Abnormal Development - Maternal Hyperthermia

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Educational Use Only - Embryology is an educational resource for learning concepts in embryological development, no clinical information is provided and content should not be used for any other purpose.


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. A difficult associated concept is that of "thermal dose", whereby in experimental conditions the thermal load variables (temperature change, temperature, time) can be highly regulated, in real biological conditions these can be extremely variable including the additional variables of absolute time of exposure and developmental stage.

Hyperthermia and hypothermia.jpg

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.

Environmental Links: Introduction | Low Folic Acid | Iodine Deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | Thalidomide | Herbal Drugs | Illegal Drugs | Smoking | Fetal Alcohol Syndrome | TORCH Infections | Viral Infection | Bacterial Infection | Zoonotic Infection | Toxoplasmosis | Malaria | Maternal Diabetes | Maternal Hypertension | Maternal Hyperthermia | Maternal Inflammation | Maternal Obesity | Hypoxia | Biological Toxins | Chemicals | Heavy Metals | Radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis

Bacterial Links: Syphilis | Gonorrhea | Tuberculosis | Listeria | TORCH Infections | Environmental | Category:Bacteria
Viral Links: TORCH Infections | Cytomegalovirus | Hepatitis Virus | HIV | Parvovirus | Polio Virus | Rubella Virus | Chickenpox | Lymphocytic Choriomeningitis Virus | Zika Virus | Vaccination | Environmental

Some Recent Findings

  • Effects of maternal hyperthermia on myogenesis-related factors in developing upper limb.[1] "Our data suggest that maternal hyperthermia delays limb myogenesis in part by disregulating the expression of key myogenesis-related factors."
  • Multiple congenital abnormality syndrome in the offspring of pregnant women affected with high fever-related disorders[2] "Our previous study showed an association between high fever-related maternal diseases during the second and/or third gestational months and a higher risk of multiple congenital abnormalities (MCA) in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities."
More recent papers
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

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Search term: Maternal Hyperthermia

Alexandre Delamou, Alison M El Ayadi, Sidikiba Sidibe, Therese Delvaux, Bienvenu S Camara, Sah D Sandouno, Abdoul H Beavogui, Georges W Rutherford, Junko Okumura, Wei-Hong Zhang, Vincent De Brouwere Effect of Ebola virus disease on maternal and child health services in Guinea: a retrospective observational cohort study. Lancet Glob Health: 2017; PubMed 28237252

L M Cranmer, A Langat, K Ronen, C J McGrath, S LaCourse, J Pintye, B Odeny, B Singa, A Katana, L Nganga, J Kinuthia, G John-Stewart Integrating tuberculosis screening in Kenyan Prevention of Mother-To-Child Transmission programs. Int. J. Tuberc. Lung Dis.: 2017, 21(3);256-262 PubMed 28225335

Mariam M Mirambo, Said Aboud, Uwe Groß, Mtebe Majigo, Martha F Mushi, Stephen E Mshana Rubella Seromarkers and Determinants of Infection among Tanzanian Children and Adolescents in Prevaccination Era: Are We in the Right Track? Int J Prev Med: 2017, 8;3 PubMed 28217265

Craig V Towers, Angela Yates, Nikki Zite, Casey Smith, Lindsey Chernicky, Bobby Howard Incidence of Fever in Labor and Risk of Neonatal Sepsis. Am. J. Obstet. Gynecol.: 2017; PubMed 28216060

S Allison Staley, Marcela C Smid, Sarah K Dotters-Katz, Elizabeth M Stringer Epstein-Barr Virus-Induced Mononucleosis as an Imitator of Severe Preeclampsia. AJP Rep: 2017, 7(1);e5-e7 PubMed 28210518

Diurnal Temperature Changes

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 there natural diurnal small changes in core body temperature that occur each day.

Diurnal body temperature.jpg

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.

Neural Tube Defects

Neural tube and other developmental anomalies in the guinea pig following maternal hyperthermia during early neural tube development.[3] "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."

Marsh Edwards

Edwards: discoverer of maternal hyperthermia as a human teratogen.[4] "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.

Pregnancy Exercise Guidelines

American College of Obstetricians and Gynecologists

These new recommendations and guidelines for exercise during pregnancy and the postpartum period were first published in 2002.[5] The recommendations classified absolute and relative contraindications to aerobic exercise during pregnancy. Note that regular exercise is also promoted for overall health benefits including prevention and management of gestational diabetes.

