title: Causal Inference in Developmental Origins of Health and Disease (DOHaD) Research.
abstract: Studies of the developmental origins of health and disease (DOHaD) often rely on prospective observational data, from which associations between developmental exposures and outcomes in later life can be identified. Typically, conventional statistical methods are used in an attempt to mitigate problems inherent in observational data, such as confounding and reverse causality, but these have serious limitations. In this review, we discuss a variety of methods that are increasingly being used in observational epidemiological studies to help strengthen causal inference. These methods include negative controls, cross-contextual designs, instrumental variables (including Mendelian randomization), family-based studies, and natural experiments. Applications within the DOHaD framework, and in relation to behavioral, psychiatric, and psychological domains, are considered, and the considerable potential for expanding the use of these methods is outlined.
authors.affiliation: MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol BS8 2BN, United Kingdom; email: kz.davey-smith@bristol.ac.uk.|UK Center for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol BS8 1TU, United Kingdom.
authors.forename: Suzanne H
authors.initials: SH
authors.lastname: Gage
authors.affiliation: MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol BS8 2BN, United Kingdom; email: kz.davey-smith@bristol.ac.uk.|UK Center for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol BS8 1TU, United Kingdom.
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Munafò
authors.affiliation: MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol BS8 2BN, United Kingdom; email: kz.davey-smith@bristol.ac.uk.
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
mesh_terms: D015984:Causality; D015340:Epidemiologic Research Design; D006304:Health Status; D006801:Humans; D064887:Observational Studies as Topic; D011446:Prospective Studies; D012107:Research Design
keywords: DOHaD; causal inference; cross-contextual comparison; instrumental variable; negative control; twin study