Vitamin D Deficiency in Pregnancy is Linked to Autism

Posted on:January 27, 2017

Last Updated: October 10, 2020

Time to read: 5 minutes

Autism-spectrum disorder (ASD) is a group of neurodevelopmental disorders that are characterised by deficits in social interactions including verbal and nonverbal behaviours. Researchers believe that these ASD-like behaviours are a result of a complex interplay between genetic defects and environmental risk factors causing abnormal neurodevelopment during maturation in utero and in early childhood.

Neuroimaging studies have shown that there is micro- and macro-structural neural disorganisation particularly in areas involved in socioemotional processing. Genetic studies have identified mutations in well-conserved pathways that are important for functional network connectivity in these areas. In-depth gene analysis studies also appear show that pathways associated with neuroplasticity and synaptogenesis have been interfered with.

Environmental factors associated with ASD also significantly contribute to autism-related traits. These include epigenetic changes (heritable changes not caused by alteration in the genetic code), immunological processes (maternal infections), obstetric complications (e.g. hypoxia) and toxin-related factors (e.g. pesticides, medications). Other possible ASD-related environmental risk factors include smoking, alcohol, and nutrient deficiencies in the mother during fetal development.

More recently, scientists at the Queensland Brain Institute showed that a deficiency in vitamin D during pregnancy is also mechanistically associated with the development of ASD. Previous studies have shown evidence of vitamin D deficiency playing a role in autism as well as other psychiatric disorders such as schizophrenia, depression and attention deficit hyperactivity disorder.

WHO AND WHAT WAS STUDIED?

Vitamin D levels during gestation

In this study, 4229 mothers were included with approximately 70% of Dutch origin and the other 30% coming from non-Dutch ethnic groups. Mothers at intake were recorded as having an age between 25 and 35 (n=2995) and a BMI of 20 to 30 (n=3572). Ethnicity, smoking status, and educational level were also recorded. Details of children included sex, birth weight, and gestational age at birth with the majority (n=2971) born between 38.5 to 41.5 weeks at a healthy weight of 3 to 4 kilograms (n=2847).

The status of the mother’s vitamin D level was measured during gestation and at birth. Definition of thresholds were taken from the literature and set at: deficient (< 25 nmol L^-1), insufficient (25-49.9 nmol L^-1), and sufficient (≥50 nmol L^-1). The researchers hypothesised that there was an association with a non-sufficient vitamin D level and autism-related traits in children.

Social Responsiveness Scale (SRS)

The Social Responsiveness Scale (SRS) is a rating scale that measures the severity of autism-related traits in the general population. The questionnaire was an 18-item abridged version based on a 4-point Likert scale. Scores were weighted based on the sex of the child and focused on social behavioural features such as cognition, communication, and mannerisms.

Cognition was measured through recognition of social cues, tone of voice and facial expressions. Communication analysis includes how the child expresses themselves and their level of social interaction whereas mannerism analysis is determining repetitive behaviours, or highly restricted interests, both of which are key autism-related traits.

WHAT WERE THE FINDINGS?

The prevalence of vitamin D deficiency in mothers was remarkably high with 16% deficient and 26% with insufficient vitamin D levels at mid-gestation. At birth, the prevalence of this deficiency was even greater, with 36% of all mothers deficient and 40% insufficient.

Compared with those who were sufficient, mothers who were deficient at mid-gestation or at birth were significantly more likely to have a child with a higher SRS score (P < 0.001 and P = 0.01, respectively). In addition, compared with those who were sufficient, those who were insufficient at mid-gestation were also significantly more likely to have a higher SRS score (P = 0.007).

WHAT DOES THE STUDY REALLY TELL US?

The researchers showed that there is a significant association between gestational vitamin D levels and the SRS analysis of their children at 6 years old, after accounting for confounding variables. Overall, those who were deficient in vitamin D at mid-gestation, were 3.8 times more likely to have a 6-year-old child that would test positive for ASD.

THE BIG PICTURE

Vitamin D is a fat-soluble vitamin that is produced in the body after skin exposure to sun.

7-dehydrocholesterol is converted to cholecalciferol in the skin after irradiation by UV light. Cholecalciferol is then transported to the liver where it undergoes hydroxylation to calcidiol. This is then transported to the kidneys to produce finally produce calcitriol [i.e., 1,25-dihydroxycalciferol OR 1,25(OH)2D, OR cholecalcitriol], the active
compound (vitamin D1).

Although it is known as a vitamin, it doesn’t fulfil the definition for one as it is produced within the body. More recently, it is being viewed as a powerful steroid hormone that has a complex cellular function.

Vit D’s Multiple Functions at the Cellular Level

Vitamin D and its metabolites have many roles in normal brain development and functioning with compelling evidence suggesting that vitamin D deficiency is implicated in the development of psychiatric and neurological diseases. Calcitrol is known to downregulate inflammatory cytokines which have been found to be elevated in children with autism.

In addition to gestational vitamin D deficiency causing abnormal brain development in children, another recent study showed that vitamin D supplementation could significantly reduce autism severity in children with ASD. In this double-blind, randomised clinical trial, 109 children aged between 3 and 10 years old received vitamin D daily for 4 months. Social maturity, aberrant behaviour and SRS scores were all improved suggesting that vitamin D supplementation is a safe recommendation for children with ASD.

From a public health perspective, this is of great importance as vitamin D is a nontoxic, cheap and easily accessible therapeutic that could potentially influence the outcome of ASD.

WHAT SHOULD I KNOW?

This study was embedded in the Generation R Study, a large general population based study that is currently ongoing and began in the Netherlands in 2002. The Generation R Study is a prospective cohort study set in a multi-ethical urban population that is analysing fetal life and early adulthood. It focuses on physical, cognitive, and behavioural development as well as the causes of key childhood diseases in an attempt to optimise healthcare for pregnant women and children.

The Generation R Study included 9778 mothers with a delivery date between 2002 and 2006. Over the course of the study there are periodic scans, examinations and blood sampling through each stage of a child’s growth and development. It was designed to identify environmental and genetic causes of normal and abnormal growth, development and health with the aim to improve global health and healthcare strategies.

CONCLUSION

In this large population-based multi-ethnic study, the data showed that gestational vitamin D deficiency is associated with altered brain development resulting in higher SRS scores in children aged 6 years old.