Maternal caffeine consumption and childhood behavioural and neurocognitive development: A focused narrative review
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Abstract
Rationale: The majority of pregnant women regularly consume caffeine, a habit-forming substance of no nutritional value for mother or baby.
Objectives: To examine evidence of association between maternal caffeine consumption and childhood behavioural and neurocognitive development, and to consider the soundness of current health guidance concerning the consumption of caffeine during pregnancy.
Methods: Database searches identified a large pool of peer-reviewed articles, which when culled for relevance yielded a modest corpus of animal and human research for inclusion in this focussed narrative review of potential caffeine-related threats to childhood behavioural and neurocognitive development.
Results: High biological plausibility of potential harm from maternal caffeine exposure indicated by early animal research is confirmed by more recent animal studies that sought to mimic human consumption patterns. Reported negative outcomes include increased neuronal network excitability and susceptibility to seizures in offspring, and disruptions to electrophysiological activity, learning, and memory. In contrast, human observational studies have yielded inconsistent findings. Some studies have reported evidence of negative behavioural and neurocognitive outcomes, including hyperkinetic disorder, attention deficit disorder, and intelligence level in preschool- and elementary-aged children. Other studies, however, reported no associations with maternal caffeine consumption for similar parameters.
Conclusions: Current understanding of caffeine-related increased risk of harm for childhood development is limited due to inconsistent findings from human research. However, persistent reports of possible negative outcomes indicate high priority need for further research. In the meantime, the cumulative scientific evidence supports advice to pregnant women and women contemplating pregnancy to avoid caffeine.
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James JE (1991) Caffeine and health. London: Academic Press.
Gilbert RM (1984) Caffeine consumption. In G. A. Spiller (Ed.), The methylxanthine beverages and foods: Chemistry, consumption, and health effects. New York: Alan R. Liss 185-214.
Gilbert RM (1976) Caffeine as a drug of abuse. In R. J. Gibbins, Y. Israel, H. Kalant, R. E. Popham, W. Schmidt, & R. G. Smart (Eds.), Research advances in alcohol and drug problems. New York: Wiley & Sons 3: 49-176.
Morgan KJ, Stults VJ, Zabik ME (1982) Amount and dietary sources of caffeine and saccharin intake by individuals ages 5 to 18 years. Regul Toxicol Pharmacol 2: 296-307. Link: https://bit.ly/3cF0RCA
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. Link: https://bit.ly/3zrxHAv
Galéra C, Bernard JY, van der Waerden J, Bouvard MP, Lioret S, et al. (2016) Prenatal caffeine exposure and child IQ at age 5.5 years: The EDEN mother-child cohort. Biol Psychiatry 80: 720-726. Link: https://bit.ly/3zlQM7f
James JE (1997) Understanding caffeine: A biobehavioral analysis. Thousand Oaks, CA: Sage Publications. Link: https://bit.ly/3cIUjTd
James JE (2020) Maternal caffeine consumption and pregnancy outcomes: A narrative review with implications for advice to mothers and mothers-to-be. BMJ Evid Based Med 25: 10. Link: https://bit.ly/3iLYL7B
James JE, Paull I (1985) Caffeine and human reproduction. Rev Environ Health 7: 151-167. Link: https://bit.ly/3vqEyXy
European Food Safety Authority (2015) Panel on Dietetic Products, Nutrition and Allergies. Scientific opinion on the safety of caffeine. EFSA Journal 13: 4102.
NHS (2018) Should I limit caffeine during pregnancy? United Kingdom National Health Service. Link: https://bit.ly/3wuz1AS
American College of Obstetricians and Gynecologists Committee (2016) Moderate caffeine consumption during pregnancy. Link:
Rall TW (1990) Drugs used in the treatment of asthma. The methylxanthines, cromolyn sodium, and other agents. In Gilman, A. G., Rall, T. W., Nies, A. S., & Taylor, P. (eds.) Goodman and Gilman’s the pharmacological basis of therapeutics. New York: Pergamon.
