Second-Trimester Maternal Serum Paraxanthine, CYP1A2 Activity, and the Risk of Severe Preeclampsia.
OBJECTIVE
To measure the association between second-trimester maternal caffeine intake and caffeine metabolism through the CYP1A2 system and the risk of subsequent severe preeclampsia.


METHODS
This was a nested case-control study of women who had undergone second-trimester screening for fetal aneuploidy and had banked serum available for analysis. The outcome of interest was severe preeclampsia, and exposures were serum paraxanthine (1,7-dimethylxanthine), measured through high-performance liquid chromatography, and CYP1A2 activity, assessed by paraxanthine/caffeine ratios.


RESULTS
We identified 51 cases of severe preeclampsia from our population of 3,992 women (1.3%), of whom 33 had sufficient serum for analysis. These were compared with 99 healthy women. Median paraxanthine concentrations were not significantly higher in women in the control group than women in the case group (96.4 ng/mL compared with 38.0 ng/mL, P=.12), and higher serum paraxanthine was not associated with lower odds of severe preeclampsia (odds ratio [OR] 0.72, confidence interval [CI] 0.48-1.08). However, we found a significantly higher paraxanthine/caffeine ratio in women in the control group than women in the case group (0.37 compared with 0.23, P=.02) and a decreased risk of preeclampsia per every log standard deviation increase in paraxanthine/caffeine ratio (OR 0.53, 95% CI 0.31-0.90).


CONCLUSIONS
Faster caffeine metabolism in the second trimester, assessed by paraxanthine/caffeine ratios, is associated with a reduced risk of subsequent severe preeclampsia.


METHODS
II.
Departments of Obstetrics & Gynecology, Divisions of Maternal-Fetal Medicine, University of South Carolina-Greenville School of Medicine, Greenville Health Systems, Greenville, South Carolina; Memorial Health University Medical Center, Mercer School of Medicine, Savannah and Macon, Georgia, Baylor College of Medicine & Texas Children's Hospital, Houston, Texas, and University of North Carolina, Chapel Hill, North Carolina; and the Department of Maternal and Child Health, Gillings School of Global Public Health, Chapel Hill, North Carolina.
Kacey Y
KY
Eichelberger
Arthur M
AM
Baker
Padmashree C
PC
Woodham
Sina
S
Haeri
Robert A
RA
Strauss
Alison M
AM
Stuebe
D000328:Adult; D002110:Caffeine / Q000378:metabolism*; D016022:Case-Control Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood; D018570:Risk Assessment; D013806:Theophylline / Q000097:blood*; D055815:Young Adult
D002110:Caffeine; D013806:Theophylline; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; C021183:1,7-dimethylxanthine