Ronald Ruggiero, clinical professor in the departments of pharmacy and medicine, University of California, San Francisco, CA
Yes, a morning cup of coffee won't hurt anyone. I generally recommend decaffeinated products, but if you must have caffeine, then don't have more than three cups a day. That's the limit because in studies of dairy cattle, when pregnant cows were given more than that dose, their calves were born smaller. And too much caffeine cuts down on blood flow to the placenta, and you don't want to do that because the baby won't be getting as much oxygen or as many nutrients. But in moderate amounts, caffeine poses no measurable risk to the fetus.
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This study reports an association between spontaneous abortions, primarily in the second trimester, and unusually high levels of consumption of caffeine, equivalent to more than six cups of coffee a day. Unlike previous studies, in which exposure was estimated from the women's reports of the amount of caffeinated beverages they consumed, this study used a biologic marker of caffeine intake, the levels of the caffeine metabolite paraxanthine in serum, to estimate exposure.
Paraxanthine stays in the blood at more consistent levels than caffeine, so researchers consider it a good measure of daily caffeine consumption. Besides coffee, tea, soft drinks and chocolate contain caffeine.
The most obvious effects of caffeine in nonpregnant adults are cardiovascular and neurobehavioral. Knowledge of the effects of caffeine on the nervous system dates back centuries, to the time when Ethiopian shepherds noticed that their sheep stayed awake all night after grazing on wild coffee cherries. In fact, caffeine is the most widely consumed behaviorally active substance in the world, with the U.S. per capita consumption at nearly 3.5 kg of coffee per year, or more than 150 mg of caffeine per day.
Caffeine, like nicotine, albeit to a lesser extent, meets some of the criteria of the World Health Organization and the American Psychiatric Association for a drug of dependence and acts on the dopamine system in the same way as amphetamines and cocaine. Caffeine and its metabolites are known to cross the blood-brain barrier readily in adults and fetuses alike.
Intake of caffeine during pregnancy or the early postnatal period would be expected to have similar or more profound cardiovascular and neurobehavioral effects on fetuses and infants than on the caffeine-consuming mothers.
This is because of caffeine's ready passage through the placenta, its presence in breast milk, and its increasing half-life during pregnancy (up to 11 hours late in pregnancy) and in infants (up to 100 hours), the smaller body mass of fetuses and infants, and the inability of the fetus and neonate to detoxify caffeine.
Changes in fetal heart rate and breathing patterns have been noticed even when maternal intake of caffeine is moderate and when it has no apparent effects on the mother.
In animals, in utero or early postnatal exposure to moderate-to-high doses of caffeine has been associated with decreased brain weight and alterations in brain development and in learning and memory, and it has been associated with an increased incidence of apnea in adult rats. Unfortunately, the results of the few studies of the neurobehavioral effects in children after in utero or early postnatal exposure are conflicting.
There may be subgroups of pregnant women and children who are particularly susceptible to the effects of caffeine. Usually, legal regulation of allowable levels of exposure to a chemical includes a safety factor of 10 to 100 when data are extrapolated from animals to humans, in order to protect the most susceptible.
However, many of the effects of caffeine in animals occur after doses that are within the range of human consumption, once metabolic differences among species are taken into account. Several factors alter susceptibility to the effects of caffeine, including exposure to other substances. For example, the half-life of caffeine is halved in smokers and doubled in women taking oral contraceptives.
Caffeine may increase the cancer causing potential and other adverse effects of substances such as alcohol, nicotine, and certain drugs. Also, infants with poor nutritional status may be particularly vulnerable to the neurochemical and concomitant neurobehavioral effects of caffeine.
Given these considerations, what is the appropriate course of action for clinicians and policy makers? In 1981, the Food and Drug Administration (FDA) advised pregnant women to "avoid caffeine-containing foods and drugs, if possible, or consume them only sparingly."
This advisory has not percolated down to the general population. And no advisories have targeted breast-feeding women or parents of young children. In part because of our own dependence on our morning cup of coffee, and because of our inability to find strong associations with effects on health in humans, we have accepted that more than 75 percent of pregnant women consume caffeinated beverages.
In 1997, the Center for Science in the Public Interest petitioned the FDA to require that caffeine content be disclosed on food labels, but Congress has not yet acted. Food labeling is an appropriate first step in educating the public and should be undertaken. In the meantime, health care providers should continue to counsel women who are pregnant or breast-feeding to limit their caffeine intake.
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