It’s often one of the first questions a woman asks her physician when she learns she’s pregnant: Can I keep drinking coffee or caffeinated sodas? Soon-to-be moms are generally told by doctors not to drink more than a cup or two of coffee a day, a recommendation in line with a 2010 review concluding moderate caffeine consumption doesn’t promote premature births or miscarriages or harm fetal growth. But a new study in mice offers the controversial suggestion that at larger doses, caffeine can impair memory and increase the risk of having seizures.
While the study authors and others are quick to note that the findings may not hold in humans, the work may prompt a closer look at the world's most commonly used psychoactive drug.
To date, no large-scale study in people has found any negative effect of caffeine exposure on fetal brain development, says Kimford Meador, a neurologist at Emory University in Atlanta. One reason for that could be that few high-quality studies exist because of the challenges of teasing apart the effects of caffeine from other variables affecting pregnant women, such as nutrition, stress, and other drug use, he says. Considering that one "Venti" coffee at Starbucks contains 410 mg of caffeine—more than twice the dose recommended for pregnant women by the American College of Obstetricians and Gynecologists, which conducted the 2010 review on caffeine—it's probably time to take a closer look at the substance that so many rely on to get out of bed in the morning, Meador says.
One of the ways that caffeine speeds up brain activity in adults is by blocking the activity of a neurotransmitter called adenosine, which acts as a brake on neuronal firing and makes us sleepy. Carla Silva, a neuroscientist at the University of Coimbra in Portugal, was studying the role of adenosine in fetal brain development when an obvious experiment occurred to her: Why not use caffeine to study how adenosine alters brain development?
Silva and colleagues at INSERM in Marseille, France, decided to focus on the fate of a small subpopulation of a type of cells called GABA neurons, which, along with other functions, can help regulate the flow of information in the brain by keeping the electrical impulses of their neighbors in check. Without enough GABA neurons to balance out the brain's electrical activity, disorders such as epilepsy can result, she says.
Over the course of early brain development in mammals, GABA neurons migrate from a transitory, heart-shaped embryonic structure called the ganglionic eminence to the hippocampus, two curved ridges of brain tissue deep in the brain that are key to memory and learning. To determine whether caffeine would interfere with this mass migration of cells, Silva laced the drinking water of female mice 15 days prior to pregnancy with enough caffeine to mimic the blood concentration that a human would get from drinking about three to four cups of coffee per day. After a day or so of getting accustomed to caffeine's bitter taste, the mice lapped up the caffeinated water throughout pregnancy and while their pups were nursing.
After the mouse pups were born, Silva and her colleagues examined slices of brain tissue to see if being exposed to caffeine had altered their GABA neurons' maturation or migration. (The mice were bred to produce a glowing green protein only in these cells.) At 6 days after birth, the drug-exposed mouse pups had 41% fewer of one subtype of GABA neuron in the hippocampus, the authors report today in Science Translational Medicine. The numbers of this subtype of GABA neuron in the hippocampus were similar in non-drug exposed and drug-exposed pups a few months later, however, suggesting that the cells had simply been slow to arrive, says Silva. Other subtypes of GABA neuron showed a dramatic decrease in number in the hippocampus and cortex, a finding similar to those seen in animal models of cocaine and amphetamine exposure.
The caffeine-exposed offspring performed badly on a series of memory tests and were more susceptible to seizures as they matured, Silva says. "We still don't know how or why," she says, but "caffeine exposure in early life resulted in long-term consequences" for the mice.
Although the work is an "interesting, necessary start" to understanding the influence of significant caffeine consumption on pregnancies, "a number of questions need to be answered before sounding the alarm," says Barbara Thompson, a neuroscientist at the University of Southern California in Los Angeles and an expert in the effects of cocaine on fetal brain development. The subtype of GABA neurons that Silva studied were a very small population of cells, so it's not possible to know how widespread such an effect might be in the brain, she says, and the effects on the mouse pups' behavior and cognition were mild. Although there are some general similarities between the brain changes that Silva found in the caffeine-exposed mice and those that have been observed in cocaine-exposed mice, "I wouldn't say caffeine should be banned like cocaine should be banned," she says. "The results don't show that at all."
To rule out the possibility that individual differences in sensitivity to caffeine between mouse mothers or pups didn't lead to any misleading effects, the work needs to be replicated several times in much larger groups, and in different breeds of mice, Silva says. After that, more work will be done to show that the findings apply to humans. For now, however, “this study is not enough to give advice to pregnant women," she says.
*Clarification, 9 August, 11:50 a.m.: This version clarifies that the work was done at INSERM in Marseille, France.
*Correction, 20 August: This SNOW has been changed to make several corrections, including that the mice began consuming caffeine-laced water 15 days (not weeks) before pregnancy. Other changes reflect that the research addressed different subtypes of GABA neurons, not a uniform population, and their fate in adult animals, not fetuses.