November 24, 1999

Moderate Caffeine Use Does Not Increase Miscarriage Risk But High Caffeine Use Doubles Risk

Consuming the amount of caffeine equivalent to that found in one to two cups of coffee does not appear to increase a pregnant woman's chances of having a miscarriage. However, consuming the amount of caffeine contained in five or more cups of coffee a day appears to double miscarriage risk, according to results of a study by researchers at the National Institute of Child Health and Human Development and the University of Utah in Salt Lake City. The study appears in the November 25 issue of the New England Journal of Medicine.

Caffeine and related compounds are found not only in coffee, but also in tea, soft drinks, and chocolate. About 200 milligrams of caffeine are found in one-and-a-half to two cups of brewed coffee or two cups of brewed tea, according to NIH's National Institute of Environmental Health Sciences. (A review of the research on caffeine, fertility, pregnancy, and breast-feeding is available on the NIEHS website: http://cerhr.niehs.nih.gov/common/caffeine.html.)

Using a new method to estimate overall caffeine consumption, the researchers analyzed stored blood samples from a large group of women. Specifically, they measured blood levels of paraxanthine, a substance produced when caffeine is broken down by the liver. Caffeine reaches high levels in the blood shortly after consumption, but then plummets a short time later. Because paraxanthine remains in the blood longer--and at more consistent levels--than does caffeine, the investigators believe it is a more accurate barometer of daily caffeine consumption.

"Because many studies of caffeine consumption have relied on self reporting, it has been difficult to gauge the effects of caffeine," said Duane Alexander, M.D., Director of the NICHD. "This research not only shows a risk of miscarriage from consuming large amounts of caffeine, it also provides a valuable research tool for other investigators studying caffeine consumption."

Previous studies on whether caffeine consumption during pregnancy increases the chances for miscarriage have produced conflicting results, explained the study's principal investigator, Mark Klebanoff, M.D., Director of NICHD's Division of Epidemiology, Statistics and Prevention Research. Several studies suggested that consuming the amount of caffeine equivalent to one or two cups of coffee a day might double the miscarriage risk. Other studies have reported that caffeine consumption increases the risk for miscarriage only in women who experience morning sickness during pregnancy. Still other studies have not found any risk for miscarriage, even among women who consume large amounts of caffeine during pregnancy.

There are a number of possible reasons why these results might conflict, Dr. Klebanoff said. Some of the studies may have contained too few women to allow for statistically valid results. Other studies asked the women to recall how much caffeine they consumed when they were pregnant. In many such cases, volunteers may either overestimate or underestimate their caffeine intake.

In their study, Dr. Klebanoff and his colleagues measured paraxanthine levels in stored blood samples from women in the Collaborative Perinatal Project (CPP). Approximately 42,000 women enrolled in the CPP at 12 sites in the United States, from 1959 to 1966. Samples were obtained from the women every two months during pregnancy, at delivery, and six weeks after they gave birth.

The researchers detected paraxanthine in the samples of 82 percent of the women who had miscarried as well as in 82 percent of a similar group of women who did not have a miscarriage. However, after accounting for smoking and other factors known to increase the chances for miscarriage, women who miscarried were found to have higher paraxanthine levels than did women who did not miscarry.

In fact, women who consumed the caffeine equivalent of five or more cups of coffee per day were more than twice as likely to miscarry as those who consumed less caffeine or no caffeine at all.

"Our results show that drinking very large amounts of coffee or other caffeine-containing beverages may increase a pregnant woman's miscarriage risk," Dr. Klebanoff said. "However, serum levels of paraxanthine that are usually seen among women consuming only about two or three cups of coffee a day do not appear to increase this risk."

Dr. Klebanoff noted, however, that the study did not obtain chromosome analyses for the miscarried fetuses. For this reason, the researchers could not rule out the possibility that some of the miscarriages may have resulted from chromosomal abnormalities. The study also did not have information on morning sickness during pregnancy, and so could not determine if the miscarriage risk was the same for women who experienced morning sickness as it was for those who did not. However, researchers found that high levels of paraxanthine were associated with an increased risk of miscarriage among women who did and did not have vomiting (an indication of morning sickness), which suggests that vomiting did not influence the miscarriage risk from caffeine.

In addition, the women's blood samples had been stored for more than 30 years so the researchers cannot rule out the possibility that some of the paraxanthine in the samples may have deteriorated over time. However, an earlier study of samples stored for eight years suggests that paraxanthine in blood samples remains stable for a long period of time.

The researchers added that caffeine consumption in the late 50s and early 60s was higher than it is today. For this reason, the researchers were able to analyze blood samples from a large number of women who consumed high levels of caffeine. Because caffeine consumption is much lower in the 1990s, current studies may not have been able to recruit a sufficiently large enough number of women to gauge the effects of high caffeine consumption.