Top

Published in:

01-12-2020 | Paracetamol | Research

Modulation of CYP2E1 metabolic activity in a cohort of confirmed caffeine ingesting pregnant women with preterm offspring

Authors: M. R. Alcorta-García, C. N. López-Villaseñor, G. Sánchez-Ferrer, H. Flores-Mendoza, F. Castorena-Torres, M. A. Aguilar-Torres, C. M. Sepúlveda-Treviño, J. A. Hernández-Hernández, R. C. López-Sánchez, V. J. Lara-Díaz

Published in: Molecular and Cellular Pediatrics | Issue 1/2020

Abstract

Background

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. 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.

Results

In 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.

Conclusion

Environmental exposures, especially acetaminophen ingestion during human preterm pregnancy, can modulate CYP2E1 metabolic activity.

Fredholm BB, Bättig K, Holmén J et al (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133PubMed

Ådén U (2011) Methylxanthines During Pregnancy and Early Postnatal Life. In: Small Animal Toxicology. pp 373–389

Moura-Nunes, N. and Farah A (2012) Caffeine Consumption and Health. In: Russo PF RF (ed) Caffeine Consumption and Health. New York: Nova Science Publishers, Inc, New York

Grosso LM, Bracken MB (2005) Caffeine metabolism, genetics, and perinatal outcomes: A review of exposure assessment considerations during pregnancy. Ann Epidemiol 15:460–466 https://doi.org/10.1016/j.annepidem.2004.12.011 CrossRef

Tsutsumi K, Kotegawa T, Matsuki S et al (2001) The effect of pregnancy on cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activities in humans. Clin Pharmacol Ther 70:121–125 https://doi.org/10.1067/mcp.2001.116495 CrossRef

Tracy TS, Venkataramanan R, Glover DD et al (2005) Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy. Am J Obstet Gynecol 192:633–639 https://doi.org/10.1016/j.ajog.2004.08.030 CrossRef

Yu T, Campbell SC, Stockmann C et al (2016) Pregnancy-induced changes in the pharmacokinetics of caffeine and its metabolites. J Clin Pharmacol 56:590–596 https://doi.org/10.1002/jcph.632 CrossRef

Tasnif Y, Morado J, Hebert MF (2016) Pregnancy-related pharmacokinetic changes. Clin Pharmacol Ther 100:53–62 https://doi.org/10.1002/cpt.382 CrossRef

Hakkola J, Pasanen M, Hukkanen J, et al (1996) Expression of xenobiotic-metabolizing cytochrome P450 forms in human full-term placenta. Biochem Pharmacol 51:403–411. https://doi.org/10.1016/0006-2952(95)02184-1CrossRef

10.

Bracken MB, Triche E, Grosso L et al (2002) Heterogeneity in assessing self-reports of caffeine exposure: Implications for studies of health effects. Epidemiology 13:165–171 https://doi.org/10.1097/00001648-200203000-00011 CrossRef

11.

Quiñones L, Lee K, Varela FN et al (2006) Famacogénica del cáncer: Estudio de variaciones genéticamente determinadas en la susceptibilidad a cáncer por exposición a xenobióticos. Rev Med Chil 134:499–515 https://doi.org/10.4067/S0034-98872006000400015 CrossRef

12.

Mose T, Kjaerstad MB, Mathiesen L et al (2008) Placental Passage of Benzoic acid, Caffeine, and Glyphosate in an Ex Vivo Human Perfusion System. J Toxicol Environ Heal Part A 71:984–991 https://doi.org/10.1080/01932690801934513 CrossRef

13.

Nau H (1986) Species differences in pharmacokinetics and drug teratogenesis. Environ Health Perspect Vol. 70:113–129 https://doi.org/10.1289/ehp.8670113 CrossRef

14.

Hentges CR, Guedes RR, Silveira RC, Procianoy RS (2010) Serum levels of caffeine in umbilical cord and apnea of prematurity. J Pediatr (Rio J) 86:137–142 https://doi.org/10.2223/JPED.1990 PubMed

15.

Schmidt B, Roberts RS, Davis P et al (2006) Caffeine Therapy for Apnea of Prematurity. New England Journal of Medicine 354(20):2112–2121. https://doi.org/10.1056/nejmoa054065 CrossRefPubMed

16.

Fenton TR, Nasser R, Eliasziw M et al (2013) Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant. BMC Pediatr 13:92 https://doi.org/10.1186/1471-2431-13-92 CrossRef

17.

