Modest maternal caffeine exposure affects developing embryonic cardiovascular function and growth

Abstract

Momoi N, Tinney JP, Liu LJ, Elshershari H, Hoffmann PJ, Ralphe JC, Keller BB, Tobita K. Modest maternal caffeine exposure affects developing embryonic cardiovascular function and growth. Am J Physiol Heart Circ Physiol 294: H2248-H2256, 2008. First published March 21, 2008 doi:10.1152/ajpheart.91469.2007.-Caffeine consumption during pregnancy is reported to increase the risk of in utero growth restriction and spontaneous abortion. In the present study, we tested the hypothesis that modest maternal caffeine exposure affects in utero developing embryonic cardiovascular (CV) function and growth without altering maternal hemodynamics. Caffeine (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 subcutaneous) was administered daily to pregnant CD-1 mice from embryonic days (EDs) 9.5 to 18.5 of a 21-day gestation. We assessed maternal and embryonic CV function at baseline and at peak maternal serum caffeine concentration using high-resolution echocardiography on EDs 9.5, 11.5, 13.5, and 18.5. Maternal caffeine exposure did not influence maternal body weight gain, maternal CV function, or embryo resorption. However, crownrump length and body weight were reduced in maternal caffeine treated embryos by ED 18.5 (P Ͻ 0.05). At peak maternal serum caffeine concentration, embryonic carotid artery, dorsal aorta, and umbilical artery flows transiently decreased from baseline at ED 11.5 (P Ͻ 0.05). By ED 13.5, embryonic aortic and umbilical artery flows were insensitive to the peak maternal caffeine concentration; however, the carotid artery flow remained affected. By ED 18.5, baseline embryonic carotid artery flow increased and descending aortic flow decreased versus non-caffeine-exposed embryos. Maternal treatment with the adenosine A 2A receptor inhibitor reproduced the embryonic hemodynamic effects of maternal caffeine exposure. Adenosine A 2A receptor gene expression levels of ED 11.5 embryo and ED 18.5 uterus were decreased. Results suggest that modest maternal caffeine exposure has adverse effects on developing embryonic CV function and growth, possibly mediated via adenosine A 2A receptor blockade. adenosine A 2A receptor; cardiovascular development; carotid artery; pregnancy CAFFEINE IS A NATURALLY OCCURRING compound contained in many beverages, foods, and medications and is frequently consumed as a central nervous system stimulant. Human caffeine intake has increased in all age groups for the last two decades and 68 -74% of pregnant women consume caffeine at an average intake of 125-193 mg/day (14). Caffeine metabolism becomes slower in pregnancy, and ingested caffeine easily crosses the placenta (1,11,18). Although it has been suggested that the risk of fetal toxicity from caffeine in humans is low, several studies have shown that moderate to heavy caffeine consumption increases the risk of spontaneous abortion or low fetal birth weight (13,17,21,22,26,32,36). Moreover, recent studies identified a dose-dependent increase in the risk of spontaneous abortion in women who ingested at least 100 mg of caffeine daily (9, 45).The pharmacokinetics of ...

Expression and Distribution of Nucleoside Transporter Proteins in the Human Syncytiotrophoblast

“…Both xenobiotics have been comprehensively studied as risk factors during pregnancy. Among many other observations in the literature, it is known that caffeine intake increases the risk of early spontaneous abortion among nonsmoking women (Cnattingius et al, 2000), whereas modest maternal caffeine exposure may impair fetal cardiovascular function and growth (Momoi et al, 2008) and also promotes long-lasting behavioral changes in mouse offspring (Björklund et al, 2008). Nicotine exposure during pregnancy has also been related to a variety of harmful effects, including, among many others, intrauterine growth retardation (Einarson and Riordan, 2009).…”

Caffeine Intake during Pregnancy: What Are the Real Evidences?

“…Thereafter, it was also suggested that caffeine intake should be restricted up to 300 mg/day after quantification studies in a large food sample and after clinical trials with humans and animals performed [3]. Currently, some research groups suggested that the maximum intake should be 100 mg/day or less [9,37,38]. However, a consensus among the maximum caffeine intake has not been established up to now.…”

“…Caffeine intake is negatively associated with gestational changes in animals, such as lower rates of fertilization and embryonic implantation, low birth and placental weight, greater number of stillbirths, increased expression of apoptotic markers and altered placental and bone formation [9,27,[40][41][42][43][44][45][46] ( Table 1).…”

“…For example: a 150 mL cup of coffee may contain, on average, 100 to 150 mg of caffeine varying according to the species of grain, the type of roasting and the beverage preparation method. On the other hand, a 150mL of instant coffee contains about 27 mg of caffeine, while the same amount of boiled coffee may contain up to 111 mg [6,9,10]. In other sources, the caffeine content is also variable.…”

The effects of prenatal exposure to methylxanthines

“…Hence, caffeine as a nonselective adenosine antagonist is expected to influence cardiovascular system. Cardiovascular embryonic function has been assessed by the use of noninvasive high-resolution echocardiography in embryonic mice exposed to caffeine via subcutaneous maternal intake (Momoi et al 2008). The results have shown transient reduced flows in embryonic carotid artery, dorsal aorta and umbilical artery during the highest caffeine concentration in maternal serum.…”