Horning MG, Butler CM, Nowlin J, Hill RB (1975) Drug metabolism in the human neonate. Life Sci 16: 651-671. Link: https://bit.ly/35i6na6
Darakjian LI, Kaddoumi A (2019) Physiologically based pharmacokinetic/pharmacodynamic model for caffeine disposition in pregnancy. Mol Pharm 16: 1340-1349. Link: https://bit.ly/3iOLgnw
Parsons WD, Neims AH (1981) Prolonged half-life of caffeine in healthy term newborn infants. J Pediatr 98: 640-641. Link: https://bit.ly/3xebfsK
Pearlman SA, Duran C, Wood MA, Maisels MJ, Berlin CM (1989) Caffeine pharmacokinetics in preterm infants older than 2 weeks. Dev Pharmacol Ther 12: 65-69. Link: https://bit.ly/3wql32B
Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24: 31-55. Link:
Franchetti P, Messini L, Cappellacci L, Grifantini M, Lucacchini A, et al. (1994) 8-Azaxanthine derivatives as antagonists of adenosine receptors. J Med Chem 37: 2970-2975. Link: https://bit.ly/3iI9fFg
LeBlanc J, Soucy J (1994) Hormonal dose–response to an adenosine receptor agonist. Can J Physiol Pharmacol 72: 113-116. Link: https://bit.ly/35pesd7
Carter AJ, O’Connor WT, Carter MJ, Ungerstedt U (1995) Caffeine enhances acetylcholine release in the hippocampus in vivo by a selective interaction with adenosine A1 receptors. J Pharmacol Exp Ther 273: 637-642. Link: https://bit.ly/2SACVJt
Garrett BE, Holtzman SG (1994) D1 and D2 dopamine receptor antagonists block caffeine-induced stimulation of locomotor activity in rats. Pharmacol Biochem Behav 47: 89-94. Link: https://bit.ly/3iIhXmA
Ferré S (2016) Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders. Psychopharmacology 233: 1963-1979. Link: https://bit.ly/2TxE1pL
Lane JD, Pieper CF, Phillips-Bute BG, Bryant JE, Kuhn CM (2002) Caffeine affects cardiovascular and neuroendocrine activation at work and home. Psychosom Med 64: 595-603. Link: https://bit.ly/3cIa64O
Kirkinen P, Jouppila P, Koivula A, Vuori J, Puukka M (1983) The effect of caffeine on placental and fetal blood flow in human pregnancy. Am J Obstet Gynecol 147: 939-942. Link: https://bit.ly/3pVHaf5
Resch BA, Papp JG (1983) Effects of caffeine on the fetal heart. American Journal of Obstetrics and Gynecology 146: 231-232.
Fujii T, Nishimura H (1972) Adverse effects of prolonged administration of caffeine on rat fetus. Toxicol Appl Pharmacol 22: 449-457. Link:
Nishimura H, Nakai K (1960) Congenital malformations in offspring of mice treated with caffeine. Proc Soc Exp Biol Med 104: 140-142. Link:
Palm PE, Arnold EP, Rachwall PC, Leyczek JC, Teague KW, et al. (1978) Evaluation of the teratogenic potential of fresh-brewed coffee and caffeine in the rat. Toxicol Appl Pharmacol 44: 1-16. Link: https://bit.ly/3xo4x3u
Terada M, Nishimura H (1975) Mitigation of caffeine induced teratogenicity in mice by prior chronic caffeine ingestion. Teratology 12: 79-82. Link:
Goyan J (1980) Food and Drug Administration news release, No. P80-36. Washington DC:FDA.
James JE (2002) “Third‐party” threats to research integrity in public–private partnerships. Addiction 97: 1251-1255. Link: https://bit.ly/35kjVBI
Thayer P, Palm P (1975) A current assessment of mutagenic and teratogenic effects of caffeine. CRC Crit Rev Toxicol 5: 345-380. Link: h
ttps://bit.ly/3vs6Yk5
Furuhashi N, Sato S, Suzuki M, Hiruta M, Tanaka M, et al. (1985) Effects of caffeine ingestion during pregnancy. Gynecol Obstet Invest 19: 187-191. Link: https://bit.ly/3cJZZfN
Kurppa K, Holmberg PC, Kuosma E, Saxen L (1983) Coffee consumption during pregnancy and selected congenital malformations: A nation wide case-control study. Am J Public Health 73: 1397-1399. Link: https://bit.ly/2RZbNUq
Linn S, Schoenbaum SC, Monson RR, Rosner B, Stubblefield PG, et al. (1982) No association between coffee consumption and adverse outcomes of pregnancy. N Engl J Med 306: 141-145. Link: https://bit.ly/35mUWOg
McDonald AD, Armstrong BG, Sloan M (1992) Cigarette, alcohol, and coffee consumption and congenital defects. Am J Public Health 82: 91-93. Link: https://bit.ly/3cHIOLI
Rosenberg L, Mitchell AA, Shapiro S, Slone D (1982) Selected birth defects in relation to caffeine-containing beverages. JAMA 247: 1429-1432. Link: https://bit.ly/3pSZ9CR
Lehtonen A, Uusitalo L, Auriola S, Backman K, Heinonen S, et al. (2020) Caffeine content in newborn hair correlates with maternal dietary intake. Eur J Nutr 59.
