Risk factors of neuroblastoma: a systematic review and meta-analysis

IntroductionNeuroblastoma (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.MethodsPubMed, Web of Science, and Embase...

Full description

Saved in:
Bibliographic Details
Main Authors: Felix M. Onyije, Roya Dolatkhah, Ann Olsson, Liacine Bouaoun, Joachim Schüz
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Public Health
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2025.1576101/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849418597966807040
author Felix M. Onyije
Roya Dolatkhah
Ann Olsson
Liacine Bouaoun
Joachim Schüz
author_facet Felix M. Onyije
Roya Dolatkhah
Ann Olsson
Liacine Bouaoun
Joachim Schüz
author_sort Felix M. Onyije
collection DOAJ
description IntroductionNeuroblastoma (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.MethodsPubMed, 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.ResultsWe 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.DiscussionThis 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.
format Article
id doaj-art-17a3f5ff722045d9bd7947849b6fbd24
institution Kabale University
issn 2296-2565
language English
publishDate 2025-06-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Public Health
spelling doaj-art-17a3f5ff722045d9bd7947849b6fbd242025-08-20T03:32:24ZengFrontiers Media S.A.Frontiers in Public Health2296-25652025-06-011310.3389/fpubh.2025.15761011576101Risk factors of neuroblastoma: a systematic review and meta-analysisFelix M. OnyijeRoya DolatkhahAnn OlssonLiacine BouaounJoachim SchüzIntroductionNeuroblastoma (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.MethodsPubMed, 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.ResultsWe 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.DiscussionThis 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.https://www.frontiersin.org/articles/10.3389/fpubh.2025.1576101/fullneuroblastomahigh birthweightCesarean sectionbreastfeedingpesticidessystematic review and meta-analysis
spellingShingle Felix M. Onyije
Roya Dolatkhah
Ann Olsson
Liacine Bouaoun
Joachim Schüz
Risk factors of neuroblastoma: a systematic review and meta-analysis
Frontiers in Public Health
neuroblastoma
high birthweight
Cesarean section
breastfeeding
pesticides
systematic review and meta-analysis
title Risk factors of neuroblastoma: a systematic review and meta-analysis
title_full Risk factors of neuroblastoma: a systematic review and meta-analysis
title_fullStr Risk factors of neuroblastoma: a systematic review and meta-analysis
title_full_unstemmed Risk factors of neuroblastoma: a systematic review and meta-analysis
title_short Risk factors of neuroblastoma: a systematic review and meta-analysis
title_sort risk factors of neuroblastoma a systematic review and meta analysis
topic neuroblastoma
high birthweight
Cesarean section
breastfeeding
pesticides
systematic review and meta-analysis
url https://www.frontiersin.org/articles/10.3389/fpubh.2025.1576101/full
work_keys_str_mv AT felixmonyije riskfactorsofneuroblastomaasystematicreviewandmetaanalysis
AT royadolatkhah riskfactorsofneuroblastomaasystematicreviewandmetaanalysis
AT annolsson riskfactorsofneuroblastomaasystematicreviewandmetaanalysis
AT liacinebouaoun riskfactorsofneuroblastomaasystematicreviewandmetaanalysis
AT joachimschuz riskfactorsofneuroblastomaasystematicreviewandmetaanalysis