Too little sunlight – and specifically UVB exposure – in pregnancy has been linked with a higher risk of learning disabilities.
In a new study looking at more than 422,500 school-age children from across Scotland, researchers found that low UVB exposure during pregnancy was associated with risk of learning disabilities.
UVB exposure from sunlight is linked to the production of the essential nutrient vitamin D in the body.
Publishing their results in the journal Scientific Reports, University of Glasgow researchers linked sunshine hours data from the Met Office with the month in which children were conceived.
They found that there was a statistically significant relationship between lower UVB exposure over the whole of pregnancy and the risk of learning disabilities.
The relationship was specific to UVB (not UVA) suggesting that the effect of sunlight was likely to be working via production of vitamin D.
During the antenatal period, the foetus undergoes rapid development and growth, making it susceptible to environmental exposures, with the potential of long-term consequences.
Maternal UVB exposure promotes the production of vitamin D, which is important for normal brain development of a foetus.
The researchers also found a slightly stronger relationship with low UVB exposure in the first trimester, suggesting that early pregnancy may be the most vulnerable to the effects of insufficient UVB.
As a result of low levels of UVB radiation from sunlight, vitamin D deficiency is common over winter months in high latitude countries such as Scotland.
With Scottish residents twice as likely to be vitamin D deficient than people living in other parts of the UK.
Professor Jill Pell, Director of the University of Glasgow’s Institute of Health and Wellbeing and lead author of the study, said: “Learning disabilities can have profound life-long effects on both the affected child and their family.
The importance of our study is that it suggests a possible way to prevent learning disabilities in some children.
Clinical trials are now needed to confirm whether taking vitamin D supplements during pregnancy could reduce the risk of learning disabilities.”
Image Caption:
The researchers also found a slightly stronger relationship with low UVB exposure in the first trimester, suggesting that early pregnancy may be the most vulnerable to the effects of insufficient UVB. The image is in the public domain.
Of the 422,512 schoolchildren included in the study, 79,616 (18.8%) had a learning disability, 49,770 (23.1%) boys and 29,846 (14.4%) girls.
The percentage of children with learning disabilities varied by month of conception, ranging from 16.5% among children conceived in July, to 21.0% among those conceived in February, March and April.
Dr Claire Hastie, who did the analysis, said “Our study linked routinely collected health and education data with environmental data enabling us to study a very large number of children in a way that would not be possible using traditional methods.”
The study, ‘Antenatal exposure to solar radiation and learning disabilities: Population cohort study of 422,512 children’ is published in Scientific Reports.
Over the last decades, the role of maternal nutrient status in fetal development has generated considerable research interest.
Many reports worldwide have demonstrated high prevalences of vitamin D (VD)4 deficiency in pregnant women (1).
VD diffuses across the placenta from mother to fetus; hence, the mother is the sole source of VD substrate for her developing child.
It has been shown that in cases of maternal VD deficiency, defined as serum 25-hydroxyvitamin D [25(OH)D] status <50 nmol/L (2), the fetus is also deficient (3).
Discoveries have revealed that many tissues and cells in the body express VD receptors (VDRs) (4, 5) and that both placenta and embryonic kidneys exhibit an enzymatic machinery, which converts 25(OH)D, the inactive VD metabolite, into 1,25-dihydroxycholecalciferol [1,25(OH)2D3], the metabolically active VD metabolite (6).
These discoveries have provided new insights into the function of VD. Low VD status during pregnancy has, for instance, been associated with rickets and growth retardation (1, 2) as well as various adverse extra-skeletal outcomes, including type 2 diabetes mellitus and inflammatory disorders in offspring (1, 7, 8).
Furthermore, research has suggested that low maternal VD status may affect neuronal development and could result in the onset of various mental illnesses like schizophrenia and autism (1, 7, 8).
Therefore, the purpose of this systematic review is to provide a brief overview of current evidence on the impact of maternal VD deficiency on brain development and function and to identify knowledge gaps warranting further research.
Two topics will be discussed:
1) animal studies focusing on biological effects of developmental VD (DVD) deficiency on brain development and function and
2) human studies examining the impact of maternal 25(OH)D status on both offspring neurocognitive function and psychological health.
To achieve comprehensive retrieval of relevant articles, a systematic search within Medline (on Ovid) was conducted until 7 May 2015, without time or language limits. Studies investigating potential relations between maternal VD status and offspring brain function and development were systematically reviewed.
Gray literature and conference proceedings were not searched.
The search string was designed to include search terms on maternal VD intake and status and offspring brain function and development (Table 1).
Because no search strategy can guarantee completeness, additional hand searches were conducted to identify studies that were not retrieved by the systematic search in Medline.
The selection process started with a title and abstract screening based on inclusion and exclusion criteria; articles identified as potentially relevant were ordered as full text. During full-text screening, articles were included if they met both of the following criteria:
1) providing data on DVD deficiency or maternal 25(OH)D status during gestation obtained before or at delivery and
2) providing data on offspring brain development and/or function.
