From October 1996 through October 1998, all women enrolled in the Kaiser Permanente Medical Care Program who lived in the San Francisco and South San Francisco areas and who had a positive pregnancy test result in these facilities were identified as potentially eligible for the study. Of 2729 eligible women, 164 (6%) were contacted too far along in their pregnancy for an interview, 317 (12%) initially agreed to participate but were unable to schedule an interview, 1185 (43%) refused to participate, and 1063 (39%) completed the interview.

Compared with no caffeine intake, an increasing dose of daily caffeine intake during pregnancy was associated with an increased risk for miscarriage. Adjusted hazard ratio (aHR) was 1.42 (95% confidence interval [CI], 0.93 - 2.15) for caffeine intake less than 200 mg/day, and aHR was 2.23 (95% CI, 1.34 - 3.69) for intake of 200 mg/day or more.

This observed association was not significantly affected by nausea or vomiting during pregnancy or by the change in intake pattern of caffeine during pregnancy. The magnitude of this association was stronger in women who had no history of a miscarriage (aHR, 2.33; 95% CI, 1.48 - 3.67) vs women with a history of a miscarriage (aHR, 0.81; 95% CI, 0.34 - 1.94).

Limitations of the study include potential misclassification of caffeine intake, potential recall bias, and low participation rates causing potential selection bias.

"Our results demonstrated that high doses of caffeine intake during pregnancy increase the risk of miscarriage, independent of pregnancy-related symptoms," the study authors write. "We provided new evidence that the observed association was not likely the result of confounding by the pregnancy-related symptoms of nausea, vomiting, and aversion to caffeine consumption. Therefore, it may be prudent to stop or reduce caffeine intake during pregnancy."

The California Public Health Foundation supported this study in part. One of the study authors has obtained funding.
Am J Obstet Gynecol. Published online January 21, 2008.

Clinical Context

Caffeine has been extensively studied as a possible deleterious substance during pregnancy. It readily crosses the placental barrier, and clearance of caffeine is slower in pregnant vs nonpregnant women. The fetus has low levels of enzymes which break down caffeine, so fetal metabolism of caffeine is delayed.

Some research has suggested that caffeine can reduce intervillous blood flow, but data regarding the role of caffeine in promoting miscarriage are limited because of questions regarding the methodology of this research. The current study recruited women early in pregnancy and adjusted for possible confounders in an attempt to address these methodologic flaws.

Study Highlights

*       The study focused on members of the Kaiser Permanente Medical Care Program in the San Francisco area. Women who became pregnant between 1996 and 1998 were invited for study participation if their estimated gestational age was 15 weeks or less.
*       Study participants underwent an interview examining their consumption of caffeinated beverages, including coffee, tea, soda, and hot chocolate. The standard concentrations of caffeine for each 150 mL of these respective beverages were 100 mg, 39 mg, 15 mg, and 2 mg.
*       Researchers followed subjects' reports and medical records for pregnancy outcomes through 20 weeks of gestation.
*       The main outcome of the study was the relationship between the risk for miscarriage and consumption of caffeine, which was divided into groups based on intake of no caffeine during pregnancy, consumption above 0 but below 200 mg/day, and 200 mg/day or more. This relationship was adjusted for multiple possible confounders, including maternal age, race, education, household income, marital status, smoking, alcohol consumption, Jacuzzi use, magnetic field exposure, and nausea and vomiting.
*       39% of women invited into the study participated, yielding 1063 women with data for analysis. One fourth of women reported no caffeine intake during pregnancy, whereas 60% reported consumption of 0 to 200 mg/day, and 15% consumed 200 mg/day or more.
*       Women who drank more caffeine tended to be older, have a previous miscarriage, and were more likely to smoke or use alcohol during pregnancy.
*       The respective rates of miscarriage among women with no caffeine use, 0 to 200 mg/day, and 200 mg/day or more were 12%, 15%, and 25%. Compared with no use, the aHR of miscarriage for caffeine use less than 200 mg/day was 1.42, which was not statistically significant. The respective aHR for caffeine consumption at 200 mg/day or more was 2.23, which was significant.
*       63% of total caffeine consumption was from coffee, but it seemed that all caffeinated beverages contributed to an increased risk for miscarriage.
*       Caffeine increased the risk for miscarriage, regardless of whether women tried to change their pattern of caffeine consumption during pregnancy.
*       Women who were nonsmokers and who had no history of a miscarriage experienced higher risks for miscarriage associated with caffeine consumption.
*       Caffeine intake contributed to the risk for miscarriage before and after 8 weeks of gestation, although this risk was more pronounced for later vs earlier miscarriage.
Pearls for Practice
*       Caffeine readily crosses the placental barrier, and clearance of caffeine is slower in pregnant vs nonpregnant women. The fetus also clears caffeine slowly, and caffeine may reduce intervillous placental blood flow.
*       The current study demonstrates that consumption of caffeine in doses of 200 mg/day or more increases the risk for miscarriage before 20 weeks of gestation, regardless of the type of caffeinated beverage consumed or if women had changed their caffeine consumption after becoming pregnant.

From www.berkleycenter.com