Onyije Felix M, Dolatkhah Roya, Olsson Ann, Bouaoun Liacine, Schüz Joachim
Environment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Front Public Health. 2025 Jun 25;13:1576101. doi: 10.3389/fpubh.2025.1576101. eCollection 2025.
Neuroblastoma (NB) is the most common extracranial tumor in children. Synthesizing and elucidating modifiable risk factors is fundamental to inform primary prevention of NB. The objective is to review literature and synthesize risk factors for NB.
PubMed, Web of Science, and Embase databases were searched using lists of key words and MeSH terms related to exposures and risk of NB. Studies were included if they were case-control or cohort studies of children under the age of 20 years at diagnosis and reported Relative Risks (RRs) with 95% confidence intervals (CIs). Pooled effect sizes (ES) and 95% CIs for risk factors associated with NB were estimated using random-effects models.
We included 50 eligible studies from Asia, Europe, and North America, and Oceania on cases of NB diagnosed between 1964 and 2016. We observed associations for maternal occupational exposure to pesticides during preconception/pregnancy (ES 1.62, CI 1.04-2.54), high birthweight [(>4,000 g) ES 1.21, CI 1.02-1.42], and Cesarean section (ES 1.14, CI 1.00-1.30) and the risk of NB. Parental smoking showed a weak association, while breastfeeding ≥6 months (ES 0.50, CI 0.30-0.84) was inversely associated with NB. Birth characteristics such as low birthweight (<2,500 g), small and large-for-gestational age, gestation age <37 weeks and gestation age >40 weeks, and assisted reproductive technology were not associated with NB. Similarly, no associations were suggested for parental age, gestational diabetes, and pre-eclampsia. Maternal alcohol consumption during preconception/pregnancy, maternal intake of vitamin and folic acid during pregnancy, paternal occupational exposure to extremely low-frequency magnetic fields (ELF-MF), and maternal X-ray exposure during pregnancy were also not associated with the risk of NB. Paternal occupational and child's postnatal exposure to pesticides were also not associated with NB.
This systematic review and meta-analysis suggest that maternal occupational exposure to pesticides during preconception/pregnancy, high birthweight, Cesarean section, and breastfeeding (beneficial) were associated with the risk of NB, but all associations were rather modest in strength. Synthesizing of these risk factors are needed to inform whether there are avenues for primary prevention of NB.
神经母细胞瘤（NB）是儿童最常见的颅外肿瘤。综合并阐明可改变的风险因素是为NB的一级预防提供依据的基础。目的是回顾文献并综合NB的风险因素。
使用与NB暴露和风险相关的关键词列表及医学主题词（MeSH）在PubMed、Web of Science和Embase数据库中进行检索。纳入的研究需为诊断时年龄在20岁以下儿童的病例对照研究或队列研究，并报告相对风险（RRs）及95%置信区间（CIs）。使用随机效应模型估计与NB相关的风险因素的合并效应量（ES）及95% CIs。
我们纳入了来自亚洲、欧洲、北美洲和大洋洲的50项符合条件的研究，这些研究涉及1964年至2016年间诊断的NB病例。我们观察到孕前/孕期母亲职业性接触杀虫剂（ES 1.62，CI 1.04 - 2.54）、高出生体重[（>4000克）ES 1.21，CI 1.02 - 1.42]、剖宫产（ES 1.14，CI 1.00 - 1.30）与NB风险之间的关联。父母吸烟显示出较弱的关联，而母乳喂养≥6个月（ES 0.50，CI 0.30 - 0.84）与NB呈负相关。出生特征如低出生体重（<2500克）、小于胎龄儿和大于胎龄儿、孕周<37周和孕周>40周以及辅助生殖技术与NB无关。同样，未发现父母年龄、妊娠期糖尿病和子痫前期与NB有关联。孕前/孕期母亲饮酒、孕期母亲维生素和叶酸摄入、父亲职业性接触极低频磁场（ELF - MF）以及孕期母亲接受X线照射也与NB风险无关。父亲职业性接触和儿童出生后接触杀虫剂也与NB无关。
这项系统评价和荟萃分析表明，孕前/孕期母亲职业性接触杀虫剂、高出生体重、剖宫产以及母乳喂养（有益）与NB风险相关，但所有关联的强度都相当适中。需要综合这些风险因素来确定是否存在NB一级预防的途径。
