Testing maternal effects of vitamin-D and omega-3 levels on offspring neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study
Year: 2024
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Maternal vitamin-D and omega-3 fatty acid (DHA) deficiencies during pregnancy have previously been associated with offspring neurodevelopmental traits. However, observational study designs cannot distinguish causal effects from confounding. METHODS: First, we conducted Mendelian randomisation (MR) using genetic instruments for vitamin-D and DHA identified in independent genome-wide association studies (GWAS). Outcomes were (1) GWAS for traits related to autism and ADHD, generated in the Norwegian mother, father, and child cohort study (MoBa) from 3 to 8 years, (2) autism and ADHD diagnoses. Second, we used mother-father-child trio-MR in MoBa (1) to test causal effects through maternal nutrient levels, (2) to test effects of child nutrient levels, and (3) as a paternal negative control. RESULTS: Associations between higher maternal vitamin-D levels on lower ADHD related traits at age 5 did not remain after controlling for familial genetic predisposition using trio-MR. Furthermore, we did not find evidence for causal maternal effects of vitamin-D/DHA levels on other offspring traits or diagnoses. In the reverse direction, there was evidence for a causal effect of autism genetic predisposition on lower vitamin-D levels and of ADHD genetic predisposition on lower DHA levels. CONCLUSIONS: Triangulating across study designs, we did not find evidence for maternal effects. We add to a growing body of evidence that suggests that previous observational associations are likely biased by genetic confounding. Consequently, maternal supplementation is unlikely to influence these offspring neurodevelopmental traits. Notably, genetic predisposition to ADHD and autism was associated with lower DHA and vitamin-D levels respectively, suggesting previous associations might have been due to reverse causation.
Source: Psychological Medicine
Authors: Robyn E. Wootton, Kyle Dack, Hannah J. Jones, Lucy Riglin, Paul Madley-Dowd, Carolina Borges, Panagiota Pagoni, Christine Roth, Anne Lise Brantsæter, Elizabeth C. Corfield, Camilla Stoltenberg, Anne-Siri Øyen, George Davey Smith, Helga Ask, Anita Thapar, Evie Stergiakouli, Alexandra Havdahl
Institutions: Norwegian Institute of Public Health, University of Bristol, Lovisenberg Diakonale Sykehus, MRC Integrative Epidemiology Unit, NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust, Cardiff University, University of Bergen, University of Oslo
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,450
Funders: Stiftelsen Kristian Gerhard Jebsen, Wellcome Trust, Trond Mohn stiftelse, National Institute for Health and Care Research, Department of Health and Social Care, European Commission, University of Bristol, Helse- og Omsorgsdepartementet, Novo Nordisk, Helse Vest, Universitetet i Bergen, Universitetet i Oslo, Norges Forskningsråd, HORIZON EUROPE Framework Programme, Medical Research Council, Helse Sør-Øst RHF, Norwegian Institute of Public Health, National Institute of Neurological Disorders and Stroke
Awards: Understanding the role of fatty acids in the aetiology of cardiovascular disease using novel causal inference methods, G1274085498, G138799298, G1684393010, G1793884970, G1906086737, G2230720350, G240382578, G2498202452, G2572253437, Running in the FAMILY - Understanding and predicting the intergenerational transmission of mental illness, G2606538822, G2822846613, G310833229, G3201241063, G3433676821, Neurodevelopmental disorders: what happens when children grow up and why?, G3507283293, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G3691419938, G3742410397, G3987754321, G4261458305, G429437450, G5371351582, G67063899, G7095874527, G7737178365, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource focusing on life course health and well-being., G8637614474, G8732656901, G8745459150, G8789231540, G8793412166, G971472329
OpenAlex ID: W4402373236