Studying Genetic Predisposition Among Small-for-Gestational-Age Newborns

The objective of this report is to provide a summary overview of genetic association studies for the small-for-gestational-age (SGA) pregnancy outcome. Only the thrombophilia and xenobiotic-metabolizing genetic pathways were studied with any frequency. Most studies used case-control designs and analyzed only the maternal genotype. A brief critique of some features of the published studies is presented: it addresses mainly the selection of controls, study power, the need to evaluate gene–environment interaction, and the potential for population stratification bias, believed likely to affect such studies. Alternative designs, not vulnerable to the population structure bias, are also discussed; they include case-parental trios and a mixture of both case trios and case-control data. Aspects that have almost never been considered in the published studies, but that are particularly relevant for adverse pregnancy outcomes, are maternally mediated and parent-of-origin effects. These are defined and methods to evaluate them are briefly presented.

Keywords: intrauterine growth restriction, small-for-gestational age, genetic polymorphisms, thrombophilia, xenobiotic-metabolizing genes, genetic epidemiology