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

Torkel Carlsson,Mark J Taylor,Ulf Jonsson,Sven Bölte,Felix Molander

doi:10.1017/s0954579420000620

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.

Highlights

Neurodevelopmental disorders (NDD) are characterized by alterations in the functioning, architecture, and maturation of the brain causing impairments in cognitive and adaptive functioning
In the current systematic review, we found evidence, beyond familial confounding, that advanced paternal age, low birth weight, birth defects, and perinatal hypoxia and respiratory stress are consistently associated with a diagnosis of autism spectrum disorder (ASD)
We found evidence that low birth weight, gestational age and low family income or transient income decline during childhood are associated with attention-deficit/hyperactivity disorder (ADHD), both categorically and dimensionally

Summary

Introduction

Neurodevelopmental disorders (NDD) are characterized by alterations in the functioning, architecture, and maturation of the brain causing impairments in cognitive and adaptive functioning. The prevalence of NDDs is 10–15% of all births in the United States (Aschner & Costa, 2015), and they are increasingly being diagnosed worldwide (Elsabbagh et al, 2012). ASD and ADHD are currently the most commonly diagnosed NDDs, with prevalence estimates ranging. In face of the substantial individual burden and the societal costs these conditions incur on public health care, educational, and long-term support systems, it is of paramount importance to identify specific factors involved in the etiology of NDDs that might facilitate earlier detection and open up for earlier interventions (Bellinger, 2012; Grandjean, Pichery, Bellanger, & Budtz-Jørgensen, 2012; Trasande & Liu, 2011)

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