Female AYA cancer survivors: Are they at risk for adverse obstetric outcomes?

Female adolescent and young adult (AYA) survivors of certain types of cancer appear to be at risk of birth rate deficits and obstetric complications, suggests a retrospective study from the UK.

Many young female cancer survivors are concerned about fertility and obstetric complications, but data on the risks for these outcomes in this population are scarce. [J Clin Oncol 2018;36:2169–2180] Moreover, most of the existing evidence only report risks for all cancer types combined.

“[T]o our knowledge, no study has ascertained the risks of a wide spectrum of obstetric complications by specific types of cancer in AYAs,” said the researchers. “[Hence, we aimed] to quantify deficits in birth rates and risks of obstetric complications for female AYA survivors of 17 specific types of cancer [based on a specific classification scheme for AYA tumours].”

TYACSS* is a population-based cohort of 200,945 5-year survivors of cancer diagnosed at age 15–39 years from England and Wales that was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997 to March 31, 2022. The researchers ascertained 27 specific obstetric complications through the HES in 96,947 women from TYACSS.

The main study objectives were to identify survivors of specific types of cancer who were at increased risk of potential birth deficits and obstetric complications by comparing the observed number of births affected against the expected number based on general population rates. [Lancet Oncol 2024;doi:10.1016/S1470-2045(24)00269-9]

Birth rate deficits

During a median follow-up of 11.9 years, 21,437 births were observed among 13,886 female AYA cancer survivors. According to the researchers, this was lower than expected. The overall observed-to-expected ratio (O:E) was 0.68 (p<0.0001).

Survivors of most types of cancer had fewer observed births than expected in the general population, except for survivors of bladder (O:E, 0.89; p=0.080) and lung cancer (O:E, 0.84; p=0.060).

Survivors of other genitourinary cancers (other than cervical, ovarian, bladder, or renal) had the greatest birth deficit (O:E, 0.35), followed by cervical cancer (O:E, 0.42), breast cancer (O:E, 0.49), and leukaemia (O:E, 0.53; p<0.0001 for all).

Obstetric complications

Cervical cancer survivors were at a heightened risk of a variety of serious pregnancy and labour complications compared with women in the general population. These include malpresentation of foetus during labour (standardized incidence ratio [SIR], 1.31), obstructed labour due to malposition and malpresentation of foetus (SIR, 1.72), amniotic fluid and membranes disorders (SIR, 2.49), premature rupture of membranes (SIR, 1.57), preterm labour and delivery (SIR, 2.74), placental disorders (SIR, 1.53) including placenta praevia (SIR, 1.6), and antepartum haemorrhage (SIR, 1.45).

“These [findings] suggest that cervical cancer survivors require a high-risk pregnancy care plan that requires close monitoring and assessment with input from an obstetric multidisciplinary team,” said the researchers.

“Our results provide evidence for the potential development of guidelines for the management of pregnancies in cervical cancer survivors to complement existing guidelines on the management of cervical cancer and a benchmark against which the obstetric risks of future cancer treatment can be compared,” they continued.

Leukaemia survivors were at risk of preterm labour and delivery (SIR, 1.5), obstructed labour (SIR, 1.65), postpartum haemorrhage (SIR, 1.25), and retained placenta and membranes without haemorrhage (SIR, 1.97).

Leukaemia patients may require a haematopoietic stem-cell transplant (HSCT), which involves total body irradiation as conditioning treatment. “Although the exact biological mechanism needs clarification, previous exposure of the uterus to total body irradiation given as conditioning treatment as part of HSCT might cause fibrosis or affect muscular or vascular functioning of the uterus analogous to that observed in survivors of childhood cancer treated with abdominal radiotherapy,” the researchers explained.

Survivors of all other** specific cancers had no more than two obstetric complications that exceeded an O:E of ≥1.25. “[This provides] reassurance for almost all AYA cancer survivors concerning their risks in pregnancy,” the researchers said.

In a nutshell

“This study, to our knowledge, is the largest ever cohort study to comprehensively investigate obstetric outcomes among female AYA cancer survivors,” said the researchers.

After characterizing the risk of 27 different obstetric complications in women who survived one of 17 different cancer types in AYAs diagnosed from age 15 to 39 years, the results provide vital evidence to inform the development of clinical guidelines for managing pregnancies in AYAs with a history of cancer, specifically for cervical cancer and leukaemia survivors, as current formal guidelines are lacking, they said.