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Associations between vitamin D status in pregnancy and offspring neurodevelopment: a systematic literature review

Janbek J, Specht IO, Heitmann BL (2019) Nutr Rev.  May 1;77(5): 330-349. doi: 10.1093/nutrit/nuy071. Epub 26 Feb 2019 

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Vitamin D plays an important role in the development of the brain, which is one of the earliest fetal organs to develop. Results from epidemiological studies investigating associations between maternal levels of vitamin D during pregnancy and offspring neurodevelopment are mixed and inconclusive.


This systematic review of studies that examined vitamin D levels in pregnancy and offspring neurodevelopment used 3 specific domains-timing of exposure during pregnancy trimesters, neurodevelopmental outcomes, and offspring age at assessment of outcomes-to determine whether vitamin D status in pregnancy is associated with offspring neurodevelopment.


A search of the Embase, PsychInfo, Scopus, and The Cochrane Library databases in September 2017 and February 2018 identified 844 articles, of which 46 were retrieved for full-text assessment.


Eligibility criteria were used to select studies. All authors examined the studies, and consensus was reached through discussion. Results were divided according to the 3 domains.


Authors examined the studies independently, and data from eligible studies were extracted using a modified version of the Cochrane data collection form. Using the modified Downs and Black checklist, 2 authors assessed the quality of the studies independently and were blinded to each other's assessment. Consensus was reached upon discussion and with the involvement of the third author.


Fifteen observational studies were included. Vitamin D in pregnancy was associated with offspring language and motor skills in young children. Associations persisted into adolescence, and results were not dependent on the timing of vitamin D exposure during pregnancy. No supplementation studies were identified.


There is some evidence that low vitamin D status in pregnancy is associated with offspring language and motor development, particularly in young children.


The evidence that low maternal Vitamin D status in pregnancy raises risks for poor neurodevelopmental outcomes in children has been building for many years. 

Animal studies show very clear evidence of mechanisms, with maternal Vitamin D deficiency leading to permanent brain impairments similar to those associated with ADHD, Autistic Spectrum Disorders, Developmental Co-ordination Disorder, and related childhood developmental conditions, as well as schizophrenia and other serious mental health problems. 

Observational studies in humans - as this systematic review concludes - also show some supporting evidence. 

As ever, definitive evidence of causailty requires human randomised controlled trials of Vitamin D supplementation during pregnancy, and long-term follow-up over many years. However, obvious ethical and practical reasons make such RCTs extremely difficult.

Meanwhile, given the known importance of adequate Vitamin D even for the physical health of mothers and children, its safety profile, and the public health implications of the rising rates of brain disorders, better screening for Vitamin D deficiency and/or supplementation of those known to be at high risk, would seem a sensible and 'evidence-based' approach.

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