The potential dangers of caffeine in pregnancy

Sir, Caffeine is a methylxanthine that acts as a psychoactive stimulant. Caffeine is probably the most frequently ingested pharmacologically active substance in the world. It is found in common beverages (coffee, tea, soft drinks), in products containing cocoa or chocolate, and in medications. Maternal caffeine consumption during pregnancy may have adverse effects on fetal, neonatal, and maternal outcomes. Reproductive-aged and pregnant women are ‘at risk’ subgroups of the population who may require specific advice on moderating their daily caffeine intake. Clinical research indicates that withdrawal symptoms can occur when daily consumption of caffeine is abruptly interrupted (e.g., in labor). The caffeine physical dependence syndrome may lead to peripartum complications such as nausea, vomiting, muscular aches, and headache. In parturients receiving epidural analgesia for labor caffeine withdrawal headache may be mistaken for post-dural puncture headache (PDPH). In his practice of obstetric anesthesia (in the course of 8 months), the author of this report encountered two otherwise healthy pregnant patients who received uneventful epidural labor analgesia. Postpartum, each patient developed severe headache initially thought to resemble PDPH, however, upon detailed questioning each patient admitted to heavy caffeine intake throughout pregnancy. In each case, the diagnosis of caffeine withdrawal headache was established, and the headache was successfully ‘treated’ with a cup of coffee. Most Americans consume caffeine daily in one of its many forms. A cup of coffee, for example, contains 29–176 mg of caffeine depending on its strength. It has been reported that approximately 80% of women drink caffeine-containing beverages daily. Caffeine is readily absorbed from the mucosa of the gastrointestinal tract. It crosses the human placenta rapidly reaching concentration in the fetus similar to maternal plasma levels. Caffeine has been implicated as a cause of spontaneous abortion, intrauterine growth restriction, low birth weight and pre-term delivery. Boylan et al. conducted a prospective longitudinal observational study designed to examine the association of maternal caffeine intake with fetal growth restriction. The study included 2635 low-risk pregnant women recruited between 8 and 12 weeks of pregnancy. Investigations quantification of total caffeine intake from 4 weeks before conception and throughout pregnancy was undertaken with a validated caffeine assessment tool. Caffeine half-life (proxy for clearance) was determined by measuring caffeine in saliva after a caffeine challenge. Fetal growth restriction, as defined by customized birth weight centile, adjusted for alcohol intake and salivary cotinine concentrations. Caffeine consumption throughout pregnancy was associated with an increased risk of fetal growth restriction [odds ratios 1.2 (95% confidence interval (CI) 0.9–1.6] for 100–199 mg/day, 1.5 (1.1–2.1) for 200–299 mg/day, and 1.4 (1.0–2.0) for 4300 mg/ day compared with o100 mg/day; test for trend (Po0.001). Mean caffeine consumption decreased in the first trimester and increased in the third. The association between caffeine and fetal growth restriction was stronger in women with a faster caffeine clearance compared with a slower caffeine clearance (test for interaction, P 5 0.06). The authors concluded that caffeine consumption during pregnancy was associated with an increased risk of fetal growth restriction and this association continued throughout pregnancy. Sensible advice would be to reduce caffeine intake before conception and throughout pregnancy. Bech et al. conducted randomized double-blinded controlled trial designed to estimate the effect of reducing caffeine intake during pregnancy on birth weight and length of gestation. The study included 1207 pregnant women drinking at least three cups of coffee (caffeinated or decaffeinated instant coffee) a day, recruited before 20 weeks’ gestation. Data on birth weight were obtained for 1150 live born singletons and on length of gestation for 1153 live born singletons. No significant differences were found for mean birth weight or mean length of gestation between women in the decaffeinated coffee group (whose mean caffeine intake was 182 mg lower than that of the other group) and women in the caffeinated coffee group. After adjustment for length of gestation, parity, pre-pregnancy body mass index, and smoking at entry to the study, the mean birth weight of babies born to women in the decaffeinated group was 16 g (95% CI 40 to 73) higher than those born to women in the caffeinated group. The adjusted difference (decaffeinated group–caffeinated group) of length of gestation was 1.31 days ( 2.87 to 0.25). The authors concluded that a moderate reduction in caffeine intake in the second half of pregnancy has no effect on birth weight or length of gestation. Weng et al. conducted a population-based prospective cohort study designed to examine whether the risk of miscarriage is associated with caffeine consumption during pregnancy after controlling for pregnancy-related symptoms. An increasing dose of daily caffeine intake during pregnancy was associated with an increased risk of miscarriage, compared with no caffeine intake, with an adjusted hazard ratio (aHR) of 1.42 (95% CI 0.93–2.15) for caffeine intake of o200 mg/day, and aHR of 2.23 (1.34–3.69) for an intake of 200 or more mg/day, respectively. Nausea or vomiting during pregnancy did not materially affect this observed association, nor did the change in the intake pattern of caffeine during pregnancy. In addition, the magnitude of the association appeared to be stronger among women without a history of miscarriage (aHR 2.33, 1.48–3.67) than that among women with such a history (aHR 0.81, 0.34–1.94). The authors concluded that high doses of caffeine intake during pregnancy increase the risk of miscarriage, independent of pregnancy-related symptoms. Maternal use of caffeine in pregnancy continues to increase worldwide. Nawrot et al. investigated the possibility that caffeine ingestion adversely affects human health. Based on the data reviewed, the authors concluded that for the healthy adult population, moderate daily caffeine intake at a dose level up to 400 mg/day (equivalent to 6 mg/kg body weight (bw)/day in a 65-kg person) is not associated with adverse effects such as general toxicity, cardiovascular effects, effects on bone status and calcium balance (with consumption of adequate calcium), changes in adult behavior, increased incidence of cancer and effects on fertility. The data also show that reproductive-aged women and children are ‘at risk’ subgroups who may require specific advice on moderating their caffeine intake. Based on