The effects of caffeine administered at different temperatures on foetal development
More details
Hide details
Department of Human Anatomy, Medical University of Lublin, Poland
Department of Biophysics, Medical University of Lublin, Poland
I Department of Radiology, Medical University of Lublin, Poland
Corresponding author
Marek Tomaszewski   

Department of Human Anatomy, Medical University of Lublin, Poland
Ann Agric Environ Med. 2016;23(1):148-152
An easy access to products containing caffeine makes it widely consumed to excess by the general population, including pregnant women. Beverages containing caffeine are consumed at different temperatures (iced, hot, room temperature). Caffeine easily passes through biological membranes, including the blood-brain barrier, the placental barrier, and can also enter the amniotic fluid, breast milk and semen. The aim of this study was to evaluate the relationship between caffeine’s developmental toxicity, and the solution’s temperature (both low and high) administered to pregnant female rats. Fertilized females were randomly divided into two main groups: an experimental (E) and a control group (C). The experimental groups received caffeine (30mg/day) in 10 (E1), 25 (E2) and 45oC (E3). The females in the control group were given water at the same temperature (C1, C2 and C3). On the day 21 of pregnancy, the pregnant females were killed by decapitation, using a specially prepared laboratory guillotine, after which the mothers’ internal organs were weighed. Additionally, the offspring were examined using standard teratological methods. The study found that caffeine administered to pregnant females at a dose of 30mg/day and at the temperatures of 10°C, 25°C or 45°C did not produce any teratogenic effects. The only sign of its adverse effect was the appearance of developmental abnormalities in the form of haematomas and saturated bleeding in the internal organs. These changes most frequently occurred in foetuses of females which received caffeine at 10°C or 45°C.
Nikolic J, Bjelakovic G, Stojanovic I. Effect of caffeine on metabolizm of L-arginine in the brain. Mol Cell Biochem. 2003; 244: 125–128.
Christian MS. Test methods for assessing female reproductive and developmental toxicology. In: Hayes AW. (ed): Principles and method of toxicology. Ed. 4. Taylor and Francis. Philadelphia. 2001: 1301–1381.
Christian MS, Brent RL. Teratogen update: Evaluation of the reproductive and developmental risks of caffeine. Teratology. 2001; 64: 51–78.
Nawrot P, Jordan S, Eastwood J, Hugenholtz A, Feeley M. Effects of caffeine on human health. Food Addit Contam. 2003; 20: 1–30.
Soellner DE, Grandys T, Nunez JL. Chronic prenatal caffeine exposure impairs novel object recognition and radial arm maze behaviors in adult rats. Behav Brain Res. 2009; 14, 205, 1, 191–199.
Kujawa-Hadryś M, Tosik D, Bartel H. Changes in thickness of each layer of developing chicken cornea after administration of caffeine. Folia Histochem Cytobiol. 2010a; 48(2): 273–277.
Kujawa-Hadryś M, Tosik D, Bartel H. Ultrastructural changes in the developing chicken cornea following caffeine administration. Folia Histochem Cytobiol. 2010b; 48(3): 371–376.
Olchowik G, Chadaj-Polberg E, Tomaszewski M, Polberg M, Tomaszewska M. The influence of caffeine on the biomechanical properties of bone tissue Turing pregnancy in a population of rats. Folia Histochem Cytobiol. 2011; 49(3): 504–511.
Tomaszewski M, Olchowik G, Tomaszewska M, Burdan F. Use of X-ray microprobe to diagnose bone tissue demineralization after caffeine administration. Folia Histochem Cytobiol. 2012; 50(3): 436–443.
EMEA 2000. Note for guidance on repated dose toxity. CMP/SWP/1042/99.
WHO 2001. World Health Organization. Principles for evaluating health risks to reproduction associated with exposure to chemicals. Environ Health Criteria 225, 1–185.
ICH 2000. ICH Harmonised tripartite guideline. Maintenance of the ICH guideline on toxicity to male fertility. An addendum to ICH tripartite guideline on detection of toxicity to reproduction for medicinal products.
Elmazar MMA, McElhatton PR, Sullivan FM. Studies on the teratogenic effects of different oral preparations of caffeine in mice. Toxicology. 1982; 23: 57–71.
Burdan F, Madej B, Wójtowicz Z, Maciejewski R, Radzikowska E. The effects of short – time caffeine administration on skeleton development in Wistar rats. Folia Morphol (Warsz). 2000; 59: 91–95.
Burdan F, Szumiło J, Dudka J, Klepacz R, Błaszczak M, Solecki M, Korobowicz A, Chłas A, Klepacki J, Palczak M, Zuchnik-Wrona A, Hadała-Kiś A, Urbanowicz Z, Wojtowicz Z. Morphological studies in modern teratological investigations. Folia Morphol (Warsz). 2005; 64: 1–8.
DevTox 2007 http//
Nishimura H, Nakai K. Congenital malformations in offspring of mice treated with caffeine. Proc Soc Exp Med. 1960; 104: 140–142.
Evereklioglu C, Sari I, Alasehirli B, Guldur E, Cengiz B, Balat Z, Bagci C. High dose of caffeine administered to pregnant rats causeshistopathological changes in the cornea of newborn pups. Med Sci Monit. 2003; 9: 168–173.
Wilkinson J, Pollard I. In utero exposure to caffeine causes delayed neural tube closure in rat embryos. Teratog Carcinog Mutagen. 1994; 14: 205–211.
Fedrick B. Anencephalus and maternal tea drinking: evidence for a possible association. Proc R Soc Med. 1974; 67: 356–360.
Borlee I, Lechat MF, Bouckaert A, Misson C. Le cafè, facteur de risqué pedant la grossesse? Louvain Med. 1978; 97: 279–284.
Furuhashi N, Sato S, Suzuki M, Hiruta M, Tanaka M, Takahashi T. Effect of caffeine ingestion during pregnancy. Gynecol Obstet Invest. 1985; 19: 187–191.
Linn S, Schoenbaum SC, Monson RR, Rosner B, Stubblefield PG, Ran KJ. No association between coffee consumption and adverse outcomes of pregnancy. N Engl J Med. 1982; 306: 141–145.
Kurppa K, Holmberg PC, Kuosma E, Saxen L. Coffee consumption during pregnancy and selected congenital malformtions: a nationwide case – control study. Am J Public Health. 1983; 73: 1397–1399.
Oei SG, Vosters RPL. Fetal arrhythmia caused by excessive intake caffeine by pregnant women. BMJ. 1989; 28: 568.
Journals System - logo
Scroll to top