Supplementary file 1_Parental and childhood exposures and the risk of retinoblastoma, hepatoblastoma, and germ cell, bone, and soft tissue tumors in children: a systematic review and meta-analysis.docx

Birth weight <2,500 g was associated with hepatoblastoma (ES 3.33, 95% CI 1.30–8.54) with considerable heterogeneity across studies. A borderline association was observed for retinoblastoma (ES 1.27, 95% CI 0.99–1.63), while the estimate for germ cell tumors was elevated, albeit with a wide CI (ES 1.20, 95% CI 0.80–1.80). No association was observed for bone tumors or soft tissue tumors.

Small for gestation age was associated with hepatoblastoma (ES 1.76, 95% CI 1.28–2.43). Birth weight >4,000 g was not associated with any of the studied cancer types. Assisted reproductive technology (ES 2.82, 95% CI 1.82–4.39), Caesarean section (ES 1.47, 95% CI 1.20–1.79), and parental age >35 years (mothers ES 1.97, 95% CI 1.45–2.68; fathers ES 1.33, 95% CI 0.99–1.79) were observed to be associated with hepatoblastoma.

Paternal smoking during preconception/pregnancy was associated with an increased risk of hepatoblastoma (ES = 1.58, 95% CI 1.18–2.12). Paternal occupational exposure to pesticides during preconception/pregnancy was associated with an increased risk of retinoblastoma (ES = 1.55, 95% CI 1.09–2.21). For some other exposures, we found several raised ES but with very wide CIs.</p>Discussion<p>We identified only a few modifiable risk factors for certain childhood cancers, notably paternal smoking for hepatoblastoma and paternal occupational exposure to pesticides for retinoblastoma.

Larger studies for rare childhood cancers are needed, with international collaboration to increase sample sizes.</p>