Level 1: Likely reliable evidence
…BUT AVOIDING HIGH CAFFEINE DOSES IS GENERALLY RECOMMENDED
Level 2: Mid-level evidence
A randomized trial evaluated the effect of caffeine in 1,207 pregnant women who drank at least three cups of coffee per day (BMJ. 2007;334:409; full-text available online free of charge at: www.bmj.com/cgi/, accessed November 12, 2007). Women were randomized before 20 weeks’ gestation (mean gestational age 18 weeks) to caffeinated vs. decaffeinated instant coffee for the duration of their pregnancy. There were no restrictions on caffeine consumption, but there was no significant difference in caffeine intake outside of study coffee.
Comparing caffeinated vs. decaffeinated groups, the median daily caffeine intake was 317 mg vs. 117 mg. There were five (0.88%) vs. seven (1.11%) fetal deaths. No significant differences were observed in mean birth weight (3,539 g vs. 3,519 g, adjusted mean difference -16 g) or mean length of gestation (280.2 days vs. 279.3 days, adjusted mean difference 1.31 days).
Nevertheless, avoidance of high caffeine doses is generally recommended, based on observational evidence. A meta-analysis reported a small but significant increased risk of miscarriage and low birth weight associated with high caffeine intake, i.e., >150 mg/day (Can Fam Physician. 2000;46:801-803). In another prospective study of 18,478 singleton pregnancies, maternal coffee consumption of eight or more cups per day during pregnancy was associated with a threefold increased risk of stillbirth (BMJ. 2003;326:420; full-text available online free of charge at: www.bmj.com/cgi/content/full/326/, accessed November 12, 2007). The risk was still more than twofold after adjustment for other factors. There was no significant association with infant death in the first year of life after adjustment for maternal smoking.
Heavy caffeine consumption was associated with neonatal caffeine withdrawal (e.g., feeding difficulties, vomiting, excessive crying, irritability, and poor sleep lasting days to weeks) and increased fetal loss in a case-control study of 331 women with fetal loss and 993 controls with a normal pregnancy (JAMA. 1993;270:2940-2943). Another case-control study reported that heavy caffeine intake may increase risk of sudden infant death syndrome (SIDS); 28% of mothers of infants with SIDS had caffeine intake >400 mg/day (four or more cups of coffee) during pregnancy, compared with 14% of 1,592 controls (Arch Dis Child. 1998;78:9-13; full-text available online free of charge at: http://adc.bmj.com/cgi/content/full/78/1/9, accessed November 12, 2007).
Moderate caffeine intake during pregnancy is controversial. A twofold increased risk of spontaneous abortion was reported with as little caffeine as 163 mg/day during the first trimester, based on a case-control study of 331 women with fetal loss and 993 controls with a normal pregnancy (JAMA. 1993;270:2940-2943). In another case-control study, the use of caffeine >100 mg/day during early pregnancy was associated with increased risk for spontaneous abortion in nonsmokers, but not in smokers; caffeine intake was determined based on interviews (N Engl J Med. 2000;343:1839-1845). However, a prospective study of 5,144 pregnant women found no increased risk of spontaneous abortion with caffeine use (Epidemiology. 1997;8:515-523).