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Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC).
Lancet Haematol. 2016 Apr; 3(4):e176-85.LH

Abstract

BACKGROUND

Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery.

METHODS

We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis.

FINDINGS

The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1·06 (95% CI 0·99-1·13), and was significant for prelabour caesarean delivery and ALL (1·23 [1·04-1·47]; p=0·018). Emergency caesarean delivery was not associated with ALL (OR 1·02 [95% CI 0·81-1·30]). AML was not associated with caesarean delivery (all indications OR 0·99 [95% CI 0·84-1·17]; prelabour caesarean delivery 0·83 [0·54-1·26]; and emergency caesarean delivery 1·05 [0·63-1·77]).

INTERPRETATION

Our results suggest an increased risk of childhood ALL after prelabour caesarean delivery. If this association is causal, maladaptive immune activation due to an absence of stress response before birth in children born by prelabour caesarean delivery could be considered as a potential mechanism.

FUNDING

National Cancer Institute.

Authors+Show Affiliations

Department of Pediatrics, University of Minnesota, MN, USA. Electronic address: marcotte@umn.edu.Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.Department of Epidemiology, Biostatistics and Occupational Health, Faculty of Medicine, McGill University, Montreal, QC, Canada.INSERM Unit 1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center, Epidemiology of Childhood and Adolescent Cancers Team, Villejuif, France; Paris-Descartes University, UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center, Paris, France.Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.International Agency for Research on Cancer, Section of Environment and Radiation, Lyon, France.National Liver Institute, Menoufia University, Menoufia, Egypt.Dean's Department and Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.University of California, School of Public Health, Berkeley, CA, USA.Dipartimento di Medicina Traslazionale, Università del Piemonte Orientale, SCDU Epidemiologia dei Tumori, Novara, Italy.Baylor College of Medicine, Department of Pediatrics, Section of Hematology-Oncology, Houston, TX, USA; Texas Children's Cancer Center, Houston, TX, USA.Epidemiology Department, University of Washington School of Public Health, Seattle, WA, USA; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.Central American Institute for Studies on Toxic Substances, Universidad Nacional, Heredia, Costa Rica; Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA.Central American Institute for Studies on Toxic Substances, Universidad Nacional, Heredia, Costa Rica.Department of Women's and Children's Health, Obstetrics and Gynecology, Akademiska Sjukhuset, Uppsala, Sweden.Research Department, Children's Cancer Hospital Egypt 57357, Cairo, Egypt.University of California, School of Public Health, Berkeley, CA, USA; University of California, San Francisco, Neuro and Molecular Epidemiology Laboratory, San Francisco, CA, USA.INSERM Unit 1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center, Epidemiology of Childhood and Adolescent Cancers Team, Villejuif, France; Paris-Descartes University, UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center, Paris, France.International Agency for Research on Cancer, Section of Environment and Radiation, Lyon, France.INSERM Unit 1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center, Epidemiology of Childhood and Adolescent Cancers Team, Villejuif, France; Paris-Descartes University, UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center, Paris, France.Department of Pediatrics, University of Minnesota, MN, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27063976

Citation

Marcotte, Erin L., et al. "Caesarean Delivery and Risk of Childhood Leukaemia: a Pooled Analysis From the Childhood Leukemia International Consortium (CLIC)." The Lancet. Haematology, vol. 3, no. 4, 2016, pp. e176-85.
Marcotte EL, Thomopoulos TP, Infante-Rivard C, et al. Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC). Lancet Haematol. 2016;3(4):e176-85.
Marcotte, E. L., Thomopoulos, T. P., Infante-Rivard, C., Clavel, J., Petridou, E. T., Schüz, J., Ezzat, S., Dockerty, J. D., Metayer, C., Magnani, C., Scheurer, M. E., Mueller, B. A., Mora, A. M., Wesseling, C., Skalkidou, A., Rashed, W. M., Francis, S. S., Ajrouche, R., Erdmann, F., ... Spector, L. G. (2016). Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC). The Lancet. Haematology, 3(4), e176-85. https://doi.org/10.1016/S2352-3026(16)00002-8
Marcotte EL, et al. Caesarean Delivery and Risk of Childhood Leukaemia: a Pooled Analysis From the Childhood Leukemia International Consortium (CLIC). Lancet Haematol. 2016;3(4):e176-85. PubMed PMID: 27063976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC). AU - Marcotte,Erin L, AU - Thomopoulos,Thomas P, AU - Infante-Rivard,Claire, AU - Clavel,Jacqueline, AU - Petridou,Eleni Th, AU - Schüz,Joachim, AU - Ezzat,Sameera, AU - Dockerty,John D, AU - Metayer,Catherine, AU - Magnani,Corrado, AU - Scheurer,Michael E, AU - Mueller,Beth A, AU - Mora,Ana M, AU - Wesseling,Catharina, AU - Skalkidou,Alkistis, AU - Rashed,Wafaa M, AU - Francis,Stephen S, AU - Ajrouche,Roula, AU - Erdmann,Friederike, AU - Orsi,Laurent, AU - Spector,Logan G, Y1 - 2016/02/27/ PY - 2015/08/07/received PY - 2015/12/10/revised PY - 2015/12/23/accepted PY - 2016/4/12/entrez PY - 2016/4/12/pubmed PY - 2017/10/19/medline SP - e176 EP - 85 JF - The Lancet. Haematology JO - Lancet Haematol VL - 3 IS - 4 N2 - BACKGROUND: Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. METHODS: We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. FINDINGS: The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1·06 (95% CI 0·99-1·13), and was significant for prelabour caesarean delivery and ALL (1·23 [1·04-1·47]; p=0·018). Emergency caesarean delivery was not associated with ALL (OR 1·02 [95% CI 0·81-1·30]). AML was not associated with caesarean delivery (all indications OR 0·99 [95% CI 0·84-1·17]; prelabour caesarean delivery 0·83 [0·54-1·26]; and emergency caesarean delivery 1·05 [0·63-1·77]). INTERPRETATION: Our results suggest an increased risk of childhood ALL after prelabour caesarean delivery. If this association is causal, maladaptive immune activation due to an absence of stress response before birth in children born by prelabour caesarean delivery could be considered as a potential mechanism. FUNDING: National Cancer Institute. SN - 2352-3026 UR - https://www.unboundmedicine.com/medline/citation/27063976/Caesarean_delivery_and_risk_of_childhood_leukaemia:_a_pooled_analysis_from_the_Childhood_Leukemia_International_Consortium__CLIC__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2352-3026(16)00002-8 DB - PRIME DP - Unbound Medicine ER -