A new perspective on hyperthermia-induced birth defects: The role of activation energy and its relation to obstetric ultrasound

Abstract This paper concerns the rate of birth defects that is induced by hyperthermic conditions during gestation. These defects occur with low rates under apparently normal physiologic conditions, but with substantially higher rates with appropriate timing of a hyperthermic event during gestation. The concept of “free energy of activation” is invoked to explain not only the background rate but also the effect of a short-term, acute (additive) thermal dosing at a highly heat-sensitive stage of embryogenesis. In this respect, this paper is both retrospective and prospective in approach. It briefly and retrospectively addresses the historical data in this area and then, following a novel mathematical procedure whereby the activation energy for a specific type of hyperthermia-induced birth defect is determined, prospectively applies this information to predict what the outcomes would be in a clinical situation such as obstetric diagnostic ultrasound where it is known that the clinical procedure can involve a temperature increment for a specific duration. A major outcome of this review is that there appear to be no thresholds for hyperthermic events, that any temperature elevation for any duration during pregnancy has some potential for inducing a deleterious effect. The paper includes an analysis that for the first time allows a calculation of risk for such defined thermal insults, with broader implications for any natural or other clinical situation in which the temperature of the embryo or fetus is raised above the normal physiologic level. The topic of hyperthermia-induced birth defects and related activation energies needs thorough, long-term testing of this prospective position.