Marshall J. Edwards: Discoverer of maternal hyperthermia as a human teratogen

Abstract

In a series of animal studies performed over a career spanning 40 years at the University of Sydney, Professor Marshall J. Edwards investigated the hypothesis that maternal hyperthermia during gestation can be teratogenic to the developing fetus. He is one of few investigators to have discovered a known human teratogen primarily through animal studies. In 1970 he earned his Ph.D. from the University of Sydney, writing a doctoral thesis entitled "A Study of Some Factors Affecting Fertility of Animals with Particular Reference to the Effects of Hyperthermia on Gestation and Prenatal Development of the Guinea-Pig." He went on to prove that hyperthermia-induced malformations in animals involve many organs and structures, particularly the central nervous system. Other defects include craniofacial anomalies, heart defects and hypodactyly, cataracts and coloboma, kyphoscoliosis, renal anomalies, dental agenesis, and abdominal wall defects. In a series of carefully planned and executed experiments, he demonstrated that the type of defect is related to the timing of the hyperthermic insult, and analyzed the underlying mechanisms. Cell death, membrane disruption, vascular disruption, and placental infarction were all implicated in causing embryonic damage. This special article reviews the scientific discoveries and personal philosophy of Marshall J. Edwards, the discoverer of maternal hyperthermia as a human teratogen.

A Population-Based Case–Control Study of Extreme Summer Temperature and Birth Defects

“…Given the weight of evidence supporting the teratogenic effects of hyperthermia in animals and humans, and that the central nervous system has been demonstrated to be the most sensitive to hyperthermic insult (Edwards 2006; Edwards et al 1995; Graham 2005; Graham et al 1998; Warkany 1986), we expected to see elevated odds ratios for central nervous system defects. Nevertheless, we did not find evidence of associations in our population, and neither did Suarez et al (2004) in their study of exposures to hot environments and the occurrence of neural-tube defects.…”

“…Hyperthermia is a well-known animal teratogen, and maternal fever has been associated with birth defects in human studies (Edwards 2006; Edwards et al 1995; Graham 2005; Graham et al 1998; Warkany 1986). In all species, the teratogenic effect of the hyperthermic insult depends on timing, intensity, and duration of exposure, and the central nervous system appears to be most vulnerable.…”

Bioeffects of Diagnostic Dynamic 3-Dimensional (4-Dimensional) Ultrasound on Ultrastructure of Cerebral Cells of Fetal Mice in Late Pregnancy

“…4 Investigations with laboratory animals have documented that pulsed ultrasound can produce damage to biological tissues in vivo through nonthermal mechanisms. 5,6 The bioeffects of ultrasound are generally classified into 2 types: thermal and mechanical effects.…”

The safety of obstetrical ultrasound: a review

“…Edwards has demonstrated multiple teratogenic effects within mammalian offspring exposed to hyperthermic temperatures in utero, including musculoskeletal, cardiac, renal, and central nervous system anomalies (Edwards, 1986;Graham, 2005). These findings are less established although proposed in human studies (Chambers et al, 1998;Church and Miller, 2007;Layde et al, 1980;Medveczky et al, 2004).…”