Basic Experimental and Clinical Advances in the Mechanisms Underlying Abnormal Pregnancy Outcomes

Abstract

Development and growth of the embryo and fetus are complex processes inextricably linked to the ability of the individual to reach childhood developmental milestones. Insults or stimuli to which the embryo or fetus responds during critical periods of intrauterine growth and development are now understood to alter the genetically dictated growth trajectory of the fetus and reprogram the newborn's long-term development and physiological path. Basic experimental and clinical human studies demonstrate that intrauterine growth restriction may result from in utero insults such as uteroplacental insufficiency and/or hypoxia, preeclampsia, preterm labor, and imbalanced nutrition. The fetal responses to these insults manifest as a predisposition to the development of the metabolic syndrome in postnatal life. The “thrifty phenotype hypothesis” has been proposed to explain the mechanism by which in utero responsive adaptations set in motion the series of developmental and physiological adaptations to maximize the chances of in utero survival [1–3]. While intrauterine growth restriction resulting in low birth weight is recognized as a major risk factor for noncommunicable diseases associated with the metabolic syndrome, it is now apparent that both ends of the birth weight spectrum are associated with having an increased risk of adult-onset disease in later life [4, 5]. This further highlights the necessity to understand both optimal growth patterns that result in optimal birth weight and the critically important role that they play in setting the stage for health and the risk of disease in postnatal life. In this special issue, we have gathered a number of excellent reviews, each focussing upon different facets of how an altered in utero environment results in adaptations in fetal organ systems, expanding our understanding of how perturbations at early stages of development may have long-term consequences.