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Purpose: We sought to examine associations among measures of caffeine exposure, including maternal urine, umbilical cord blood, and maternal self report., Methods: Pregnant women were recruited from 56 obstetric practices and 15 clinics associated with six hospitals in Connecticut and Massachusetts between September 1996 and January 2000; 3633 women were enrolled. Maternal urine throughout pregnancy and umbilical cord blood samples were analyzed for caffeine, paraxanthine, theophylline, and theobromine. Maternal caffeine intake was assessed throughout pregnancy., Results: Urinary and cord blood biomarkers were correlated with reported intake throughout pregnancy (range r = 0.35-0.66; p < 0.0001). Infants of smokers had greater cord blood concentrations of paraxanthine, reflecting faster caffeine metabolism in smokers, and cord blood paraxanthine levels were more strongly correlated with intake in smokers., Conclusion: Maternal self reported intake may still be the optimal and most valid measure of antenatal caffeine exposure, since biomarkers do not reflect exposure over pregnancy.

Purpose: To review the methodologic issues complicating caffeine exposure assessment during pregnancy; to discuss maternal and fetal caffeine metabolism, including genetic polymorphisms affecting caffeine metabolism; and to discuss the endogenous and exogenous risk factors known to influence caffeine metabolism., Methods: A review of the relevant literature., Results: There is wide inter-individual variation in caffeine metabolism, primarily due to variations in CYP1A2 enzyme activity. Some variability in CYP1A2 activity is due to genetic polymorphisms in the CYP1A2 gene which can cause increased or decreased inducibility of the enzyme. Considerable evidence exists that maternal caffeine metabolism is influenced by a variety of endogenous and exogenous factors and studying the genetic polymorphisms may improve understanding of the potential effects of caffeine and its metabolites on perinatal outcomes. There is substantial evidence that measurement of maternal, fetal, and neonatal caffeine metabolites may allow for a more precise measure of fetal caffeine exposure., Conclusions: Research on the genetic polymorphisms affecting caffeine metabolism may further explain the potential effects of caffeine and its metabolites on perinatal outcomes.