In Utero Exposure to Hormonal Contraception and Mortality in Offspring with and without Cancer: A Nationwide Cohort Study

SIMPLE SUMMARY: Hormonal contraception is widely used among reproductive-aged women. In spite of the high effectiveness of hormonal contraception, some users become pregnant, probably due to irregular use. We previously reported an increased morbidity of childhood cancer in a nationwide cohort of offspring exposed in utero to maternal use of hormonal contraception. However, it remains unknown if mortality is increased in offspring with and without cancer after in utero exposure to hormonal contraception. The present study indicates that in utero exposure to hormonal contraception has an influence on long-term child mortality and survival after a diagnosis of leukemia. These novel findings have potential use in guidelines for hormonal contraception use in relation to pregnancy and expand our understanding of the etiology and prognosis of childhood leukemia. ABSTRACT: Approximately 400 million women of reproductive age use hormonal contraceptives worldwide. Eventually, pregnancy sometimes occurs due to irregular use. Use in early pregnancy is found to be associated with child morbidities including cancer, the main reason for disease-related death in children. Here, we add the missing piece about in utero exposure to hormonal contraception and mortality in offspring, including assessments of prognosis in children with cancer. In utero exposure to hormonal contraception may be associated with death since we found a hazard ratio (HR) of 1.22 (95% confidence interval (CI) 1.01–1.48) compared to children of mothers with previous use. The HRs were 1.22 (95% CI 0.99–1.13) for oral combined products and 2.92 (95% CI 1.21–7.04) for non-oral progestin-only products. A poorer prognosis was also found in exposed children with leukemia (3.62 (95% CI: 1.33–9.87)). If causal, hormonal contraception in pregnancy seems detrimental for offspring health and a marker of poorer prognosis in children with leukemia.