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I4C Research Activity

As of June 2016, the I4C International Data Coordinating Centre houses data on:

  • 388,190 mothers and babies, including
  • 719 cases of childhood cancer (215 leukemia), from
  • 7 cohorts contributing data to the pooled analysis
    • ALSPAC
    • CPP
    • DNBC (10% sample)
    • JPS
    • MoBa (10% sample)
    • NINFEA
    • TIHS


  1. Patel DM, Gyldenkærne S, Jones RR, Olsen SF, Tikellis G, Granström C, Dwyer T, Stayner LT, Ward MH. Residential proximity to agriculture and risk of childhood leukemia and central nervous system tumors in the Danish national birth cohort. Environ Int. 2020 Oct;143:105955. doi:10.1016/j.envint.2020.105955. Epub 2020 Jul 22.

  2. Lewis P, Hellmich M, Fritschi L, Tikellis G, Morfeld P, Groß JV, Foster RG, Paltiel O, Klebanoff MA, Golding J, Olsen S, Magnus P, Ponsonby AL, Linet MS, Ward MH, Caporaso N, Dwyer T, Erren TC. Perinatal photoperiod and childhood cancer: pooled results from 182,856 individuals in the international childhood cancer cohort consortium (I4C). Chronobiol Int. 2020 Jul;37(7):1034-1047. doi: 10.1080/07420528.2020.1740724. Epub 2020 Apr 1.

  3. He JR, Ramakrishnan R, Hirst JE, Bonaventure A, Francis SS, Paltiel O, Håberg SE, Lemeshow S, Olsen S, Tikellis G, Magnus P, Murphy MFG, Wiemels JL, Linet MS, Dwyer T.

    Maternal Infection in Pregnancy and Childhood Leukemia: A Systematic Review and Meta-analysis.   J Pediatr. 2020 Feb;217:98-109.e8. doi: 10.1016/j.jpeds.2019.10.046. Epub 2019 Dec 4.           

  4. Patel DM, Jones RR, Booth BJ, Olsson AC, Kromhout H, Straif K, Vermeulen R, Tikellis G, Paltiel O, Golding J, Northstone K, Stoltenberg C, Håberg SE, Schüz J, Friesen MC, Ponsonby AL, Lemeshow S, Linet MS, Magnus P, Olsen J, Olsen SF, Dwyer T, Stayner LT, Ward MH; International Childhood Cancer Cohort Consortium. Parental occupational exposure to pesticides, animals and organic dust and risk of childhood leukemia and central nervous system tumors: Findings from the International Childhood Cancer Cohort Consortium (I4C).

    Int J Cancer. 2020 Feb 15;146(4):943-952. doi: 10.1002/ijc.32388. Epub 2019 May 24.

  5. Paltiel O, Lemeshow S, Phillips GS, Tikellis G, Linet MS, Ponsonby AL, Magnus P, Håberg SE, Olsen SF, Granström C, Klebanoff M, Golding J, Herceg Z, Ghantous A, Hirst JE, Borkhardt A, Ward MH, Holst Søegaard S, Dwyer T. The association between birth order and childhood leukemia may be modified by paternal age and birth weight. Pooled results from the International Childhood Cancer Cohort Consortium (I4C). International Journal of Cancer. 2019;144(1):26-33. doi: 10.1002/ijc.31635. Epub 2018 Oct 26.

  6. Tikellis G, Dwyer T, Paltiel O, Phillips GS, Lemeshow S, Golding J, Northstone K, Boyd A, Olsen S, Ghantous A, Herceg Z, Ward MH, Håberg SE, Magnus P, Olsen J, Ström M, Mahabir S, Jones RR, Ponsonby AL, Clavel J, Charles MA, Trevathan E, Qian ZM, Maule MM, Qiu X, Hong YC, Brandalise S, Roman E, Wake M, He JR, Linet MS; International Childhood Cancer Cohort Consortium.

    The International Childhood Cancer Cohort Consortium (I4C): A research platform of prospective cohorts for studying the aetiology of childhood cancers.

