Background: Caffeine is consumed in coffee, tea, soft drinks, and chocolate, and is the most commonly ingested chemical during pregnancy. Data on its effect on pregnancy outcomes are mixed; consuming more than 300 mg of caffeine daily seems to be associated with fetal growth restriction and spontaneous miscarriage, but the evidence for adverse effects with smaller amounts is inconclusive. Previous studies may be confounded by significant variations in mothers' rates of caffeine metabolism and incomplete measurement of caffeine consumption. Konje and colleagues measured comprehensive caffeine intake, estimated variations in caffeine metabolism, and reported pregnancy outcomes to establish a safe upper limit of caffeine consumption.

The Study: The authors of this prospective observational study recruited 2,635 low-risk patients from two large teaching hospitals in the United Kingdom between 2003 and 2006. Women were identified in the first trimester through pregnancy screening notes, and were invited to participate. Those who agreed were interviewed between eight and 12 weeks' gestation to assess demographic information, including age, parity, maternal height and weight, socioeconomic status, and gestational age. Women with medical conditions, including human immunodeficiency virus or hepatitis B infection, or psychiatric disorders were excluded.

Caffeine intake was estimated with a previously validated caffeine assessment questionnaire, which recorded habitual caffeine intake before and during the pregnancy. The amounts and brand names of caffeinated foods, beverages, and medications were tallied for three time periods: four weeks before pregnancy until the first interview at eight to 12 weeks', 13 to 28 weeks', and 29 to 40 weeks' gestation. Possible confounders to caffeine metabolism rates, including smoking, alcohol use, and nausea, were also assessed. Participants' baseline caffeine metabolism rate and smoking status were measured using salivary cotinine (for nicotine exposure) and salivary caffeine levels at one and five hours after a caffeine challenge.

Pregnancy outcomes included fetal growth restriction defined as birth weight less than the 10th centile (using a customized growth chart that accounted for the women's demographic data), late miscarriage, preterm delivery, gestational hypertension and preeclampsia, and stillbirth. Birth outcomes were obtained from the electronic maternity database.

Results: Caffeine intake was reported as milligrams per day and was averaged for each trimester and over the full pregnancy. Participants consumed an average of 159 mg per day during pregnancy. Pre-pregnancy consumption averaged 238 mg per day, which decreased to 139 mg per day by week 12, and remained fairly stable until the third trimester, when it gradually increased to 153 mg per day. In this study, approximately 62 percent of the caffeine came from tea; 14 percent from coffee; and 22 percent from colas, chocolate, and other soft drinks. Other beverages contributed less than 4 percent of the total caffeine consumed.

The prevalence of fetal growth restriction was 13 percent in this population and rose with increasing caffeine consumption. Women who consumed less than 50 mg per day by the end of the first trimester had babies weighing on average 161 g (5.75 oz) more than those of women who maintained a caffeine consumption of more than 300 mg per day throughout the pregnancy. Similarly, women who consumed more than 200 mg per day had babies who weighed 60 to 70 g (2.15 to 2.50 oz) less than those of women with minimal caffeine intake. This relationship persisted across all trimesters. When measured as a continuous variable, the risk of fetal growth restriction increased sharply from baseline up to 30 mg of daily caffeine consumption, and continued to increase in an almost linear fashion. At no point did the estimated risk stop increasing as caffeine intake increased.

Conclusion: Caffeine intake is directly correlated with small but notable fetal growth restriction. Although a safe threshold cannot be determined, maternal caffeine intake of less than 100 mg per day minimizes the risk of fetal growth restriction.

editor's note: This study provides additional support for limiting caffeine during pregnancy beyond current recommendations; the American College of Obstetricians and Gynecologists suggests a maximum of 300 mg per day, and the U.K. government's Food Standards Agency recommends no more than 200 mg per day. In an accompanying editorial, Olsen and Bech highlight the complexities of measuring caffeine intake and caffeine's potential fetotoxic effects.¹ Several earlier studies used coffee use as a prime measure of caffeine intake, whereas this study carefully included caffeine from all sources, and found tea to provide the majority of caffeine. Additionally, the authors measured each participant's individual caffeine metabolism and found some evidence that those with faster caffeine metabolism were at higher risk of fetal growth restriction, suggesting that a metabolite may prove more harmful than caffeine itself. Further study is needed to clarify this relationship. Finally, the amount of growth restriction needs to be put into perspective with other risks; with the highest caffeine intake (more than 300 mg per day), birth-weight reduction is about 140 g (5 oz). In an otherwise healthy infant, this amount may not have clinical significance. However, if added to growth restriction from maternal smoking and alcohol use, the difference may affect infant mortality and morbidity. Consequently, the editorial tempers the study's recommendation: although it may be helpful to reduce maternal caffeine intake, it is not advantageous to do so by replacing caffeinated beverages with those containing alcohol or high amounts of sugar.—a.c.f.