Loomans EM, Hofland L, Van der Stelt O, van der Wal MF, Koot HM, et al. (2012) Caffeine intake during pregnancy and risk of problem behavior in 5-to 6-year-old children. Pediatrics 130: e305- e313. Link: https://bit.ly/3xoV3Fg
Grimm VE, Frieder B (1988) Prenatal caffeine causes long lasting behavioral and neurochemical changes. Int J Neurosci 41: 15-28. Link:
Hughes RN, Beveridge IJ (1990) Sex-and age-dependent effects of prenatal exposure to caffeine on open-field behavior, emergence latency and adrenal weights in rats. Life Sci 47: 2075-2088. Link: https://bit.ly/3pYoE5F
Nakamoto T, Roy G, Gottschalk SB, Yazdani M, Rossowska M (1991) Lasting effects of early chronic caffeine feeding on rats’ behavior and brain in later life. Physiol Behav 49: 721-727. Link: https://bit.ly/3pSXNrL
Chen LW, Murrin CM, Mehegan J, Kelleher CC, Phillips CM, et al. (2019) maternal, but not paternal or grandparental, caffeine intake is associated with childhood obesity and adiposity: The Lifeways Cross-Generation Cohort Study. Am J Clin Nutr 109: 1648-1655. Link: https://bit.ly/3cCWlEz
Li J, Luo H, Wu Y, He Z, Zhang L, et al. (2015) Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet. Toxicol Appl Pharmacol 284: 3453-3453. Link: https://bit.ly/3goc2Sg
Papadopoulou E, Botton J, Brantsæter AL, Haugen M, Alexander J, et al. (2018) Maternal caffeine intake during pregnancy and childhood growth and overweight: Results from a large Norwegian prospective observational cohort study. BMJ Open 8: e018895. Link: https://bit.ly/2U6Rllb
Voerman E, Jaddoe VW, Gishti O, Hofman A, Franco OH, et al. (2016) Maternal caffeine intake during pregnancy, early growth, and body fat distribution at school age. Obesity 24: 1170-1177. Link: https://bit.ly/3grdMtO
Silva CG, Métin C, Fazeli W, Machado NJ, Darmopil S, et al. (2013) Adenosine receptor antagonists including caffeine alter fetal brain development in mice. Sci Transl Med 5: 197-204. Link: https://bit.ly/3gu8oVM
Li Y, Zhang W, Shi R, Sun M, Zhang L, et al. (2018) Prenatal caffeine damaged learning and memory in rat offspring mediated by ARs/PKA/CREB/BDNF pathway. Physiol Res 67: 975-983. Link: https://bit.ly/35qbrZO
Soellner DE, Grandys T, Nuñez JL (2009) Chronic prenatal caffeine exposure impairs novel object recognition and radial arm maze behaviors in adult rats. Behav Brain Res 205: 191-199. Link: https://bit.ly/3gtfqtW
Fazeli W, Zappettini S, Marguet SL, Grendel J, Esclapez M, et al. ( 2017) Early-life exposure to caffeine affects the construction and activity of cortical networks in mice. Exp Neurol 295: 88-103. Link: https://bit.ly/35sO0z3
Zappettini S, Faivre E, Ghestem A, Carrier S, Buée L, et al. (2019) Caffeine consumption during pregnancy accelerates the development of cognitive deficits in offspring in a model of tauopathy. Front Cell Neurosci 13: 438. Link: https://bit.ly/3xrGNLT
Linnet KM, Wisborg K, Secher NJ, Thomsen PH, Obel C, et al. (2009) Coffee consumption during pregnancy and the risk of hyperkinetic disorder and ADHD: A prospective cohort study. Acta Paediatrica 98: 173-179. Link: https://bit.ly/3vk4eFm
Bekkhus M, Skjøthaug T, Nordhagen R, Borge AI (2010) Intrauterine exposure to caffeine and inattention/overactivity in children. Acta Paediatr 99: 925-928. Link: https://bit.ly/3zrwKrV
Klebanoff MA, Keim SA (2015) Maternal serum paraxanthine during pregnancy and offspring body mass index at ages 4 and 7 years. Epidemiology 26: 185-191. Link: https://bit.ly/2TqcMgF