    Paediatr Perinat Epidemiol. 2018 Nov;32(6):568-583. doi: 10.1111/ppe.12519. Epub 2018 Nov 22

  7. Paltiel O, Tikellis G, Linet M, Golding J, Lemeshow S, Phillips G, Lamb K, Stoltenberg C, Håberg SE, Strøm M, Granstrøm C, Northstone K, Klebanoff M, Ponsonby AL, Milne E, Pedersen M, Kogevinas M, Ha E, Dwyer T; International Childhood Cancer Cohort Consortium. Birthweight and Childhood Cancer: Preliminary Findings from the International Childhood Cancer Cohort Consortium (I4C). Paediatr Perinat Epidemiol. 2015 Jul;29(4):335-45. doi: 10.1111/ppe.12193.
  8. Ghantous, A., Hernandez-Vargas, H., Byrnes, G., Dwyer, T., & Herceg, Z. (2015). Characterising the epigenome as a key component of the fetal exposome in evaluating in utero exposures and childhood cancer risk. Mutagenesis, 30(6), 733-742. doi:10.1093/mutage/gev010
  9. Dwyer T, Tikellis G, Ghantous A, Lemeshow S, Haberg SE, Olsen J, Paltiel O, Golding G, Linet MS, Herceg Z, Munthe-Kaas MC, Stoltenberg C.  MoBa and the International Childhood Cancer Cohort Consortium (I4C).  Norsk Epidemiologi 2014; 24 (1-2): 129-133
  10. Ghantous A, Saffery R, Cros MP, Ponsonby AL, Hirschfeld S, Kasten C, Dwyer T, Herceg Z, Hernandez-Vargas H. Optimized DNA extraction from neonatal dried blood spots: application in methylome profiling. BMC Biotechnol. 2014 Jul 1;14:60. doi: 10.1186/1472-6750-14-60.

I4C Working Groups

Working groups have been established to examine epigenetic changes and various environmental exposures with childhood cancer.

This working group is being headed by Dr Zdenko Herceg and Akram Ghantous (IARC, Lyon)

See the Epigenetic Working Group page on the NCI I4C Portal.

Led by Ora Paltiel from the Jerusalem Perinatal Study this group investigated the association between childhood cancer, specifically leukaemia, with specific attention to maternal adiposity measures using prospectively collected pooled data from six birth/childhood cohorts in the I4C consortium. The results of this work have been published in the Journal of Paediatric and Perinatal Epidemiolpgy. [See Publications list]

There are two working groups examining pesticide exposure both being led by Mary Ward, Leslie T. Stayner and Benjamin Booth from NIH/NCI

1. Parental Occupational Exposure
The NCI led team are examining the association between parental occupations that involve exposure to pesticides (mainly farming) and the subsequent development of childhood cancer in the offspring. This will involve the development of an automatic conversion table from national classification systems for job classifications to one international classification.
The group aims to pool prospectively collected data from a number of I4C cohorts with detailed parental occupation and pesticide data.
For more information contact Mary Ward (

2. Residential proximity and Agricultural pesticide exposures
The intention of this work is to evaluate the risk of childhood cancers in relation to residence in and distance from agricultural areas during pregnancy and early life, while accounting for parental occupational exposure to pesticides. This will involve access to historical land cover maps for the I4C cohorts during the time period of the cohort births and geocoding of residential addresses at the time of the index child's birth.

See Publications List 

Led by Terry Dwyer, the group is examining the hypothesis that maternal prenatal folic acid supplementation is associated with a reduced risk of the index child developing childhood cancers and in particular childhood leukaemia. The NIH has recently provided financial support to take this work forward. The group will analyse data from four more established I4C cohorts who have data on folic acid: TIHS, ALSPAC, DNBC and MoBa. Newer cohorts such as the Japanese Environmental Children's Study (JECS) may soon be in a position to contribute data to this work.

See the Folate Working Group page on the NCI I4C Portal.

The association of birth order with the development of childhood cancer is being examined using the pooled dataset comprising of six established birth cohorts (ALSPAC, CPP, DNBC, MoBa, TIHS). The hypothesis is that not being first born or higher parity is associated with a decreased risk of childhood cancer, particularly leukemia. The work is being led by Ora Paltiel at the Hadassah Medical Center, Jerusalem.

See Publication LIst: The association between birth order and childhood leukemia may be modified by paternal age and birth weight. Pooled results from the International Childhood Cancer Cohort Consortium (I4C).