Cancer Causes & Control

, Volume 29, Issue 6, pp 539–550 | Cite as

Maternal consumption of coffee and tea during pregnancy and risk of childhood ALL: a pooled analysis from the childhood Leukemia International Consortium

  • Elizabeth Milne
  • Kathryn R. Greenop
  • Eleni Petridou
  • Helen D. Bailey
  • Laurent Orsi
  • Alice Y. Kang
  • Margarita Baka
  • Audrey Bonaventure
  • Maria Kourti
  • Catherine Metayer
  • Jacqueline Clavel
Original paper



The early onset of childhood acute lymphoblastic leukemia (ALL) suggests that critical exposures occurring during pregnancy may increase risk. We investigated the effects of maternal coffee and tea consumption during pregnancy on ALL risk by pooling data from eight case–control studies participating in the Childhood Leukemia International Consortium.


Data on maternal coffee intake were available for 2,552 cases and 4,876 controls, and data on tea intake were available for 2,982 cases and 5,367 controls. Coffee and tea intake was categorized into 0, > 0–1, > 1–2, and > 2 cups/day, and covariates were combined and harmonized. Data on genetic variants in NAT2, CYP1A1, and NQO1 were also available in a subset. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression, and linear trends across categories were assessed.


No association was seen with ‘any’ maternal coffee consumption during pregnancy, but there was evidence of a positive exposure–response; the pooled OR for > 2 cups/day versus none was 1.27 (95% CI 1.09–1.43), p trend = 0.005. No associations were observed with tea consumption. No interactions were seen between coffee or tea intake and age, maternal smoking or genotype, and there was little or no evidence that associations with coffee or tea differed among cases with and without chromosomal translocations.


Despite some limitations, our findings suggest that high coffee intake during pregnancy may increase risk of childhood ALL. Thus, current advice to limit caffeine intake during pregnancy to reduce risk of preterm birth may have additional benefits.


