孕中期孕妇血清中对甲黄嘌呤、CYP1A2活性与重度子痫前期风险

Second-Trimester Maternal Serum Paraxanthine, CYP1A2 Activity, and the Risk of Severe Preeclampsia.

作者信息

Eichelberger Kacey Y, Baker Arthur M, Woodham Padmashree C, Haeri Sina, Strauss Robert A, Stuebe Alison M

机构信息

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.

出版信息

Obstet Gynecol. 2015 Oct;126(4):725-730. doi: 10.1097/AOG.0000000000001041.

DOI:10.1097/AOG.0000000000001041

PMID:26348183

Abstract

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).

CONCLUSION

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

LEVEL OF EVIDENCE

II.

摘要

目的

通过CYP1A2系统测量孕中期孕妇咖啡因摄入量与咖啡因代谢之间的关联以及随后发生重度子痫前期的风险。

方法

这是一项嵌套病例对照研究，研究对象为接受孕中期胎儿非整倍体筛查且保存有可供分析血清的女性。感兴趣的结局是重度子痫前期，暴露因素为通过高效液相色谱法测量的血清副黄嘌呤（1,7 - 二甲基黄嘌呤）以及通过副黄嘌呤/咖啡因比值评估的CYP1A2活性。

结果

在我们的3992名女性人群中，我们确定了51例重度子痫前期病例（1.3%），其中33例有足够的血清用于分析。将这些病例与99名健康女性进行比较。对照组女性的副黄嘌呤浓度中位数并不显著高于病例组女性（分别为96.4 ng/mL和38.0 ng/mL，P = 0.12），且较高的血清副黄嘌呤与重度子痫前期较低的发病几率无关（比值比[OR]为0.72，置信区间[CI]为0.48 - 1.08）。然而，我们发现对照组女性的副黄嘌呤/咖啡因比值显著高于病例组女性（分别为0.37和0.23，P = 0.02），并且副黄嘌呤/咖啡因比值每增加一个对数标准差，子痫前期的风险就降低（OR为0.53，95%CI为0.31 - 0.90）。