Introduction
Adolescent and young adult (AYA) cancer survivors are those diagnosed with cancer between ages 15 and 39. As 5-year survival rates in the U.S. are over 80%, there are 400,000 female AYA cancer survivors of reproductive age.1 AYA cancer survivors can face more infertility and adverse pregnancy outcomes compared to females without cancer,2-4 contributing to reproductive distress and family planning decisions.5-7 Cohort studies report increased preterm birth in young cancer survivors compared to females without cancer, but estimates vary by country.2,4,8,9
Data on the magnitude and mechanisms of perinatal risks in female AYA cancer survivors in the U.S. are limited. Preterm birth before 37 weeks (10% of U.S. births) is the leading cause of neonatal mortality and long-term health.10 In the U.S., the only two sizeable cohort studies approached this question by linking single state cancer registry data to birth certificate data. A prevalence ratio of 1.5 for preterm birth was reported among 2,598 births to AYA cancer survivors relative to controls,4 while the second study of 2,983 births to young cancer survivors reported a relative risk of 1.2.11
A significant but understudied maternal outcome in AYA cancer survivors is severe maternal morbidity (SMM), which encompasses labor and delivery outcomes that result in significant short or long-term consequences to a woman’s health.12 The overall incidence of SMM in the U.S. is around 1.4% among all pregnancies and rising.13 While pre-eclampsia and postpartum hemorrhage have been reported among AYA cancer survivors,9 data on SMM are lacking.
Importantly, little is known about mediators and moderators of increased perinatal risks in this population. AYA cancer survivors can experience late effects of some cancer treatments, such as cardiopulmonary disease,14 that may increase comorbidities before and during pregnancy. While it is unknown if screening for comorbidities risk-stratified by cancer treatments is routine, identification of comorbidities as a mediator would inform screening practices. Assisted reproductive technology (ART) is increasingly used for fertility preservation and infertility treatment in cancer15 and general populations.16 ART is itself a risk factor for preterm birth17 and SMM,18 but large-scale studies of impact of ART on perinatal risks in cancer survivors are needed.
To address these gaps in knowledge, we used a national administrative claims dataset to estimate the association between AYA cancer and adverse perinatal outcomes of preterm birth and SMM and to investigate mediation by pre-pregnancy and pregnancy maternal comorbidities and moderation by ART. We hypothesized that female AYA cancer survivors experience more maternal comorbidities than females without cancer, and these co-morbidities mediate the effect of prior cancer on preterm birth and SMM.