Low vitamin D in pregnancy linked to autism-like behaviour

Researchers at The University of Western Australia (UWA) have found vitamin D plays an important role in the brain development of children, with low levels of vitamin D during pregnancy and breastfeeding potentially related to autism-like social behaviour in later life.

Autism spectrum disorder (ASD) is a lifelong condition that impacts on how individuals interact and communicate with the world. Studies have found that lower levels of maternal vitamin D during pregnancy are associated with an increased risk of ASD in children. However, the biological mechanisms underpinning this relationship remain unclear.

To examine how maternal vitamin D levels influence brain development, Dr Caitlin Wyrwoll and her colleagues assessed alterations in markers of brain function and social behaviours of adult rats, born to mothers that were vitamin D deficient during pregnancy and lactation. They found that rats with vitamin D-deficient mothers displayed abnormal social behaviours, altered brain chemistry and impaired learning and memory.

“For example, offspring of vitamin D-deficient mothers had less interest in interacting with an unfamiliar rat, compared to those who had mothers with healthy levels of vitamin D,” said Dr Wyrwoll, whose study has been published in the Journal of Endocrinology.

She added that the researchers conducted memory tests, including an object recognition test, and found, “The ability to differentiate between familiar and new objects was much lower in those rats with vitamin D deficiency in early life.”

Dr Wyrwoll said although the study focused on rats, the data indicated vitamin D levels during pregnancy were important for brain development, and may point to a contributing factor in the development of neurodevelopmental conditions such as ASD.

“Differences in social behaviour are a hallmark of numerous human conditions, such as autism spectrum disorder (ASD), and these findings provide further evidence of the importance of maternal vitamin D levels during pregnancy in the brain development of offspring,” she said.

“However, further work is needed to establish whether these associations apply to humans.”

The research has received generally positive commentary from fellow scientists, with Associate Professor Darryl Eyles from The University of Queensland noting that Wyrwoll’s work is “the latest in an emerging number of … preclinical studies” which are helping to build a case for public health interventions. Associate Professor Eyles noted that vitamin D supplementation is already recommended during pregnancy in Australia and suggested that its use should be encouraged “especially in situations of either deficiency or the presence of known autism risk modifiers, ie, infections during pregnancy”.

Dr Edwin Lim from Macquarie University said the finding ties in with his own previous studies on brain metabolism. He explained, “Vitamin D can activate a biochemical pathway responsible for foetal development known as the kynurenine pathway, which produces a compound known as nicotinamide adenine dinucleotide (commonly known as NAD). This compound not only provides protection to the brain against oxidative stress (ie, ageing) but also promotes cellular growth.

“What this means is that lower maternal vitamin D may result in lower NAD production during pregnancy, compared to those who have a normal vitamin D level. This is consistent with what we see in our previous study, published last year in the New England Journal of Medicine, that defective genes to this biochemical pathway can reduce NAD production responsible for brain development. Our earlier study also showed that this biochemical pathway (ie, kynurenine pathway) is perturbed in autism.”

Professor Robyn Young from Flinders University meanwhile noted that the link between vitamin D deficiency and ASD has “long been speculated”, citing a Swedish study in adults in 2016. The authors of that study wrote, “Diagnosed lifetime maternal vitamin D deficiency was associated with risk of ASD and, in particular, of ASD with intellectual disability … although there was some attenuation upon adjustment for parental characteristics.”

Professor Young did note, however, that vitamin D deficiency “could not be randomly allocated, and given it is also linked to other factors such as low SES, the link may not be direct”. She added that vitamin D deficiency is particularly rare in Sweden and thus “cannot account for the majority of people with ASD”.

Finally, Professor Ulrich Schall from The University of Newcastle described the study as “well-designed”, noting that vitamin D is well known to play an important role in brain development. “Any deficiency is therefore likely to increase the risk for so-called ‘pervasive’ or ‘neurodevelopmental’ disorders, such as autism or schizophrenia,” he said.

“However,” Professor Schall pointed out, “‘risk’ means that the developing brain is more susceptible for these conditions, rather than that the vitamin D deficiency is ‘causing’ it. Other factors such as a genetic predisposition and life events have also shown to increase risk but can also facilitate resilience.

“Notwithstanding, perinatal vitamin D supplementation is an important public health measure for vitamin D-deficient populations.”

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