A decade-long follow-up of Danish children links higher prenatal vitamin D3 supplementation to stronger memory performance, highlighting pregnancy as a possible window for shaping childhood cognition.
Study: High-Dose Vitamin D3 Supplementation During Pregnancy and Test-Based Cognitive Performance at Age 10 Years. Image Credit: Buntovskikh Olga / Shutterstock
High-dose vitamin D3 supplementation during pregnancy may be associated with improved cognitive performance in offspring at the age of ten years, according to a new study published in JAMA Network Open.
Prenatal Vitamin D and Cognition Background
Childhood cognitive development refers to the changes in and attainment of cognitive abilities as children grow and mature. It is a major determinant of personal, social, and professional achievements and well-being later in life. Early-life exposure to environmental factors, including prenatal exposures, plays a pivotal role in shaping cognitive development in children.
Vitamin D deficiency is a major public health concern worldwide, as this vitamin is involved in fetal brain development. Several animal studies have linked vitamin D deficiency to cognitive deficits, including impairments in learning and memory.
Prenatal vitamin D deficiency has also been linked to neuropsychiatric disorders, including autism spectrum disorder, attention-deficit hyperactivity disorder, and schizophrenia. Individuals living with these disorders experience substantial cognitive deficits, including attention and executive functioning.
However, previous human studies investigating the impact of maternal vitamin D deficiency on offspring's cognitive performance have produced mixed results, with some reporting no significant effect and others reporting a positive effect.
Given the crucial role of vitamin D in neurodevelopment, University of Copenhagen researchers assessed whether high-dose vitamin D3 supplementation during pregnancy was associated with cognitive performance in offspring at age 10.
This study is part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 randomized controlled trial that investigated the effect of vitamin D supplementation during pregnancy on the risk of persistent wheeze or asthma among offspring during the first three years of life.
Pregnancy Vitamin D Trial Design
The study included 623 pregnant women from the 700 mother-child pairs enrolled in the original trial. The women were randomized to receive either high-dose vitamin D3 supplementation totaling 2,800 IU/day or standard-dose supplementation (control) from pregnancy week 24 to 1 week postpartum. The randomization led to 247 children prenatally exposed to high-dose vitamin D3 and 251 prenatally exposed to standard-dose vitamin D3.
Cognitive performance in children was assessed at the age of 10 using validated neuropsychological tests.
Child Cognitive Performance Findings
The researchers tested 11 cognitive functions in children aged 10. The test results indicated that high-dose vitamin D3 supplementation was positively associated with verbal memory, visual memory, and cognitive flexibility, which is the mental ability to rapidly switch attention between different tasks. However, the observed association with cognitive flexibility disappeared after multiple test corrections.
The findings of the sensitivity analysis showed that the sex of children, mothers’ pre-supplementation vitamin D levels, children’s vitamin D levels at the ages of six months and six years, and Omega-3 long-chain polyunsaturated fatty acid supplementation did not significantly modify the observed associations.
Antenatal Vitamin D Supplementation Implications
The study suggests that prenatal exposure to high-dose vitamin D3 is associated with improved visual and verbal memory in middle childhood. The study also finds a marginally better cognitive flexibility in children born to mothers who were supplemented with high-dose vitamin D3 during pregnancy.
To investigate whether neurodevelopmental disorders have any influence, the researchers explored the association between maternal vitamin D supplementation and cognitive performance among children with or without attention-deficit hyperactivity disorder (ADHD). They found that the observed associations did not appear to be driven by ADHD status, although subgroup analyses were limited.
Notably, the study reports that the positive association between prenatal vitamin D3 supplementation and cognitive performance is not explained by early childhood vitamin D levels, specifically during the six-month to six-year age range. This finding suggests that prenatal exposure may represent a critical window during which vitamin D may be associated with cognitive development. However, vitamin D levels in children after birth can be influenced by several confounding factors, including dietary vitamin intake, body composition, and ethnic background, and may not accurately represent long-term vitamin D status.
Consistent with these findings, a growing body of evidence indicates that vitamin D supplementation during pregnancy is associated with improved bone density, dental health, and fewer fractures in childhood. These benefits, together with the cognitive benefits observed in this study, support further consideration of increasing routine antenatal vitamin D supplementation doses, rather than issuing a definitive clinical recommendation based on this post hoc analysis alone.
The pregnant women enrolled for the study had relatively high baseline vitamin D status, with only a minority classified as deficient. This may have restricted the opportunity to explore the cognitive benefits of supplementation among children born to mothers with vitamin D deficiency.
The majority of study participants were White women with high baseline vitamin D levels. This may restrict the generalizability of the findings to individuals with different ethnic or sociodemographic backgrounds.
Furthermore, the study used a single neurocognitive assessment at age 10, which may have limited insight into cognitive developmental patterns across childhood. As a post hoc analysis that was not prespecified in the original trial, the study also carries an increased risk of chance findings.
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