Long-term development of 12- and 15-year-old offspring after maternal cancer diagnosis during pregnancy: a prospective multicentre cohort study

Background: Evidence is lacking on the long-term effects of prenatal exposure to maternal cancer and its treatment on adolescent neurocognitive, cardiac, and physical health. Methods: In a multicentre cohort study, children aged 12 and/or 15 years, prenatally exposed to maternal cancer (treatment), underwent clinical, echocardiographic, and neurocognitive evaluations. Standardized assessments were used, and associations between neurocognitive outcomes and covariates were examined using one-way and multivariable analysis of variance. Further analyses examined the need for extra support and the impact of chemotherapy exposure on puberty onset. Results: Of 166 children, 122 were exposed to chemotherapy, 17 to surgery alone, 14 to radiotherapy, 1 to trastuzumab, 1 to rituximab, and 21 to no treatment. Cardiac function was within normal ranges, with a median ejection fraction of 56.7% (z-score: −1.6) and two cases showed mild systolic dysfunction (ejection fraction <50%). Neurocognitive outcomes, including intelligence, memory, and attention, were also within normal limits. Nine children, however, had lower verbal memory scores linked to chemotherapy exposure (β = −0.52, P = 0.044). Visuospatial memory was negatively correlated with maternal death (β = −0.55, P = 0.019), and attention was influenced by prematurity (β = 0.034 per gestational week, P = 0.020) and male sex (β = −0.17, P = 0.024). Extra support was needed in 21 children, primarily associated with lower intelligence, attention, and executive function scores, as well as prematurity. Pubertal development was within standard ranges, with no significant associations found between chemotherapy exposure and puberty onset. Conclusion: Overall, no significant disruptions were found in the neurocognitive, cardiac, or physical development of adolescents prenatally exposed to maternal cancer and its treatment. Observed vulnerabilities, such as lower verbal memory and attention scores, were primarily linked to prematurity and maternal death rather than maternal cancer or its treatment. Ongoing monitoring is recommended to understand long-term outcomes into adulthood.