High core body temperature, hyperthermia, has been shown in animal models to be a potent teratogen. Hyperthermia in humans (greater than 39.5°C/103°F) during the first trimester increases the risk of a miscarriage and neural defects. Hyperthermia can be due to many different factors including: environment, hot tubs, spas, sauna, exercise, infection fever (viral, bacterial), physiological abnormalities of thermoregulation.
Hyperthermia and Hypothermia (Image: USARIEM)
Guinea pigs have been successfully used as a sensitive model system for the effects of maternal hyperthermia (high body temperature/fever) upon development. This is an example of a maternal environmental effect on embryonic development and neurological effects has also been demonstrated in other rodent model systems. (More? Other Embryos - Guinea Pig Development)
Page Links: Introduction | Some Recent Findings | Diurnal Temperature Changes | Neural Tube Defects | Marsh Edwards | Australian NHMRC Recommendations | WWW Links | References | Glossary
Chambers CD. Risks of hyperthermia associated with hot tub or spa use by pregnant women. Birth Defects Res A Clin Mol Teratol. 2006 Aug;76(8):569-73. "...human studies that have demonstrated an association between high maternal fever in early pregnancy and NTDs. In addition, there is a large volume of animal literature suggesting that, regardless of the heat source, an elevated core maternal temperature at or above the threshold of 2 degrees C over baseline, as well as timing and duration of exposure, are the critical factors in conferring risk."
In humans there are a number of small changes that occur each day and associated with the menstral cycle, neither of which are significant enough to cause hyperthermia.
Firstly tthere natural diurnal small changes in core body temperature that occur each day.
Typical diurnal changes in normal core body temperature
Secondly, in women of reproductive age there occurs also a small approximately 0.5°C increase in body temperature associated with ovulation during the menstral cycle. This temperature rise is often used in reproductive cycle monitoring to aid or avoid pregnancy. (More? Human Menstrual Cycle)
Human Menstrual Cycle Temperature change
Cawdell-Smith J, Upfold J, Edwards M, Smith M. Neural tube and other developmental anomalies in the guinea pig following maternal hyperthermia during early neural tube development. Teratog Carcinog Mutagen. 1992;12(1):1-9. "Guinea pigs were exposed to hyperthermia for 1 hr once or twice on day 11, 12, 13, or 14 (E11-E14) of pregnancy. The mean rectal temperatures were elevated by 3.4°C -4.0°C. This treatment resulted in a marked elevation of rates of resorption and developmental defects in embryos examined at day E23. The defects observed were those affecting the neural tube (NTD) (exencephaly, encephaloceles, and microphthalmia), kyphosis/scoliosis, branchial arch defects, and pericardial edema. Embryos with NTD and kyphosis/scoliosis have not been found among newborn guinea pigs to date following maternal heat exposure on days E12-E14. It appears that embryos with these defects are filtered out by resorption or abortion by days E30-E35." (More? see Marsh Edwards)
"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. His doctoral thesis was 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. ... 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.
(Text modified from review: Graham JM Jr. Marshall J. Edwards: discoverer of maternal hyperthermia as a human teratogen. Birth Defects Res A Clin Mol Teratol. 2005 Nov;73(11):857-64.)
The Australian NHMRC (1988) recommends neonates be assessed for follow-up care under the following conditions.
(see the NHMRC WWW Page)
Links: Reviews | Articles | Online Textbooks | Search Textbooks | Search PubMed | Glossary
International Journal of Hyperthermia "The official journal of the Society for Thermal Medicine, the European Society for Hyperthermic Oncology, and the Japanese Society of Hyperthermic Oncology, the International Journal of Hyperthermia provides a forum for the publication of research and clinical studies and trials on hyperthermia which fall largely into the three main categories of clinical studies, biological studies and techniques of heat delivery and temperature measurement."
Edwards MJ. Review: Hyperthermia and fever during pregnancy. Birth Defects Res A Clin Mol Teratol. 2006 Jul;76(7):507-16.
Graham JM Jr. Marshall J. Edwards: discoverer of maternal hyperthermia as a human teratogen. Birth Defects Res A Clin Mol Teratol. 2005 Nov;73(11):857-64.)
Chambers CD. Risks of hyperthermia associated with hot tub or spa use by pregnant women. Birth Defects Res A Clin Mol Teratol. 2006 Aug;76(8):569-73.
Padmanabhan R, Al-Menhali NM, Tariq S, Shafiullah M. Mitochondrial dysmorphology in the neuroepithelium of rat embryos following a single dose of maternal hyperthermia during gestation. Exp Brain Res. 2006 Aug;173(2):298-308.
Search Textbooks
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Search Oct 2006 "maternal hyperthermia" 515 reference articles of which 51 were reviews.
Search PubMed: term = maternal hyperthermia
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These links require online access to Merck Manuals on Women's Health Issues. http://www.merck.com/mrkshared/mmanual_home2/sec22/sec22.jsp
Risk Factors Present Before Pregnancy
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see also Normal Childhood Development
You should look at normal development of the effected systems in the embryo. Development Notes
Alternatively, go on to look at Systematic Development of organs and tissues.
For those wanting to see dynamic processes of development (and have a reasonably quick connection) then the Movies pages are good for watching changes occur.
The study of human development has relied extensively on studying the process in other model animals. For those wanting to see the process of development in other species then the other embryos pages are a good start.
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