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.