Lopez-Sanchez RDC, Lara-Diaz VJ, Aranda-Gutierrez A et al (2018) HPLC Method for Quantification of Caffeine and Its Three Major Metabolites in Human Plasma Using Fetal Bovine Serum Matrix to Evaluate Prenatal Drug Exposure. J Anal Methods Chem 2018:2085059 https://doi.org/10.1155/2018/2085059 CrossRef

18.

Reynolds F (1998) Drug transfer across the term placenta. Placenta 19:239–255. https://doi.org/10.1016/S0143-4004(98)80046-5CrossRef

19.

Roco Á, Quiñones L, Agúndez JAG et al (2012) Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: Comparison with caucasian and asian populations. Front Genet 3:1–9 https://doi.org/10.3389/fgene.2012.00229 CrossRef

20.

Tassaneeyakul W, Birkett DJ, McManus ME, et al (1994) Caffeine metabolism by human hepatic cytochromes P450: contributions of 1A2, 2E1 and 3A isoforms. Biochem Pharmacol 47:1767–1776. https://doi.org/10.1016/0006-2952(94)90304-2CrossRef

21.

Tough SC, McDonald SW, Collisson BA et al (2017) Cohort Profile: The All Our Babies pregnancy cohort (AOB). Int J Epidemiol 46:1–13 https://doi.org/10.1093/ije/dyw363 CrossRef

22.

Bourget P, Roulot C, Fernandez H (1995) Models for placental transfer studies of drugs. Clin Pharmacokinet 28:161–180 https://doi.org/10.2165/00003088-199528020-00006 CrossRef

23.

1000 Genomes Project Consortium, Auton A, Brooks LD et al (2015) A global reference for human genetic variation. Nature 526:68–74 https://doi.org/10.1038/nature15393 CrossRef

24.

Frary CD, Johnson RK, Wang MQ (2005) Food sources and intakes of caffeine in the diets of persons in the United States. J Am Diet Assoc 105:110–113 https://doi.org/10.1016/j.jada.2004.10.027 CrossRef

25.

Vitti FP, Grandi C, Cavalli RDC et al (2018) Association between Caffeine Consumption in Pregnancy and Low Birth Weight and Preterm Birth in the birth Cohort of Ribeirão Preto. Rev Bras Ginecol e Obstet 40:749–756 https://doi.org/10.1055/s-0038-1675806 CrossRef

26.

Sengpiel V, Elind E, Bacelis J et al (2013) Maternal caffeine intake during pregnancy is associated with birth weight but not with gestational length: results from a large prospective observational cohort study. BMC Med 11:42 https://doi.org/10.1186/1741-7015-11-42 CrossRef

27.

Santiago SE, Park GH, Huffman KJ (2013) Consumption habits of pregnant women and implications for developmental biology: A survey of predominantly Hispanic women in California. Nutr J 12:1–14 https://doi.org/10.1186/1475-2891-12-91 CrossRef

28.

Grosso LM, Triche E, Benowitz NL, Bracken MB (2008) Prenatal caffeine assessment: fetal and maternal biomarkers or self-reported intake? Ann Epidemiol 18:172–178 https://doi.org/10.1016/j.annepidem.2007.11.005 CrossRef

29.

Chen L-W, Fitzgerald R, Murrin CM et al (2018) Associations of maternal caffeine intake with birth outcomes: results from the Lifeways Cross Generation Cohort Study. Am J Clin Nutr:1–8 https://doi.org/10.1093/ajcn/nqy219 CrossRef

30.

Dott M, Rasmussen SA, Hogue CJ, Reefhuis J (2010) Association between pregnancy intention and reproductivehealth related behaviors before and after pregnancy recognition, National Birth Defects Prevention Study, 1997-2002. Matern Child Health J 14:373–381 https://doi.org/10.1007/s10995-009-0458-1 CrossRef

31.

Błaszczyk-Bębenek E, Piórecka B, Kopytko M et al (2018) Evaluation of Caffeine Consumption among Pregnant Women from Southern Poland. Int J Environ Res Public Health 15:2373 https://doi.org/10.3390/ijerph15112373 CrossRef

32.

ENSANUT (2016) Encuesta Nacional de salud y nutrición 2016 https://www.gob.mx/cms/uploads/attachment/file/209093/ENSANUT.pdf

33.

Brown, A., Lopez MH (2013) Mapping the latino population, by state, county and city. In: Washington, DC Pew Res. Cent. https://www.pewhispanic.org/2013/08/29/mapping-the-latino-population-by-state-county-and-city/

34.

