Abstract
BackgroundTo ascertain interactions of caffeine ingestion, food, medications, and environmental exposures during preterm human gestation, under informed consent, we studied a cohort of Mexican women with further preterm offspring born at ≤ 34 completed weeks. At birth, blood samples were taken from mothers and umbilical cords to determine caffeine and metabolites concentrations and CYP1A2 (rs762551) and CYP2E1 (rs2031920, rs3813867) polymorphisms involved in caffeine metabolism.ResultsIn 90 pregnant women who gave birth to 98 preterm neonates, self-informed caffeine ingestion rate was 97%, laboratory confirmed rate was 93 %. Theobromine was the predominant metabolite found. Consumption of acetaminophen correlated significantly with changes in caffeine metabolism (acetaminophen R2 = 0.637, p = 0.01) due to activation of CYP2E1 alternate pathways. The main caffeine source was cola soft drinks.ConclusionEnvironmental exposures, especially acetaminophen ingestion during human preterm pregnancy, can modulate CYP2E1 metabolic activity.
Highlights
To ascertain interactions of caffeine ingestion, food, medications, and environmental exposures during preterm human gestation, under informed consent, we studied a cohort of Mexican women with further preterm offspring born at ≤ 34 completed weeks
Caffeine metabolism is substantially slowed during pregnancy, mainly due to a reduction in CYP1A2 (CYP1A2, cytochrome P450 family 1 subfamily A member 2) and N-acetyltransferase-2 (NAT2) activities
When the metabolic activity of CYP1A2 and CYP2E1 was correlated with environmental factors, we found a moderate correlation of consumption of charbroiled meat and increased metabolic activity of CYP2E1, Spaearman’s Rho 0.263(77), p = 0.021; the same was true for acetaminophen ingestion, that exhibited a moderate correlation with increased metabolic activity of CYP2E1, Spearman’s Rho 0.256(84), p = 0.019
Summary
To ascertain interactions of caffeine ingestion, food, medications, and environmental exposures during preterm human gestation, under informed consent, we studied a cohort of Mexican women with further preterm offspring born at ≤ 34 completed weeks. One of the naturally occurring methylxanthines, is the most widely consumed behaviorally active substance in the world. Almost all caffeine comes from dietary sources (beverages and food), most of it from coffee and tea, but some other sources, like soft drinks, are showing increased prevalence. The majority of expecting mothers in the Western world drink beverages containing methylxanthines. Caffeine metabolism is substantially slowed during pregnancy, mainly due to a reduction in CYP1A2 (CYP1A2, cytochrome P450 family 1 subfamily A member 2) and N-acetyltransferase-2 (NAT2) activities. NAT2 metabolic ratio is lower in early pregnancy than after delivery; CYP1A2 activity decreases in late pregnancy and in early and middle pregnancy, while the ratio of 8-hydroxilation increases in both middle and late pregnancy [5,6,7,8]
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