Evaluation of the Reproductive and Developmental Risks of Caffeine

被引:85
作者
Brent, Robert L. [1 ]
Christian, Mildred S. [2 ]
Diener, Robert M.
机构
[1] Thomas Jefferson Univ, Alfred I duPont Hosp Children, Wilmington, DE 19899 USA
[2] Argus Int Inc, Horsham, PA USA
关键词
caffeine; spontaneous abortion; congenital malformations; growth retardation; toxicokinetics; biological plausibility; METABOTROPIC GLUTAMATE RECEPTORS; MATERNAL COFFEE-DRINKING; FEMALE SEX-HORMONES; LIFE-STYLE FACTORS; BIRTH-WEIGHT; SPONTANEOUS-ABORTION; PRENATAL EXPOSURE; RESTRAINT STRESS; THEOPHYLLINE PHARMACOKINETICS; CONGENITAL-MALFORMATIONS;
D O I
10.1002/bdrb.20288
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A risk analysis of in utero caffeine exposure is presented utilizing epidemiological studies and animal studies dealing with congenital malformation, pregnancy loss, and weight reduction. These effects are of interest to teratologists, because animal studies are useful in their evaluation. Many of the epidemiology studies did not evaluate the impact of the "pregnancy signal," which identifies healthy pregnancies and permits investigators to identify subjects with low pregnancy risks. The spontaneous abortion epidemiology studies were inconsistent and the majority did not consider the confounding introduced by not considering the pregnancy signal. The animal studies do not support the concept that caffeine is an abortafacient for the wide range of human caffeine exposures. Almost all the congenital malformation epidemiology studies were negative. Animal pharmacokinetic studies indicate that the teratogenic plasma level of caffeine has to reach or exceed 60 mu g/ml, which is not attainable from ingesting large amounts of caffeine in foods and beverages. No epidemiological study described the "caffeine teratogenic syndrome." Six of the 17 recent epidemiology studies dealing with the risk of caffeine and fetal weight reduction were negative. Seven of the positive studies had growth reductions that were clinically insignificant and none of the studies cited the animal literature. Analysis of caffeine's reproductive toxicity considers reproducibility and plausibility of clinical, epidemiological, and animal data. Moderate or even high amounts of beverages and foods containing caffeine do not increase the risks of congenital malformations, miscarriage or growth retardation. Pharmacokinetic studies markedly improve the ability to perform the risk analyses. Birth Defects Res (Part B) 92:152-187, 2011. (C) 2011 Wiley-Liss, Inc.
引用
收藏
页码:152 / 187
页数:36
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