Transgenerational effects of chemotherapy: Both male and female children born to women exposed to chemotherapy have fewer children.

Background: There is little known about the transgenerational effect of chemotherapy. For example, chemotherapy is known to decrease fecundity in women. But if women are able to have offspring after chemotherapy exposure, do these children also have decreased fecundity?

Methods: This study is a retrospective cohort study utilizing the Utah Population Database (UPDB), a comprehensive resource that links birth, medical, death and cancer records for individuals in the state of Utah. The male and female children (F1 generation) of chemotherapy-exposed women (F0 generation) were identified. The number of live births (F2 generation) to this F1 generation was compared to two sets of chemotherapy-unexposed, matched controls using conditional Poisson regression models (regression coefficient, 95% confidence interval, P-value). The first unexposed was established using the general population and the second unexposed was established using first cousins to the F1 generation.

Results: The exposed F1 individuals had 77.2% fewer children (-1.48; -2.51 to -0.70; p = 0.001) relative to the unexposed general population. F1 males had 86.9% fewer children (-2.03; -4.91 to -0.51; p = 0.005) and F1 females had 70.5% fewer children (-1.22; -2.40 to -0.36; p = 0.016). When comparing to their unexposed cousins, the F1 generation (both sexes combined) had 74.3% (-1.36; -2.82 to -0.29; p = 0.029) fewer children.

Conclusion: The sons and daughters (F1 generation) of chemotherapy-exposed women have fewer live births when compared to both matched, unexposed general population and cousin controls. Chemotherapy may have a transgenerational effect in exposed women which needs further investigation.