Abstract
Background
Findings from previous studies on maternal 25-hydroxyvitamin D [25(OH)D] levels during
pregnancy and autism spectrum disorder (ASD) in offspring are inconsistent.
Methods
The association between maternal 25(OH)D levels during pregnancy and offspring ASD
was examined using data from a nationwide population-based register with a nested
case-control study design. The ASD cases (n = 1558) were born between 1987 and 2004 and received a diagnosis of ASD by 2015;
cases were matched with an equal number of controls. Maternal 25(OH)D levels during
pregnancy were measured using quantitative immunoassay from maternal sera collected
during the first and early second trimesters and archived in the national biobank
of the Finnish Maternity Cohort. Conditional logistic regression examined the association
between maternal 25(OH)D levels and offspring ASD.
Results
In the adjusted model, there was a significant association between increasing log-transformed
maternal 25(OH)D levels and decreasing risk of offspring ASD (adjusted odds ratio
[aOR] 0.75, 95% confidence interval [CI] 0.62–0.92, p = .005). Analyses by quintiles of maternal 25(OH)D levels revealed increased odds
for ASD in the 2 lowest quintiles, <20 (aOR 1.36, 95% CI 1.03–1.79, p = .02) and 20–39 (aOR 1.31, 95% CI 1.01–1.70, p = .04), compared with the highest quintile. The increased risk of ASD was observed
in association with deficient (<30 nmol/L) (aOR 1.44, 95% CI 1.15–1.81, p = .001) and insufficient (30–49.9 nmol/L) maternal 25(OH)D levels (aOR 1.26, 95%
CI 1.04–1.52, p = .01) compared with sufficient levels.
Conclusions
This finding has implications for understanding the role of maternal vitamin D during
fetal brain development and increased risk of ASD.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Autism.Lancet. 2014; 383: 896-910
- Gestational vitamin D deficiency and autism spectrum disorder.BJPsych Open. 2017; 3: 85
- Distribution of the Vitamin D receptor and 1α-hydroxylase in human brain.J Chem Neuroanat. 2005; 29: 21-30
- Evidence of functional vitamin D receptors in rat hippocampus.Neuroscience. 2001; 104: 49-56
- Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease.Front Neuroendocrinol. 2013; 34: 47-64
- A prospective population-based study of gestational vitamin D status and brain morphology in preadolescents.Neuroimage. 2020; 209: 116514
- The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain.Neuroscience. 2013; 236: 77-87
- Developmental vitamin D deficiency alters dopamine-mediated behaviors and dopamine transporter function in adult female rats.Psychopharmacology. 2010; 208: 159-168
- Developmental vitamin D deficiency alters dopamine turnover in neonatal rat forebrain.Neurosci Lett. 2009; 461: 155-158
- Lower maternal serum 25(OH) D in first trimester associated with higher autism risk in Chinese offspring.J Psychosom Res. 2016; 89: 98-101
- Maternal circulating vitamin D3 levels during pregnancy and behaviour across childhood.Sci Reports. 2019; 9: 14792
- Maternal vitamin D Levels and the autism phenotype among offspring.J Autism Dev Disord. 2013; 43: 1495-1504
- Gestational vitamin D deficiency and autism-related traits: The Generation R Study.Mol Psychiatry. 2018; 23: 240
- Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: A study of 62 serum biomarkers.Mol Autism. 2020; 11: 7
- Developmental vitamin D and autism spectrum disorders: Findings from the Stockholm Youth Cohort.Mol Psychiatry. 2021; 26: 1578-1588
- Brief report: Validity of Finnish registry-based diagnoses of autism with the ADI-R.Acta Paediatr. 2010; 99: 1425-1428
- Vitamin D status during pregnancy and risk of multiple sclerosis in offspring of women in the Finnish Maternity Cohort.JAMA Neurol. 2016; 73: 515
- Maternal vitamin D levels and the risk of offspring attention-deficit/hyperactivity disorder.J Am Acad Child Adolesc Psychiatry. 2021; 60: 142-151.e2
- Season, dietary factors, and physical activity modify 25-hydroxyvitamin D concentration during pregnancy.Eur J Nutr. 2018; 57: 1369-1379
- Maternal vitamin D concentrations during pregnancy, fetal growth patterns, and risks of adverse birth outcomes.Am J Clin Nutr. 2016; 103: 1514-1522
- Smoking during pregnancy reduces vitamin D levels in a Finnish birth register cohort.Public Health Nutr. 2020; 23: 1273-1277
- Vitamin D and risk of preterm birth: Up-to-date meta-analysis of randomized controlled trials and observational studies.J Obstet Gynaecol Res. 2017; 43: 247-256
- Obstetric risk factors and autism spectrum disorders in Finland.J Pediatr. 2014; 164: 358-365
- Maternal socioeconomic status based on occupation and autism spectrum disorders: A national case-control study.Nordic J Psychiatry. 2015; 69: 523
- Parental psychiatric disorders and autism spectrum disorders.Psychiatry Res. 2013; 207: 203
- Smoking during pregnancy and risk of autism spectrum disorder in a Finnish National Birth Cohort.Paediatr Perinat Epidemiol. 2013; 27: 266-274
- Autism risk associated with parental age and with increasing difference in age between the parents.Mol Psychiatry. 2016; 21: 693
- Birth seasonality and risk of autism spectrum disorder.Eur J Epidemiol. 2019; 34: 785
- Risk of autism spectrum disorders in low birth weight and small for gestational age infants.J Pediatr. 2012; 161: 830
- Modern Epidemiology.2nd ed. Lippincott Williams & Wilkins, Philadelphia1998
- Prenatal primary prevention of mental illness by micronutrient supplements in pregnancy.Am J Psychiatry. 2018; 175: 607
- The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention.Rev Endocr Metab Disord. 2017; 18: 153-165
- The effects of vitamin D on brain development and adult brain function.Mol Cell Endocrinol. 2011; 347: 121-127
- Vitamin D supplementation during the first year of life and risk of schizophrenia: A Finnish birth cohort study.Schizophr Res. 2004; 67: 237-245
- The association between neonatal vitamin D status and risk of schizophrenia.Sci Rep. 2018; 8: 17692
- Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development.Pediatrics. 2012; 129: 485-493
- Neonatal vitamin D levels and cognitive ability in young adulthood.Eur J Nutr. 2019; 59: 1919-1928
- What’s wrong with Bonferroni adjustments.BMJ. 1998; 316: 1236
- Genome-wide association study identifies 143 loci associated with 25 hydroxyvitamin D concentration.Nat Commun. 2020; 11: 1647
Article info
Publication history
Published online: July 20, 2021
Accepted:
July 14,
2021
Received in revised form:
July 14,
2021
Received:
April 20,
2021
Identification
Copyright
© 2021 Society of Biological Psychiatry.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Gestational Vitamin D and Autism Spectrum DisorderBiological PsychiatryVol. 90Issue 11
- PreviewThe potential relationship between vitamin D status and autism spectrum disorder (ASD) has been of interest since a link was hypothesized based on geographic and seasonal trends in ASD prevalence. The biologic plausibility for an association between gestational vitamin D and autism is ample, given vitamin D’s contributions to neurodevelopmentally relevant processes, including neurogenesis, cell proliferation, differentiation, apoptosis, and neurotransmitter metabolism (1–3). As summarized in the current issue of Biological Psychiatry by Sourander et al.
- Full-Text
- Preview
