Coffee drinking is common, and in many countries it is considered a harmless habit, although caffeine has powerful effects on a wide range of organ systems. Coffee is the main source of caffeine in Denmark, and coffee consumption there is high (1). Coffee or caffeine has been linked to various adverse pregnancy outcomes, including fetal loss (2), birth defects (3), and fetal growth retardation (4, 5); thus, coffee consumption during pregnancy has been subject to preventive action in some countries. However, these putative effects have been questioned, and many countries, including Denmark, have no official policy against coffee drinking during pregnancy.
Caffeine is a methylxanthine which is rapidly absorbed by the digestive system. It crosses the placenta freely, which implies that caffeine concentrations in the fetus are the same as those in the mother's plasma (6). Caffeine clearance slows down during pregnancy, and in the second and third trimesters, the half-life of caffeine is tripled in comparison with nonpregnant women (7–9). Moreover, the fetus has low levels of enzymes that metabolize caffeine (10). Caffeine increases levels of cellular cyclic adenosine monophosphate, which may influence cell development (11); it also increases levels of circulating catecholamines that could interfere with uteroplacental circulation through vasoconstriction (12).
Research on caffeine intake and spontaneous abortion or stillbirth has produced conflicting results (2, 13, 14). Many studies have been too small to detect an effect or have relied on retrospective information, which is subject to recall bias. Our aim in this study was to evaluate the association between coffee consumption during pregnancy and the risk of fetal death, taking into account a number of potential confounders.