Cancer chemotherapy in pregnancy and adverse pediatric outcomes: a population-based cohort study

Abstract

Background Administration of chemotherapy during pregnancy is often delayed, while preterm delivery is common. If in utero exposure to chemotherapy is associated with adverse pediatric outcomes, it is unknown whether that relationship is directly attributable to the chemotherapy or is mediated by preterm birth. Methods Cases were identified from Canadian cancer registries and administrative data in Alberta, British Columbia, and Ontario, 2003-2017, with follow-up until 2018. The primary exposure was receipt of chemotherapy during pregnancy. Severe neonatal morbidity and mortality (SNM-M), neurodevelopmental disorders and disabilities (NDDs) and pediatric complex chronic conditions (PCCC) reflected short- and long-term pediatric outcomes. Modified Poisson and Cox proportional hazard regression models generated adjusted risk ratios (RR) and hazard ratios (HR), respectively. The influence of preterm birth on the association between exposure to chemotherapy in pregnancy and each study outcome was explored using mediation analysis. Results Of the 1150 incident cases of cancer during pregnancy, 142 (12.3%) received chemotherapy during pregnancy. Exposure to chemotherapy in pregnancy was associated with a higher risk of SNM-M (RR 1.67, 95% CI: 1.13-2.46), but not NDD (HR 0.93, 95% CI: 0.71-1.22) or PCCC (HR 0.96, 95% CI: 0.80-1.16). Preterm birth <34 and <37 weeks mediated 75.8% and 100% of the observed association between chemotherapy and SNM-M, respectively. Conclusions Most children born to people with cancer during pregnancy appear to have favourable long-term outcomes, even following exposure to chemotherapy in pregnancy. However, preterm birth is quite common, and may contribute to increased rates of adverse neonatal outcomes.