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.