Absolute contraindications include:

  • Haemodynamically significant heart disease
  • Restrictive lung disease
  • Incompetent cervix/cerclage
  • Multiple gestation at risk for premature labour
  • Persistent second or third trimester bleeding
  • Placenta praevia after 26 weeks gestation
  • Premature labour during the current pregnancy
  • Ruptured membranes
  • Pregnancy induced hypertension

Links: PMC1724598 | Br J Sports Med. | PDF


  1. Jin Lee, Philip E Mirkes, Doo Jin Paik, Won Kyu Kim Effects of maternal hyperthermia on myogenesis-related factors in developing upper limb. Birth Defects Res. Part A Clin. Mol. Teratol.: 2009, 85(3);184-92 PubMed 19180648
  2. Andrew E Czeizel, Erzsébet H Puhó, Nándor Acs, Ferenc Bánhidy Delineation of a multiple congenital abnormality syndrome in the offspring of pregnant women affected with high fever-related disorders: a population-based study. Congenit Anom (Kyoto): 2008, 48(4);158-66 PubMed 18983582
  3. J Cawdell-Smith, J Upfold, M Edwards, M Smith 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 PubMed 1354895
  4. John M Graham Marshall J. Edwards: discoverer of maternal hyperthermia as a human teratogen. Birth Defects Res. Part A Clin. Mol. Teratol.: 2005, 73(11);857-64 PubMed 16265640
  5. R Artal, M O'Toole Guidelines of the American College of Obstetricians and Gynecologists for exercise during pregnancy and the postpartum period. Br J Sports Med: 2003, 37(1);6-12; discussion 12 PubMed 12547738 | PMC1724598 | Br J Sports Med. | PDF


  • International Journal of Hyperthermia There are currently 165 issues available, published between 1985 and 2010.
    • The official journal of the Society for Thermal Medicine, the European Society for Hyperthermic Oncology, and the Asian Society of Hyperthermic Oncology, the International Journal of Hyperthermia provides a forum for the publication of Research and Clinical Papers
    • Clinical Studies. Whole body, regional or local treatment, practical considerations in therapy, clinical trials, physiological effects, heat treatment in combination with other modalities, thermal ablation and treatment optimization.
    • Biological Studies. Mechanisms of thermal injury, thermotolerance, modification of thermal response, heat treatment in combination with other modalities, effects on normal and malignant cells and tissues, immunological effects, physiological effects, thermal dosimetry, drug delivery, gene therapy.
    • Techniques of Heat Delivery and Temperature Measurement. Methods of producing whole-body, regional and local hyperthermia; modelling of temperature distributions; performance and evaluation of hyperthermia and thermal ablation equipment; safety and protection; thermal dosimetry; invasive and non-invasive thermometry; calibration; and data acquisition and system control.



Christina D Chambers Risks of hyperthermia associated with hot tub or spa use by pregnant women. Birth Defects Res. Part A Clin. Mol. Teratol.: 2006, 76(8);569-73 PubMed 16998815

Rengasamy Padmanabhan, Noura Musaed Al-Menhali, Saeed Tariq, Mohamed Shafiullah Mitochondrial dysmorphology in the neuroepithelium of rat embryos following a single dose of maternal hyperthermia during gestation. Exp Brain Res: 2006, 173(2);298-308 PubMed 16847614

A Milunsky, M Ulcickas, K J Rothman, W Willett, S S Jick, H Jick Maternal heat exposure and neural tube defects. JAMA: 1992, 268(7);882-5 PubMed 1640616

Myla E Moretti, Benjamin Bar-Oz, Shawn Fried, Gideon Koren Maternal hyperthermia and the risk for neural tube defects in offspring: systematic review and meta-analysis. Epidemiology: 2005, 16(2);216-9 PubMed 15703536

S B Field The concept of thermal dose. Recent Results Cancer Res.: 1988, 107;1-6 PubMed 3375545

W C Dewey Interaction of heat with radiation and chemotherapy. Cancer Res.: 1984, 44(10 Suppl);4714s-4720s PubMed 6467225

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June 2010 "Maternal Hyperthermia"

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Cite this page: Hill, M.A. 2017 Embryology Abnormal Development - Maternal Hyperthermia. Retrieved February 28, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Maternal_Hyperthermia

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© Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G