Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC)

Marcotte, Erin L.; Thomopoulos, Thomas; Infante‐Rivard, Claire; Clavel, Jacqueline; Petridou, Eleni; Schüz, Joachim; Ezzat, Sameera; Dockerty, John D.; Metayer, Catherine; Magnani, Corrado; Scheurer, Michael E.; Mueller, Beth A.; Mora, Ana M.; Wesseling, Catharina; Skalkidou, Alkistis; Rashed, Wafaa M.; Francis, Stephen; Ajrouche, Roula; Erdmann, Friederike; Orsi, Laurent; Spector, Logan G.

doi:10.1016/s2352-3026(16)00002-8

Cited by 96 publications

(109 citation statements)

References 67 publications

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“…The relationship between birth weight more than 4 kg and subsequent cancer is also not new. Larger birthweight may be associated with insulin‐like growth factor gene overexpression or with certain chromosomal abnormalities, such as the Beckwith–Wiedemann syndrome . These infants are susceptible to accelerated rates of cell growth from increased insulin‐like growth factor 1 overexpression as a consequence of poorly controlled maternal hyperglycaemia.…”

Section: Discussionmentioning

confidence: 99%

“…Infants born by elective caesarean delivery have been shown to have higher rates of global DNA methylation of leucocytes in cord blood immediately after birth than those born by vaginal delivery, which was postulated to have a persistent influence on the development of future immunological diseases . Additionally, the lack of exposure to stress hormones associated with delivery with labour was suggested by Thomopolos et al to increase the risk of early‐onset (less than four years) acute lymphoblastic leukaemia .…”

Section: Discussionmentioning

confidence: 99%

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Treatment with nitric oxide in the neonatal intensive care unit is associated with increased risk of childhood cancer

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Treatment with nitric oxide in the neonatal intensive care unit is associated with increased risk of childhood cancer

et al. 2018

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“…These patients were matched with 200 controls who were free of childhood leukemia and were alive at the diagnosis date of the index ALL patient. We matched patients and controls on potential confounders, including age (exact date of birth), sex, gestational age (AE1 week), birth order (1, 2, or !3), mode of delivery (vaginal or by cesarean section), and selected only offspring of Danish-born parents (16)(17)(18). Furthermore, controls were matched as closely as possible to the index patient's date of neonatal blood spot sampling.…”

Section: Study Participantsmentioning

confidence: 99%

Neonatal Inflammatory Markers Are Associated with Childhood B-cell Precursor Acute Lymphoblastic Leukemia

et al. 2018

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It has been proposed that children with acute lymphoblastic leukemia (ALL) are born with a dysregulated immune function that together with postnatal environmental exposures causes childhood ALL. Despite its importance for the understanding of ALL etiology, this hypothesis has been inadequately explored. In a population-based case-control study, we measured the concentrations of 10 cytokines and other inflammatory markers on neonatal dried blood spots from 178 children who at ages 1 to 9 years were diagnosed with B-cell precursor ALL and 178 matched controls. Through linkage with Danish nationwide registers, we also assessed whether neonatal inflammatory markers were associated with previously demonstrated risk factors for childhood ALL. Children who developed B-cell precursor ALL had significantly lower neonatal concentrations of IL8, soluble IL6 receptor (sIL6R) α, TGFβ1, monocyte chemotactic protein (MCP)-1, and C-reactive protein (CRP) and higher concentrations of IL6, IL17, and IL18 compared with matched controls. Concentrations of IL10 were below the detection level for both patients and controls. Birth order (IL18 and CRP), gestational age (sIL6Rα, TGFβ1, and CRP), and sex (sIL6Rα, IL8, and CRP), but not maternal age, infections during pregnancy, birth weight nor mode of delivery were significantly associated with the neonatal concentrations of inflammatory markers. Our findings support the hypothesis that children who later develop B-cell precursor ALL are born with a dysregulated immune function. Children who develop acute lymphoblastic leukemia are immunologically distinct at birth and could potentially react abnormally to infections in early childhood. .

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“…1 Established risk factors include prenatal exposure to diagnostic X-rays, 2 genetic syndromes 3 and high birthweight 4 that combined, account for <10% of childhood cancer (CC) incidence. 5 More recently, pooled case-control studies of childhood leukaemia (CL) suggest modestly increased risks associated with residential painting and pesticide use and pre-labour caesarean delivery [6][7][8] and slightly decreased risks from day care attendance, extended breast feeding, and maternal vitamin and folic acid supplement use. 9,10 Known and suspected risk factors for CC 2 are briefly summarised in Appendix S1.…”

Section: Introductionmentioning

confidence: 99%

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

Tikellis

Dwyer

Paltiel

et al. 2018

Paediatric Perinatal Epid

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Background Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case‐control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre‐diagnostic exposure assessments and biological samples. Methods Eligibility criteria, follow‐up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses. Results Currently, six cohorts recruited over six decades (1950s‐2000s) contribute data on 388 120 mother‐child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother‐child pairs within 5 years. Harmonised data currently includes over 20 “core” variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades. Conclusions The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case‐control studies offer the potential for breakthroughs in paediatric cancer aetiologic research.

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Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC)

Cited by 96 publications

References 67 publications

Treatment with nitric oxide in the neonatal intensive care unit is associated with increased risk of childhood cancer

Treatment with nitric oxide in the neonatal intensive care unit is associated with increased risk of childhood cancer

Neonatal Inflammatory Markers Are Associated with Childhood B-cell Precursor Acute Lymphoblastic Leukemia

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

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