Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct;33(4):1448-1495.
doi: 10.1017/S0954579420000620.

Early environmental risk factors for neurodevelopmental disorders - a systematic review of twin and sibling studies

Affiliations

Early environmental risk factors for neurodevelopmental disorders - a systematic review of twin and sibling studies

Torkel Carlsson et al. Dev Psychopathol. 2021 Oct.

Abstract

While neurodevelopmental disorders (NDDs) are highly heritable, several environmental risk factors have also been suggested. However, the role of familial confounding is unclear. To shed more light on this, we reviewed the evidence from twin and sibling studies. A systematic review was performed on case control and cohort studies including a twin or sibling within-pair comparison of neurodevelopmental outcomes, with environmental exposures until the sixth birthday. From 7,315 screened abstracts, 140 eligible articles were identified. After adjustment for familial confounding advanced paternal age, low birth weight, birth defects, and perinatal hypoxia and respiratory stress were associated with autism spectrum disorder (ASD), and low birth weight, gestational age and family income were associated with attention-deficit/hyperactivity disorder (ADHD), categorically and dimensionally. Several previously suspected factors, including pregnancy-related factors, were deemed due to familial confounding. Most studies were conducted in North America and Scandinavia, pointing to a global research bias. Moreover, most studies focused on ASD and ADHD. This genetically informed review showed evidence for a range of environmental factors of potential casual significance in NDDs, but also points to a critical need of more genetically informed studies of good quality in the quest of the environmental causes of NDDs.

Keywords: confounding factors; environmental exposure; neurodevelopmental disorders; systematic review; twin and sibling studies.

PubMed Disclaimer

Conflict of interest statement

None

Figures

Figure 1.
Figure 1.
The 2009 PRISMA Flow Diagram

References

    1. World Health Organization, santé, O. m. d. l., Staff, W., Health, W. H. O. D. o. M., AC01696920], A., WHO, & Zivetz, L. (1992). The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines: World Health Organization.
    1. Aagaard, K., Bach, C. C., Henriksen, T. B., Larsen, R. T., & Matthiesen, N. B. (2018). Head circumference at birth and childhood developmental disorders in a nationwide cohort in Denmark. Paediatric and Perinatal Epidemiology, 32, 458–466. doi:10.1111/ppe.12479 - DOI - PubMed
    1. Abd Elhameed, M. A., Abd Elbaky, A. E. O., & Kamel, E. A. (2011). A controlled study of the risk factors and clinical picture of children with Autism in an Egyptian sample. Egyptian Journal of Neurology, Psychiatry and Neurosurgery, 48, 271–276.
    1. Altink, M. E., Arias-Vasquez, A., Franke, B., Slaats-Willemse, D. I., Buschgens, C. J., Rommelse, N. N., … Buitelaar, J. K. (2008). The dopamine receptor D4 7-repeat allele and prenatal smoking in ADHD-affected children and their unaffected siblings: No gene-environment interaction. Journal of Child Psychology and Psychiatry and Allied Disciplines, 49, 1053–1060. doi:10.1111/j.1469-7610.2008.01998.x - DOI - PMC - PubMed
    1. American Psychiatric Association (1987). Diagnostic and statistical manual of mental disorders: DSM-III-R. Washington DC: American Psychiatric Publishing.

Publication types