Can a Single Drop of Newborn Blood Reveal Childhood Cancer Risk Early?

Newborn heel-prick blood sampling was originally used to identify a small number of congenital conditions that can be treated early. Researchers are now asking whether the same dried blood spot could also identify children who are more likely to develop cancer later. A retrospective study suggests that the genetic risk of some early childhood cancers may indeed leave a detectable signal at birth.

The research team linked the Michigan cancer registry with the newborn blood spot repository and identified 1,948 children born between 1987 and 2020 who developed solid tumors or tumors of the brain and central nervous system before age 8. The researchers extracted DNA from dried blood spots stored for many years and sequenced 11 early-onset cancer predisposition genes: RB1, TP53, WT1, RET, SMARCB1, PTCH1, SUFU, APC, DICER1, ALK, and PHOX2B. Sufficient sequencing coverage was obtained for 99.9% of the samples.

Among these children who later developed cancer, 133, or about 6.8%, carried heterozygous variants classified as pathogenic or likely pathogenic. These included 116 single-nucleotide variants or short insertions and deletions, as well as 17 copy-number variants. The median age at cancer diagnosis was 14 months among those carrying such variants, compared with 32 months among those in whom none were detected, indicating that these genetic changes were particularly concentrated among those who developed cancer early in life.

Detection rates varied widely among cancer types. Among 50 patients with bilateral retinoblastoma, the study detected pathogenic RB1 variants in the newborn blood spots of 40. Among 132 patients with medulloblastoma, 14 carried variants in SUFU, PTCH1, SMARCB1, or TP53. RET variants were detected in all 6 patients with medullary thyroid carcinoma. By contrast, among 450 patients with neuroblastoma, only 1 had a variant covered by the panel, and no pathogenic activating ALK variants were found, illustrating that a small gene panel cannot cover most childhood cancers.

If risk can be identified before symptoms appear, medical teams may be able to arrange genetic counseling and regular surveillance based on the associated cancer predisposition syndrome, intervening while tumors are smaller or have not yet spread. The study also found that people carrying pathogenic variants had a higher rate of subsequently developing a second cancer. However, these associations do not yet prove that newborn genetic screening itself can reduce mortality or the burden of treatment.

The most important limitation is that the study included only children who later developed cancer and did not use the general newborn population as a control. The 6.8% figure therefore represents the detection rate within this specific group of cases, not the positive rate among all newborns. The study also cannot estimate how many false positives, variants of uncertain significance, or risk markers in people who never develop disease would result from large-scale screening. Genetic findings may also have implications for parents and siblings, raising questions about consent, privacy, insurance equity, and responsibility for long-term follow-up.

This study demonstrates that newborn blood spots stored for decades can still support targeted sequencing of cancer predisposition genes and provides preliminary technical and case data for an 11-gene panel. Before it can be incorporated into public health screening, the next step remains prospective research that includes newborns who do not develop cancer, assessing the positive predictive value, the harms and costs of surveillance, and whether learning about risk earlier truly improves children’s health outcomes.