Patients with early-stage cervical cancer have an increased risk of preterm birth in a population-based cohort study

Objectives: Cancer therapy can impact not only fertility but also the course of a subsequent pregnancy. Over 40% of women with cervical cancer will be diagnosed prior to age 45 and many will have not completed childbearing. Those with early-stage disease are eligible for fertility-sparing surgery (FSS), which is increasingly utilized. We sought to evaluate obstetric outcomes among cervical cancer patients in a population-based cohort. Methods: This is a population based retrospective study of women age 18-45 years with a history of (FIGO 2009) stage IA1-IB1 cervical cancer reported to the California Cancer Registry (CCR) for the years 2000-2012. CCR data were linked to the 2000-2015 California Office of Statewide Health Planning and Development (OSPHD) birth and discharge datasets to establish a linked database with both oncologic characteristics and obstetric outcomes. Exposure status was defined as cervical cancer patients who conceived at least 3 months after fertility-sparing surgery (FSS) and delivered after 23 weeks gestational age (GA). The primary outcome was preterm birth, and only the first pregnancy following cancer diagnosis was considered. Secondary outcomes included growth restriction, fetal demise, neonatal morbidity (any of the following: need for respiratory support within 72 hours of life, hypoxic-ischemic encephalopathy, seizure, sepsis/pneumonia, meconium aspiration syndrome, birth trauma, and intracranial or subgaleal hemorrhage), and severe maternal morbidity (SMM) as defined by the CDC. Propensity score was used to match similar women in 2 groups in a 1:2 ratio (when possible) of cases to controls: group 1: women who conceived at least 1 year prior to their cervical cancer diagnosis; group 2: healthy controls. Wald statistics and logistic regression were used to evaluate outcomes. Results: Of the 4087 patients who were 18-45 years at time of cervical cancer diagnosis, 40.9% (n=1671) had a recorded pregnancy. Of those, 113 conceived following FSS and were primarily non-Hispanic White (52.2%) followed by Hispanic (31.9%) with a median age of 32 years (29-36). The majority had squamous cell carcinoma histology (62.8%), and of those with known type of surgery (97.3%), 90.9% had a LEEP or conization and 9.1% had a trachelectomy. Prematurity rates prior to 32 and 37 weeks were 5.3% and 26.5% respectively, and the live birth rate was 99.1%. Propensity score matching yielded 213 group 1 controls and 226 group 2 controls. Cervical cancer was associated with higher odds of preterm birth before 32 weeks compared to healthy controls (OR 4.17 95% CI 1.023-16.99), but not compared to control group 1, and higher odds of preterm birth before 37 weeks compared to both control groups (OR 2.39, 95% CI 1.34-4.25; OR 3.94, 95% CI 2.10-7.38, control 1, 2 respectively). There were no differences between the groups in rates of: growth restriction (5th or 10th percentile), fetal demise, and delivery via cesarean section. Neonatal morbidity was more common among the cervical cancer cohort compared to both control groups (OR 2.69, 95% CI 1.29-5.64; OR 2.3, 95% CI 1.15-4.72, control 1,2 respectively). Conclusions: In a population-based cohort, patients who conceived at least 3 months following surgery for early-stage cervical cancer had a high live birth rate, but higher odds of preterm delivery and consequent neonatal morbidity compared to matched controls who had a pregnancy prior to their diagnosis as well as healthy controls.