剖宫产与儿童白血病风险：来自国际儿童白血病协会（CLIC）的汇总分析
Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC).
作者信息
Marcotte Erin L, Thomopoulos Thomas P, Infante-Rivard Claire, Clavel Jacqueline, Petridou Eleni Th, 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 S, Ajrouche Roula, Erdmann Friederike, Orsi Laurent, Spector Logan G
机构信息
Department of Pediatrics, University of Minnesota, MN, USA.
Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
出版信息
Lancet Haematol. 2016 Apr;3(4):e176-85. doi: 10.1016/S2352-3026(16)00002-8. Epub 2016 Feb 27.
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.
背景
病例对照研究结果显示，剖宫产出生的幼儿患急性淋巴细胞白血病（ALL）的风险增加，尤其是临产前剖宫产；然而，分娩方式与儿童白血病亚型之间的关联尚未确立。因此，我们对数据进行了汇总分析，以研究儿童白血病与剖宫产之间的关联。
方法
我们汇总了来自儿童白血病国际联盟在9个国家（加拿大、哥斯达黎加、埃及、法国、德国、希腊、意大利、新西兰和美国）开展的13项病例对照研究的数据，涵盖1970年至2013年的出生情况。我们分析了总体剖宫产情况以及可能导致临产前剖宫产或急诊剖宫产的指征。我们使用多变量逻辑回归模型，对儿童的出生体重、性别、年龄、种族、父母教育程度、母亲年龄和研究进行了调整，以估计0至14岁确诊儿童患ALL和急性髓细胞白血病（AML）风险的比值比（OR）和95%置信区间（CI）。
结果
这些研究提供了8780例ALL病例、1332例AML病例和23459例对照的数据，其中8655例（99%）ALL病例、1292例（97%）AML病例和23351例（>99%）对照的分娩方式已知。四项研究提供了剖宫产指征（4313例ALL病例中有1061例进行了剖宫产，664例AML病例中有138例，5884例对照中有1401例）。剖宫产所有指征与ALL的OR为1.06（95%CI 0.99 - 1.13），临产前剖宫产与ALL的关联具有统计学意义（1.23 [1.04 - 1.47]；p = 0.018）。急诊剖宫产与ALL无关联（OR 1.02 [95%CI 0.81 - 1.30]）。AML与剖宫产无关联（所有指征OR 0.99 [95%CI 0.84 - 1.17]；临产前剖宫产0.83 [0.54 - 1.26]；急诊剖宫产1.05 [0.63 - 1.77]）。
解读
我们的结果表明临产前剖宫产术后儿童患ALL的风险增加。如果这种关联是因果关系，那么临产前剖宫产出生的儿童由于出生前缺乏应激反应导致的适应性免疫激活不良可被视为一种潜在机制。
资金来源
美国国立癌症研究所。
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