Mother's caffeine consumption affects foetal brain development, in mice

In Britain, and the US, the guideline daily amount of caffeine for pregnant women is between one and two cups of coffee a day. This advice is based on possible links between caffeine consumption and the risk of miscarriage or low birth weight. Recent research may reinforce advice for women to avoid caffeine during pregnancy and breastfeeding.

The research from Christophe Bernard (Research Director at Inserm) and an international team of researchers, from the University of Coimbra, University of Bonn, University of Hamburg and Université Aix Marseille, was published by Science Translational Medicine in August 2013. Christophe Bernard et al. tested the effect of caffeine on the offspring of mice given low levels of caffeine whilst pregnant. Female mice were given the caffeine in their drinking water throughout pregnancy and lactation. The dose given was equivalent to a human drinking three to four cups of coffee a day.

The study found that caffeine affected the migration of somatostatin-containing GABA neurons and their insertion into the hippocampal circuitry. At postnatal day six (P6) GFP labelled sections of the caffeine exposed hippocampal neurons appeared similar to control P3 sections - suggesting a delay in GABA neuron migration. Given that activity in the hippocampus is associated with spatial memory, it is perhaps unsurprising that the group then found that caffeine-exposed offspring performed poorly in spatial memory tasks as adults.

Further exploration of the hippocampal electrophysiology, using Scientifica PatchStars, revealed a general increase in synaptic activity and network activity in the hippocampus of caffeine-exposed offspring compared to controls. This hyperactivity is thought to be the result of over compensation by the remaining GABA neurons. Hyper-excitability in immature neuronal networks is associated with an increased susceptibility to seizures. The group also found this correlation in their results: mice pups exposed to caffeine during development had increased susceptibility to seizures.

"This study is the first demonstration of the harmful effects of exposure to caffeine on the developing brain, and while questioning caffeine consumption by pregnant women, it is necessary to emphasize caution in extrapolating the results obtained in animal models to the human population without taking into account differences in brain development and maturation between species" said Carla G. Silva, main author of the paper.

Paper Details: C. G. Silva, C. Métin, W. Fazeli, N. J. Machado, S. Darmopil, P.-S. Launay, A. Ghestem, M.-P. Nesa, E. Bassot, E. Szabó, Y. Baqi, C. E. Müller, A. R. Tomé, A. Ivanov, D. Isbrandt, Y. Zilberter, R. A. Cunha, M. Esclapez, C. Bernard, Adenosine Receptor Antagonists Including Caffeine Alter Fetal Brain Development in Mice. Sci. Transl. Med. 5, 197ra104 (2013)
http://stm.sciencemag.org/content/5/197/197ra104.abstract?sid=fc6150ee-8cb5-4f9a-ae75-b84c86ffd126