Leukemia Child Coffee Tea Pooled analysis 



We would like to thank our colleague, mentor, and dear friend, Patricia Buffler, who passed away before the submission of this manuscript. She was a founding member and Chair of CLIC as well as the driving force behind the NCCLS. She provided unconditional support to finding the causes of childhood leukemia, and her scientific leadership and guiding force within CLIC will be remembered. The Aus-ALL consortium conducted the study and the Telethon Kids Institute (Telethon Kids) (formerly Telethon Institute for Child Health Research), University of Western Australia, was the coordinating center. Non-author investigators include Bruce Armstrong (Sydney School of Public Health), Elizabeth Milne (Telethon Kids), Frank van Bockxmeer (Royal Perth Hospital), Michelle Haber (Children’s Cancer Institute Australia), Rodney Scott (University of Newcastle), John Attia (University of Newcastle), Murray Norris (Children’s Cancer Institute Australia), Carol Bower (Telethon Kids), Nicholas de Klerk (Telethon Kids), Lin Fritschi (WA Institute for Medical Research, WAIMR), Ursula Kees (Telethon Kids), Margaret Miller (Edith Cowan University), Judith Thompson (WA Cancer Registry). The clinical Investigators were: Frank Alvaro (John Hunter Hospital, Newcastle); Catherine Cole (Princess Margaret Hospital for Children, Perth); Luciano Dalla Pozza (Children’s Hospital at Westmead, Sydney); John Daubenton (Royal Hobart Hospital, Hobart); Peter Downie (Monash Medical Centre, Melbourne); Liane Lockwood (Royal Children’s Hospital, Brisbane); Maria Kirby (Women’s and Children’s Hospital, Adelaide); Glenn Marshall (Sydney Children’s Hospital, Sydney); Elizabeth Smibert (Royal Children’s Hospital, Melbourne); Ram Suppiah (formerly Mater Children’s Hospital, Brisbane). Helen Bailey (Telethon Kids) was the project coordinator. The Greek authors would like to thank Alexandros Alexopoulos and all NARECHEM-ST Nationwide Registry of Childhood Hematological Malignancies and Solid Tumors Clinicians: Margarita Baka MD: Department of Pediatric Hematology-Oncology, ‘‘Pan.&Agl. Kyriakou’’ Children’s Hospital, Athens, Greece, Thivon & Levadeias, Goudi; Maria Moschovi MD: Hematology-Oncology Unit, First Department of Pediatrics, Athens University Medical School, ‘‘Aghia Sophia’’ General Children’s Hospital, Athens, Greece, Thivon&Papadiamantopoulou, Goudi, 11527 Athens, Greece; Sophia Polychronopoulou MD: Department of Pediatric Hematology-Oncology, ‘‘Aghia Sophia’’ General Children’s Hospital, Athens, Greece, Thivon&Papadiamantopoulou, Goudi, 11527 Athens, Greece; Emmanuel Hatzipantelis MD, PhD: Pediatric Hematology Oncology Unit, 2nd Pediatric Department of Aristotle University, AHEPA General Hospital, Thessaloniki, Greece, 1 St. Kyriakidi, 54636 Thessaloniki, Greece; Ioanna Fragandrea MD: Pediatric Oncology Department, Hippokration Hospital, Thessaloniki, Greece; Eftychia Stiakaki MD: Department of Pediatric Hematology-Oncology, University Hospital of Heraklion, Heraklion, Greece; Nick Dessypris, MSc, PhD and Evdoxia Bouka, MPH: Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece; Maria Karalexi MD: Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece. The CCLS thanks the families for their participation and the clinical investigators at the following collaborating hospitals for help in recruiting patients (1995–2008): University of California, Davis Medical Center (Dr. J. Ducore); University of California, San Francisco (Drs. M. Loh and K. Matthay); Children’s Hospital of Central California (Dr. V. Crouse), Lucile Packard Children’s Hospital (Dr. G. Dahl), Children’s Hospital Oakland (Dr. J. Feusner), Kaiser Permanente Roseville (former Sacramento; Drs. K. Jolly and V. Kiley), Kaiser Permanente Santa Clara (Drs. C. Russo, A. Wong, and D. Taggart), Kaiser Permanente San Francisco (Dr. K. Leung), and Kaiser Permanente Oakland (Drs. D. Kronish and S. Month). Finally, the CCLS thanks the entire study staff and former University of California, Berkeley Survey Research Center for their effort and dedication. The French authors would like to thank all of the Société Française de lutte contre les Cancers de l’Enfant et de l’Adolescent (SFCE) principal investigators: André Baruchel (Hôpital Saint-Louis/Hôpital Robert Debré, Paris), Claire Berger (Centre Hospitalier Universitaire, Saint-Etienne), Christophe Bergeron (Centre Léon Bérard, Lyon), Jean-Louis Bernard (Hôpital La Timone, Marseille), Yves Bertrand (Hôpital Debrousse, Lyon), Pierre Bordigoni (Centre Hospitalier Universitaire, Nancy), Patrick Boutard (Centre Hospitalier Régional Universitaire, Caen), Gérard Couillault (Hôpital d’Enfants, Dijon), Christophe Piguet (Centre Hospitalier Régional Universitaire, Limoges), Anne-Sophie Defachelles (Centre Oscar Lambret, Lille), François Demeocq (Hôpital Hôtel-Dieu, Clermont-Ferrand), Alain Fischer (Hôpital des Enfants Malades, Paris), Virginie Gandemer (Centre Hospitalier Universitaire—Hôpital Sud, Rennes), Dominique Valteau-Couanet (Institut Gustave Roussy, Villejuif), Jean-Pierre Lamagnere (Centre Gatien de Clocheville, Tours), Françoise Lapierre (Centre Hospitalier Universitaire Jean Bernard, Poitiers), Guy Leverger (Hôpital Armand-Trousseau, Paris), Patrick Lutz (Hôpital de Hautepierre, Strasbourg), Geneviève Margueritte (Hôpital Arnaud de Villeneuve, Montpellier), Françoise Mechinaud (Hôpital Mère et Enfants, Nantes), Gérard Michel (Hôpital La Timone, Marseille), Frédéric Millot (Centre Hospitalier Universitaire Jean Bernard, Poitiers), Martine Münzer (American Memorial Hospital, Reims), Brigitte Nelken (Hôpital Jeanne de Flandre, Lille), Hélène Pacquement (Institut Curie, Paris), Brigitte Pautard (Centre Hospitalier Universitaire, Amiens), Stéphane Ducassou (Hôpital Pellegrin Tripode, Bordeaux), Alain Pierre-Kahn (Hôpital Enfants Malades, Paris), Emmanuel Plouvier (Centre Hospitalier Régional, Besançon), Xavier Rialland (Centre Hospitalier Universitaire, Angers), Alain Robert (Hôpital des Enfants, Toulouse), Hervé Rubie (Hôpital des Enfants, Toulouse), Stéphanie Haouy (Hôpital Arnaud de Villeneuve, Montpellier), Christine Soler (Fondation Lenval, Nice), and Jean-Pierre Vannier (Hôpital Charles Nicolle, Rouen). We thank all families for their generous participation.