Studies were excluded if
1) they were reviews, case reports, letters, editorials, or correspondence;
2) blood samples to determine maternal 25(OH)D status were obtained after delivery;
3) the exposure was indirectly related to VD such as season of birth or latitude;
4) the associations between prenatal 25(OH)D status and brain development, function, and/or behavior were not explored in the study; and
5) VD mutant or VDR knockout model was used rather than maternal VD–deficient model.
In total, 36 articles met the inclusion criteria of this review (Figure 1).
Vitamin D and brain development and function: what we know from animal studies
VD has been suggested to affect numerous endocrine functions, such as the regulation of serum calcium and phosphorus concentrations, as well as health outcomes, like bone health, muscle function, and type 2 diabetes (reviewed in 1, 2).
Furthermore, VD has been proposed to influence brain processes (9–11).
Animal studies and in vitro studies have substantially contributed to our understanding concerning the role of VD in brain development and function. I
n this section, data resulting from animal studies examining the impact of low maternal 25(OH)D status on fetal brain and offspring brain development, function, and behavior are summarized.
Vitamin D and fetal brain development in animals
Most animal studies investigating the effect of maternal VD depletion on brain development and function used the DVD deficiency model as described by Eyles et al. (12).
In this DVD deficiency model, female Sprague-Dawley rats were fed a VD-deficient diet from ~6 wk before conception until birth.
As a consequence, the developing fetus was exposed to hypovitaminosis D during gestation. When a DVD deficiency model is discussed in this review, it refers to the model as described by Eyles et al. (12), unless stated otherwise.
DVD and alterations in brain morphology, physiology, and gene expression in rat models.
Data resulting from the DVD model have shown that offspring of VD-deficient mothers exhibit differences in brain morphology, physiology, and gene expression (Table 2).
To illustrate this, neonatal offspring of VD-deficient Sprague-Dawley rats were reported to have longer and thinner cerebral hemispheres in comparison to offspring of normal fed rats (12).
Furthermore, cell proliferation and the number of mitotic cells were significantly higher and the number of differentiating cells significantly lower throughout the VD-deficient neonatal brain (12, 14, 22).
In addition, in a study by Ko et al. (22), a subtle decline in the number of apoptotic cells in both embryos and pups from VD-deficient rats was observed.
This decline was most pronounced at birth (embryonic day 23), suggesting an age-dependent alteration in brain apoptotic activity.
Low prenatal 1,25(OH)2D3 status has also been shown to affect neurotrophin signaling through its effect on the synthesis of nerve growth factor (NGF) and glial cell line neurotrophic factor, and expression of neurotrophin receptor p75 (12).
Low fetal 1,25(OH)2D3 status was not related to other neurotrophin receptors, Vdr expression, or the neurons:glia ratio (12).
DVD deficiency has also been related to larger ventricles, reduced NGF synthesis, decreased expression of genes involved in neuronal structure (17), and decreased cell proliferation (20).
Experimental studies in rats have also suggested a role for VD in dopaminergic systems, which may be of clinical relevance for certain disorders that are associated with abnormal dopaminergic signaling such as schizophrenia (23, 24), Parkinson disease (25), depression (26), and autism (27).
For instance, VD deficiency has been shown to alter gene expression of factors such as nuclear receptor related 1 protein and cyclin-dependent kinase inhibitor 1C, which are involved in the dopaminergic development in the embryonic midbrain (15).
Changes in dopaminergic metabolic profile were also observed in offspring forebrain, showing a decreased dihydroxyphenylacetic acid:homovanillic acid ratio as well as catechol-O-methyl transferase expression (21).
With the use of Affymetrix gene microarrays, prenatal hypovitaminosis D has been linked to multiple alterations in gene and protein expression patterns involved in neuronal structure later in life.
Specifically, DVD deficiency has been shown to affect the expression of 36 protein molecules that are involved in numerous biological pathways in offspring rat brain, including oxidative phosphorylation, synaptic plasticity, and neurotransmission.
With the use of computational analyses these impairments were subsequently associated with the pathogenesis of several neurodevelopmental and psychiatric disorders like schizophrenia and multiple sclerosis (13, 16).
DVD deficiency did not affect subcellular Vdr distribution in Sprague-Dawley rats (5).
Funding: The work was funded by HDR UK (Health Data Research UK).
Source:
University of Glasgow
Media Contacts:
Ali Howard – University of Glasgow
Image Source:
The image is in the public domain.
Original Research: Open access
“Antenatal exposure to solar radiation and learning disabilities: Population cohort study of 422,512 children”. Ola Nakken, Haakon E. Meyer, Hein Stigum, Trygve Holmøy.
Scientific Reports. doi:10.1038/s41598-019-45562-9