Lopez, M.H., Gonzalez-Barrera, A., Cuddington D (2013) Diverse origins: The nation’s 14 largest Hispanic-origin groups. In: Washington, DC Pew Hisp. Cent. https://www.pewhispanic.org/2013/06/19/diverse-origins-the-nations-14-largest-hispanic-origin-groups/

35.

Wierzejska R, Jarosz M, Siuba M, Sawicki W (2014) Comparison of maternal and fetal blood levels of caffeine and its metabolite. A pilot study. Polish Gynaecol 85:500–503 https://doi.org/10.17772/gp/1760

36.

Cornelis MC, El-Sohemy A, Campos H (2007) Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption. Am J Clin Nutr 86:240–244 https://doi.org/10.1093/ajcn/86.1.240 CrossRef

37.

Kobayashi S, Sata F, Sasaki S et al (2013) Genetic association of aromatic hydrocarbon receptor (AHR) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms with dioxin blood concentrations among pregnant Japanese women. Toxicol Lett 219:269–278 https://doi.org/10.1016/j.toxlet.2013.03.013 CrossRef

38.

Ramachandran A, Jaeschke H (2017) Mechanisms of acetaminophen hepatotoxicity and their translation to the human pathophysiology. J Clin Transl Res 3:157–169 https://doi.org/10.18053/jctres.03.2017S1.002 PubMedPubMedCentral

39.

Küster A, Tea I, Ferchaud-Roucher V et al (2011) Cord blood glutathione depletion in preterm infants: Correlation with maternal cysteine depletion. PLoS One 6. https://doi.org/10.1371/journal.pone.0027626 CrossRef

40.

Servey J, Chang J (2014) Over-the-Counter Medications in Pregnancy. Am Fam Physician 90:548–555. PMID: 25369643.

41.

van den Anker JN, Allegaert K (2018) Acetaminophen in the Neonatal Intensive Care Unit: Shotgun Approach or Silver Bullet. J Pediatr 198:10–11 https://doi.org/10.1016/j.jpeds.2018.02.046 CrossRef

42.

Padilla Martínez, Yadira Mayela & Hernández Herrera, Ricardo Jorge. (2010). Condiciones asociadas a la mortalidad neonatal específica en < 1000 g, en el Hospital de Gineco-Obstetricia N° 23, periodo 2005-2006. Boletín médico del Hospital Infantil de México, 67(4), 335-343. Recuperado en 12 de abril de 2020, de http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-11462010000400005&lng=es&tlng=es.

43.

Aleman A, Cafferata ML, Gibbons N et al (2013) Use of antenatal corticosteroids for preterm birth in Latin America: provider’s knowledge, attitudes and practices. Reproductive Health 10(1). https://doi.org/10.1186/1742-4755-10-4

Title: Modulation of CYP2E1 metabolic activity in a cohort of confirmed caffeine ingesting pregnant women with preterm offspring
Authors: M. R. Alcorta-García
C. N. López-Villaseñor
G. Sánchez-Ferrer
H. Flores-Mendoza
F. Castorena-Torres
M. A. Aguilar-Torres
C. M. Sepúlveda-Treviño
J. A. Hernández-Hernández
R. C. López-Sánchez
V. J. Lara-Díaz
Publication date: 01-12-2020
Publisher: Springer Berlin Heidelberg
Keyword: Paracetamol
Published in: Molecular and Cellular Pediatrics / Issue 1/2020
Electronic ISSN: 2194-7791
DOI: https://doi.org/10.1186/s40348-020-00096-3

At a glance: The STEP trials

Springer Medicine

Modulation of CYP2E1 metabolic activity in a cohort of confirmed caffeine ingesting pregnant women with preterm offspring

Abstract

Background

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2020

Shedding light on pediatric diseases: multispectral optoacoustic tomography at the doorway to clinical applications

Diagnostic and therapeutic odyssey of two patients with compound heterozygous leptin receptor deficiency

Mutations of uncertain significance in heterozygous variants as a possible cause of severe short stature: a case report

A case of recurrent herpes simplex 2 encephalitis, VZV reactivations, and dominant partial interferon-gamma-receptor-1 deficiency supports relevance of IFNgamma for antiviral defense in humans

Early clinical course after hematopoietic stem cell transplantation in children with juvenile metachromatic leukodystrophy

A role for the alpha-8 integrin chain (itga8) in glomerular homeostasis of the kidney