Author contributions

The authors who were involved in planning the analyses were EM, JC, EP, CM, KG; conducting the statistical analyses were EM, KG; participating in the core writing group were EM, JC, EP, CM, KG. All authors are principal investigators, co-investigators or designates of participating CLIC studies. All authors have reviewed the intellectual content and approve of the final version submitted for publication.


Aus-ALL was funded by the National Health and Medical Research Council of Australia Grant Number 254539. The French studies were funded by INSERM, the French Ministère de l’Environnement, the Agence Nationale de la Recherche (ANR) (Grant id: ANR-10-COHO-0009), the Association pour la Recherche sur le Cancer (ARC), the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS), the Agence Française de Sécurité Sanitaire de l’Environnement et du Travail (AFSSET), the Agence Nationale de Sécurité Sanitaire de l’alimentation, de l’Environnement et du Travail (PNREST Anses, Cancer TMOI AVIESAN, 2013/1/248), the association Cent pour sang la vie, the association Enfants et Santé, the Cancéropôle Ile-de-France, the Fondation de France, the Fondation Jeanne Liot, the Fondation pour la Recherche Médicale, the Fondation Weisbrem-Berenson, the Institut National du Cancer (INCa), the Ligue Contre le Cancer du Val de Marne, the Ligue Nationale Contre le Cancer (LNCC), the Institut Electicité Santé. NARECHEM-ST is partially supported by the National and Kapodistrian University of Athens, Athens Greece. The California Childhood Leukemia Study (CCLS) was funded by the National Institutes of Health, USA (R01ES009137) with additional support from the CHILDREN with CANCER, UK. The Childhood Leukemia International Consortium (CLIC) administration, annual meetings, and pooled analyses are partly supported by the National Cancer Institute (NCI), USA (R03CA132172, Cancer Epidemiology Consortia), National Institute of Environmental Health Sciences (NIEHS), USA (P01ES018172, R01ES009137, R13ES021145, R13ES022868, R13ES024632, and U13ES026496), the US Environmental Protection Agency (USEPA), USA (RD83451101), as part of the Center for Integrative Research on Childhood Leukemia and the Environment, CHILDREN with CANCER, UK (CwC UK), Alex’s Lemonade Stand Foundation (ALSF), the São Paulo Research Foundation (FAPESP), Northwestern Mutual (NM), Texas Children’s Hospital (TCH), and our individual member study institutions. The content is solely the responsibility of the authors and does not necessarily represent the official views of the institutions named above.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10552_2018_1024_MOESM1_ESM.docx (43 kb)
Supplementary material 1 (DOCX 43 KB)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Elizabeth Milne
    • 1
  • Kathryn R. Greenop
    • 1
  • Eleni Petridou
    • 2
    • 3
  • Helen D. Bailey
    • 1
  • Laurent Orsi
    • 4
  • Alice Y. Kang
    • 5
  • Margarita Baka
    • 6
  • Audrey Bonaventure
    • 4
    • 7
  • Maria Kourti
    • 8
  • Catherine Metayer
    • 5
  • Jacqueline Clavel
    • 4
    • 9
  1. 1.Telethon Kids InstituteUniversity of Western AustraliaWest PerthAustralia
  2. 2.Department of Hygiene, Epidemiology and Medical Statistics Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  3. 3.Department of Clinical Epidemiology, Department of MedicineKarolinska InstituteStockholmSweden
  4. 4.INSERM U1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Epidemiology of Childhood and Adolescent Cancers Team (EPICEA)Paris-Descartes UniversityVillejuifFrance
  5. 5.School of Public HealthUniversity of California, BerkeleyBerkeleyUSA
  6. 6.Department Pediatric Hematology-OncologyKyriakou Children’s HospitalAthensGreece
  7. 7.Cancer Survival Group, Department of Non-Communicable Disease EpidemiologyLondon School of Hygiene and Tropical MedicineLondonUK
  8. 8.Pediatric Oncology DepartmentHippokration General HospitalThessalonikiGreece
  9. 9.RNCE - National Registry of Childhood Cancers, Inserm, Villejuif and CHU de NancyVillejuifFrance

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