Del-Ponte B, Santos IS, Tovo-Rodrigues L, Anselmi L, Munhoz TN, et al. ( 2016) Caffeine consumption during pregnancy and ADHD at the age of 11 years: A birth cohort study. BMJ Open 6: e012749. Link: https://bit.ly/35mSp6I
Mikkelsen SH, Obel C, Olsen J, Niclasen J, Bech BH (2017) Maternal caffeine consumption during pregnancy and behavioral disorders in 11-year-old offspring: A Danish National Birth Cohort study. J Pediatr 189: 120-127. Link: https://bit.ly/2TyanAI
Bernard JY, Heude B, Galéra C (2016) Maternal caffeine intake during pregnancy and child cognition and behavior at 4 and 7 years of age. American Journal of Epidemiology 183: 871-872. Link: https://bit.ly/3zuwmZw
Klebanoff MA, Keim SA (2016) Maternal caffeine intake during pregnancy and child cognition and behavior at 4 and 7 years of age. American Journal of Epidemiology 183: 872–873. Link: https://bit.ly/3gpCc7b
Berglundh S, Vollrath M, Brantsæter AL, Brandlistuen R, Solé-Navais P, et al. (2021) Maternal caffeine intake during pregnancy and child neurodevelopment up to eight years of age: Results from the Norwegian Mother, Father and Child Cohort Study. Eur J Nutr 60: 791–805. Link: https://bit.ly/3gxhIIs
Christensen ZP, Freedman EG, Foxe JJ (2021) Caffeine exposure in utero is associated with structural brain alterations and deleterious neurocognitive outcomes in 9–10 year old children. Neuropharmacology 186: 108479. Link: https://bit.ly/3guK2wx
Leviton A (1988) Caffeine consumption and the risk of reproductive hazards. J Reprod Med 33: 175-178.
Leviton A (2018) Biases inherent in studies of coffee consumption in early pregnancy and the risks of subsequent events. Nutrients 10: 1152. Link: https://bit.ly/2Szba4a
Peck JD, Leviton A, Cowan LD (2010) A review of the epidemiologic evidence concerning the reproductive health effects of caffeine consumption: A 2000–2009 update. Food Chem Toxicol 48: 2549-2576. Link: https://bit.ly/3zu63CQ
Wikoff D, Welsh BT, Henderson R, Brorby GP, Britt J, et al. (2017) Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol 109: 585-648. Link: https://bit.ly/3cD0k3Z
Doepker C, Franke K, Myers ., et al. (2018) Key findings and implications of a recent systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Nutrients 10: 1536. Link: doi:10.3390/nu10101536”
Dietary Guidelines Advisory Committee (2015) Scientific report of the 2015 Dietary Guidelines Advisory Committee. Washington DC: US Department of Agriculture, Agricultural Research Service. Link: https://bit.ly/3zpHRBz
Dietary Guidelines Advisory Committee Dietary Guidelines for Americans, 2020-2025 (2020) US Department of Agriculture and US Department of Health and Human Services, 9th Edition December 2020. Link: https://bit.ly/3vriI6e
Jahanfar S, Jaafar SH (2015) Effects of restricted caffeine intake by mother on fetal, neonatal and pregnancy outcomes. Cochrane Database Syst Rev 6.
Modzelewska D, Bellocco R, Elfvin A, Brantsæter AL, Meltzer HM, et al. (2019) Caffeine exposure during pregnancy, small for gestational age birth and neonatal outcome: results from the Norwegian Mother and Child Cohort Study. BMC Pregnancy Childbirth 19: 80. Link: https://bit.ly/3pU0WaC
Sengpiel V, Elind E, Bacelis J, Nilsson S, Grove 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. Link: https://bit.ly/3cHzHLe