Caffeine metabolism, genetics, and perinatal outcomes: a review of exposure assessment considerations during pregnancy.
OBJECTIVE
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.
Grosso
Laura M
LM
Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale University School of Medicine, Department of Epidemiology and Public Health, New Haven, CT 06510, USA. laura.grosso@yale.edu
Bracken
Michael B
MB
D002110:Caffeine / Q000009:adverse effects / Q000378:metabolism*; D005260:Female; D047109:Fetal Development; D005865:Gestational Age; D006801:Humans; D018811:Maternal Exposure; D018743:Perinatal Care; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011256:Pregnancy Outcome; D018456:Reproductive Medicine; D012307:Risk Factors; D014481:United States
D002110:Caffeine