clinical trial) and assesses children’s cognitive development at a relatively late age, 10 years old, which is unusual in this field. 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.

”However, the findings should be interpreted with caution. This is a post hocanalysis, 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 generalisable 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.”

‘High-Dose Vitamin D3 Supplementation During Pregnancy and Test-Based Cognitive Performance at Age 10 Years A Post Hoc Secondary Analysis of a Randomized Clinical Trial’ by Olivia Frigast Frederiksen, et al. was published in JAMA Network Open at 16:00 UK time on Monday the 18th of May 2026 UK time. 

DOI: 10.1001/jamanetworkopen.2026.11464

Declared interests

Prof Asma Khalil: “I have no relevant conflicts of interest to declare.”

Prof Andrew Shennan: “No conflicts to declare”

Lucía Iglesias Vázquez: “She declares no conflicts of interest relating to this study.”